Sources and method
How we worked – and where the limits of this review lie.
Primary sources
On 25 October 2026 we saved and analysed the following publicly accessible sources:
- the archive eltayebat.com: home page, food list, 17 rule pages in Arabic and English, and 339 studies cited there;
- 307 video pages with transcripts stored in the archive (March 2021 to April 2026);
- the unofficial sites altayybat.com and mytayibat.com.
According to the archive, the transcripts come from YouTube subtitles or an AI transcription. They contain no timestamps, may contain errors, and do not always distinguish between different speakers. We did not watch the videos themselves individually.
Who said what? Source status
Each statement has a source status:
- Video transcript: Elawady's own words (machine-transcribed). Arabic quotations were checked automatically for verbatim agreement with the transcript.
- Archive quote: a quotation the archive attributes to Elawady without naming the video. We searched for where these quotations occur in the transcripts. Only one was found verbatim, most as paraphrases.
- Archive editors: texts and study selection by the archive operators. According to the archive, the studies were compiled “independently of Dr. Diaa's words”. When we assess how a study is used, we therefore assess the archive, not Elawady.
- Food list of the archive and third-party sites: system rules without a reference, or unofficial presentations. Where the sources contradict each other, we show all versions.
Verification of the cited studies
All 339 studies cited by the archive were automatically matched against the PubMed database (via the official interface of the US National Library of Medicine) or Crossref: existence, title, year, journal, DOI, retraction and correction notices.
- All 339 studies exist. None has been retracted.
- For 8 entries, the PMID given by the archive led to an entirely different paper. We identified the correct publication by title search and marked it.
- PubMed lists corrections (errata) for 22 studies. This is noted for each study.
Independent cross-check
For each statement we also searched for independent evidence: systematic reviews, meta-analyses, randomised trials, large cohort studies, guidelines and statements by authorities and professional societies (including WHO, EFSA, BfR, BVL, the European Commission, IARC, ADA/EASD, NHS). Every study added was also checked via PubMed, and every official page was actually retrieved. We explicitly also searched for evidence supporting Elawady's position. The search logs are documented in the project.
Assessing studies and statements
We explain the basics under Understanding science. In short:
- Each study is assessed along several dimensions (including methodological quality, risk of bias, precision, directness, regional transferability) and, if cited by the archive, for the adequacy of how it is reported.
- Each statement receives a verdict on a seven-point scale and, separately, a certainty of evidence following GRADE logic.
- Studies are classified per statement as supporting, contradicting/limiting or mixed.
- All assessments are provisional until an external expert review has taken place.
Limits
- Most studies were checked on the basis of the abstract, only a few in full text. This is stated for each.
- Bias tools (RoB 2, ROBINS-E, AMSTAR 2, ROBIS) were applied for orientation only. No full formal assessment with independent double review took place.
- Some official documents (e.g. EUR-Lex, Egyptian regulations) could not be retrieved for technical reasons. This is noted for the sources concerned.
- The research was carried out with the support of an AI system (see About the project).
Study register
| ID | Authors / Title | Year | DOI / PMID | Study design | Population | Results | 7. Weaknesses | Methodological quality | Claims |
|---|---|---|---|---|---|---|---|---|---|
| A-ABX-01 | Association of antibiotics in infancy with early childhood obesity. Bailey LC, Forrest CB, Zhang P et al. | 2014 | PMID 25265089 DOI 10.1001/jamapediatrics.2014.1539 | Cohort study | Children in CHOP primary-care network | Children with 4+ antibiotic courses before age 2 were about 11% more likely to be obese. | Observational; residual confounding; Infections may confound | moderate | C-ABX-05 |
| A-ABX-02 | Infant antibiotic exposures and early-life body mass. Trasande L, Blustein J, Liu M et al. | 2013 | PMID 22907693 DOI 10.1038/ijo.2012.132 | Cohort study | Children born >=2500 g in Avon, UK, 1991-1992 (92.6% white; slightly more affluent than UK population; 85% of eligible births captured) | Antibiotics before 6 months were linked to slightly higher body mass later. | Parental recall of antibiotic use over 3-9 months; no type, dose or route; Confounding by indication (infections) not addressed; residual confounding acknowledged by authors | moderate | C-ABX-05 |
| A-ABX-03 | Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cox LM, Yamanishi S, Sohn J et al. | 2014 | PMID 25126780 DOI 10.1016/j.cell.2014.05.052 | Animal study | Laboratory mice (C57BL/6J, male and female; germ-free female Swiss-Webster recipients) | Low-dose penicillin early in life made mice fatter via their gut bacteria. | Mice; very small groups (3-10) with many t-tests and no multiplicity correction; Sub-therapeutic continuous dosing (growth-promoter model) unlike short human therapeutic courses | moderate | C-ABX-05 C-RES-05 |
| A-ABX-04 | Antibiotic exposure in the first two years of life and development of asthma and other allergic diseases by 7.5 yr: a dose-dependent relationship. Hoskin-Parr L, Teyhan A, Blocker A et al. | 2013 | PMID 24299467 DOI 10.1111/pai.12153 | Cohort study | Children | More antibiotic courses were linked to more asthma at age 7. | Maternal report; Protopathic bias likely | moderate | C-ABX-06 |
| A-ABX-05 | Antibiotic exposure by 6 months and asthma and allergy at 6 years: Findings in a cohort of 1,401 US children. Risnes KR, Belanger K, Murk W et al. | 2011 | PMID 21190986 DOI 10.1093/aje/kwq400 | Cohort study | US children | Antibiotics before 6 months were linked to asthma at age 6. | Small; Two errata | moderate | C-ABX-06 |
| A-ABX-06 | Antibiotic use in children is associated with increased risk of asthma. Marra F, Marra CA, Richardson K et al. | 2009 | PMID 19255032 DOI 10.1542/peds.2008-1146 | Cohort study | BC births 1997-2003 | Infant antibiotics were linked to a small increased asthma risk. | No sibling control | moderate | C-ABX-06 |
| A-ABX-07 | Antibiotics associated with increased risk of new-onset Crohn's disease but not ulcerative colitis: a meta-analysis. Ungaro R, Bernstein CN, Gearry R et al. | 2014 | PMID 25223575 DOI 10.1038/ajg.2014.246 | Meta-analysis | 7208 IBD patients | Antibiotic exposure was linked to higher odds of Crohn's disease, especially in children. | Observational studies only; Heterogeneity not in abstract | moderate | C-ABX-07 |
| A-ABX-08 | Antibiotic exposure and IBD development among children: a population-based cohort study. Kronman MP, Zaoutis TE, Haynes K et al. | 2012 | PMID 23008454 DOI 10.1542/peds.2011-3886 | Cohort study | UK children | IBD was more common after antianaerobic antibiotics, but absolute rates remained low. | Protopathic bias possible | moderate | C-ABX-07 |
| A-ABX-09 | Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Dethlefsen L, Relman DA | 2011 | PMID 20847294 DOI 10.1073/pnas.1000087107 | Case series / case report | 3 healthy adults | In 3 people, gut bacteria changed quickly and did not fully return to the original state. | n=3; No clinical outcomes | moderate | C-ABX-04 |
| A-ABX-10 | Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. Jakobsson HE, Jernberg C, Andersson AF et al. | 2010 | PMID 20352091 DOI 10.1371/journal.pone.0009836 | Cohort study | Adults treated vs untreated controls | Changes and resistance genes persisted in some people up to 4 years. | Small | moderate | C-ABX-04 |
| A-ABX-11 | Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Yassour M, Vatanen T, Siljander H et al. | 2016 | PMID 27306663 DOI 10.1126/scitranslmed.aad0917 | Cohort study | 39 children | Children given antibiotics had less diverse gut bacteria. | n=39 | moderate | C-ABX-04 |
| A-ABX-12 | Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infection. Brown KA, Khanafer N, Daneman N et al. | 2013 | PMID 23478961 DOI 10.1128/AAC.02176-12 | Meta-analysis | Non-hospitalised | Some antibiotics (e.g. clindamycin) strongly raise C. difficile risk; tetracyclines did not. | Few studies | moderate | C-ABX-09 |
| A-ABX-13 | Azithromycin and the risk of cardiovascular death. Ray WA, Murray KT, Hall K et al. | 2012 | PMID 22591294 DOI 10.1056/NEJMoa1003833 | Cohort study | Tennessee Medicaid enrollees aged 30-74 years without life-threatening non-cardiovascular illness (azithromycin users 77.5% women, mean age 48.6) | Azithromycin was linked to about 47 extra heart deaths per million courses compared with amoxicillin. | Observational; residual confounding (smoking, BMI, infection severity) possible as acknowledged; Small numbers of events (29 CV deaths on azithromycin) | high | C-ABX-08 |
| A-ABX-14 | Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids. van der Linden PD, Sturkenboom MC, Herings RM et al. | 2003 | PMID 12912715 DOI 10.1001/archinte.163.15.1801 | Case-control study | UK GP patients | Current quinolone use was linked to about 4 times higher odds of Achilles rupture. | Case-control | moderate | C-ABX-09 |
| A-ABX-15 | Risk of Aortic Dissection and Aortic Aneurysm in Patients Taking Oral Fluoroquinolone. Lee CC, Lee MT, Chen YS et al. | 2015 | PMID 26436523 DOI 10.1001/jamainternmed.2015.5389 | Case-control study | 1 million insured | Current use was linked to higher risk of rare aortic events. | Observational | moderate | C-ABX-09 |
| A-ABX-16 | Fluoroquinolone use and risk of aortic aneurysm and dissection: nationwide cohort study. Pasternak B, Inghammar M, Svanström H | 2018 | PMID 29519881 DOI 10.1136/bmj.k678 | Cohort study | Treatment episodes | About 82 extra cases per million treatment courses compared with amoxicillin. | Observational | high | C-ABX-09 |
| A-ABX-17 | Antibiotic use in relation to the risk of breast cancer. Velicer CM, Heckbert SR, Lampe JW et al. | 2004 | PMID 14970061 DOI 10.1001/jama.291.7.827 | Case-control study | Women >19 y | More antibiotic use was linked to breast cancer, but cause and effect could not be determined. | Minimal adjustment; Confounding by indication | low | C-ABX-10 |
| A-ABX-18 | Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Antimicrobial Resistance Collaborators | 2022 | PMID 35065702 DOI 10.1016/S0140-6736(21)02724-0 | Risk assessment | Global | About 1.27 million deaths were directly caused by resistant bacteria in 2019. | Model-based; sparse data in many countries | high | C-ABX-02 C-ABX-03 C-ABX-12 |
| A-ABX-19 | Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011. Fleming-Dutra KE, Hersh AL, Shapiro DJ et al. | 2016 | PMID 27139059 DOI 10.1001/jama.2016.4151 | Cross-sectional study | US ambulatory visits | About 30% of outpatient antibiotic prescriptions were judged unnecessary. | Appropriateness estimated, not chart-reviewed | high | C-ABX-01 C-ABX-12 |
| A-ABX-20 | Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. Costelloe C, Metcalfe C, Lovering A et al. | 2010 | PMID 20483949 DOI 10.1136/bmj.c2096 | Meta-analysis | Patients | After an antibiotic, resistant bacteria are more common for months. | Mostly observational | moderate | C-ABX-01 |
| A-ABX-21 | Risk of meticillin resistant Staphylococcus aureus and Clostridium difficile in patients with a documented penicillin allergy: population based matched cohort study. Blumenthal KG, Lu N, Zhang Y et al. | 2018 | PMID 29950489 DOI 10.1136/bmj.k2400 | Cohort study | UK adults | People labelled penicillin-allergic had more MRSA and C. difficile, partly due to alternative antibiotics. | Observational | high | C-ABX-09 |
| A-BAR-01 | Perioperative safety in the longitudinal assessment of bariatric surgery. Longitudinal Assessment of Bariatric Surgery (LABS) Consortium, Flum DR, Belle SH et al. | 2009 | PMID 19641201 DOI 10.1056/NEJMoa0901836 | Cohort study | Adults with extreme obesity (median BMI 46.5) undergoing first-time RYGB or LAGB | About 3 in 1000 patients died within 30 days; 4.3% had a serious complication. | Only 30-day outcomes; Sleeve gastrectomy (n=117) excluded from outcome analyses | high | C-BAR-01 |
| A-BAR-02 | Effects of bariatric surgery on mortality in Swedish obese subjects. Sjöström L, Narbro K, Sjöström CD et al. | 2007 | PMID 17715408 DOI 10.1056/NEJMoa066254 | Cohort study | Adults with obesity in Sweden | Over about 11 years, people who had surgery had roughly 24-29% lower risk of dying than matched controls. | Not randomized (self-selection); Mostly older procedures (VBG, banding); few bypass, no sleeve | moderate | C-BAR-01 C-BAR-12 |
| A-BAR-03 | Long-term mortality after gastric bypass surgery. Adams TD, Gress RE, Smith SC et al. | 2007 | PMID 17715409 DOI 10.1056/NEJMoa066603 | Cohort study | Severely obese adults, Utah | Total deaths were 40% lower after surgery, while deaths from accidents and suicide were higher (11.1 vs 6.4 per 10,000 person-years). | Retrospective; controls from licence registry with limited health data; Residual confounding | moderate | C-BAR-01 C-BAR-07 C-BAR-12 |
| A-BAR-04 | Weight and Metabolic Outcomes 12 Years after Gastric Bypass. Adams TD, Davidson LE, Litwin SE et al. | 2017 | PMID 28930514 DOI 10.1056/NEJMoa1700459 | Cohort study | Adults 18-72 years with severe obesity (mean baseline BMI about 45-47; 84% women in surgery group) | Half of the patients with diabetes were still in remission after 12 years; new diabetes was about 90% less frequent than in non-operated people. | Non-randomized; residual confounding acknowledged by authors; Small diabetic subgroup (n=84-88) with wide CIs for remission ORs | moderate | C-BAR-08 C-BAR-14 |
| A-BAR-05 | Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study. Carlsson LMS, Sjöholm K, Jacobson P et al. | 2020 | PMID 33053284 DOI 10.1056/NEJMoa2002449 | Cohort study | Swedish adults with obesity; general-population reference sample | Operated patients lived about 3 years longer than non-operated patients with obesity, but still about 5.5 years less than the general population (non-operated: about 8.5 years less). | Not randomized; Old procedures; little sleeve data | moderate | C-BAR-01 C-BAR-09 C-BAR-10 C-BAR-12 |
| A-BAR-06 | Seven-Year Weight Trajectories and Health Outcomes in the Longitudinal Assessment of Bariatric Surgery (LABS) Study. Courcoulas AP, King WC, Belle SH et al. | 2018 | PMID 29214306 DOI 10.1001/jamasurg.2017.5025 | Cohort study | US adults undergoing bariatric surgery | About 60% of bypass patients with diabetes were still in remission at 7 years. | No non-surgical control; No sleeve gastrectomy | moderate | C-BAR-08 |
| A-BAR-07 | Effect of Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass on Weight Loss, Comorbidities, and Reflux at 10 Years in Adult Patients With Obesity: The SLEEVEPASS Randomized Clinical Trial. Salminen P, Grönroos S, Helmiö M et al. | 2022 | PMID 35731535 DOI 10.1001/jamasurg.2022.2229 | Randomised controlled trial | Adults 18-60 with severe obesity (median BMI 44.6) | Esophagitis was found in 31% after sleeve vs 7% after bypass; Barrett's esophagus was 4% in both groups. | 77% endoscopy completion; No non-surgical arm | high | C-BAR-02 C-BAR-03 C-BAR-04 C-BAR-10 C-BAR-14 |
| A-BAR-08 | Reflux, Sleeve Dilation, and Barrett's Esophagus after Laparoscopic Sleeve Gastrectomy: Long-Term Follow-Up. Felsenreich DM, Kefurt R, Schermann M et al. | 2017 | PMID 28593484 DOI 10.1007/s11695-017-2748-9 | Case series / case report | SG patients without preoperative symptomatic reflux or hiatal hernia | Many patients had reflux and 15% had Barrett's changes, but the study was very small. | Very small; Early SG technique | low | C-BAR-02 C-BAR-04 |
| A-BAR-09 | Systematic Endoscopy 5 Years After Sleeve Gastrectomy Results in a High Rate of Barrett's Esophagus: Results of a Multicenter Study. Sebastianelli L, Benois M, Vanbiervliet G et al. | 2019 | PMID 30666544 DOI 10.1007/s11695-019-03704-y | Cross-sectional study | SG patients without preoperative BE | About 1 in 5 had Barrett's changes; reflux symptoms rose from 22% to 76%. | Small; No control | low | C-BAR-02 C-BAR-03 C-BAR-04 |
| A-BAR-10 | Causes of small bowel obstruction after Roux-en-Y gastric bypass: a review of 2,395 cases at a single institution. Elms L, Moon RC, Varnadore S et al. | 2014 | PMID 24380988 DOI 10.1007/s00464-013-3361-1 | Case series / case report | LRYGB patients | About 4 in 100 patients needed another operation for possible bowel obstruction. | Single centre; Retrospective | low | C-BAR-14 |
| A-BAR-11 | Risk Factors for Marginal Ulcer After Gastric Bypass Surgery for Obesity: A Population-based Cohort Study. Sverdén E, Mattsson F, Sondén A et al. | 2016 | PMID 26106845 DOI 10.1097/SLA.0000000000001300 | Cohort study | Gastric bypass patients | Diabetes and earlier ulcers increased the risk of ulcers at the new stomach connection. | Register data | moderate | C-BAR-14 |
| A-BAR-12 | Early complications after laparoscopic gastric bypass surgery: results from the Scandinavian Obesity Surgery Registry. Stenberg E, Szabo E, Agren G et al. | 2014 | PMID 24374541 DOI 10.1097/SLA.0000000000000431 | Cohort study | Primary LRYGB patients | Serious complications 3.4%; deaths within 90 days 4 in 10,000. | Short-term only | high | C-BAR-01 |
| A-BAR-13 | Prevalence of alcohol use disorders before and after bariatric surgery. King WC, Chen JY, Mitchell JE et al. | 2012 | PMID 22710289 DOI 10.1001/jama.2012.6147 | Cohort study | Adults (78.8% female, 87.0% white, median age 47, median BMI 45.8) undergoing a first bariatric procedure (69.9% RYGB, 25.2% LAGB, 2.6% sleeve, 1.5% banded bypass, 0.8% BPD-DS) | Alcohol use disorder symptoms rose from 7.6% before surgery to 9.6% in the second year, mostly after gastric bypass. | No non-surgical control group (authors); Self-report; possible under-reporting before surgery and after a safety-referral trigger (authors) | moderate | C-BAR-07 |
| A-BAR-14 | Alcohol and other substance use after bariatric surgery: prospective evidence from a U.S. multicenter cohort study. King WC, Chen JY, Courcoulas AP et al. | 2017 | PMID 28528115 DOI 10.1016/j.soard.2017.03.021 | Cohort study | Adults with severe obesity undergoing first RYGB or LAGB (79.2% women, median age 47, median BMI 45.6, 87.0% white) | One in five bypass patients reported new alcohol problem symptoms within 5 years. | No non-surgical control and no randomization; findings cannot necessarily be attributed to surgery (authors); Retention 66-78% per year; MAR assumption | moderate | C-BAR-07 C-BAR-14 |
| A-BAR-15 | Self-harm Emergencies After Bariatric Surgery: A Population-Based Cohort Study. Bhatti JA, Nathens AB, Thiruchelvam D et al. | 2016 | PMID 26444444 DOI 10.1001/jamasurg.2015.3414 | Cohort study | Ontario adults undergoing bariatric surgery (98.5% gastric bypass) | Emergency visits for self-harm rose from 2.33 to 3.63 per 1000 patient-years after surgery. | Time trends not controlled; Only gastric bypass | moderate | C-BAR-07 |
| A-BAR-16 | Risk of suicide and non-fatal self-harm after bariatric surgery: results from two matched cohort studies. Neovius M, Bruze G, Jacobson P et al. | 2018 | PMID 29329975 DOI 10.1016/S2213-8587(17)30437-0 | Cohort study | Swedish adults with obesity attempting weight loss. SOS: age 37-60, BMI >=34 (men)/>=38 (women), excluding drug/alcohol abuse and psychiatric contraindications. SOReg/Itrim: age >=18, BMI 30-49.9 | Self-harm and suicide were more frequent after surgery, but absolute risks were low. | Non-randomised; selection bias and residual confounding acknowledged (self-harm history more common in SOS surgery group: 3.4% vs 1.9%); Itrim participants paid for treatment (socioeconomic selection), partly addressed by adjustment | moderate | C-BAR-01 C-BAR-07 |
| A-BAR-17 | Risk of fracture after bariatric surgery in the United Kingdom: population based, retrospective cohort study. Lalmohamed A, de Vries F, Bazelier MT et al. | 2012 | PMID 22867649 DOI 10.1136/bmj.e5085 | Cohort study | UK adults BMI>=30 | No significant increase in fractures in the first 2-3 years. | Mean follow-up 2.2 years; Many banding procedures likely | moderate | C-BAR-06 |
| A-BAR-18 | Bone loss after bariatric surgery: discordant results between DXA and QCT bone density. Yu EW, Bouxsein ML, Roy AE et al. | 2014 | PMID 23929784 DOI 10.1002/jbmr.2063 | Cohort study | Morbidly obese adults | Spine bone density fell about 3% in one year; hip loss seen on DXA was not confirmed by CT. | Small; 1 year | moderate | C-BAR-06 |
| A-BAR-19 | Bone Density and Trabecular Morphology at Least 10 Years After Gastric Bypass and Gastric Banding. Lindeman KG, Rushin CC, Cheney MC et al. | 2020 | PMID 32663365 DOI 10.1002/jbmr.4112 | Cross-sectional study | 25 RYGB, 25 AGB, BMI-matched controls | Bypass patients had weaker bone structure than people of the same weight; band patients did not. | Small; Cross-sectional | moderate | C-BAR-06 |
| A-BAR-20 | Bariatric surgery and long-term nutritional issues. Lupoli R, Lembo E, Saldalamacchia G et al. | 2017 | PMID 29204255 DOI 10.4239/wjd.v8.i11.464 | Narrative review | Bariatric patients | Deficiencies are common but can be prevented with lifelong supplements and monitoring. | Non-systematic narrative review; selection of cited studies not described; Wide prevalence ranges from heterogeneous studies and definitions | low | C-BAR-05 C-BAR-10 |
| A-BAR-21 | Nutritional deficiencies after bariatric surgery. Bal BS, Finelli FC, Shope TR et al. | 2012 | PMID 22525731 DOI 10.1038/nrendo.2012.48 | Narrative review | Bariatric patients | Protein, vitamins and minerals can become deficient; many patients were already deficient before surgery. | Non-systematic; 2012 | low | C-BAR-05 |
| A-BAR-22 | Outcomes of pregnancy after bariatric surgery. Johansson K, Cnattingius S, Näslund I et al. | 2015 | PMID 25714159 DOI 10.1056/NEJMoa1405789 | Cohort study | Singleton pregnancies | Less gestational diabetes and fewer large babies, but more small babies. | Small number of deaths | moderate | C-BAR-01 |
| A-BAR-23 | Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications. Sjöström L, Peltonen M, Jacobson P et al. | 2014 | PMID 24915261 DOI 10.1001/jama.2014.5988 | Cohort study | SOS participants with T2D at baseline | Remission fell from 72% at 2 years to 30% at 15 years after surgery (controls: 16% to 6.5%); diabetes complications were about halved. | Low participation at 15 years (41-47%); Non-randomized | moderate | C-BAR-08 |
| A-BAR-24 | Bariatric Surgery versus Intensive Medical Therapy for Diabetes - 5-Year Outcomes. Schauer PR, Bhatt DL, Kirwan JP et al. | 2017 | PMID 28199805 DOI 10.1056/NEJMoa1600869 | Randomised controlled trial | Adults 20-60 years with uncontrolled T2D (HbA1c >7.0%) and BMI 27-43; analysed patients: mean age 49, 66% women, HbA1c 9.2%, BMI 37 (37% BMI <35), diabetes duration 8.4 years, 44% on insulin | After 5 years, 23-29% of operated patients reached near-normal HbA1c vs 5% with medicines alone. | Single centre, small; underpowered for hard clinical endpoints and for RYGB vs sleeve differences (authors); Non-blinded | moderate | C-BAR-08 C-BAR-10 C-BAR-14 |
| A-CHK-01 | Multidrug-Resistant Staphylococcus aureus in US Meat and Poultry. Waters AE, Contente-Cuomo T, Buchhagen J et al. | 2011 | PMID 21498385 DOI 10.1093/cid/cir181 | Cross-sectional study | Retail beef (ground), chicken (breasts, thighs), pork (chops, ground) and turkey (ground, cutlets) from 80 brands in 26 grocery stores | Almost half of meat samples carried S. aureus; about half of the isolates were multidrug-resistant, but for chicken it was about a quarter and no MRSA was found on chicken. | Small sample; authors state it was insufficient to estimate prevalence accurately; Convenience sampling; sampling period not reported | moderate | C-CHK-05 |
| A-CHK-02 | Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains. Leverstein-van Hall MA, Dierikx CM, Cohen Stuart J et al. | 2011 | PMID 21463397 DOI 10.1111/j.1469-0691.2011.03497.x | Cross-sectional study | Retail chicken, poultry, human clinical samples from 31 labs | Most retail chicken had ESBL bacteria, and many human isolates shared the same genes and plasmids. | Cross-sectional; direction of transmission inferred; 2009 data | high | C-CHK-05 |
| A-CHK-03 | Extended-spectrum β-lactamase genes of Escherichia coli in chicken meat and humans, The Netherlands. Overdevest I, Willemsen I, Rijnsburger M et al. | 2011 | PMID 21762575 DOI 10.3201/eid1707.110209 | Cross-sectional study | Retail chicken; patients in 4 hospitals | Four in five chicken samples had ESBL genes, matching those found in people. | Directionality inferred; Sample sizes not in abstract | moderate | C-CHK-05 |
| A-CHK-04 | Roxarsone, inorganic arsenic, and other arsenic species in chicken: a U.S.-based market basket sample. Nachman KE, Baron PA, Raber G et al. | 2013 | PMID 23694900 DOI 10.1289/ehp.1206245 | Measurement / residue study | Conventional, antibiotic-free and organic retail chicken in 10 US metro areas | Conventional chicken had about three times more inorganic arsenic than organic chicken; estimated extra cancer risk was small. | Speciation only in samples with total As >=10 ug/kg DW (selection of higher-arsenic samples); Breast meat only; one sampling period (2010-2011) before US withdrawal of roxarsone | moderate | C-CHK-07 |
| A-CHK-05 | Global trends in antimicrobial use in food animals. Van Boeckel TP, Brower C, Gilbert M et al. | 2015 | PMID 25792457 DOI 10.1073/pnas.1503141112 | Other | Global livestock (cattle, chicken, pigs) | Models estimated about 63,000 tons used in 2010 with a projected 67% increase by 2030. | Extrapolation from high-income data; Model uncertainty larger than reported SD may suggest | moderate | C-CHK-05 |
| A-CHK-06 | Modern organic and broiler chickens sold for human consumption provide more energy from fat than protein. Wang Y, Lehane C, Ghebremeskel K et al. | 2010 | PMID 19728900 DOI 10.1017/S1368980009991157 | Other | Whole chickens and cuts (skinless breast fillets, breast with skin, legs with skin, whole birds with skin) from organic farms and supermarkets ('farmed' = conventional); one wild pheasant as reference | Whole chickens with skin had more energy from fat than protein; skinless breast was lean, and organic chickens were similar. | Total sample size not reported; very small subgroups (often n=2-3); Opportunistic sourcing including media-supplied samples; no sampling frame | low | C-CHK-11 |
| A-CHK-07 | Fluoroquinolone-resistant Campylobacter infections: eating poultry outside of the home and foreign travel are risk factors. Kassenborg HD, Smith KE, Vugia DJ et al. | 2004 | PMID 15095200 DOI 10.1086/381597 | Case-control study | Patients with Campylobacter infection and matched controls | Domestic resistant infections were linked to eating chicken or turkey at restaurants. | Very wide CI (only 33 pairs); Recall bias | moderate | C-CHK-05 C-CHK-09 |
| A-CHK-08 | Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story. Nelson JM, Chiller TM, Powers JH et al. | 2007 | PMID 17342653 DOI 10.1086/512369 | Narrative review | US | Resistance concerns led the US to withdraw enrofloxacin from poultry in 2005. | Narrative; Authors from US agencies | moderate | C-CHK-05 |
| A-CHK-09 | High concentrations of the carcinogen 2-amino-1-methyl-6-phenylimidazo- [4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method. Sinha R, Rothman N, Brown ED et al. | 1995 | PMID 7553619 | Measurement / residue study | Chicken breasts and whole chickens | Well-done grilled or fried chicken breast had high PhIP levels; stewed chicken had none. | 1995 data; No health outcome | moderate | C-CHK-10 |
| A-CHK-10 | A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cross AJ, Ferrucci LM, Risch A et al. | 2010 | PMID 20215514 DOI 10.1158/0008-5472.CAN-09-3929 | Cohort study | US adults | Red and processed meat and some cooking mutagens were linked to colorectal cancer. | Self-reported cooking; database estimates; Red/processed meat, not poultry | moderate | C-CHK-10 |
| A-CHK-11 | Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Liu YY, Wang Y, Walsh TR et al. | 2016 | PMID 26603172 DOI 10.1016/S1473-3099(15)00424-7 | Other | E. coli and K. pneumoniae from food animals, raw meat and inpatients in five provinces | A transferable gene making bacteria resistant to the last-resort antibiotic colistin was found in animals, meat and some patients. | China-specific surveillance; Index strain from a pig; poultry-specific share not given in abstract | high | C-CHK-05 |
| A-CHK-12 | Consumption of meat and dairy and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition. Rohrmann S, Linseisen J, Jakobsen MU et al. | 2011 | PMID 20473877 DOI 10.1002/ijc.25387 | Cohort study | European adults | No overall link; poultry was linked to some lymphoma subtypes, possibly by chance. | Multiple subgroup tests; Authors note chance plausible | moderate | C-CHK-01 C-DRY-12 |
| A-CHK-13 | Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Chen Y, Liang W, Yang S et al. | 2013 | PMID 23623390 DOI 10.1016/S0140-6736(13)60903-4 | Case series / case report | Four hospital inpatients (3 men, 1 woman; age 39-68, mean 56) with laboratory-confirmed H7N9 pneumonia at three hospitals in Zhejiang; 86 birds (20 chickens, 4 quails, 5 pigeons, 57 ducks) from six epidemiologically linked wet markets | Four patients caught H7N9 after contact with live poultry; two died. | Only four patients, all severe hospitalised cases (selection towards severity); Genome comparison for a single human-chicken pair | moderate | C-CHK-13 |
| A-CHK-14 | MRSA in conventional and alternative retail pork products. O'Brien AM, Hanson BM, Farina SA et al. | 2012 | PMID 22276147 DOI 10.1371/journal.pone.0030092 | Cross-sectional study | Retail pork from 36 stores | Pork raised without antibiotics carried MRSA as often as conventional pork. | Pork, not poultry | moderate | C-CHK-05 |
| A-CHK-15 | Lower prevalence of antibiotic-resistant Enterococci on U.S. conventional poultry farms that transitioned to organic practices. Sapkota AR, Hulet RM, Zhang G et al. | 2011 | PMID 21827979 DOI 10.1289/ehp.1003350 | Cross-sectional study | 10 conventional and 10 newly organic poultry houses | Poultry houses that switched to organic had far fewer multidrug-resistant bacteria. | Small number of houses; Farm environment, not meat | moderate | C-CHK-05 |
| A-CHK-16 | Poultry Consumption and Arsenic Exposure in the U.S. Population. Nigra AE, Nachman KE, Love DC et al. | 2017 | PMID 27735790 DOI 10.1289/EHP351 | Cross-sectional study | US participants >=6 years with undetectable arsenobetaine | Heavy poultry eaters had about 12% higher urine arsenic. | Single 24-h recall; Cross-sectional | moderate | C-CHK-07 |
| A-CHK-17 | National Outbreak of Multidrug Resistant Salmonella Heidelberg Infections Linked to a Single Poultry Company. Gieraltowski L, Higa J, Peralta V et al. | 2016 | PMID 27631492 DOI 10.1371/journal.pone.0162369 | Outbreak report | 634 case-patients with laboratory-confirmed S. Heidelberg (1 of 7 PFGE patterns) in 29 states and Puerto Rico (77% California); median age 18 years (<1-93) | 634 people fell ill from resistant Salmonella traced to one company's chicken. | No formal analytic study; comparison with an older (2006-2007) population survey; Recall bias for foods and brands (interviews weeks after onset); brand data available for only 175 cases | moderate | C-CHK-05 C-CHK-08 C-CHK-09 |
| A-CHK-18 | Increased risk of pneumonia in residents living near poultry farms: does the upper respiratory tract microbiota play a role? Smit LAM, Boender GJ, de Steenhuijsen Piters WAA et al. | 2017 | PMID 28702305 DOI 10.1186/s41479-017-0027-0 | Cross-sectional study | (i) 92,548 GP patients (70,142 adults 18-70 y, 22,406 children) in Noord-Brabant, a region with dense intensive livestock farming; (ii) 126 adults hospitalised with CAP near Tilburg (26 living <1 km, 100 >=1 km from a poultry farm), no antibiotics in prior 2 weeks, C. burnetii-negative | People living within about 1 km of poultry farms had 11% more pneumonia. | Kernel model contains no individual-level confounder adjustment (e.g. smoking, SES, age structure); Exposure is residential distance only; no measured PM/endotoxin; misclassification from activity patterns acknowledged | moderate | C-CHK-13 |
| A-CHK-19 | Broiler chickens, broiler chicken meat, pigs and pork as sources of ExPEC related virulence genes and resistance in Escherichia coli isolates from community-dwelling humans and UTI patients. Jakobsen L, Spangholm DJ, Pedersen K et al. | 2010 | PMID 20656368 DOI 10.1016/j.ijfoodmicro.2010.06.025 | Cross-sectional study | 964 E. coli isolates | E. coli from meat had virulence genes similar to those from patients with urinary infections. | Gene presence, not transmission proof | moderate | C-CHK-05 |
| A-CHM-01 | Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Cardinale D, Colombo A, Bacchiani G et al. | 2015 | PMID 25948538 DOI 10.1161/CIRCULATIONAHA.114.013777 | Cohort study | Heterogeneous adult cohort receiving anthracycline-containing chemotherapy | About 9 in 100 patients developed a measurable drop in heart pumping function, mostly within one year; most recovered fully or partly with heart medication. | Single centre; heterogeneous cancers; No untreated comparison group | moderate | C-CHM-01 |
| A-CHM-02 | Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. Lipshultz SE, Colan SD, Gelber RD et al. | 1991 | PMID 1997853 DOI 10.1056/NEJM199103213241205 | Cohort study | Children treated for ALL with doxorubicin 1-15 years earlier, in continuous remission | More than half of 115 childhood leukaemia survivors had heart function abnormalities, more often at higher doses. | Small, single-institution sample; Historical high cumulative doses | moderate | C-CHM-01 |
| A-CHM-03 | Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. Mulrooney DA, Yeazel MW, Kawashima T et al. | 2009 | PMID 19996459 DOI 10.1136/bmj.b4606 | Cohort study | Five-year survivors of childhood cancer diagnosed <21 years in 1970-1986 | Survivors reported heart failure about 6 times as often as siblings (1.7% vs 0.2%); by 30 years after diagnosis about 4% had heart failure. Risk rose with anthracycline dose and heart radiation. | Self/proxy-reported outcomes; medical-record validation attempted but abandoned (e.g. records obtainable for only 103 of 292 CHF reporters); Possible surveillance bias (exposed survivors monitored more) inflating relative hazards (authors) | moderate | C-CHM-01 C-CHM-06 |
| A-CHM-04 | Risk of ischemic heart disease in women after radiotherapy for breast cancer. Darby SC, Ewertz M, McGale P et al. | 2013 | PMID 23484825 DOI 10.1056/NEJMoa1209825 | Case-control study | Women irradiated for breast cancer 1958-2001 | Each extra Gray of average heart dose increased the rate of major coronary events by about 7%. | Historical techniques with higher heart doses; Case-control design | high | C-CHM-02 C-CHM-01 |
| A-CHM-05 | Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. Romond EH, Perez EA, Bryant J et al. | 2005 | PMID 16236738 DOI 10.1056/NEJMoa052122 | Randomised controlled trial | Women with surgically removed HER2-positive breast cancer | Fewer recurrences and a third fewer deaths; serious heart problems in about 3-4 in 100 treated women. | Interim analysis (early stopping can overestimate effect); Joint analysis amended post hoc | high | C-CHM-01 C-CHM-09 |
| A-CHM-06 | Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. Travis LB, Hill DA, Dores GM et al. | 2003 | PMID 12876089 DOI 10.1001/jama.290.4.465 | Case-control study | 3,817 female 1-year survivors of HD diagnosed at age <=30 years, 1965-1994 | Risk was about 3 times higher with >=4 Gy and 8 times higher with >40 Gy to the breast. | Wide CIs; Historical mantle-field doses much higher than modern involved-site RT | high | C-CHM-03 |
| A-CHM-07 | Proportion of second cancers attributable to radiotherapy treatment in adults: a cohort study in the US SEER cancer registries. Berrington de Gonzalez A, Curtis RE, Kry SF et al. | 2011 | PMID 21454129 DOI 10.1016/S1470-2045(11)70061-4 | Cohort study | Adults aged 20+ with a first primary invasive solid cancer at 15 sites routinely treated with radiotherapy (oral/pharynx, salivary gland, rectum, anus, larynx, lung, soft tissue, breast, cervix, endometrium, prostate, testis [seminoma], eye/orbit, brain/CNS, thyroid), SEER-9 registries, surviving >=5 years | About 5 extra cancers per 1,000 treated patients within 15 years; 8% of second cancers in irradiated patients. | No randomisation; confounding by indication (authors); No data on smoking, chemotherapy or hormonal therapy; higher RRs for smoking-related second cancers suggest residual confounding by smoking (authors) | moderate | C-CHM-03 C-CHM-09 |
| A-CHM-08 | Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. Fisher B, Costantino JP, Redmond CK et al. | 1994 | PMID 8133536 DOI 10.1093/jnci/86.7.527 | Randomised controlled trial | Node-negative ER-positive invasive breast cancer | Uterine cancer about 1.6 vs 0.2 per 1,000 women per year; 38% fewer recurrence-type events. | Small number of endometrial events; Data-integrity issue disclosed in the abstract (fraudulent records from one investigator) | moderate | C-CHM-03 C-CHM-09 |
| A-CHM-09 | Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. Ahles TA, Saykin AJ, Furstenberg CT et al. | 2002 | PMID 11786578 DOI 10.1200/JCO.2002.20.2.485 | Cross-sectional study | 5-year disease-free survivors of breast cancer or lymphoma | 39% of chemotherapy-treated vs 14% of locally treated survivors scored in the lowest quarter on memory/thinking tests. | Small sample; Cross-sectional; no pre-treatment baseline | low | C-CHM-04 |
| A-CHM-10 | Meta-analysis of cognitive functioning in breast cancer survivors previously treated with standard-dose chemotherapy. Jim HS, Phillips KM, Chait S et al. | 2012 | PMID 22927526 DOI 10.1200/JCO.2011.39.5640 | Meta-analysis | Breast cancer survivors | Breast-cancer survivors performed slightly worse in two of eight areas of thinking. | Heterogeneous designs; Small total sample | moderate | C-CHM-04 |
| A-CHM-11 | Reduction in Late Mortality among 5-Year Survivors of Childhood Cancer. Armstrong GT, Chen Y, Yasui Y et al. | 2016 | PMID 26761625 DOI 10.1056/NEJMoa1510795 | Cohort study | Five-year survivors of childhood cancer diagnosed <21 years with leukaemia, CNS malignancy, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma or bone tumour, initially treated 1970-1999 at 31 US/Canadian institutions (about 20% of US children diagnosed in the period) | 15-year death rate after surviving 5 years dropped from 12.4% to 6.0% between the 1970s and 1990s. | Observational era comparison; changes in supportive care, screening and medical care cannot be measured (authors); Health-related deaths cannot be directly attributed to treatment sequelae (authors) | high | C-CHM-06 C-CHM-09 C-CHM-13 |
| A-CHM-12 | Chronic health conditions in adult survivors of childhood cancer. Oeffinger KC, Mertens AC, Sklar CA et al. | 2006 | PMID 17035650 DOI 10.1056/NEJMsa060185 | Cohort study | Adults diagnosed with childhood cancer 1970-1986 | 62% had at least one chronic condition and 27.5% a severe one. | Self-reported conditions; Historical treatments | high | C-CHM-06 |
| A-CHM-13 | Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer. Frisina RD, Wheeler HE, Fossa SD et al. | 2016 | PMID 27354478 DOI 10.1200/JCO.2016.66.8822 | Cross-sectional study | North American male germ-cell tumour survivors | Almost 1 in 5 testicular-cancer survivors had severe-to-profound hearing loss; 40% had tinnitus. | Cross-sectional; Single cancer type, men only | moderate | C-CHM-05 |
| A-CHM-14 | Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors. Fung C, Dinh P, Ardeshir-Rouhani-Fard S et al. | 2018 | PMID 29670654 DOI 10.1155/2018/8671832 | Narrative review | Long-term testicular cancer survivors (TCS), disease-free >=5 years after primary treatment with cisplatin-based chemotherapy and/or radiotherapy; single-dose carboplatin and 1-2 cycles of BEP for stage I disease explicitly not reviewed | 10-year relative survival is 95%; heart disease and second cancers are the main serious late effects. | Narrative review; no systematic search, eligibility criteria or risk-of-bias appraisal; Selection of cited studies not reproducible; overlapping registry cohorts in SMN table (authors note overlap) | low | C-CHM-05 C-CHM-09 C-CHM-13 C-CHM-11 |
| A-CHM-15 | Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Smith SM, Le Beau MM, Huo D et al. | 2003 | PMID 12623843 DOI 10.1182/blood-2002-11-3343 | Case series / case report | Patients referred with t-MDS/t-AML since 1972 | In 306 patients, median survival after diagnosis was 8 months. | No denominator; cannot estimate incidence; Referral bias | low | C-CHM-03 |
| A-CHM-16 | Early palliative care for patients with metastatic non-small-cell lung cancer. Temel JS, Greer JA, Muzikansky A et al. | 2010 | PMID 20818875 DOI 10.1056/NEJMoa1000678 | Randomised controlled trial | Ambulatory patients with newly diagnosed metastatic NSCLC | Better quality of life, less depression, and longer median survival (11.6 vs 8.9 months) when added to cancer care. | Single centre, small; Survival a secondary outcome | moderate | C-CHM-07 |
| A-CHM-17 | Chemotherapy Use, Performance Status, and Quality of Life at the End of Life. Prigerson HG, Bao Y, Shah MA et al. | 2015 | PMID 26203912 DOI 10.1001/jamaoncol.2015.2378 | Cohort study | Adults (>=20 y) with end-stage cancer (distant metastases, refractory to >=1 chemotherapy line, physician-estimated life expectancy <=6 months) with an informal caregiver; ECOG 0: 2.9%, 1: 39.1%, 2: 37.2%, 3: 18.6%, 4: 2.2% | In patients still fit, chemotherapy near death was linked to worse quality of the last week. | Non-randomised; strong confounding by indication (chemotherapy users younger, fitter, academic centres) and no adjustment in stratum-specific models; Only decedents analysed (312 of 661 participants); patients who lived longer, possibly due to treatment, are excluded | moderate | C-CHM-07 |
| A-CHM-18 | Aggressiveness of cancer care near the end of life: is it a quality-of-care issue? Earle CC, Landrum MB, Souza JM et al. | 2008 | PMID 18688053 DOI 10.1200/JCO.2007.15.8253 | Narrative review | Cancer patients near death (US data) | Review of chemotherapy overuse and late hospice referral in the USA. | Narrative; no abstract numbers | low | C-CHM-07 |
| A-CHM-19 | The financial toxicity of cancer treatment: a pilot study assessing out-of-pocket expenses and the insured cancer patient's experience. Zafar SY, Peppercorn JM, Schrag D et al. | 2013 | PMID 23442307 DOI 10.1634/theoncologist.2012-0279 | Cross-sectional study | Insured US cancer patients contacting a copay foundation plus academic-centre comparison | 42% reported a heavy financial burden and many skipped medicines to save money. | Pilot, selected sample; US-specific | low | C-CHM-08 |
| A-DRY-01 | Milk intake and risk of mortality and fractures in women and men: cohort studies. Michaëlsson K, Wolk A, Langenskiöld S et al. | 2014 | PMID 25352269 DOI 10.1136/bmj.g6015 | Cohort study | 61,433 women aged 39-74 (baseline 1987-90) and 45,339 men aged 45-79 (baseline 1997) in three central Swedish counties. | Women drinking 3 or more glasses a day had a 1.93-fold mortality hazard compared with less than 1 glass (17.7 vs 10.7 deaths per 1,000 person-years); no fewer hip fractures. Yogurt/fermented milk and cheese showed the opposite: lower mortality. | Observational; residual confounding acknowledged (socioeconomic nuances; in men high milk intake went with lower education and more smoking); Reverse causation not excluded by authors | moderate | C-DRY-02 C-DRY-03 C-DRY-11 |
| A-DRY-02 | Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Aune D, Navarro Rosenblatt DA, Chan DS et al. | 2015 | PMID 25527754 DOI 10.3945/ajcn.113.067157 | Meta-analysis | Men in prospective cohorts. | About 7% higher risk per 400 g dairy a day and 9% per 50 g cheese a day. | Small relative risks; Possible detection bias (PSA screening) | high | C-DRY-04 C-DRY-11 |
| A-DRY-03 | Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study. Chan JM, Stampfer MJ, Ma J et al. | 2001 | PMID 11566656 DOI 10.1093/ajcn/74.4.549 | Cohort study | US male physicians | More than 2.5 servings/day: 34% higher relative risk. | Abbreviated dietary questionnaire; Single baseline assessment | moderate | C-DRY-04 |
| A-DRY-04 | Consumption of milk and calcium in midlife and the future risk of Parkinson disease. Park M, Ross GW, Petrovitch H et al. | 2005 | PMID 15781824 DOI 10.1212/01.WNL.0000154532.98495.BF | Cohort study | Japanese-American men aged 45-68 in Hawaii | Incidence rose from 6.9 to 14.9 per 10,000 person-years. | Single dietary assessment decades before outcome; Few cases (128) | moderate | C-DRY-09 |
| A-DRY-05 | Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies. Genkinger JM, Hunter DJ, Spiegelman D et al. | 2006 | PMID 16492930 DOI 10.1158/1055-9965.EPI-05-0484 | Meta-analysis | Women in 12 cohorts (North America, Europe) | No link for milk, cheese, yogurt or calcium; borderline result only for very high lactose. | Few cases per subgroup; Single dietary assessment in many cohorts | high | C-DRY-05 |
| A-DRY-06 | Milk and lactose intakes and ovarian cancer risk in the Swedish Mammography Cohort. Larsson SC, Bergkvist L, Wolk A | 2004 | PMID 15531686 DOI 10.1093/ajcn/80.5.1353 | Cohort study | Swedish women aged 38-76 | Serous ovarian cancer about twice as common with >=2 glasses of milk/day; other subtypes not linked. | Few cases (125 serous); Subgroup finding; multiple testing | moderate | C-DRY-05 |
| A-DRY-07 | High school dietary dairy intake and teenage acne. Adebamowo CA, Spiegelman D, Danby FW et al. | 2005 | PMID 15692464 DOI 10.1016/j.jaad.2004.08.007 | Cross-sectional study | US nurses (NHS II) reporting high-school diet in 1998 and severe teenage acne in 1989 | Total milk PR 1.22 (1.03-1.44) | Self-reported acne; Recall of adolescent diet decades later (A-DRY-07) | low | C-DRY-08 |
| A-DRY-08 | Milk consumption and acne in adolescent girls. Adebamowo CA, Spiegelman D, Berkey CS et al. | 2006 | PMID 17083856 | Cohort study | Girls in the Growing Up Today Study | Highest (>=2 servings/day) vs lowest (<1/week): total milk PR 1.20 (1.09-1.31), whole 1.19 (1.06-1.32), low-fat 1.17 (1.04-1.31), skim 1.19 (1.08-1.31). | Self-reported acne; Acne assessed once by questionnaire | moderate | C-DRY-08 |
| A-DRY-09 | Milk consumption and acne in teenaged boys. Adebamowo CA, Spiegelman D, Berkey CS et al. | 2008 | PMID 18194824 DOI 10.1016/j.jaad.2007.08.049 | Cohort study | Boys in the Growing Up Today Study | Highest (>2 servings/day) vs lowest (<1/wk): total milk PR 1.16 (1.01-1.34), whole/2% 1.10 (0.94-1.28), low-fat 1.17 (0.99-1.39), skim 1.19 (1.01-1.40). | Self-reported acne; Acne assessed once by questionnaire | moderate | C-DRY-08 |
| A-DRY-10 | Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk. Jianqin S, Leiming X, Lu X et al. | 2016 | PMID 27039383 DOI 10.1186/s12937-016-0147-z | Randomised controlled trial | Han Chinese adults aged 25-68 (mean 46.6 +/- 14.0 y; 21 men, 24 women) with irregular milk consumption and self-reported mild-to-moderate digestive discomfort after milk; 23/45 lactose intolerant by urinary galactose test. Recruited via community-hospital noticeboards; IBS, constipation and unmedicated IBD excluded. | People who felt milk did not agree with them had more symptoms with ordinary milk than with A2 milk. | Industry-funded; company employee conceived the study and selected outcomes; company-supplied products and company-funded medical writing; Small exploratory trial (n=45), no sample-size calculation, 2-week periods | low | C-DRY-02 C-DRY-07 |
| A-DRY-11 | Intake of dairy foods and risk of Parkinson disease. Hughes KC, Gao X, Kim IY et al. | 2017 | PMID 28596209 DOI 10.1212/WNL.0000000000004057 | Cohort study | US nurses and health professionals | Skim/low-fat milk HR 1.39; total dairy not significant in these cohorts. | Observational; Modest effects | moderate | C-DRY-09 |
| A-DRY-12 | Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial. Writing Group for the TRIGR Study Group, Knip M, Åkerblom HK et al. | 2018 | PMID 29297078 DOI 10.1001/jama.2017.19826 | Randomised controlled trial | Infants with HLA-conferred susceptibility and a first-degree relative with T1D | Type 1 diabetes in 8.4% vs 7.6%; no significant difference. | Specific high-risk infant population; Compares formula types, not dairy vs no dairy in adults | high | C-DRY-12 |
| A-DRY-13 | Dairy Product Consumption and Risk of Non-Hodgkin Lymphoma: A Meta-Analysis. Wang J, Li X, Zhang D | 2016 | PMID 26927171 DOI 10.3390/nu8030120 | Meta-analysis | Participants of 16 articles | Cohort studies found no association (RR 1.02). | Association driven by case-control studies (recall bias); Null in cohort studies | low | C-DRY-12 |
| A-DRY-14 | Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis. Harrison S, Lennon R, Holly J et al. | 2017 | PMID 28361446 DOI 10.1007/s10552-017-0883-1 | Systematic review | Humans (observational and experimental) and animals | IGF-I +0.10 SD per SD of milk; prostate cancer OR 1.09 per SD IGF-I. | Milk-IGF effect size is a visual estimate from albatross plots, not a pooled estimate; heterogeneous exposures (milk, dairy products, dairy protein); Largest milk-IGF effects come from very small, short-term trials in children with large doses | high | C-DRY-04 C-DRY-06 |
| A-DRY-15 | Galactose-Induced Skin Aging: The Role of Oxidative Stress. Umbayev B, Askarova S, Almabayeva A et al. | 2020 | PMID 32655772 DOI 10.1155/2020/7145656 | Narrative review | In vitro and animal models; galactosemia | Describes how high-dose galactose ages cells in experiments; no data on drinking milk. | Narrative, non-systematic; Animal/in vitro D-galactose models use non-dietary doses/routes | very low | C-DRY-12 |
| A-EGG-01 | The Belgian PCB and dioxin incident of January-June 1999: exposure data and potential impact on health. van Larebeke N, Hens L, Schepens P et al. | 2001 | PMID 11333188 DOI 10.1289/ehp.01109265 | Measurement / residue study | Belgian food chain (feed, cattle, pork, poultry, eggs, milk, fat-containing foods); population of 10 million | After contaminated feed was distributed, some eggs reached very high dioxin and PCB levels; modelled extra cancers ranged from 40 to 8,000. | Incident-specific; maxima are not representative of normal supply; Cancer estimate is a model with a 200-fold range | moderate | C-EGG-08 |
| A-EGG-02 | Level changes and human dietary exposure assessment of halogenated flame retardant levels in free-range chicken eggs: A case study of a former e-waste recycling site, South China. Huang CC, Zeng YH, Luo XJ et al. | 2018 | PMID 29631140 DOI 10.1016/j.scitotenv.2018.03.386 | Measurement / residue study | Free-range chicken eggs from Baihe village | Pollutant levels fell after regulation; in the worst case, exposure margins indicated possible concern. | Single highly polluted site; Worst-case scenario (highly polluted eggs) | moderate | C-EGG-08 |
| A-EGG-03 | PCDD/Fs and Dioxin-like PCBs in Chicken Eggs and Soils in Dong Nai Province, Southern Vietnam: Impacts of Raising Methods and Nearby Pollution Sources. Nghiem TX, Hoang AQ, Nguyen TD et al. | 2022 | PMID 35037074 DOI 10.1007/s00128-021-03419-w | Measurement / residue study | Chicken eggs and soils near Bien Hoa Airbase and industrial areas | Some eggs, especially from free-range hens, had dioxin levels well above EU limits; the typical (median) egg was much lower. | Hotspot area (former Agent Orange airbase); Sample size not in abstract | moderate | C-EGG-08 |
| A-EGG-04 | Dioxins, PCBs, chlorinated pesticides and brominated flame retardants in free-range chicken eggs from peri-urban areas in Arusha, Tanzania: Levels and implications for human health. Polder A, Müller MB, Brynildsrud OB et al. | 2016 | PMID 26897409 DOI 10.1016/j.scitotenv.2016.02.021 | Measurement / residue study | 159 eggs from households in five locations | Some backyard eggs exceeded EU limits for dieldrin and dioxins; backyard fires were a likely source. | Pooled samples; Backyard free-range eggs only | moderate | C-EGG-08 |
| A-EGG-05 | Reviewing the relevance of dioxin and PCB sources for food from animal origin and the need for their inventory, control and management. Weber R, Herold C, Hollert H et al. | 2018 | PMID 30464877 DOI 10.1186/s12302-018-0166-9 | Narrative review | Food-producing animals (laying hens outdoors, suckler calves, beef) | In Germany, contaminated soils and old PCB materials are the main sources; outdoor hens can exceed EU limits even at low soil levels. | Narrative, not systematic; Abstract only | moderate | C-EGG-08 C-CHK-12 |
| A-EGG-06 | Per- and poly-fluoroalkyl substances in commercial organic eggs via fishmeal in feed. Granby K, Ersbøll BK, Olesen PT et al. | 2024 | PMID 37944762 DOI 10.1016/j.chemosphere.2023.140553 | Measurement / residue study | Commercial eggs from larger Danish farms (free-range, barn, organic) | Organic eggs had PFAS from fishmeal; ordinary free-range and barn eggs had little or none; removing fishmeal solved the problem. | Exposure at 95th percentile and solely from eggs; Small number of farms | moderate | C-EGG-08 |
| A-EGG-07 | Potential Health Effects of Heavy Metals and Carcinogenic Health Risk Estimation of Pb and Cd Contaminated Eggs from a Closed Gold Mine Area in Northern Thailand. Aendo P, De Garine-Wichatitsky M, Mingkhwan R et al. | 2022 | PMID 36140919 DOI 10.3390/foods11182791 | Measurement / residue study | Chicken farms, duck farms and free-grazing duck farms <25 km and >25 km from a gold mine | Eggs from free-grazing ducks near the mine had more mercury and lead. | Mining hotspot; ILCR model assumptions (Pb carcinogenicity slope) | low | C-EGG-08 |
| A-EGG-08 | Heavy metals in eggs and chicken and the associated human health risk assessment in the mining areas of Singhbhum copper belt, India. Giri S, Singh AK | 2019 | PMID 29236582 DOI 10.1080/19338244.2017.1407284 | Measurement / residue study | Locally reared chicken and eggs | Most metal levels were below national standards; combined risk index was slightly above 1 at some sites. | Hotspot; HI above 1 only at some locations | low | C-EGG-08 |
| A-EGG-09 | Antibiotic residues in poultry tissues and eggs: human health concerns? Donoghue DJ | 2003 | PMID 12710482 DOI 10.1093/ps/82.4.618 | Narrative review | US poultry supply | The author says US poultry foods are monitored and very safe. | Narrative, 2003; No data in abstract | low | C-EGG-10 |
| A-EGG-10 | Prevalence and Genetic Analysis of Salmonella enterica from a Cross-Sectional Survey of the New Zealand Egg Production Environment. Kingsbury JM, Thom K, Erskine H et al. | 2019 | PMID 31742446 DOI 10.4315/0362-028X.JFP-19-159 | Cross-sectional study | 28 commercial layer farms | Barn samples from cage farms were far more often positive (44%) than from cage-free farms (3%); most farms had no Salmonella. | Environmental samples, not eggs; Confounding by practices | moderate | C-EGG-09 |
| A-EGG-11 | Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate-specific antigen-era: incidence and survival. Richman EL, Kenfield SA, Stampfer MJ et al. | 2011 | PMID 21930800 DOI 10.1158/1940-6207.CAPR-11-0354 | Cohort study | US male health professionals in the Health Professionals Follow-up Study, free of cancer in 1994 and reporting a PSA test (PSA era); case-only analysis of men diagnosed with clinically localised or regional prostate cancer after 1994 | Men who ate 2.5+ eggs per week had a higher rate of lethal prostate cancer (199 cases in total), but the link weakened and was not significant in a check for reverse causation. | Few events (199; 55 in the top egg category); low egg consumption limits power, as authors note; Egg association attenuated and non-significant with 2-6 year lag (HR 1.50, 0.90-2.48), raising reverse-causation/instability concerns | moderate | C-EGG-06 |
| A-EGG-12 | Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality. Zhong VW, Van Horn L, Cornelis MC et al. | 2019 | PMID 30874756 DOI 10.1001/jama.2019.1572 | Cohort study | US adults (mean age 51.6; 31.1% black) | More eggs or dietary cholesterol were linked to slightly more heart disease and deaths; the egg link disappeared when cholesterol intake was accounted for. | Single baseline dietary assessment; Residual confounding | moderate | C-EGG-04 |
| A-EGG-13 | Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. Tang WH, Wang Z, Levison BS et al. | 2013 | PMID 23614584 DOI 10.1056/NEJMoa1109400 | Cohort study | (1) 40 healthy adults without chronic illness or recent antibiotics/probiotics (6 received antibiotics); (2) 4,007 stable patients undergoing elective diagnostic cardiac catheterisation without acute coronary syndrome (mean age 63, 64% men, 32% diabetes, 72% hypertension, 42% prior MI) | Gut bacteria make TMAO from egg-yolk components; heart patients with the highest TMAO had more events (about 1.4-fold after adjustment, 2.5-fold unadjusted); egg eating itself was not studied against outcomes. | Cohort measured plasma TMAO only, not egg or phosphatidylcholine intake; Effect size shrinks from HR 2.54 (unadjusted) to 1.43 (fully adjusted), indicating substantial confounding (age, kidney function, disease severity) | moderate | C-EGG-05 |
| A-EGG-14 | Egg consumption and risk of type 2 diabetes: a meta-analysis of prospective studies. Djoussé L, Khawaja OA, Gaziano JM | 2016 | PMID 26739035 DOI 10.3945/ajcn.115.119933 | Meta-analysis | 12 cohorts | No overall link; higher risk only in US studies. | High heterogeneity; Observational primary studies | moderate | C-EGG-07 |
| A-EGG-15 | Vitamins A, E and fatty acid composition of the eggs of caged hens and pastured hens Karsten H.D., Patterson P.H., Stout R. et al. | 2010 | DOI 10.1017/S1742170509990214 | Other | 75 pastured sister hens and 50 caged sister hens | Pastured hens laid eggs with more omega-3 fat and vitamin E. | Small, single site; Nutrient composition, not health outcomes | moderate | C-EGG-11 |
| A-FSH-01 | Global assessment of organic contaminants in farmed salmon. Hites RA, Foran JA, Carpenter DO et al. | 2004 | PMID 14716013 DOI 10.1126/science.1091447 | Measurement / residue study | Farmed Atlantic salmon from farms/retail in Europe, North and South America; wild Pacific salmon | Around 2002, farmed salmon - especially from Europe - had more PCBs and dioxins than wild Pacific salmon. | Compares farmed Atlantic with wild Pacific salmon (different species); Historical samples (c. 2002) | high | C-FSH-01 C-FSH-02 |
| A-FSH-02 | Global assessment of polybrominated diphenyl ethers in farmed and wild salmon. Hites RA, Foran JA, Schwager SJ et al. | 2004 | PMID 15506184 DOI 10.1021/es049548m | Measurement / residue study | Same salmon set as A-FSH-01 | Farmed salmon had more PBDE flame retardants than wild salmon around 2002. | Historical; No health-risk metric in abstract | moderate | C-FSH-01 C-FSH-02 |
| A-FSH-03 | Polychlorinated biphenyls in salmon and salmon feed: global differences and bioaccumulation. Carlson DL, Hites RA | 2005 | PMID 16245806 DOI 10.1021/es048023r | Measurement / residue study | Farmed Atlantic salmon worldwide; wild NE Pacific salmon; feed samples | PCB patterns in farmed salmon matched their feed. | Historical; Few feed samples | moderate | C-FSH-01 |
| A-FSH-04 | Risk-based consumption advice for farmed Atlantic and wild Pacific salmon contaminated with dioxins and dioxin-like compounds. Foran JA, Carpenter DO, Hamilton MC et al. | 2005 | PMID 15866762 DOI 10.1289/ehp.7626 | Risk assessment | Hypothetical 70 kg adult; salmon samples from Hites 2004 | Depending on the safety criterion, northern European farmed salmon (2002 samples) allowed under 4 or under 1 meal per month. | Conservative criteria (20% above background; US EPA draft slope factor); 2002 samples | moderate | C-FSH-03 |
| A-FSH-05 | Quantitative analysis of the benefits and risks of consuming farmed and wild salmon. Foran JA, Good DH, Carpenter DO et al. | 2005 | PMID 16251623 DOI 10.1093/jn/135.11.2639 | Risk assessment | Modelled consumers | The omega-3 benefit of salmon partly offsets contaminant risk; some farmed salmon was similar to wild. | Same conservative cancer-risk framework; Old samples | moderate | C-FSH-03 |
| A-FSH-06 | Lipid composition and contaminants in farmed and wild salmon. Hamilton MC, Hites RA, Schwager SJ et al. | 2005 | PMID 16323755 DOI 10.1021/es050898y | Measurement / residue study | 459 farmed Atlantic, 135 wild Pacific salmon, 144 supermarket fillets (16 cities) | Farmed salmon had more fat, a lower omega-3:omega-6 ratio (3-4 vs ~10) and more pollutants, but was still a good omega-3 source. | Historical; Different species compared | high | C-FSH-01 C-FSH-04 C-FSH-05 |
| A-FSH-07 | Consumption advisories for salmon based on risk of cancer and noncancer health effects. Huang X, Hites RA, Foran JA et al. | 2006 | PMID 16198332 DOI 10.1016/j.envres.2005.08.011 | Risk assessment | Farmed salmon from 8 regions, retail fillets from 16 cities, 5 wild Pacific species | Using a strict US method, northern European farmed salmon (2002 samples) got an advisory of one meal per 5 months; wild salmon was also restricted. | Additive mixture assumption with upper-bound slope factors; 2002 samples | moderate | C-FSH-03 |
| A-FSH-08 | Investigation of polychlorinated dibenzo-p-dioxins, dibenzo-p-furans and selected coplanar biphenyls in Scottish farmed Atlantic salmon (Salmo salar). Jacobs M, Ferrario J, Byrne C | 2002 | PMID 11993634 DOI 10.1016/s0045-6535(01)00201-6 | Measurement / residue study | Farmed and wild Scottish Atlantic salmon | Farmed Scottish salmon had relatively high dioxins/PCBs in 1999. | Small, 1999, single region | low | C-FSH-01 |
| A-FSH-09 | The content of favorable and unfavorable polyunsaturated fatty acids found in commonly eaten fish. Weaver KL, Ivester P, Chilton JA et al. | 2008 | PMID 18589026 DOI 10.1016/j.jada.2008.04.023 | Measurement / residue study | Fish samples | Farmed salmon and trout had good omega-3 profiles; tilapia and catfish had little omega-3. | Few samples per species; No health outcomes | low | C-FSH-06 C-FSH-07 |
| A-FSH-10 | Polyunsaturated fatty acid content of wild and farmed tilapias in Thailand: effect of aquaculture practices and implications for human nutrition. Karapanagiotidis IT, Bell MV, Little DC et al. | 2006 | PMID 16756360 DOI 10.1021/jf0581877 | Measurement / residue study | Nile and red hybrid tilapia | Intensively farmed tilapia had less omega-3 than wild tilapia. | Thailand only | moderate | C-FSH-06 |
| A-FSH-11 | Antimicrobial use in aquaculture re-examined: its relevance to antimicrobial resistance and to animal and human health. Cabello FC, Godfrey HP, Tomova A et al. | 2013 | PMID 23711078 DOI 10.1111/1462-2920.12134 | Narrative review | Most aquaculture antibiotics reach the environment and may spread resistance genes to human pathogens. | Narrative, not systematic; 80% figure is an estimate | moderate | C-FSH-08 | |
| A-FSH-12 | Aquaculture as yet another environmental gateway to the development and globalisation of antimicrobial resistance. Cabello FC, Godfrey HP, Buschmann AH et al. | 2016 | PMID 27083976 DOI 10.1016/S1473-3099(16)00100-6 | Narrative review | Aquaculture antibiotics can help resistance spread globally. | Narrative | moderate | C-FSH-08 | |
| A-FSH-13 | Reconnaissance of 47 antibiotics and associated microbial risks in seafood sold in the United States. Done HY, Halden RU | 2015 | PMID 25449970 DOI 10.1016/j.jhazmat.2014.08.075 | Measurement / residue study | Shrimp, salmon, catfish, trout, tilapia, swai from 11 countries | Traces of five antibiotics were found; all samples were within US limits. | Small, pooled sample; One residue found in WILD shrimp | moderate | C-FSH-09 |
| A-FSH-14 | Aquaculture practices and potential human health risks: current knowledge and future priorities. Sapkota A, Sapkota AR, Kucharski M et al. | 2008 | PMID 18565584 DOI 10.1016/j.envint.2008.04.009 | Narrative review | Aquaculture can introduce drug residues, resistant bacteria and pollutants; risks vs wild fish need more research. | Narrative; 'can lead' | low | C-FSH-08 | |
| A-FSH-15 | Negative effects of the sea lice therapeutant emamectin benzoate at low concentrations on benthic communities around Scottish fish farms. Bloodworth JW, Baptie MC, Preedy KF et al. | 2019 | PMID 30878944 DOI 10.1016/j.scitotenv.2019.02.430 | Cross-sectional study | Benthic communities | The drug was found in 97% of seabed samples and was linked to fewer small crustaceans. | Cross-sectional; Collinearity | moderate | C-FSH-10 |
| A-FSH-16 | Salmon lice in the Pacific Ocean show evidence of evolved resistance to parasiticide treatment. Godwin SC, Bateman AW, Kuparinen A et al. | 2022 | PMID 35347162 DOI 10.1038/s41598-022-07464-1 | Other | Salmon lice collected from Atlantic salmon farms in the Broughton Archipelago, British Columbia (11 farms with bioassays; all BA farms for treatment data) | Pacific salmon lice have become much less sensitive to emamectin since 2010. | One region (11 farms), small number of bioassays (34); No genetic confirmation of resistance (lice not retained) | moderate | C-FSH-10 |
| A-FSH-17 | Levels of synthetic antioxidants (ethoxyquin, butylated hydroxytoluene and butylated hydroxyanisole) in fish feed and commercially farmed fish. Lundebye AK, Hove H, Måge A et al. | 2010 | PMID 20931417 DOI 10.1080/19440049.2010.508195 | Measurement / residue study | Farmed salmon, halibut, cod, rainbow trout; feed | A portion of farmed salmon gave up to 75% of the acceptable daily intake of BHT. | 2010 data | moderate | C-FSH-02 |
| A-FSH-18 | Determining the arsenic, cadmium, lead, copper and chromium contents by atomic absorption spectrometry in Pangasius fillets from Vietnam. Molognoni L, Vitali L, Ploêncio LA et al. | 2016 | PMID 26439310 DOI 10.1002/jsfa.7486 | Measurement / residue study | Pangasius fillets exported to Brazil | Most toxic metals were undetectable; some samples exceeded the cadmium limit. | n=20 | low | C-FSH-02 |
| A-FSH-19 | Effect of aquaculture on world fish supplies. Naylor RL, Goldburg RJ, Primavera JH et al. | 2000 | PMID 10890435 DOI 10.1038/35016500 | Narrative review | Farming carnivorous fish uses many wild fish as feed, but aquaculture overall still adds fish. | Old (2000) | moderate | C-FSH-11 | |
| A-FSH-20 | Mercury Levels in the Worldwide Farmed Fish: A Systematic Review. de Oliveira Novaes E, de Oliveira AT, Araruna LT et al. | 2025 | PMID 39715977 DOI 10.1007/s12011-024-04493-x | Systematic review | Farmed fish (50 species) | Farmed fish had low mercury and were judged safer than wild fish. | Only 18 studies; Few countries | low | C-FSH-02 C-FSH-14 |
| A-FSH-21 | Contaminant levels in Norwegian farmed Atlantic salmon (Salmo salar) in the 13-year period from 1999 to 2011. Nøstbakken OJ, Hove HT, Duinker A et al. | 2015 | PMID 25454244 DOI 10.1016/j.envint.2014.10.008 | Measurement / residue study | Market-size (3-5 kg) Norwegian farmed Atlantic salmon collected from processing plants in all coastal regions with aquaculture | Pollutant levels fell from 1999 to 2011 and no sample exceeded EU limits; the authors calculated up to 1.3 kg per week to reach the safety limit then in force, which EFSA has since made much stricter. | Uses SCF 2001 TWI (14 pg TEQ/kg bw/week); EFSA lowered the TWI to 2 pg TEQ/kg bw/week in 2018 (I-FSH-17), so the 1.3 kg figure is outdated; Other dietary sources excluded from consumption limits | high | C-FSH-01 C-FSH-02 C-FSH-03 C-FSH-13 |
| A-FSH-22 | Organic contaminants in imported salmon feed and their effects on reef ecosystems in New Zealand. McMullin RM, Chen R, Niu S et al. | 2022 | PMID 35033615 DOI 10.1016/j.envpol.2022.118853 | Measurement / residue study | Feed; reef species | Imported salmon feed had relatively low pollutant levels. | NZ-specific | moderate | C-FSH-02 |
| A-INS-01 | Effects of intensive glucose lowering in type 2 diabetes. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME et al. | 2008 | PMID 18539917 DOI 10.1056/NEJMoa0802743 | Randomised controlled trial | Type 2 diabetes, mean age 62.2, median HbA1c 8.1%, established CVD or additional risk factors | Pushing HbA1c below 6% increased deaths by about one-fifth and did not reduce heart attacks or strokes significantly. | Strategy trial: cannot attribute harm to a specific drug; Intensive arm stopped early | high | C-INS-04 C-INS-11 C-ODD-03 C-ODD-06 |
| A-INS-02 | Intensive versus conventional glucose control in critically ill patients. NICE-SUGAR Study Investigators, Finfer S, Chittock DR et al. | 2009 | PMID 19318384 DOI 10.1056/NEJMoa0810625 | Randomised controlled trial | Adult ICU patients expected to stay >=3 days | Aiming for normal blood sugar in ICU patients raised deaths from 24.9% to 27.5%. | ICU population, not ambulatory diabetes; Open-label | high | C-INS-04 C-DIAB-01 |
| A-INS-03 | Glucose control and vascular complications in veterans with type 2 diabetes. Duckworth W, Abraira C, Moritz T et al. | 2009 | PMID 19092145 DOI 10.1056/NEJMoa0808431 | Randomised controlled trial | Military veterans, mean age 60.4, diabetes 11.5 years, 40% prior CV event | Lower sugar did not reduce heart events or deaths, and side effects (mainly hypoglycaemia) were more frequent. | Smaller sample, limited power; Mostly men | moderate | C-INS-04 |
| A-INS-04 | Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Hemkens LG, Grouven U, Bender R et al. | 2009 | PMID 19565214 DOI 10.1007/s00125-009-1418-4 | Cohort study | Adults (>=18 years) starting first-time insulin therapy exclusively with one insulin type (human insulin, aspart, lispro or glargine), insulin-naive for 1 year and without any cancer diagnosis or suspicion for 3 years before entry; type 1 vs type 2 diabetes not distinguishable (mostly type 2: 77-92% on oral agents). Mean age 66-70 years. | Without adjustment glargine users actually had slightly fewer cancers; only after statistical dose adjustment did glargine look somewhat worse, and follow-up was under 2 years. | Very short follow-up (mean 1.63 years; glargine 1.31 years), implausibly short for insulin-induced carcinogenesis; detection or promotion of pre-existing tumours cannot be separated; Direction of the glargine effect reverses on dose adjustment (crude HR 0.85 -> adjusted 1.09-1.31); result depends on the dose-interaction model | low | C-INS-06 |
| A-INS-05 | Insulin glargine use and short-term incidence of malignancies-a population-based follow-up study in Sweden. Jonasson JM, Ljung R, Talbäck M et al. | 2009 | PMID 19588120 DOI 10.1007/s00125-009-1444-2 | Cohort study | All residents aged 35-84 with >=1 insulin prescription dispensed 1 July-31 December 2005 and alive on 1 January 2006; 61% classified type 2, 15% type 1, 23% unknown diabetes type. | Overall cancer rates were the same; women using only glargine had more breast cancer (25 cases), which the authors say may be chance. | Only 2 years of follow-up; glargine on Swedish market since 2003, implausibly short latency for carcinogenesis (authors); Breast-cancer signal based on 25 cases in one of several subgroups and sites; no correction for multiple comparisons | moderate | C-INS-06 |
| A-INS-06 | Long-term effects of insulin glargine on the risk of breast cancer. Suissa S, Azoulay L, Dell'Aniello S et al. | 2011 | PMID 21614572 DOI 10.1007/s00125-011-2190-9 | Cohort study | Women aged >=40 years with type 2 diabetes and >=1 insulin prescription between 1 September 2002 and 31 December 2006 (mean age 65); excluded gestational diabetes, type 1 diabetes, prior breast cancer. | No increase in breast cancer during the first five years; a possible increase later in a subgroup. | Positive finding rests on 10 cases in one subgroup (>5 years, prevalent users) with wide CI; p=0.031 from repeated stratified analyses (authors acknowledge chance); Overall and first-5-year results null; no cases at all >5 years in first-time glargine users | moderate | C-INS-06 |
| A-INS-07 | Basal insulin and cardiovascular and other outcomes in dysglycemia. ORIGIN Trial Investigators, Gerstein HC, Bosch J et al. | 2012 | PMID 22686416 DOI 10.1056/NEJMoa1203858 | Randomised controlled trial | People aged >=50 years with cardiovascular risk factors (59% prior CV event) plus impaired fasting glucose, impaired glucose tolerance or early type 2 diabetes (mean diabetes duration 5.4 years, median HbA1c 6.4%, BMI ~29.9); mean age 63.5, 35% female. | Over six years insulin did not change heart attacks, strokes or cancers, but caused more low-sugar episodes and 2 kg weight difference. | Open-label design (hypoglycaemia and other patient-reported outcomes susceptible to ascertainment bias); Sponsor (Sanofi) funding and representation on steering committee | high | C-INS-03 C-INS-05 C-INS-06 |
| A-INS-08 | Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes. Currie CJ, Poole CD, Evans M et al. | 2013 | PMID 23372169 DOI 10.1210/jc.2012-3042 | Cohort study | Incident type 2 diabetes patients in UK primary care (mean age 61.9); insulin-monotherapy users had longer diabetes duration (5.2 vs 1.5 years for metformin), higher HbA1c (9.5% vs 8.5%), more prior large-vessel disease (22.3% vs 11.1%), more creatinine >130 umol/L (21.1% vs 2.2%), higher Charlson index (2.4 vs 1.6) and more GP contacts (16.8 vs 10.9/year). | People treated with insulin alone had about twice the death rate of metformin users, but they were also sicker. | Severe confounding by indication: insulin is started late in progressive disease; insulin users had 3.5-fold longer diabetes duration, more renal impairment (metformin contraindicated), more vascular disease and comorbidity; Short follow-up (~3 years) for cancer outcomes (authors) | very low | C-INS-05 C-ODD-11 |
| A-INS-09 | Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Currie CJ, Peters JR, Tynan A et al. | 2010 | PMID 20110121 DOI 10.1016/S0140-6736(09)61969-3 | Cohort study | Type 2 diabetes >=50 years intensified to combination orals or insulin | Both very low (6.4%) and very high (10.5%) HbA1c were linked to more deaths; lowest risk around 7.5%. | Observational; Confounding by indication | low | C-INS-05 |
| A-INS-10 | Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events and cancer. Holden SE, Jenkins-Jones S, Morgan CL et al. | 2015 | PMID 25399739 DOI 10.1111/dom.12412 | Cohort study | Type 2 diabetes progressing to insulin monotherapy from 2000 | People on higher insulin doses died more often, but higher doses are needed by sicker, more insulin-resistant people. | Dose reflects insulin resistance and illness; Reverse causation | low | C-INS-03 C-INS-05 |
| A-INS-11 | Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Bowker SL, Majumdar SR, Veugelers P et al. | 2006 | PMID 16443869 DOI 10.2337/diacare.29.02.06.dc05-1558 | Cohort study | New users of metformin or sulfonylureas | Insulin users had more cancer deaths than metformin users, possibly due to other differences. | No BMI/smoking; Confounding | low | C-INS-05 |
| A-INS-12 | Glucose-lowering agents and cancer mortality rates in type 2 diabetes: assessing effects of time-varying exposure. Bowker SL, Yasui Y, Veugelers P et al. | 2010 | PMID 20407744 DOI 10.1007/s00125-010-1750-8 | Cohort study | New users of metformin or sulfonylureas aged >=30 years with >=1 year prior drug coverage and >=1 year of drug exposure after index; gestational diabetes excluded. Insulin used was human insulin (pre-analogue era). | More insulin prescriptions went with more cancer deaths, which may reflect that very ill people need more insulin. | No data on BMI, smoking, HbA1c, alcohol (authors); adjustment only for age, sex and a drug-based comorbidity score; Insulin 'dose' is number of dispensations, which rises with illness, hospital discharge and terminal care - strong reverse causation/protopathic bias for cancer death | low | C-INS-05 |
| A-INS-13 | Association between intensification of metformin treatment with insulin vs sulfonylureas and cardiovascular events and all-cause mortality among patients with diabetes. Roumie CL, Greevy RA, Grijalva CG et al. | 2014 | PMID 24915260 DOI 10.1001/jama.2014.4312 | Cohort study | US veterans (95% male, ~70% white), median age 60, incident metformin users 2001-2008 with regular VHA care; median 14 months on metformin and median HbA1c 8.1% at intensification; hospice/dialysis excluded. | Veterans who added insulin died more often than those who added a sulfonylurea, but heart attacks and strokes were not more frequent. | Residual confounding by frailty/diabetes severity (authors); before matching insulin users had far more hospitalisations (35% vs 14% in last year) and comorbidities; Excess limited to non-CV, especially cancer deaths (aHR 1.85) within ~1 year - implausible as a drug effect and suggestive of confounding/reverse causation | moderate | C-INS-03 C-INS-05 |
| A-INS-14 | The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. Bonds DE, Miller ME, Bergenstal RM et al. | 2010 | PMID 20061358 DOI 10.1136/bmj.b4909 | Cohort study | ACCORD participants with type 2 diabetes, HbA1c 7.5-11%, aged 40-79 with CVD or 55-79 with subclinical atherosclerosis/risk factors; excluded recent/frequent serious hypoglycaemia, BMI >45, creatinine >133 umol/L. | People who had severe low-sugar episodes died more often, but this did not explain why the intensive group had more deaths. | Post hoc observational analysis within an RCT: hypoglycaemia is not randomised; confounding by frailty/comorbidity likely (authors); No continuous glucose monitoring; unrecognised hypoglycaemia near death cannot be excluded; glucose missing for 15% of HMA episodes | moderate | C-INS-02 C-INS-04 C-INS-09 C-ODD-03 |
| A-INS-15 | Severe hypoglycemia and risks of vascular events and death. Zoungas S, Patel A, Chalmers J et al. | 2010 | PMID 20925543 DOI 10.1056/NEJMoa1003795 | Cohort study | Patients aged >=55 with type 2 diabetes diagnosed after age 30 and macro-/microvascular disease or >=1 CV risk factor; patients with a clear indication for long-term insulin at baseline were ineligible; intensive arm used modified-release gliclazide (a sulfonylurea) plus other drugs as required (target HbA1c <=6.5%). | Severe low-sugar episodes were followed by more heart events and deaths, probably partly because frail people get them. | Only 231 patients with severe hypoglycaemia; post hoc, non-randomised exposure; Associations with unrelated outcomes (skin, digestive, respiratory) and absence of dose-response point to confounding/frailty (authors) | moderate | C-INS-02 C-INS-04 C-INS-09 C-ODD-03 |
| A-INS-16 | Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. UKPDS Group | 1998 | PMID 9742976 | Randomised controlled trial | Newly diagnosed type 2 diabetes, median age 54 | Better sugar control with tablets or insulin cut eye/kidney complications by a quarter; insulin caused more weight gain and low-sugar episodes. | Open-label; Older drug regimens | high | C-INS-01 C-INS-03 C-INS-04 C-INS-05 C-INS-09 C-ODD-11 C-DIAB-01 |
| A-INS-17 | Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis. Pontiroli AE, Miele L, Morabito A | 2011 | PMID 21645195 DOI 10.1111/j.1463-1326.2011.01433.x | Meta-analysis | Type 2 diabetes starting/intensifying insulin | The more intensive the insulin treatment, the more weight people gain in the first year. | Effect sizes not in abstract; Heterogeneous trials | moderate | C-INS-01 |
| A-INS-18 | Intensive conventional insulin therapy for type II diabetes. Metabolic effects during a 6-mo outpatient trial. Henry RR, Gumbiner B, Ditzler T et al. | 1993 | PMID 8422777 DOI 10.2337/diacare.16.1.21 | Case series / case report | Type 2 diabetes outpatients | Blood sugar normalised but patients gained almost 9 kg in six months. | n=14; No control | very low | C-INS-01 |
| A-INS-19 | Combination of insulin and metformin in the treatment of type 2 diabetes. Wulffelé MG, Kooy A, Lehert P et al. | 2002 | PMID 12453950 DOI 10.2337/diacare.25.12.2133 | Randomised controlled trial | Insulin-treated type 2 diabetes | Metformin improved sugar control and reduced insulin need and weight gain. | Short duration; Dropouts higher with metformin | moderate | C-INS-01 C-INS-05 C-INS-10 C-INS-11 |
| A-INS-20 | Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control. Famulla S, Hövelmann U, Fischer A et al. | 2016 | PMID 27411698 DOI 10.2337/dc16-0610 | Randomised controlled trial | Type 1 diabetes with lipohypertrophy | Insulin injected into lumpy fat tissue works less and less predictably. | Small n | moderate | C-INS-09 |
| A-INS-21 | Hyperinsulinemia as an independent risk factor for ischemic heart disease. Després JP, Lamarche B, Mauriège P et al. | 1996 | PMID 8596596 DOI 10.1056/NEJM199604113341504 | Case-control study | Non-diabetic men 45-76 | Men with higher fasting insulin had more heart disease. | Small number of cases; Men only | moderate | C-INS-03 |
| A-INS-22 | Insulin and risk of cardiovascular disease: a meta-analysis. Ruige JB, Assendelft WJ, Dekker JM et al. | 1998 | PMID 9529268 DOI 10.1161/01.cir.97.10.996 | Meta-analysis | General population cohorts | Higher insulin was only weakly linked to heart disease (18% higher risk). | Old assays; Heterogeneity | moderate | C-INS-03 |
| A-INS-23 | Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Calle EE, Kaaks R | 2004 | PMID 15286738 DOI 10.1038/nrc1408 | Narrative review | not applicable | Not assessed (no abstract available). | Narrative review; Not read | low | C-INS-06 |
| A-LEG-01 | Favism and Glucose-6-Phosphate Dehydrogenase Deficiency. Luzzatto L, Arese P | 2018 | PMID 29298156 DOI 10.1056/nejmra1708111 | Narrative review | Not applicable (review) | Authoritative review of favism; no abstract available to us. | No abstract available; content not verified by us | moderate | C-LEG-03 |
| A-LEG-02 | Glucose-6-phosphate dehydrogenase deficiency. Cappellini MD, Fiorelli G | 2008 | PMID 18177777 DOI 10.1016/S0140-6736(08)60073-2 | Narrative review | Global | G6PD deficiency affects over 400 million people; haemolysis is triggered by external agents and is prevented by avoiding them. | Narrative, not systematic; Abstract does not mention fava beans explicitly | moderate | C-LEG-03 C-LEG-04 C-LEG-05 |
| A-LEG-03 | Red kidney bean poisoning in the UK: an analysis of 50 suspected incidents between 1976 and 1989. Rodhouse JC, Haugh CA, Roberts D et al. | 1990 | PMID 2249712 DOI 10.1017/s095026880004810x | Outbreak report | Incidents reported to the PHLS Food Hygiene Laboratory or the Communicable Disease Surveillance Centre (Colindale), involving more than 200 cases | 50 poisoning incidents from raw or undercooked kidney beans; thorough cooking inactivates the toxin. | Passive reporting; authors document marked under-reporting; 23 of 32 incidents diagnosed on clinical history only; 6 of these had beans with <400 HAU/g | moderate | C-LEG-06 C-LEG-07 |
| A-LEG-04 | Antinutritional properties of plant lectins. Vasconcelos IM, Oliveira JT | 2004 | PMID 15302522 DOI 10.1016/j.toxicon.2004.05.005 | Narrative review | Animals, insects (review) | Active plant lectins harm animals at high intakes; human cooked-food relevance not shown. | Mainly animal and insect data; No human dose-response | moderate | C-LEG-01 C-LEG-07 |
| A-LEG-05 | Iron bioavailability and dietary reference values. Hurrell R, Egli I | 2010 | PMID 20200263 DOI 10.3945/ajcn.2010.28674F | Narrative review | Humans (isotope and intake studies) | Iron absorption is lower from vegetarian than mixed diets; in varied diets single inhibitors matter less than iron status. | Narrative; Not specific to legumes | moderate | C-LEG-08 |
| A-LEG-06 | Bioavailability of minerals in legumes. Sandberg AS | 2002 | PMID 12498628 DOI 10.1079/BJN/2002718 | Narrative review | Not applicable | Phytate reduces iron and zinc absorption, but processing reduces phytate and balanced diets are not at risk. | Narrative | moderate | C-LEG-04 C-LEG-08 |
| A-LEG-07 | Exposure of infants to phyto-oestrogens from soy-based infant formula. Setchell KD, Zimmer-Nechemias L, Cai J et al. | 1997 | PMID 9217716 DOI 10.1016/S0140-6736(96)09480-9 | Measurement / residue study | 4-month-old infants | Soy-fed infants had isoflavone blood levels hundreds of times higher than other infants. | Very small n; No clinical outcomes | moderate | C-LEG-10 |
| A-LEG-08 | Goitrogenic and estrogenic activity of soy isoflavones. Doerge DR, Sheehan DM | 2002 | PMID 12060828 DOI 10.1289/ehp.02110s3349 | Narrative review | Rats, humans (review) | Soy compounds inhibit a thyroid enzyme in the lab, but thyroid function in rats stayed normal; iodine deficiency is key. | Animal/in-vitro; Authors' concern-oriented framing | low | C-LEG-10 |
| A-LEG-09 | Soy Formula and Epigenetic Modifications: Analysis of Vaginal Epithelial Cells from Infant Girls in the IFED Study. Harlid S, Adgent M, Jefferson WN et al. | 2017 | PMID 27539829 DOI 10.1289/EHP428 | Cohort study | Healthy term singleton infant girls exclusively fed soy or cow-milk formula from birth (IFED cohort, Philadelphia); mothers mostly black, many with high-school education or less | Small study found gene-methylation differences in soy-fed girls; health meaning unknown. | Discovery scan of only 10 infants, without multiple-testing correction across 427,097 CpGs; In the scan, soy samples (4-8 weeks) and cow samples (20-32 weeks) differed strongly in age, while methylation falls with age - major confounding of the discovery signal | low | C-LEG-10 |
| A-LEG-10 | A diet low in FODMAPs reduces symptoms of irritable bowel syndrome. Halmos EP, Power VA, Shepherd SJ et al. | 2014 | PMID 24076059 DOI 10.1053/j.gastro.2013.09.046 | Randomised controlled trial | 30 IBS patients, 8 healthy controls | Diet low in fermentable sugars halved symptom scores in IBS patients; healthy people had no symptoms on either diet. | Small; Single-blind | moderate | C-LEG-12 C-VEG-01 |
| A-LEG-11 | Fatalities due to anaphylactic reactions to foods. Bock SA, Muñoz-Furlong A, Sampson HA | 2001 | PMID 11150011 DOI 10.1067/mai.2001.112031 | Case series / case report | Fatal cases reported to AAAAI registry | Most of 32 food-allergy deaths were due to peanuts or tree nuts, nearly all in people already known to be allergic. | Voluntary reporting; No denominator | moderate | C-LEG-11 |
| A-LEG-12 | Further fatalities caused by anaphylactic reactions to food, 2001-2006. Bock SA, Muñoz-Furlong A, Sampson HA | 2007 | PMID 17306354 DOI 10.1016/j.jaci.2006.12.622 | Case series / case report | US registry | Registry letter; content not available to us. | No abstract; content not verified | low | C-LEG-11 |
| A-LEG-13 | Cross-allergenicity of peanut and lupine: the risk of lupine allergy in patients allergic to peanuts. Moneret-Vautrin DA, Guérin L, Kanny G et al. | 1999 | PMID 10518837 DOI 10.1016/s0091-6749(99)70303-9 | Cross-sectional study | Peanut-allergic patients | Many peanut-allergic patients also reacted to lupin flour. | Small selected sample | moderate | C-LEG-11 |
| A-LEG-14 | Incidence of fatal food anaphylaxis in people with food allergy: a systematic review and meta-analysis. Umasunthar T, Leonardi-Bee J, Hodes M et al. | 2013 | PMID 24118190 DOI 10.1111/cea.12211 | Meta-analysis | Food-allergic people (denominator estimated by applying assumed food-allergy prevalence to defined general populations) | Among food-allergic people, fatal reactions occur about 1.8 times per million person-years, less often than accidental deaths. | Denominators rely on assumed food-allergy prevalence, not measured allergic cohorts; High heterogeneity; variable case capture (registries, media, coroners, charities) | moderate | C-LEG-11 |
| A-ODD-01 | Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. Nissen SE, Wolski K | 2007 | PMID 17517853 DOI 10.1056/NEJMoa072761 | Meta-analysis | Type 2 diabetes in trials >24 weeks, mean age 56, HbA1c 8.2% | Pooling 42 trials suggested 43% more heart attacks; the increase in heart deaths was not statistically certain. | No patient-level data; Rare events, fixed-effect model | moderate | C-ODD-05 C-ODD-09 |
| A-ODD-02 | Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial. Komajda M, McMurray JJ, Beck-Nielsen H et al. | 2010 | PMID 20118174 DOI 10.1093/eurheartj/ehp604 | Randomised controlled trial | Type 2 diabetes aged 40-75, BMI >25 kg/m2, HbA1c >7.0-<=9.0% on maximum-dose metformin or sulfonylurea monotherapy; excluded prior HF, recent major CV event, renal impairment, uncontrolled hypertension. | Heart failure doubled with rosiglitazone (2.6 extra cases per 1,000 patient-years), but overall heart deaths did not increase. | Open-label design (investigator-identified events may be influenced by knowledge of TZD fluid retention, though adjudication was blinded); Sponsor (GSK) analysed data; authors with extensive industry ties | high | C-ODD-05 C-ODD-09 |
| A-ODD-03 | Pioglitazone use and risk of bladder cancer: population based cohort study. Tuccori M, Filion KB, Yin H et al. | 2016 | PMID 27029385 DOI 10.1136/bmj.i1541 | Cohort study | Patients aged >=40 newly treated with non-insulin antidiabetic drugs who initiated a new drug class 2000-2013; excluded prior insulin, gestational diabetes, PCOS, prior bladder cancer, <1 year follow-up. Mean age 63.7; 56.8% male. | Pioglitazone users had 63% more bladder cancer, about 3 extra cases per 10,000 people per year. | Observational; residual confounding (occupational exposures, diet, ethnicity) possible; Only 54 exposed cases; dose-response steps imprecise and nearly flat across dose categories | moderate | C-ODD-05 C-ODD-12 |
| A-ODD-04 | Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. de Jager J, Kooy A, Lehert P et al. | 2010 | PMID 20488910 DOI 10.1136/bmj.c2181 | Randomised controlled trial | Patients aged 30-80 with insulin-treated type 2 diabetes at three non-academic hospital outpatient clinics; mean diabetes duration 12-14 years, mean insulin ~61-64 IU/day. | Over 4 years metformin lowered B12 by 19%, causing deficiency in about 1 of every 14 users. | Secondary analysis; trial powered for other endpoints; Baseline imbalance despite randomisation (metformin group older, 64 vs 59 years; fewer smokers 19% vs 30%) | high | C-ODD-05 C-ODD-07 |
| A-ODD-05 | Association of biochemical B₁₂ deficiency with metformin therapy and vitamin B₁₂ supplements: the National Health and Nutrition Examination Survey, 1999-2006. Reinstatler L, Qi YP, Williamson RS et al. | 2012 | PMID 22179958 DOI 10.2337/dc11-1582 | Cross-sectional study | US non-institutionalised adults >=50 years; type 2 diabetes defined as physician diagnosis after age 30 without insulin within 1 year. Excluded: HIV, high creatinine, prescription B12 injections, prediabetes, pregnancy, type 1 diabetes, metformin users without diabetes. | 5.8% of metformin users had B12 deficiency vs 2.4% of other diabetics. | Cross-sectional; associations only, no temporality (authors); Only current metformin use; non-users may have stopped metformin (possibly because of low B12) | moderate | C-ODD-05 C-ODD-07 |
| A-ODD-06 | Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. Aroda VR, Edelstein SL, Goldberg RB et al. | 2016 | PMID 26900641 DOI 10.1210/jc.2015-3754 | Randomised controlled trial | People with prediabetes and overweight | Each year of metformin raised the odds of B12 deficiency by about 13%. | Placebo group partly unblinded after DPP; Secondary analysis | moderate | C-ODD-05 C-ODD-07 |
| A-ODD-07 | Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Roumie CL, Hung AM, Greevy RA et al. | 2012 | PMID 23128859 DOI 10.7326/0003-4819-157-9-201211060-00003 | Cohort study | Veterans >=18 years initiating metformin or sulfonylurea (glyburide or glipizide) after >=365 days without antidiabetic drugs; excluded heart failure, cancer, HIV, transplant, end-stage kidney/liver disease, respiratory failure, cocaine use, creatinine >=1.5 mg/dL. 97% male, 75% white, median age 62; median HbA1c 7.0-7.3%. | Starting a sulfonylurea instead of metformin was linked to about 1-4 extra heart events or deaths per 1,000 people per year. | Observational; residual confounding by indication (sulfonylurea users older, more loop diuretics/digoxin, lower BMI) despite adjustment; Very short median follow-up (~0.6-0.8 years) with heavy censoring (66-73% stopped therapy) - possibly informative | moderate | C-ODD-05 C-ODD-11 |
| A-ODD-08 | Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. Scirica BM, Bhatt DL, Braunwald E et al. | 2013 | PMID 23992601 DOI 10.1056/NEJMoa1307684 | Randomised controlled trial | Type 2 diabetes with or at risk for CV events | No effect on heart attacks or strokes, but more heart failure hospitalisations (3.5% vs 2.8%, i.e. 0.7 percentage points). | Short follow-up; Industry funded | high | C-ODD-04 C-ODD-05 |
| A-ODD-09 | Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. Neal B, Perkovic V, Mahaffey KW et al. | 2017 | PMID 28605608 DOI 10.1056/NEJMoa1611925 | Randomised controlled trial | Type 2 diabetes (HbA1c 7.0-10.5%) aged >=30 with symptomatic atherosclerotic CVD or >=50 with >=2 CV risk factors; eGFR >30. Mean age 63.3, 35.8% women, diabetes duration 13.5 years, 65.6% prior CVD, 14.4% heart failure, 2.3% prior amputation. | Fewer heart attacks, strokes and heart deaths (-14%), but more toe/foot amputations. | Sponsor-designed randomisation schedule, sponsor co-analysis and employee authors; Integrated analysis of two trials partly necessitated by unmasked interim data used in regulatory filing (CANVAS) | high | C-ODD-05 C-ODD-06 |
| A-ODD-10 | Diabetic Ketoacidosis and Related Events in the Canagliflozin Type 2 Diabetes Clinical Program. Erondu N, Desai M, Ways K et al. | 2015 | PMID 26203064 DOI 10.2337/dc15-1251 | Other | Patients with type 2 diabetes in the canagliflozin RCT programme (history of type 1 diabetes or DKA excluded); ~31% on background insulin. | Ketoacidosis was rare (7 per 10,000 patients), often with insulin deficiency or triggers. | Sponsor analysis by employee authors; no independent adjudication; Ascertainment by investigator-reported adverse event terms - likely underreporting (authors) | low | C-INS-08 C-ODD-02 C-ODD-05 |
| A-ODD-11 | Risk of Diabetic Ketoacidosis after Initiation of an SGLT2 Inhibitor. Fralick M, Schneeweiss S, Patorno E | 2017 | PMID 28591538 DOI 10.1056/NEJMc1701990 | Cohort study | not verifiable | Content not verified (no abstract). | Not read; letter format | low | C-ODD-02 C-ODD-05 |
| A-ODD-12 | Fournier Gangrene Associated With Sodium-Glucose Cotransporter-2 Inhibitors: A Review of Spontaneous Postmarketing Cases. Bersoff-Matcha SJ, Chamberlain C, Cao C et al. | 2019 | PMID 31060053 DOI 10.7326/M19-0085 | Case series / case report | Adults with diabetes reported to FAERS | FDA received 55 reports of this rare genital infection with SGLT2 drugs; reports cannot show how often it really happens. | No incidence/causality; Reporting bias (stimulated reporting after warnings) | very low | C-ODD-05 C-ODD-08 |
| A-ODD-13 | Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. Watts NB, Bilezikian JP, Usiskin K et al. | 2016 | PMID 26580237 DOI 10.1210/jc.2015-3167 | Randomised controlled trial | Type 2 diabetes | More fractures in one trial with older high-risk patients, not in others. | Pooled post-hoc | moderate | C-ODD-05 |
| A-ODD-14 | Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. Singh S, Chang HY, Richards TM et al. | 2013 | PMID 23440284 DOI 10.1001/jamainternmed.2013.2720 | Case-control study | Adults 18-64 with type 2 diabetes | Users had about twice the odds of pancreatitis, but they also had more risk factors. | Strong confounding; Claims data | low | C-ODD-04 C-ODD-05 |
| A-ODD-15 | Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. Sodhi M, Rezaeianzadeh R, Kezouh A et al. | 2023 | PMID 37796527 DOI 10.1001/jama.2023.19574 | Cohort study | not verifiable | Not verified (no abstract). | Not read | low | C-ODD-04 C-ODD-05 |
| A-ODD-16 | Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. Hathaway JT, Shah MP, Hathaway DB et al. | 2024 | PMID 38958939 DOI 10.1001/jamaophthalmol.2024.2296 | Cohort study | Patients evaluated by neuro-ophthalmologists at one academic institution | In an eye-clinic registry, semaglutide users had about 4 times more NAION, but numbers were small. | Referral population (selection bias); Few events | low | C-ODD-05 C-ODD-10 |
| A-ODD-17 | Effects of intensive glucose lowering in type 2 diabetes. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME et al. | 2008 | PMID 18539917 DOI 10.1056/NEJMoa0802743 | Randomised controlled trial | Type 2 diabetes, mean age 62.2, median HbA1c 8.1%, established CVD or additional risk factors | Pushing HbA1c below 6% increased deaths by about one-fifth and did not reduce heart attacks or strokes significantly. | Strategy trial: cannot attribute harm to a specific drug; Intensive arm stopped early | high | C-INS-04 |
| A-ODD-18 | Glucose control and vascular complications in veterans with type 2 diabetes. Duckworth W, Abraira C, Moritz T et al. | 2009 | PMID 19092145 DOI 10.1056/NEJMoa0808431 | Randomised controlled trial | Military veterans, mean age 60.4, diabetes 11.5 years, 40% prior CV event | Lower sugar did not reduce heart events or deaths, and side effects (mainly hypoglycaemia) were more frequent. | Smaller sample, limited power; Mostly men | moderate | C-INS-04 |
| A-ORG-01 | Association of Long-Term Risk of Respiratory, Allergic, and Infectious Diseases With Removal of Adenoids and Tonsils in Childhood. Byars SG, Stearns SC, Boomsma JJ | 2018 | PMID 29879264 DOI 10.1001/jamaoto.2018.0614 | Cohort study | Children born in Denmark 1979-1999 | Children who had the operations had more respiratory illnesses later (2-3 times for upper airway disease), but the study cannot prove the operation caused it. | Confounding by indication (children operated for recurrent infections/obstruction may be prone to respiratory disease); Wide CIs for specific outcomes | moderate | C-ORG-01 C-ORG-03 C-ORG-16 |
| A-ORG-02 | Tonsillectomy associated with an increased risk of autoimmune diseases: A national cohort study. Ji J, Sundquist J, Sundquist K | 2016 | PMID 27344241 DOI 10.1016/j.jaut.2016.06.007 | Cohort study | All tonsillectomized persons in Sweden | People who had tonsils removed were diagnosed with autoimmune diseases 34% more often than the general population. | Comparison with general population, not with matched non-operated persons with similar infections; No adjustment for confounders beyond standardization | low | C-ORG-04 C-ORG-16 |
| A-ORG-03 | A randomized trial of adenotonsillectomy for childhood sleep apnea. Marcus CL, Moore RH, Rosen CL et al. | 2013 | PMID 23692173 DOI 10.1056/NEJMoa1215881 | Randomised controlled trial | Children 5-9 years with OSA (AHI >=2 or OAI >=1) without prolonged desaturation, suitable for surgery; 53% black, about 47% overweight/obese | Surgery normalized sleep studies in 79% vs 46% with waiting and improved behaviour and quality of life. | Short follow-up (7 months); Primary outcome negative | high | C-ORG-01 C-ORG-03 C-ORG-15 |
| A-ORG-04 | Appendectomy and protection against ulcerative colitis. Andersson RE, Olaison G, Tysk C et al. | 2001 | PMID 11248156 DOI 10.1056/NEJM200103153441104 | Cohort study | Swedish patients appendectomized before age 50 | People whose inflamed appendix was removed before age 20 later had less ulcerative colitis; removal for non-inflamed appendix showed no difference. | Observational; Cannot separate effect of removal from effect of the inflammation | moderate | C-ORG-05 C-ORG-16 |
| A-ORG-05 | Risk of Gastrointestinal Cancers among Patients with Appendectomy: A Large-Scale Swedish Register-Based Cohort Study during 1970-2009. Song H, Abnet CC, Andrén-Sandberg Å et al. | 2016 | PMID 26959234 DOI 10.1371/journal.pone.0151262 | Cohort study | All patients born before 2003 with appendectomy in Sweden 1970-2009 (mean age 32.5 years; 54.7% women); 327,496 appendicitis, 152,886 other diagnoses (negative or incidental appendectomy) | No increased risk of stomach, colon or rectal cancer after appendix removal. | SIR comparison with general population; no adjustment for BMI, smoking, diet, socioeconomic status (authors); Surveillance/detection bias (authors; e.g. early cardia cancer excess) | moderate | C-ORG-05 C-ORG-16 C-ORG-17 |
| A-ORG-06 | Intestinal cancer after cholecystectomy: is bile involved in carcinogenesis? Lagergren J, Ye W, Ekbom A | 2001 | PMID 11522737 DOI 10.1053/gast.2001.27083 | Cohort study | Swedish cholecystectomized patients | After gallbladder removal, rare small-bowel cancers were about 1.8 times as frequent and right-sided colon cancer 1.16 times as frequent as in the population. | Comparison with general population; gallstone disease itself and lifestyle not controlled; No confounder adjustment | low | C-ORG-06 C-ORG-16 |
| A-ORG-07 | Cholecystectomy and NAFLD: does gallbladder removal have metabolic consequences? Nervi F, Arrese M | 2013 | PMID 23735917 DOI 10.1038/ajg.2013.84 | Other | A US survey found fatty liver more often in people without a gallbladder; cause unclear. | Editorial; cross-sectional underlying data; reverse causation possible | very low | C-ORG-06 C-ORG-16 | |
| A-ORG-08 | Small Intestinal Bacterial Overgrowth Diagnosed by Glucose Hydrogen Breath Test in Post-cholecystectomy Patients. Sung HJ, Paik CN, Chung WC et al. | 2015 | PMID 26351251 DOI 10.5056/jnm15020 | Cross-sectional study | Post-cholecystectomy patients with symptoms, FGID patients, healthy controls | Breath tests were positive more often in symptomatic patients after gallbladder removal. | Small; Symptomatic selected patients | low | C-ORG-16 |
| A-ORG-09 | Postcholecystectomy diarrhoea rate and predictive factors: a systematic review of the literature. Farrugia A, Attard JA, Khan S et al. | 2022 | PMID 35177439 DOI 10.1136/bmjopen-2020-046172 | Systematic review | Adults (18-85 years) after cholecystectomy (1855 laparoscopic, 378 open where reported; 2250 women, 787 men where reported) | About 13% of patients developed diarrhoea after the operation. | Crude unweighted pooling; no CIs or heterogeneity assessment despite 2.1-57.2% range; Most included studies not powered for PCD, lacked control groups, used non-validated questionnaires and recall (authors) | low | C-ORG-01 C-ORG-08 |
| A-ORG-10 | Hysterectomy and risk of cardiovascular disease: a population-based cohort study. Ingelsson E, Lundholm C, Johansson AL et al. | 2011 | PMID 21186237 DOI 10.1093/eurheartj/ehq477 | Cohort study | Swedish women with benign hysterectomy | Women operated before 50 had about 18% more cardiovascular disease later. | Register confounding (indications, metabolic profile) | moderate | C-ORG-10 C-ORG-16 |
| A-ORG-11 | Cardiovascular and metabolic morbidity after hysterectomy with ovarian conservation: a cohort study. Laughlin-Tommaso SK, Khan Z, Weaver AL et al. | 2018 | PMID 29286988 DOI 10.1097/GME.0000000000001043 | Cohort study | Olmsted County women | Later heart and metabolic problems were modestly more frequent, especially after surgery at age 35 or younger. | Single county; Observational | moderate | C-ORG-10 C-ORG-16 |
| A-ORG-12 | Long term effects of hysterectomy on mortality: nested cohort study. Iversen L, Hannaford PC, Elliott AM et al. | 2005 | PMID 15930026 DOI 10.1136/bmj.38483.669178.8F | Cohort study | UK women | Women who had a hysterectomy did not die earlier over about 20 years. | Oophorectomy status not separated in abstract | moderate | C-ORG-10 C-ORG-16 |
| A-ORG-13 | Long-term mortality associated with oophorectomy compared with ovarian conservation in the nurses' health study. Parker WH, Feskanich D, Broder MS et al. | 2013 | PMID 23635669 DOI 10.1097/AOG.0b013e3182864350 | Cohort study | NHS participants with hysterectomy for benign disease | Removing the ovaries was linked to somewhat higher death rates (16.8% vs 13.3% over 28 years), mainly in women under 50 who never took estrogen. | Observational; reasons for oophorectomy unknown (authors' limitation); Self-reported oophorectomy (>90% accurate) | moderate | C-ORG-09 C-ORG-16 |
| A-ORG-14 | Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Rocca WA, Bower JH, Maraganore DM et al. | 2007 | PMID 17761551 DOI 10.1212/01.wnl.0000276984.19542.e6 | Cohort study | Olmsted County women, oophorectomy before menopause, non-cancer indication | Women who had ovaries removed before menopause had 46% higher risk of cognitive impairment or dementia later. | Proxy interviews; Observational | moderate | C-ORG-11 C-ORG-16 |
| A-ORG-15 | Accelerated Accumulation of Multimorbidity After Bilateral Oophorectomy: A Population-Based Cohort Study. Rocca WA, Gazzuola-Rocca L, Smith CY et al. | 2016 | PMID 27693001 DOI 10.1016/j.mayocp.2016.08.002 | Cohort study | Premenopausal women with bilateral oophorectomy <50 | Women who had both ovaries removed before 46 accumulated chronic diseases faster. | Higher baseline multimorbidity | moderate | C-ORG-09 C-ORG-16 |
| A-ORG-16 | Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up. Kristinsson SY, Gridley G, Hoover RN et al. | 2014 | PMID 24056815 DOI 10.3324/haematol.2013.092460 | Cohort study | Cancer-free US veterans with splenectomy among >4 million hospitalized veterans | Serious infections were 2-3 times more frequent and blood clots about 2 times more frequent after spleen removal. | Indications for splenectomy (trauma, haematologic disease) may confound; Male veterans only | moderate | C-ORG-12 C-ORG-13 C-ORG-16 |
| A-ORG-17 | Risk of cardiovascular events and pulmonary hypertension following splenectomy - a Danish population-based cohort study from 1996-2012. Rørholt M, Ghanima W, Farkas DK et al. | 2017 | PMID 28572164 DOI 10.3324/haematol.2016.157008 | Cohort study | Danish splenectomized patients | Compared with patients with the same diseases, only stroke risk stayed higher; heart attack risk was explained by the underlying disease. | 5-year follow-up | high | C-ORG-13 C-ORG-16 |
| A-ORG-18 | Overwhelming post-splenectomy sepsis in patients with asplenia and hyposplenia: a retrospective cohort study. Chong J, Jones P, Spelman D et al. | 2017 | PMID 27776576 DOI 10.1017/S0950268816002405 | Cohort study | Asplenic or hyposplenic registrants of the Victorian Spleen Registry (median age at splenectomy 38 years; mean 11 years since splenectomy) | Severe infections needing intensive care occurred in about 1 per 1000 patient-years. | Retrospective self-report at registration (recall bias; deaths before registration missed; possible registration because of infection); No non-splenectomised comparator, so excess risk cannot be quantified | moderate | C-ORG-12 |
| A-ORG-19 | Current thyroid cancer trends in the United States. Davies L, Welch HG | 2014 | PMID 24557566 DOI 10.1001/jamaoto.2014.1 | Ecological study | Adults in 9 SEER areas | Diagnoses nearly tripled from 1975 to 2009 while deaths stayed at about 0.5 per 100,000. | Ecological; cannot prove individual overdiagnosis | high | C-ORG-14 C-ORG-15 |
| A-ORG-20 | The enigma of persistent symptoms in hypothyroid patients treated with levothyroxine: A narrative review. Perros P, Van Der Feltz-Cornelis C, Papini E et al. | 2023 | PMID 33783849 DOI 10.1111/cen.14473 | Narrative review | A minority keep symptoms despite normal blood tests; causes are debated. | Narrative | low | C-ORG-16 | |
| A-PPI-01 | Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. Lazarus B, Chen Y, Wilson FP et al. | 2016 | PMID 26752337 DOI 10.1001/jamainternmed.2015.7193 | Cohort study | ARIC: community-based adults (visit 4, mean age ~62.5 y) from four US communities with eGFR >=60; Geisinger: patients of a rural Pennsylvania health system with outpatient eGFR >=60 (mean age ~50 y) | PPI users had about 1.2–1.5 times the rate of new chronic kidney disease compared with non-users or H2-blocker users. | Observational; PPI users more obese, hypertensive and on more medications - residual confounding by indication; Only 322 baseline PPI users in ARIC; exposure largely single baseline (updates from 2006) | moderate | C-PPI-01 |
| A-PPI-02 | Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Xie Y, Bowe B, Li T et al. | 2017 | PMID 28237709 DOI 10.1016/j.kint.2016.12.021 | Cohort study | Incident users of acid suppression | Compared with H2-blocker users, PPI users had 19–30% higher rates of kidney decline. | Mostly older male veterans; Residual confounding | moderate | C-PPI-01 |
| A-PPI-03 | Association Between Proton Pump Inhibitor Use and Risk of Progression of Chronic Kidney Disease. Klatte DCF, Gasparini A, Xu H et al. | 2017 | PMID 28583827 DOI 10.1053/j.gastro.2017.05.046 | Cohort study | New users of PPIs and H2 blockers in Stockholm | PPI starters had about 26% higher risk of kidney function decline than H2-blocker starters. | Short follow-up; Authors acknowledge residual confounding | moderate | C-PPI-01 |
| A-PPI-04 | Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. Gomm W, von Holt K, Thomé F et al. | 2016 | PMID 26882076 DOI 10.1001/jamaneurol.2015.4791 | Cohort study | Persons ≥75 years free of dementia | Regular PPI users were diagnosed with dementia 1.44 times as often. | Claims-based diagnoses; No data on education, lifestyle | low | C-PPI-09 |
| A-PPI-05 | Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis. Trifan A, Stanciu C, Girleanu I et al. | 2017 | PMID 29085200 DOI 10.3748/wjg.v23.i35.6500 | Meta-analysis | Adults in 56 observational studies | PPI users had about twice the odds of C. difficile infection. | Observational primary studies; High heterogeneity | moderate | C-PPI-02 |
| A-PPI-06 | Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Janarthanan S, Ditah I, Adler DG et al. | 2012 | PMID 22710578 DOI 10.1038/ajg.2012.179 | Meta-analysis | Hospitalised patients | Pooled risk about 1.7-fold higher with PPIs. | Observational inputs; Only Medline/PubMed searched | moderate | C-PPI-02 |
| A-PPI-07 | Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. Eom CS, Jeon CY, Lim JW et al. | 2011 | PMID 21173070 DOI 10.1503/cmaj.092129 | Meta-analysis | Adults in 31 studies | PPI users had 27% higher odds of pneumonia in observational studies, with large differences between studies. | Very high heterogeneity for PPIs; PPI evidence observational only | moderate | C-PPI-05 |
| A-PPI-08 | Long-term proton pump inhibitor therapy and risk of hip fracture. Yang YX, Lewis JD, Epstein S et al. | 2006 | PMID 17190895 DOI 10.1001/jama.296.24.2947 | Case-control study | Patients >50 years using PPIs or no acid suppression | Use for more than a year was associated with 44% higher odds of hip fracture. | Observational; Confounding by frailty, comorbidity and falls risk | moderate | C-PPI-05 |
| A-PPI-09 | Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. Lam JR, Schneider JL, Zhao W et al. | 2013 | PMID 24327038 DOI 10.1001/jama.2013.280490 | Case-control study | KPNC members | Two or more years of PPI supply was associated with 65% higher odds of B12 deficiency. | Case-control; Testing bias (users may be tested more) | moderate | C-PPI-03 C-PPI-04 |
| A-PPI-10 | Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study. Kieboom BC, Kiefte-de Jong JC, Eijgelsheim M et al. | 2015 | PMID 26123862 DOI 10.1053/j.ajkd.2015.05.012 | Cross-sectional study | General population ≥45 | PPI users had twice the odds of low magnesium, especially with long use and loop diuretics. | Single Mg measurement; Cross-sectional | moderate | C-PPI-03 C-PPI-04 |
| A-PPI-11 | Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Cheung KS, Chan EW, Wong AYS et al. | 2018 | PMID 29089382 DOI 10.1136/gutjnl-2017-314605 | Cohort study | Adults after clarithromycin-based triple therapy | Long-term PPI use was linked to more gastric cancer, about 4 extra cases per 10,000 person-years. | Few events (153); Wide CIs | moderate | C-PPI-09 |
| A-PPI-12 | Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study. Xie Y, Bowe B, Yan Y et al. | 2019 | PMID 31147311 DOI 10.1136/bmj.l1580 | Cohort study | New users of PPIs or H2 blockers | PPI users had an estimated 45 more deaths per 1,000 over about 10 years than H2-blocker users. | Older, white, male veterans; Residual confounding and channelling bias acknowledged by authors | moderate | C-PPI-01 |
| A-PPI-13 | Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. Xie Y, Bowe B, Li T et al. | 2017 | PMID 28676480 DOI 10.1136/bmjopen-2016-015735 | Cohort study | New users of PPI or H2 blockers; plus PPI vs no PPI cohorts | PPI users had about 15–34% higher hazard of death depending on method. | Observational; Same database as A-PPI-12 (not independent) | moderate | C-PPI-01 |
| A-PPI-14 | Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Reimer C, Søndergaard B, Hilsted L et al. | 2009 | PMID 19362552 DOI 10.1053/j.gastro.2009.03.058 | Randomised controlled trial | Healthy volunteers | After stopping esomeprazole, 44% of healthy volunteers had acid symptoms vs 15% on placebo. | Small; Short follow-up after withdrawal (4 weeks) | high | C-PPI-06 C-PPI-07 |
| A-PPI-15 | Proton pump inhibitors alter the composition of the gut microbiota. Jackson MA, Goodrich JK, Maxan ME et al. | 2016 | PMID 26719299 DOI 10.1136/gutjnl-2015-310861 | Cross-sectional study | Healthy twins | PPI users had fewer typical gut bacteria and more mouth bacteria in stool. | Composition change ≠ disease; Cross-sectional main analysis | moderate | C-PPI-02 |
| A-PPI-16 | Proton pump inhibitors affect the gut microbiome. Imhann F, Bonder MJ, Vich Vila A et al. | 2016 | PMID 26657899 DOI 10.1136/gutjnl-2015-310376 | Cross-sectional study | Three Dutch cohorts | PPI users had less diverse gut bacteria and more potentially harmful bacteria. | Cross-sectional; Composition ≠ outcome | moderate | C-PPI-02 |
| A-PPI-17 | Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Lo WK, Chan WW | 2013 | PMID 23270866 DOI 10.1016/j.cgh.2012.12.011 | Meta-analysis | Adults in 11 studies | Association found only with the culture test, not with breath tests. | Small studies; Publication bias | low | C-PPI-02 |
| A-PPI-18 | Analysis of Ranitidine-Associated N-Nitrosodimethylamine Production Under Simulated Physiologic Conditions. Braunstein LZ, Kantor ED, O'Connell K et al. | 2021 | PMID 33512515 DOI 10.1001/jamanetworkopen.2020.34766 | Laboratory / cell study | Commercial ranitidine 150/300 mg tablets | In simulated stomach fluid with very high nitrite, a tablet produced up to 320,000 ng NDMA. | In vitro only; Very high nitrite concentrations | low | C-PPI-08 |
| A-SOD-01 | Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis. Malik VS, Popkin BM, Bray GA et al. | 2010 | PMID 20693348 DOI 10.2337/dc10-1079 | Meta-analysis | Adults in prospective cohorts | People in the highest intake group had a 26% higher risk of type 2 diabetes than those drinking almost none. | Only MEDLINE, English only; no protocol registration; No formal risk-of-bias assessment of cohorts | low | C-SOD-01 C-DIAB-01 |
| A-SOD-02 | Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study. Pase MP, Himali JJ, Beiser AS et al. | 2017 | PMID 28428346 DOI 10.1161/STROKEAHA.116.016027 | Cohort study | Framingham Heart Study Offspring participants (predominantly of European descent): stroke sample aged >45 (mean 62, 45% men); dementia sample aged >60 (mean 69, 46% men) | Daily diet-soda drinkers had about three times more ischaemic strokes and Alzheimer's disease, but with very few cases and wide uncertainty. | Few events; very wide CIs; Reverse causation/confounding by indication: daily ASB drinkers had more diabetes (22% vs 7%), higher BMI and hypertension treatment | moderate | C-SOD-06 |
| A-SOD-03 | Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: The Framingham Osteoporosis Study. Tucker KL, Morita K, Qiao N et al. | 2006 | PMID 17023723 DOI 10.1093/ajcn/84.4.936 | Cross-sectional study | Older women and men | Women drinking cola daily had 3.7% lower hip bone density; other fizzy drinks showed no link. | Cross-sectional; Effect only in women and at hip | moderate | C-SOD-08 C-SOD-13 C-SOD-14 |
| A-SOD-04 | Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Ludwig DS, Peterson KE, Gortmaker SL | 2001 | PMID 11229668 DOI 10.1016/S0140-6736(00)04041-1 | Cohort study | Schoolchildren aged ~11.7 y | Each extra daily sugary drink was linked with higher BMI and 60% higher odds of obesity. | Small sample; Short follow-up | moderate | C-SOD-02 |
| A-SOD-05 | Long-Term Consumption of Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Mortality in US Adults. Malik VS, Li Y, Pan A et al. | 2019 | PMID 30882235 DOI 10.1161/CIRCULATIONAHA.118.037401 | Cohort study | US female nurses (NHS, aged 30-55 at entry) and male health professionals (HPFS, aged 40-75), predominantly non-Hispanic white, free of diabetes, CVD and cancer at baseline | Two or more sugary drinks a day: 21% higher death risk; diet drinks linked only at the highest intake and only in women. | Observational; residual confounding (SSB drinkers smoke more, poorer diet; AHEI 42.7 vs 50.6); Reverse causation likely for ASB (higher BMI and hypertension among ASB drinkers) (authors) | high | C-SOD-03 C-SOD-10 |
| A-SOD-06 | Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. Choi HK, Curhan G | 2008 | PMID 18244959 DOI 10.1136/bmj.39449.819271.BE | Cohort study | Male health professionals without gout | Two or more sugary sodas a day: 85% higher gout risk; fruit juice also linked; diet soda not. | Men health professionals only; Wide CI at highest intake | moderate | C-SOD-05 C-SUG-06 |
| A-SOD-07 | Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. Stanhope KL, Schwarz JM, Keim NL et al. | 2009 | PMID 19381015 DOI 10.1172/JCI37385 | Other | Overweight/obese adults aged 40-72 (BMI 25-35), postmenopausal women and men; without diabetes, renal/hepatic disease, hypertension, TG >400 mg/dl; non-smokers; habitual intake <=1 sugar-sweetened beverage/day | At very high doses, fructose drinks increased belly fat and worsened blood fats more than glucose drinks. | Small sample (32 completers); DNL subset only 18; Allocation by matching; randomisation not described | low | C-SOD-04 C-SRC-37 |
| A-SOD-08 | Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Imamura F, O'Connor L, Ye Z et al. | 2015 | PMID 26199070 DOI 10.1136/bmj.h3576 | Meta-analysis | Adults without diabetes | Each daily sugary drink was linked with 13-18% more diabetes; diet drinks and juice also showed (possibly biased) links. | Protocol not registered; High heterogeneity for SSB (I2 79-89%) | high | C-SOD-01 C-SOD-10 C-SUG-06 |
| A-SOD-09 | Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Suez J, Korem T, Zeevi D et al. | 2014 | PMID 25231862 DOI 10.1038/nature13793 | Animal study | Mice; healthy human subjects | In mice, sweeteners changed gut bacteria and caused glucose intolerance; a small human test showed similar effects. | Human data small (size not in abstract); Commercial formulations contained glucose fillers (not in abstract) | moderate | C-SOD-07 |
| A-SOD-10 | Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. Schulze MB, Manson JE, Ludwig DS et al. | 2004 | PMID 15328324 DOI 10.1001/jama.292.8.927 | Cohort study | Women aged young/middle-aged | Women drinking one or more sugary drinks daily had 83% higher diabetes risk; fruit punch similar. | Observational design; residual confounding possible; Self-reported dietary intake | high | C-SOD-01 C-SOD-02 |
| A-SOD-11 | Added Sugars and Cardiovascular Disease Risk in Children: A Scientific Statement From the American Heart Association. Vos MB, Kaar JL, Welsh JA et al. | 2017 | PMID 27550974 DOI 10.1161/CIR.0000000000000439 | Guideline / position statement | Children | The AHA recommends no more than about 6 teaspoons of added sugar a day for children and none under age 2. | Narrative, non-systematic literature review; no protocol, no formal risk-of-bias appraisal of included studies; Endpoints are CVD risk factors in children, not clinical CVD events | moderate | C-SOD-03 C-SUG-01 |
| A-SOD-12 | Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts. Ma J, Fox CS, Jacques PF et al. | 2015 | PMID 26055949 DOI 10.1016/j.jhep.2015.03.032 | Cross-sectional study | Adults | Daily sugary-drink consumers had 61% higher odds of fatty liver; diet soda showed no link. | Cross-sectional; Observational design; residual confounding possible | moderate | C-SOD-04 |
| A-SOD-13 | Carbonated beverages and chronic kidney disease. Saldana TM, Basso O, Darden R et al. | 2007 | PMID 17525693 DOI 10.1097/EDE.0b013e3180646338 | Case-control study | Newly diagnosed CKD patients and community controls | People with kidney disease more often reported drinking two or more colas a day; authors called this preliminary. | Case-control: recall and selection bias; Old data | low | C-SOD-09 |
| A-SOD-14 | Sweetened beverage consumption, incident coronary heart disease, and biomarkers of risk in men. de Koning L, Malik VS, Kellogg MD et al. | 2012 | PMID 22412070 DOI 10.1161/CIRCULATIONAHA.111.067017 | Cohort study | Male health professionals | Men with highest sugary-drink intake had 20% more heart disease; diet drinks showed no link. | Observational design; residual confounding possible; Self-reported dietary intake | high | C-SOD-03 C-SOD-10 |
| A-SOD-15 | Sweetened beverage consumption and risk of coronary heart disease in women. Fung TT, Malik V, Rexrode KM et al. | 2009 | PMID 19211821 DOI 10.3945/ajcn.2008.27140 | Cohort study | Women aged 34-59 without CHD, stroke, diabetes | Two or more sugary drinks a day: 35% higher heart disease risk; diet drinks not linked. | Observational design; residual confounding possible; Self-reported dietary intake | high | C-SOD-03 C-SOD-10 |
| A-SOD-16 | Added sugar intake and cardiovascular diseases mortality among US adults. Yang Q, Zhang Z, Gregg EW et al. | 2014 | PMID 24493081 DOI 10.1001/jamainternmed.2013.13563 | Cohort study | US adults (nationally representative) | People getting 25% or more of calories from added sugar had nearly three times the CVD death risk of those under 10%. | Single baseline exposure; not updated over up to 18 years (authors); Only ~8% of NHANES III participants had a second 24-h recall for the usual-intake model | moderate | C-SOD-03 C-SUG-01 |
| A-SOD-17 | Association Between Soft Drink Consumption and Mortality in 10 European Countries. Mullee A, Romaguera D, Pearson-Stuttard J et al. | 2019 | PMID 31479109 DOI 10.1001/jamainternmed.2019.2478 | Cohort study | EPIC participants from the general populations of 10 European countries; mean age 50.8 years; 71.1% women; free of cancer, heart disease, stroke and diabetes at baseline | Two or more soft drinks a day were linked with higher death rates; for diet drinks the link was even stronger, which may partly reflect who chooses diet drinks. | Single baseline assessment of soft-drink intake (authors); Residual confounding acknowledged by authors | high | C-SOD-03 C-SOD-10 |
| A-SOD-18 | Reducing consumption of sugar-sweetened beverages is associated with reduced blood pressure: a prospective study among United States adults. Chen L, Caballero B, Mitchell DC et al. | 2010 | PMID 20497980 DOI 10.1161/CIRCULATIONAHA.109.911164 | Cohort study | Adults with elevated BP (mean 134.9/84.8) | One sugary drink less per day was linked with about 1.8 mmHg lower systolic BP. | Observational analysis within trial; Self-reported intake | moderate | C-SOD-03 |
| A-SOD-19 | Effect of sugar-sweetened beverages on oral health: a systematic review and meta-analysis. Valenzuela MJ, Waterhouse B, Aggarwal VR et al. | 2021 | PMID 32830237 DOI 10.1093/eurpub/ckaa147 | Meta-analysis | General populations, children and adults (21 studies permanent dentition, 9 primary, 8 mixed) | More sugary drinks were linked with more tooth decay and erosion, increasing with amount. | Almost exclusively cross-sectional studies: temporality not established; Pooled data were unadjusted for confounders such as socio-economic status and fluoridation (authors) | low | C-SOD-11 |
| A-SOD-20 | Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis. Malik VS, Pan A, Willett WC et al. | 2013 | PMID 23966427 DOI 10.3945/ajcn.113.058362 | Meta-analysis | Children and adults | Adding sugary drinks increased adult weight by about 0.85 kg in trials; cohorts show weight gain per serving. | Child RCT estimate imprecise (random effects CI crosses 0); Overlap with other reviews | high | C-SOD-02 |
| A-SOD-21 | Liquid versus solid carbohydrate: effects on food intake and body weight. DiMeglio DP, Mattes RD | 2000 | PMID 10878689 DOI 10.1038/sj.ijo.0801229 | Randomised controlled trial | Healthy adults (7 men, 8 women) | People ate less to balance jelly-bean calories but not soda calories, and gained weight only with soda. | Very small; Randomisation not described in abstract | low | C-SOD-02 |
| A-SOD-22 | Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Bray GA, Nielsen SJ, Popkin BM | 2004 | PMID 15051594 DOI 10.1093/ajcn/79.4.537 | Ecological study | US population | HFCS consumption rose at the same time as obesity in the US; this suggests but does not prove a link. | Ecological: cannot show causation; HFCS is US-specific | very low | C-SOD-04 |
| A-SOD-23 | Sugar and artificially sweetened beverages and risk of obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. Qin P, Li Q, Zhao Y et al. | 2020 | PMID 32529512 DOI 10.1007/s10654-020-00655-y | Meta-analysis | Adults | Each extra 250 mL/day of sugary drinks was linked with 12-19% higher risks of obesity and diabetes; diet drinks showed similar links. | High heterogeneity; Cohorts only | moderate | C-SOD-01 C-SOD-02 C-SOD-03 C-SOD-10 |
| A-SUP-01 | Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. Bolland MJ, Avenell A, Baron JA et al. | 2010 | PMID 20671013 DOI 10.1136/bmj.c3691 | Meta-analysis | Mostly older women (patient-level median age 74.5 y, ~78% women, 97% white) in trials of calcium >=500 mg/day, >=100 participants, mean age >40, >1 year; calcium+vitamin D vs placebo trials excluded | In trials, people taking calcium had 31% more heart attacks than with placebo (143 vs 111 events). | CV events were not primary endpoints and were collected non-uniformly; blinded adjudication in only some trials; Borderline significance (P=0.035/0.038); stroke, composite and death not significant | moderate | C-SUP-04 |
| A-SUP-02 | Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women's Health Initiative limited access dataset and meta-analysis. Bolland MJ, Grey A, Avenell A et al. | 2011 | PMID 21505219 DOI 10.1136/bmj.d2040 | Meta-analysis | Postmenopausal women (WHI) + 8 trials | In women not already using calcium, calcium plus vitamin D was linked to about 13–22% more CV events. | Post-hoc subgroup analysis; Same author group | moderate | C-SUP-04 |
| A-SUP-03 | Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Miller ER, Pastor-Barriuso R, Dalal D et al. | 2005 | PMID 15537682 DOI 10.7326/0003-4819-142-1-200501040-00110 | Meta-analysis | 135,967 participants in 19 trials | In high-dose trials, 39 more deaths per 10,000 people with vitamin E. | High-dose trials small, in chronically ill patients (authors' limitation); Generalisability to healthy adults uncertain | moderate | C-SUP-03 |
| A-SUP-04 | Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. Omenn GS, Goodman GE, Thornquist MD et al. | 1996 | PMID 8602180 DOI 10.1056/NEJM199605023341802 | Randomised controlled trial | Smokers, former smokers, asbestos-exposed workers | Lung cancer was 28% more frequent with the supplements; the trial was stopped early. | Early stopping can exaggerate effects; High-risk population only | high | C-SUP-02 |
| A-SUP-05 | The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group | 1994 | PMID 8127329 DOI 10.1056/NEJM199404143301501 | Randomised controlled trial | Male smokers 50–69 years | Beta-carotene raised lung cancer by 18% and deaths by 8%; vitamin E did not prevent lung cancer. | Male smokers only; Low vitamin E dose | high | C-SUP-02 C-SUP-03 |
| A-SUP-06 | Dietary supplements and mortality rate in older women: the Iowa Women's Health Study. Mursu J, Robien K, Harnack LJ et al. | 2011 | PMID 21987192 DOI 10.1001/archinternmed.2011.445 | Cohort study | Postmenopausal women aged 55-69 in 1986 (mean 61.6 y), 99% white, Iowa | Several supplements were linked to slightly more deaths; calcium to fewer. | Observational; confounding by indication and reverse causation (e.g. iron for anaemia due to illness) possible; Self-reported supplement use; supplement questionnaire not separately validated | low | C-SUP-04 C-SUP-06 |
| A-SUP-07 | n-3 fatty acids and cardiovascular events after myocardial infarction. Kromhout D, Giltay EJ, Geleijnse JM et al. | 2010 | PMID 20929341 DOI 10.1056/NEJMoa1003603 | Randomised controlled trial | Post-MI patients 60–80 years | No reduction in cardiovascular events. | Low dose via margarine; Well-treated patients | high | C-SUP-01 C-SUP-05 |
| A-SUP-08 | Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. Manson JE, Cook NR, Lee IM et al. | 2019 | PMID 30415637 DOI 10.1056/NEJMoa1811403 | Randomised controlled trial | Men ≥50, women ≥55 | No reduction in major cardiovascular events or cancer. | Secondary MI benefit | high | C-SUP-01 C-SUP-05 |
| A-SUP-09 | Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. ASCEND Study Collaborative Group, Bowman L, Mafham M et al. | 2018 | PMID 30146932 DOI 10.1056/NEJMoa1804989 | Randomised controlled trial | Diabetes without ASCVD | No reduction in serious vascular events. | Olive-oil placebo | high | C-SUP-01 C-SUP-05 |
| A-SUP-10 | Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial. Nicholls SJ, Lincoff AM, Garcia M et al. | 2020 | PMID 33190147 DOI 10.1001/jama.2020.22258 | Randomised controlled trial | Statin-treated, high CV risk, hypertriglyceridaemia, low HDL | No benefit vs corn oil; more GI side effects. | Stopped for futility | high | C-SUP-01 C-SUP-05 |
| A-SUP-11 | Effect of Long-Term Marine ɷ-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. Gencer B, Djousse L, Al-Ramady OT et al. | 2021 | PMID 34612056 DOI 10.1161/CIRCULATIONAHA.121.055654 | Meta-analysis | Participants in CV outcome RCTs | Omega-3 pills raised AF risk by 25%, more at higher doses. | AF often not prespecified; Few trials | high | C-SUP-05 |
| A-SUP-12 | Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Abdelhamid AS, Brown TJ, Brainard JS et al. | 2020 | PMID 32114706 DOI 10.1002/14651858.CD003177.pub5 | Meta-analysis | Adults in 86 RCTs | Little or no effect on deaths; small reductions in coronary events (low certainty). | Low certainty for small benefits | high | C-SUP-01 C-SUP-05 |
| A-SUP-13 | Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. Clegg DO, Reda DJ, Harris CL et al. | 2006 | PMID 16495392 DOI 10.1056/NEJMoa052771 | Randomised controlled trial | Symptomatic knee osteoarthritis | Not better than placebo overall. | High placebo response; Exploratory subgroup | high | C-SUP-01 C-SUP-07 |
| A-SUP-14 | Ascorbic acid supplements and kidney stone incidence among men: a prospective study. Thomas LD, Elinder CG, Tiselius HG et al. | 2013 | PMID 23381591 DOI 10.1001/jamainternmed.2013.2296 | Cohort study | Men (per title) | Not read (no abstract). | Letter format; not read | low | C-SUP-07 |
| A-SUP-15 | Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Stranges S, Marshall JR, Natarajan R et al. | 2007 | PMID 17620655 DOI 10.7326/0003-4819-147-4-200708210-00175 | Randomised controlled trial | Dermatology clinic patients without T2D, low-selenium areas | Selenium pills were linked to more new diabetes (HR 1.55). | Secondary outcome; Self-reported diagnosis | moderate | C-SUP-07 |
| A-SUP-16 | Vitamin A intake and hip fractures among postmenopausal women. Feskanich D, Singh V, Willett WC et al. | 2002 | PMID 11754708 DOI 10.1001/jama.287.1.47 | Cohort study | Postmenopausal women | Women with the highest retinol intake had about 1.9 times the risk of hip fracture. | Observational; FFQ measurement error | moderate | C-SUP-07 |
| A-SUP-17 | Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. Cole BF, Baron JA, Sandler RS et al. | 2007 | PMID 17551129 DOI 10.1001/jama.297.21.2351 | Randomised controlled trial | Recent colorectal adenoma history | No prevention of polyps; possible increase in advanced lesions (borderline). | Second follow-up 59.5%; Borderline results | moderate | C-SUP-06 |
| A-SUP-18 | Cancer incidence and mortality after treatment with folic acid and vitamin B12. Ebbing M, Bønaa KH, Nygård O et al. | 2009 | PMID 19920236 DOI 10.1001/jama.2009.1622 | Randomised controlled trial | Ischaemic heart disease patients | More cancer and deaths with folic acid plus B12 in heart patients. | Post-trial observational follow-up; Not prespecified for cancer | moderate | C-SUP-06 |
| A-SUP-19 | Homocysteine lowering with folic acid and B vitamins in vascular disease. Lonn E, Yusuf S, Arnold MJ et al. | 2006 | PMID 16531613 DOI 10.1056/NEJMoa060900 | Randomised controlled trial | Vascular disease or diabetes, ≥55 years | No reduction in major CV events; fewer strokes. | high | C-SUP-07 | |
| A-SUP-20 | Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. Sanders KM, Stuart AL, Williamson EJ et al. | 2010 | PMID 20460620 DOI 10.1001/jama.2010.594 | Randomised controlled trial | Community-dwelling women ≥70 at high fracture risk | More falls and fractures with 500,000 IU once a year. | Unusual bolus regimen | high | C-SUP-07 |
| A-SUP-21 | Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ et al. | 2016 | PMID 26747333 DOI 10.1001/jamainternmed.2015.7148 | Randomised controlled trial | ≥70 years with prior fall | More people fell with the higher monthly doses. | Small; Secondary outcome falls | moderate | C-SUP-07 |
| A-SUP-22 | Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. Manson JE, Cook NR, Lee IM et al. | 2019 | PMID 30415629 DOI 10.1056/NEJMoa1809944 | Randomised controlled trial | Men ≥50, women ≥55 | No prevention of cancer or heart disease; no safety problems. | Mostly vitamin-D-replete population | high | C-SUP-01 C-SUP-07 |
| A-SUP-23 | Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Klein EA, Thompson IM, Tangen CM et al. | 2011 | PMID 21990298 DOI 10.1001/jama.2011.1437 | Randomised controlled trial | Relatively healthy men aged >=50 (African American) or >=55 (others) with PSA <=4.0 ng/mL and non-suspicious DRE; median age 62-63; 79% white, 12-13% African American | Vitamin E pills raised prostate cancer by 17% (1.6 extra cases per 1,000 men per year). | Absolute effect small (1.6 per 1000 person-years); About 16-21% of cancers diagnosed during unblinded follow-up after supplements stopped | high | C-SUP-03 |
| A-SUP-24 | Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. Bjelakovic G, Nikolova D, Gluud LL et al. | 2007 | PMID 17327526 DOI 10.1001/jama.297.8.842 | Meta-analysis | Adults in 68 RCTs | In low-bias trials, beta-carotene, vitamin A and vitamin E were linked to slightly more deaths. | Exclusion of zero-death trials and methods were debated; Heterogeneous populations | moderate | C-SUP-02 C-SUP-03 |
| A-SUP-25 | Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. Sesso HD, Christen WG, Bubes V et al. | 2012 | PMID 23117775 DOI 10.1001/jama.2012.14805 | Randomised controlled trial | Male US physicians ≥50 | No reduction in heart attacks or strokes; no increase in deaths. | Healthy physicians | high | C-SUP-01 C-SUP-06 |
| A-SUP-26 | Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials. Macpherson H, Pipingas A, Pase MP | 2013 | PMID 23255568 DOI 10.3945/ajcn.112.049304 | Meta-analysis | Independently living adults | No effect on mortality. | Heterogeneous products | high | C-SUP-01 C-SUP-06 |
| A-SUP-27 | Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Grodstein F, O'Brien J, Kang JH et al. | 2013 | PMID 24490265 DOI 10.7326/0003-4819-159-12-201312170-00006 | Randomised controlled trial | Male physicians ≥65 | No benefit for cognition. | Well-nourished; dose low | high | C-SUP-01 |
| A-SUP-28 | Enough is enough: Stop wasting money on vitamin and mineral supplements. Guallar E, Stranges S, Mulrow C et al. | 2013 | PMID 24490268 DOI 10.7326/0003-4819-159-12-201312170-00011 | Other | Opinion; not read. | Opinion, not data | very low | C-SUP-01 | |
| A-SUP-29 | Supplemental Vitamins and Minerals for CVD Prevention and Treatment. Jenkins DJA, Spence JD, Giovannucci EL et al. | 2018 | PMID 29852980 DOI 10.1016/j.jacc.2018.04.020 | Meta-analysis | RCT participants | Mostly no effect; folic acid may reduce stroke; antioxidant mixtures may increase mortality. | Abstract lacks numbers | moderate | C-SUP-01 C-SUP-04 |
| A-SUP-30 | Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation Statement. US Preventive Services Task Force, Mangione CM, Barry MJ et al. | 2022 | PMID 35727271 DOI 10.1001/jama.2022.8970 | Guideline / position statement | Community-dwelling, non-pregnant adults | Recommends against beta-carotene and vitamin E; evidence insufficient for most others. | Excludes pregnancy and deficiency | high | C-SUP-01 C-SUP-02 C-SUP-03 C-SUP-10 |
| A-UPF-01 | Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake. Hall KD, Ayuketah A, Brychta R et al. | 2019 | PMID 31105044 DOI 10.1016/j.cmet.2019.05.008 | Randomised controlled trial | 10 men and 10 women, weight-stable, age 31.2±1.6 y (mean±SE), BMI 27±1.5 kg/m2 | People ate about 500 calories more per day and gained weight on ultra-processed food. | Small (n=20) and short (2 weeks per diet); No run-in or washout period; possible carry-over (authors) | high | C-UPF-02 C-SRC-22 |
| A-UPF-02 | Association Between Ultraprocessed Food Consumption and Risk of Mortality Among Middle-aged Adults in France. Schnabel L, Kesse-Guyot E, Allès B et al. | 2019 | PMID 30742202 DOI 10.1001/jamainternmed.2018.7289 | Cohort study | Adults >=45 y, 73% women | Each 10% more ultra-processed food was linked with 14% higher death risk. | Volunteer cohort, mostly women; Few deaths | moderate | C-UPF-03 |
| A-UPF-03 | Association between consumption of ultra-processed foods and all cause mortality: SUN prospective cohort study. Rico-Campà A, Martínez-González MA, Alvarez-Alvarez I et al. | 2019 | PMID 31142450 DOI 10.1136/bmj.l1949 | Cohort study | Spanish university graduates aged 20-91 (mean age 37.6, SD 12.3); 12,113 women, 7,786 men; participants with prevalent disease were included and adjusted for | More than four servings a day was linked with 62% higher death risk. | Few deaths (335), so imprecise estimates; cause-specific analyses underpowered and non-significant; FFQ not designed for NOVA; some UPF items missing; serving counts may misclassify | moderate | C-UPF-03 |
| A-UPF-04 | Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Santé). Srour B, Fezeu LK, Kesse-Guyot E et al. | 2019 | PMID 31142457 DOI 10.1136/bmj.l1451 | Cohort study | French adults >=18 years without CVD at baseline; 79.2% women; mean age 42.7 (SD 14.5); healthier, more educated, less often overweight and diabetic than the French population | Each 10% more ultra-processed food was linked with 12% more cardiovascular disease. | Short median follow-up (5.2 years); Almost half of events are transient ischaemic attacks (674/1,409) and many angioplasties; few myocardial infarctions (106) and strokes (155) | moderate | C-UPF-03 |
| A-UPF-05 | Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort. Srour B, Fezeu LK, Kesse-Guyot E et al. | 2020 | PMID 31841598 DOI 10.1001/jamainternmed.2019.5942 | Cohort study | Adults >=18, 79% women | Each 10% more ultra-processed food was linked with 15% more diabetes. | NOVA misclassification possible; Residual confounding | moderate | C-UPF-03 |
| A-UPF-06 | Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort. Fiolet T, Srour B, Sellem L et al. | 2018 | PMID 29444771 DOI 10.1136/bmj.k322 | Cohort study | French adult volunteers >=18 years without cancer at baseline; 78.3% women; mean age 42.8 (SD 14.8) | Each 10% more ultra-processed food was linked with 12% more cancer. | Short median follow-up (5 years) relative to cancer latency (authors); Volunteer, health-conscious, mostly female cohort (authors) | moderate | C-UPF-03 |
| A-UPF-07 | Ultra-processed food consumption is associated with increased risk of all-cause and cardiovascular mortality in the Moli-sani Study. Bonaccio M, Di Castelnuovo A, Costanzo S et al. | 2021 | PMID 33333551 DOI 10.1093/ajcn/nqaa299 | Cohort study | Adults mean age 55 | Highest consumers had 58% higher cardiovascular death risk; sugar content explained about a third of the heart/stroke link. | NOVA misclassification possible; Residual confounding | moderate | C-UPF-03 |
| A-UPF-08 | Ultraprocessed food consumption and risk of overweight and obesity: the University of Navarra Follow-Up (SUN) cohort study. Mendonça RD, Pimenta AM, Gea A et al. | 2016 | PMID 27733404 DOI 10.3945/ajcn.116.135004 | Cohort study | Middle-aged graduates not overweight at baseline | Highest consumers had 26% higher risk of becoming overweight. | NOVA misclassification possible; Residual confounding | moderate | C-UPF-02 |
| A-UPF-09 | Ultra-processed food intake in association with BMI change and risk of overweight and obesity: A prospective analysis of the French NutriNet-Santé cohort. Beslay M, Srour B, Méjean C et al. | 2020 | PMID 32853224 DOI 10.1371/journal.pmed.1003256 | Cohort study | Adults, 78% women | Each 10% more ultra-processed food: 11% higher risk of overweight. | NOVA misclassification possible; Residual confounding | moderate | C-UPF-02 |
| A-UPF-10 | Consumption of ultra-processed foods and body fat during childhood and adolescence: a systematic review. Costa CS, Del-Ponte B, Assunção MCF et al. | 2018 | PMID 28676132 DOI 10.1017/S1368980017001331 | Systematic review | Healthy children and adolescents | Most studies found more body fat in children eating more ultra-processed foods, including sweets and soft drinks. | No pooling; Heterogeneous exposures | low | C-UPF-02 |
| A-UPF-11 | Prospective association between ultra-processed food consumption and incident depressive symptoms in the French NutriNet-Santé cohort. Adjibade M, Julia C, Allès B et al. | 2019 | PMID 30982472 DOI 10.1186/s12916-019-1312-y | Cohort study | Adults 18-86 without depressive symptoms at baseline | Each 10% more ultra-processed food: 21% more new depressive symptoms. | Symptom scale, not diagnosis; NOVA misclassification possible | moderate | C-UPF-04 |
| A-UPF-12 | Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study. Narula N, Wong ECL, Dehghan M et al. | 2021 | PMID 34261638 DOI 10.1136/bmj.n1554 | Cohort study | Adults aged 35-70 from 21 low-, middle- and high-income countries (incl. Iran, Palestine, Saudi Arabia, UAE, Turkey; no Western European country except Sweden and Poland) | Five or more servings a day: 82% higher IBD risk; legumes, dairy and vegetables showed no link. | Few cases (467), especially Crohn's disease (90): imprecise estimates; Self-reported IBD; only ~20% validated; systematic recording started only in 2014 (authors) | moderate | C-UPF-05 |
| A-UPF-13 | Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses. Lane MM, Gamage E, Du S et al. | 2024 | PMID 38418082 DOI 10.1136/bmj-2023-077310 | Systematic review | Pooled populations across the life course (mostly adults; 5 pooled analyses in children/adolescents) | UPF was linked to 32 of 45 health outcomes; certainty was mostly low. | All underlying evidence observational; confounder adjustment and sensitivity analyses of primary studies not assessed (authors); Many pooled analyses based on 2-4 studies, often cross-sectional (e.g. anxiety, common mental disorders, obesity) | high | C-UPF-03 C-UPF-04 C-UPF-05 |
| A-UPF-14 | Consumption of ultra-processed foods and health status: a systematic review and meta-analysis. Pagliai G, Dinu M, Madarena MP et al. | 2021 | PMID 32792031 DOI 10.1017/S0007114520002688 | Meta-analysis | Adults | Highest consumers had 25% higher death risk and 29% higher CVD risk in cohorts. | Few studies per outcome | moderate | C-UPF-03 C-UPF-04 |
| A-UPF-15 | Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Chassaing B, Koren O, Goodrich JK et al. | 2015 | PMID 25731162 DOI 10.1038/nature14232 | Animal study | Mice (mostly 4 weeks old at start; also 4-month-old mice); male or female within experiments | Two common emulsifiers caused gut inflammation and metabolic problems in mice. | Animal model; human relevance unknown (authors); Exposure 0.1-1.0% in all drinking water or chow; relation to actual human intake not quantified | moderate | C-UPF-05 C-UPF-06 |
| A-UPF-16 | Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome. Chassaing B, Compher C, Bonhomme B et al. | 2022 | PMID 34774538 DOI 10.1053/j.gastro.2021.11.006 | Randomised controlled trial | Healthy adults | Seven people eating CMC for 11 days had changes in gut bacteria and mild discomfort. | Very small; Short | moderate | C-UPF-06 |
| A-UPF-17 | Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Suez J, Korem T, Zeevi D et al. | 2014 | PMID 25231862 DOI 10.1038/nature13793 | Animal study | Mice; healthy humans | Same paper as A-SOD-09. | Duplicate of A-SOD-09 | moderate | C-SOD-07 |
| A-UPF-18 | Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. Debras C, Chazelas E, Srour B et al. | 2022 | PMID 35324894 DOI 10.1371/journal.pmed.1003950 | Cohort study | Adults | Higher sweetener consumers had 13% more cancer. | Selection bias, residual confounding, reverse causation (authors) | moderate | C-UPF-07 |
| A-UPF-19 | Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. Debras C, Chazelas E, Sellem L et al. | 2022 | PMID 36638072 DOI 10.1136/bmj-2022-071204 | Cohort study | Adults, 79.8% women | Higher sweetener intake: 9% higher cardiovascular risk. | Reverse causation; Residual confounding | moderate | C-UPF-07 |
| A-UPF-20 | Carcinogenicity of aspartame, methyleugenol, and isoeugenol. Riboli E, Beland FA, Lachenmeier DW et al. | 2023 | PMID 37454664 DOI 10.1016/S1470-2045(23)00341-8 | Risk assessment | Not applicable | IARC placed aspartame in Group 2B ('possibly carcinogenic') on limited evidence. | Hazard identification, not risk assessment: does not address the dose at which any risk occurs; Human evidence limited to a few observational ASB studies with possible chance, bias or confounding | moderate | C-UPF-08 |
| A-UPF-21 | Safety assessment of titanium dioxide (E171) as a food additive. EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G et al. | 2021 | PMID 33976718 DOI 10.2903/j.efsa.2021.6585 | Risk assessment | Not applicable | EFSA could not rule out DNA damage and concluded E171 is no longer safe; the EU then banned it. | Precautionary conclusion driven by an unresolved genotoxicity concern, not by demonstrated harm in humans; No human outcome data; no adequate carcinogenicity study of TiO2 nanoparticles | high | C-UPF-09 C-UPF-11 |
| A-UPF-22 | Ultra-processed foods: what they are and how to identify them. Monteiro CA, Cannon G, Levy RB et al. | 2019 | PMID 30744710 DOI 10.1017/S1368980018003762 | Narrative review | Not applicable | NOVA's authors explain that products with industrial ingredients or cosmetic additives (e.g., emulsifiers, flavours, emulsifying salts) are ultra-processed. | Commentary; reliability not tested here | moderate | C-UPF-01 C-UPF-12 C-SUG-05 |
| A-UPF-23 | Trans fatty acids and cardiovascular disease. Mozaffarian D, Katan MB, Ascherio A et al. | 2006 | PMID 16611951 DOI 10.1056/NEJMra054035 | Narrative review | Not applicable | A review of trans fats and heart disease; no abstract was available to assess. | Content not reviewed (no abstract) | moderate | C-UPF-03 |
| A-VEG-01 | Multistate Outbreak of Escherichia coli O157:H7 Infections Associated with Consumption of Fresh Spinach: United States, 2006. Sharapov UM, Wendel AM, Davis JP et al. | 2016 | PMID 28221950 DOI 10.4315/0362-028X.JFP-15-556 | Outbreak report | Case patients in 27 states | 225 people fell ill and 5 died after eating contaminated bagged spinach. | Single event | high | C-VEG-03 |
| A-VEG-02 | German outbreak of Escherichia coli O104:H4 associated with sprouts. Buchholz U, Bernard H, Werber D et al. | 2011 | PMID 22029753 DOI 10.1056/NEJMoa1106482 | Outbreak report | HUS cases and controls; restaurant visitors | Investigation identified sprouts, not cucumbers, as the source. | Recall bias; Strain not found on seeds | high | C-VEG-04 |
| A-VEG-03 | Multistate Outbreak of Listeriosis Associated with Packaged Leafy Green Salads, United States and Canada, 2015-2016. Self JL, Conrad A, Stroika S et al. | 2019 | PMID 31310227 DOI 10.3201/eid2508.180761 | Outbreak report | Case-patients | 33 listeriosis cases linked to salads from one factory. | Small | high | C-VEG-03 |
| A-VEG-04 | Outbreak of Salmonella Newport infections linked to cucumbers--United States, 2014. Angelo KM, Chu A, Anand M et al. | 2015 | PMID 25695319 | Outbreak report | Patients in 29 states + DC | 275 people infected; cucumbers likely source. | Evidence 'suggests' | moderate | C-VEG-03 |
| A-VEG-05 | Dietary oxalate and calcium oxalate nephrolithiasis. Khan SR, Glenton PA, Byer KJ | 2007 | PMID 17870111 DOI 10.1016/j.juro.2007.06.046 | Animal study | Male Sprague-Dawley rats | Rats fed an oxalate precursor developed kidney crystals that partly cleared after stopping it. | Animal model; Precursor, not vegetables | low | C-VEG-05 |
| A-VEG-06 | Oxalate nephropathy due to 'juicing': case report and review. Getting JE, Gregoire JR, Phul A et al. | 2013 | PMID 23830537 DOI 10.1016/j.amjmed.2013.03.019 | Case series / case report | Index patient + 65 Mayo Clinic patients with biopsy-proven renal CaOx crystals | Rare kidney failure from heavy oxalate-rich juicing, mainly in people with kidney disease. | Case series; selection | low | C-VEG-06 |
| A-VEG-07 | Myxedema coma induced by ingestion of raw bok choy. Chu M, Seltzer TF | 2010 | PMID 20484407 DOI 10.1056/NEJMc0911005 | Case series / case report | One patient | One elderly woman with extreme raw bok choy intake; no generalisation possible. | Single case; No abstract | very low | C-VEG-10 |
| A-VEG-08 | Methemoglobinemia caused by the ingestion of courgette soup given in order to resolve constipation in two formula-fed infants. Savino F, Maccario S, Guidi C et al. | 2006 | PMID 16809905 DOI 10.1159/000094301 | Case series / case report | Two formula-fed infants aged 1 and 2 months | Two infants under 3 months developed methaemoglobinaemia from concentrated courgette soup. | Two cases | low | C-VEG-07 C-VEG-08 |
| A-VEG-09 | [Food poisoning by cucurbitacines]. Jung C, Steuber B, Schwörer H | 2020 | PMID 32668470 DOI 10.1055/a-1163-9741 | Case series / case report | One 66-year-old woman | A woman developed bloody colitis after eating bitter zucchini; recovered in 2 days. | Single case | low | C-VEG-09 |
| A-VEG-10 | Hair Loss Associated With Cucurbit Poisoning. Assouly P | 2018 | PMID 29590275 DOI 10.1001/jamadermatol.2017.6128 | Case series / case report | Case(s) | Case report; content not available to us. | No abstract | very low | C-VEG-09 |
| A-VEG-11 | Toxic squash syndrome: a case report. Prudhomme N, Pan A, Hendin A | 2022 | PMID 35869358 DOI 10.1007/s43678-022-00358-1 | Case series / case report | Case | Case report; content not available to us. | No abstract | very low | C-VEG-09 |
| A-VEG-12 | Profilin is a relevant melon allergen susceptible to pepsin digestion in patients with oral allergy syndrome. Rodriguez-Perez R, Crespo JF, Rodríguez J et al. | 2003 | PMID 12642849 DOI 10.1067/mai.2003.74 | Laboratory / cell study | Patients with melon OAS confirmed by DBPCFC | Allergic patients react to profilin in melon and related cucurbits; it is quickly digested in the stomach. | Small selected group | moderate | C-VEG-11 |
| A-VEG-13 | Organic diets significantly lower children's dietary exposure to organophosphorus pesticides. Lu C, Toepel K, Irish R et al. | 2006 | PMID 16451864 DOI 10.1289/ehp.8418 | Other | Children aged 3-11 years from public and Montessori elementary schools in suburban Seattle, consuming exclusively conventional diets; selected to be not very selective about food taste | Pesticide traces in children's urine dropped to undetectable when they ate organic food. | Very small, non-representative sample (authors: do not generalise); No health outcomes; no comparison with acceptable daily intakes | moderate | C-VEG-13 |
| A-VEG-14 | Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets. Curl CL, Fenske RA, Elgethun K | 2003 | PMID 12611667 DOI 10.1289/ehp.5754 | Cross-sectional study | Preschool children | Children on conventional diets had about six times more pesticide metabolites in urine. | Small; Cross-sectional | moderate | C-VEG-13 |
| A-VEG-15 | Do dietary lectins cause disease? Freed DL | 1999 | PMID 10205084 DOI 10.1136/bmj.318.7190.1023 | Narrative review | Not applicable | Opinion piece asking whether lectins cause disease; content not available to us. | Opinion; no data | very low | C-LEG-07 |
| A-VEG-16 | Cryptic diversity of cellulose-degrading gut bacteria in industrialized humans. Moraïs S, Winkler S, Zorea A et al. | 2024 | PMID 38484069 DOI 10.1126/science.adj9223 | Other | Metagenome-assembled genomes (4941 rumen MAGs, 92,143 human MAGs) and 1989 gut metagenome samples from humans (industrialised, rural, hunter-gatherer, 1000-2000-year-old paleofaeces) and 75 animal species (non-human primates, ruminants) | Humans carry cellulose-digesting bacteria; they are common in traditional populations and rare in industrialised ones. | No health outcomes and no measurement of actual cellulose fermentation in people; Prevalence comparisons are ecological and confounded by diet, antibiotics, sequencing depth and cohort methods | high | C-VEG-01 C-VEG-02 |
| A-VEG-17 | Interaction Between Dietary Vitamin K Intake and Anticoagulation by Vitamin K Antagonists: Is It Really True?: A Systematic Review. Violi F, Lip GY, Pignatelli P et al. | 2016 | PMID 26962786 DOI 10.1097/MD.0000000000002895 | Systematic review | Patients treated with vitamin K antagonists (mostly warfarin; also phenprocoumon, acenocoumarol) for AF, prosthetic valves or VTE | Review found no good evidence that patients on warfarin should restrict leafy greens; stable intake matters. | Only MEDLINE and Cochrane searched; No protocol registration; no meta-analysis | low | C-VEG-12 |
| A-WHT-01 | Associations of cereal grains intake with cardiovascular disease and mortality across 21 countries in Prospective Urban and Rural Epidemiology study: prospective cohort study. Swaminathan S, Dehghan M, Raj JM et al. | 2021 | PMID 33536317 DOI 10.1136/bmj.m4948 | Cohort study | Adults aged 35-70 y, urban and rural, 21 low-, middle- and high-income countries | People eating about 7 portions/day of refined grains had 27% higher mortality and 33% more major heart events than those eating very little. | Diet measured once at baseline by FFQ; Residual confounding acknowledged by authors | high | C-WHT-03 C-WHT-01 C-GRN-05 |
| A-WHT-02 | Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies. Aune D, Keum N, Giovannucci E et al. | 2016 | PMID 27301975 DOI 10.1136/bmj.i2716 | Meta-analysis | Participants of prospective cohorts | Each 3 servings/day of whole grains linked to 17% lower mortality and 19% lower CHD. | Observational primary studies; healthy-user and socioeconomic confounding acknowledged; High heterogeneity for all-cause mortality (I2 83%) and diabetes mortality | high | C-WHT-04 C-WHT-03 C-GRN-08 C-GRN-04 |
| A-WHT-03 | White rice consumption and risk of type 2 diabetes: meta-analysis and systematic review. Hu EA, Pan A, Malik V et al. | 2012 | PMID 22422870 DOI 10.1136/bmj.e1454 | Meta-analysis | Adults free of self-reported diabetes at baseline in 4 prospective cohort studies (7 cohort analyses): Shanghai Women's Health Study (China), JPHC (Japan; men and women analysed separately), HPFS, NHS, NHS II (USA), Melbourne Collaborative Cohort Study (Australia); ages 26-87 years | Each daily serving of white rice was linked to 11% higher diabetes risk; strongest in China/Japan. | Only 4 articles / 7 comparisons; Egger test underpowered; Substantial overall heterogeneity (I2=72.2%); the single overall estimate mixes very different intake ranges | moderate | C-GRN-05 C-WHT-05 |
| A-WHT-04 | Whole grain and refined grain consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies. Aune D, Norat T, Romundstad P et al. | 2013 | PMID 24158434 DOI 10.1007/s10654-013-9852-5 | Meta-analysis | Cohort participants | More whole grains: 32% lower diabetes risk per 3 servings/day; refined grains: no clear link. | High heterogeneity; Observational | moderate | C-WHT-05 C-GRN-05 |
| A-WHT-05 | A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Liu S, Willett WC, Stampfer MJ et al. | 2000 | PMID 10837285 DOI 10.1093/ajcn/71.6.1455 | Cohort study | 75,521 US women aged 38-63 y | Women with the highest dietary glycaemic load had about twice the CHD risk. | Women only, US nurses; GL is a whole-diet measure | moderate | C-WHT-05 |
| A-WHT-06 | Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. Liu S, Manson JE, Buring JE et al. | 2002 | PMID 11864854 DOI 10.1093/ajcn/75.3.492 | Cross-sectional study | 244 healthy women | Women with high GL diets had higher CRP. | Small, cross-sectional; Surrogate outcome | low | C-WHT-05 |
| A-WHT-07 | Glycemic index, glycemic load, and risk of type 2 diabetes: results from 3 large US cohorts and an updated meta-analysis. Bhupathiraju SN, Tobias DK, Malik VS et al. | 2014 | PMID 24787496 DOI 10.3945/ajcn.113.079533 | Cohort study | 74,248 NHS women, 90,411 NHS II women, 40,498 HPFS men | Diets high in fast-acting carbs and low in cereal fibre linked to ~50% higher diabetes risk. | Observational; US health professionals | high | C-WHT-05 C-FRU-01 |
| A-WHT-08 | Dietary glycemic load and index and risk of coronary heart disease in a large italian cohort: the EPICOR study. Sieri S, Krogh V, Berrino F et al. | 2010 | PMID 20386010 DOI 10.1001/archinternmed.2010.15 | Cohort study | 15,171 men, 32,578 women | High GL linked to CHD in women, not men. | Few cases in women (158); Sex-specific findings | moderate | C-WHT-05 |
| A-WHT-09 | Whole- and refined-grain intakes are differentially associated with abdominal visceral and subcutaneous adiposity in healthy adults: the Framingham Heart Study. McKeown NM, Troy LM, Jacques PF et al. | 2010 | PMID 20881074 DOI 10.3945/ajcn.2009.29106 | Cross-sectional study | 2834 adults 32-83 y | More refined grains, more visceral fat; more whole grains, less. | Cross-sectional; FFQ | moderate | C-WHT-06 |
| A-WHT-10 | Glycemic load, glycemic index, bread and incidence of overweight/obesity in a Mediterranean cohort: the SUN project. de la Fuente-Arrillaga C, Martinez-Gonzalez MA, Zazpe I et al. | 2014 | PMID 25335643 DOI 10.1186/1471-2458-14-1091 | Cohort study | 9267 Spanish university graduates | 2+ portions/day white bread linked to 40% higher odds of becoming overweight, but not to yearly weight gain. | Graduates only; Mixed results | moderate | C-WHT-06 |
| A-WHT-11 | Associations of Whole Grain and Refined Grain Consumption With Metabolic Syndrome. A Meta-Analysis of Observational Studies. Guo H, Ding J, Liang J et al. | 2021 | PMID 34277690 DOI 10.3389/fnut.2021.695620 | Meta-analysis | Observational study participants | Refined grains linked to 37% higher MetS risk in pooled observational studies. | Half cross-sectional; Wide CI | low | C-WHT-06 |
| A-WHT-12 | Whole-grain intake is favorably associated with metabolic risk factors for type 2 diabetes and cardiovascular disease in the Framingham Offspring Study. McKeown NM, Meigs JB, Liu S et al. | 2002 | PMID 12145012 DOI 10.1093/ajcn/76.2.390 | Cross-sectional study | 2941 adults | Whole grains linked to slightly better markers; refined grains showed no trend. | Cross-sectional | low | C-WHT-06 |
| A-WHT-13 | Whole grain, bran, and germ intake and risk of type 2 diabetes: a prospective cohort study and systematic review. de Munter JS, Hu FB, Spiegelman D et al. | 2007 | PMID 17760498 DOI 10.1371/journal.pmed.0040261 | Cohort study | 161,737 US women | Highest whole grain intake: about 25-37% lower diabetes risk. | Observational | high | C-WHT-05 C-WHT-04 |
| A-WHT-14 | Dietary fibre and incidence of type 2 diabetes in eight European countries: the EPIC-InterAct Study and a meta-analysis of prospective studies. InterAct Consortium | 2015 | PMID 26021487 DOI 10.1007/s00125-015-3585-9 | Cohort study | EPIC-InterAct: 340,234 eligible EPIC participants; analysed 26,088 (11,559 incident T2D cases, subcohort 15,258 incl. 729 cases), mean subcohort age 52.4 years. Meta-analysis: 617,968 participants, 41,066 cases (8 US, 5 European, 3 Australian, 3 Asian cohorts) | Each extra 10 g/day of cereal fibre linked to 25% lower diabetes risk. | EPIC-InterAct: associations null after BMI adjustment (BMI may be confounder and mediator); Diet measured only at baseline; FFQ measurement error | high | C-WHT-05 |
| A-WHT-15 | Glycemic index, glycemic load, and dietary fiber intake and incidence of type 2 diabetes in younger and middle-aged women. Schulze MB, Liu S, Rimm EB et al. | 2004 | PMID 15277155 DOI 10.1093/ajcn/80.2.348 | Cohort study | 91,249 women | High GI linked to 59% higher risk; cereal fibre to 36% lower risk. | Observational; GL null | moderate | C-WHT-05 |
| A-WHT-16 | Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Drago S, El Asmar R, Di Pierro M et al. | 2006 | PMID 16635908 DOI 10.1080/00365520500235334 | Laboratory / cell study | IEC6, Caco2 cells; biopsies from coeliac (remission) and non-coeliac patients | Gliadin briefly loosened gut tissue samples; strongly in coeliac tissue, slightly in others. | Lab/ex vivo only; no clinical outcomes | moderate | C-WHT-09 |
| A-WHT-17 | Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Lammers KM, Lu R, Brownley J et al. | 2008 | PMID 18485912 DOI 10.1053/j.gastro.2008.03.023 | Laboratory / cell study | Cell lines, mice, biopsies | Gliadin binds a receptor and increases permeability in mouse tissue. | Lab; COI | moderate | C-WHT-09 |
| A-WHT-18 | White rice consumption and risk of cardiometabolic and cancer outcomes: A systematic review and dose-response meta-analysis of prospective cohort studies. Lai H, Sun M, Liu Y et al. | 2023 | PMID 35852223 DOI 10.1080/10408398.2022.2101984 | Meta-analysis | Cohorts | More white rice linked to more diabetes (16 more cases per 1000), not to heart disease or cancer. | Observational | moderate | C-GRN-05 |
| A-FOOD-01 | Is there a dose-response relation of dietary glycemic load to risk of type 2 diabetes? Meta-analysis of prospective cohort studies. Livesey G et al. | 2013 | PMID 23364021 DOI 10.3945/ajcn.112.041467 | Meta-analysis | Healthy adults in prospective cohorts | Diets with more glycaemic load were linked to higher diabetes risk (45% per 100 g/day). | Whole-diet GL, not single foods; Observational | high | C-FRU-01 C-WHT-05 |
| A-FOOD-02 | Glycemic index, glycemic load, and chronic disease risk--a meta-analysis of observational studies. Barclay AW et al. | 2008 | PMID 18326601 DOI 10.1093/ajcn/87.3.627 | Meta-analysis | Cohort participants | Low-GI/GL diets linked to lower diabetes and heart disease risk. | Whole-diet measures; Observational | moderate | C-FRU-01 C-WHT-05 |
| I-ABX-01 | Global burden of bacterial antimicrobial resistance 1990-2021: a systematic analysis with forecasts to 2050. GBD 2021 Antimicrobial Resistance Collaborators | 2024 | PMID 39299261 DOI 10.1016/S0140-6736(24)01867-1 | Risk assessment | Global | About 1.14 million deaths were caused by resistance in 2021; better care and access to antibiotics could prevent tens of millions of deaths. | Sparse data in many LMICs; 7 countries with no data; heavy reliance on covariates and modelling; Pre-2000 resistance largely modelled | high | C-ABX-02 C-ABX-12 |
| I-ABX-02 | The burden of bacterial antimicrobial resistance in the WHO Eastern Mediterranean Region 1990-2021: a cross-country systematic analysis with forecasts to 2050. EMR Antimicrobial Resistance Collaborators | 2025 | PMID 41082884 DOI 10.1016/S2468-2667(25)00201-4 | Risk assessment | EMR countries | About 92,800 deaths in the region were attributed to resistance in 2021. | Model-based | high | C-ABX-02 |
| I-ABX-03 | Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population based study with sibling analysis. Örtqvist AK et al. | 2014 | PMID 25432937 DOI 10.1136/bmj.g6979 | Cohort study | Children born in Sweden 2006-2010 to pregnancies starting from 1 July 2005, followed to end of 2011 (school age at most) | When siblings were compared, most of the antibiotic-asthma link disappeared. | Indication (respiratory infection) not recorded; residual confounding by indication and reverse causation for airway antibiotics; Sibling analyses rely on exposure-discordant pairs; wider CIs (e.g. urinary/skin 0.47-1.55); sensitive to non-shared confounding and measurement error | high | C-ABX-06 |
| I-ABX-04 | Early-life exposure to antibiotics and excess body weight in childhood and adolescence: A systematic review and meta-analysis. Chagas AP et al. | 2023 | PMID 37573229 DOI 10.1016/j.orcp.2023.07.001 | Meta-analysis | Children and adolescents | A small association (about 9-10% higher odds) was found, but certainty was very low. | Observational primary studies | moderate | C-ABX-05 |
| I-ABX-05 | Antibiotic exposure in early life and childhood overweight and obesity: A systematic review and meta-analysis. Rasmussen SH et al. | 2018 | PMID 29359849 DOI 10.1111/dom.13230 | Meta-analysis | 527,504 children | Slightly higher risk, mainly with repeated or very early treatment. | Observational | moderate | C-ABX-05 |
| I-ABX-06 | Antibiotic use and the development of inflammatory bowel disease: a national case-control study in Sweden. Nguyen LH et al. | 2020 | PMID 32818437 DOI 10.1016/S2468-1253(20)30267-3 | Case-control study | Swedish residents aged >=16 years with incident, histology-confirmed IBD (2007-2016), up to 5 general-population controls matched on age, sex, county and calendar year, plus IBD-free full siblings | More antibiotic use was linked to IBD, also when compared with siblings. | Indication for antibiotics not available; confounding by indication (e.g. infections, prodromal GI symptoms) possible despite lead-in; Residual confounding by health-care-seeking and comorbidity (adjusted only via encounter counts and education) | high | C-ABX-07 |
| I-ABX-07 | Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. Seymour CW et al. | 2017 | PMID 28528569 DOI 10.1056/NEJMoa1703058 | Cohort study | Adults (>17 years) with severe sepsis or septic shock (Sepsis-2 criteria) and sepsis protocol initiated in the emergency department within 6 h of arrival, in 149 New York hospitals (median age 73) | Each hour of delay in antibiotics was linked to about 4% higher odds of death. | Not randomised; residual confounding (e.g. diagnostic difficulty delaying treatment); Appropriateness of antibiotic choice not known | high | C-ABX-12 |
| I-ABX-08 | Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Kumar A et al. | 2006 | PMID 16625125 DOI 10.1097/01.CCM.0000217961.75225.E9 | Cohort study | Adults with septic shock | Each hour of delay reduced survival by about 7.6% on average. | Retrospective | moderate | C-ABX-12 |
| I-ABX-09 | Antibiotics for acute otitis media in children. Venekamp RP et al. | 2023 | PMID 37965923 DOI 10.1002/14651858.CD000219.pub5 | Systematic review | Children with AOM | Antibiotics helped only a little with pain and caused side effects; serious complications were rare either way. | High-income settings only | high | C-ABX-12 |
| I-ABX-10 | Pelvic Inflammatory Disease: Diagnosis, Management, and Prevention. Curry A et al. | 2019 | PMID 31524362 | Narrative review | Sexually active women | Untreated infection (often gonorrhoea or chlamydia) can cause infertility; antibiotics are the treatment. | Narrative review | moderate | C-ABX-13 |
| I-ABX-101 | Immediate versus delayed versus no antibiotics for respiratory infections. Spurling GK et al. | 2023 | PMID 37791590 DOI 10.1002/14651858.CD004417.pub6 | Systematic review | Children and adults with acute respiratory infections (otitis media, sore throat, cough, common cold) in primary care, paediatric clinics and emergency departments | Delaying or not giving antibiotics for mild respiratory infections cut antibiotic use sharply with similar recovery and no difference in complications. | Only uncomplicated respiratory infections; excludes severe or high-risk patients; Complication data are sparse (low certainty) | high | C-ABX-12 |
| I-ABX-102 | Oral amoxicillin for management of fast breathing or chest indrawing pneumonia without danger signs in children aged 2-59 months: a systematic review and meta-analysis. Gadapani Pathak B et al. | 2026 | PMID 42725565 DOI 10.7189/jogh.16.04209 | Meta-analysis | Children aged 2-59 months with WHO-defined fast-breathing pneumonia (and chest-indrawing pneumonia without danger signs) in low- and middle-income countries | In randomised trials of young children with mild pneumonia, amoxicillin reduced treatment failure compared with no antibiotic. | One of four trials at high risk of bias; Low-resource settings; mostly mild pneumonia | high | C-ABX-12 |
| I-ABX-103 | Appropriate timing of antibiotic initiation in patients with sepsis or septic shock: a systematic review and meta-analysis. Ku NS et al. | 2025 | PMID 40859809 DOI 10.3904/kjim.2025.037 | Meta-analysis | Adults with sepsis or septic shock | Patients with septic shock who received antibiotics within 1 hour died less often than those treated later. | Observational studies only; confounding by severity; Effect sizes not given in abstract | moderate | C-ABX-12 |
| I-ABX-104 | Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Evans L et al. | 2021 | PMID 34599691 DOI 10.1007/s00134-021-06506-y | Guideline / position statement | Adults with sepsis or septic shock | Experts recommend antibiotics within 1 hour for possible septic shock. | Underlying evidence for exact timing is low to very low quality; Panel COI declared | high | C-ABX-12 |
| I-ABX-105 | The WHO AWaRe (Access, Watch, Reserve) antibiotic book. World Health Organization | 2022 | Guideline / position statement | Children and adults with common infections in primary care and hospital | WHO gives antibiotic treatment guidance for over 30 common infections and warns against overuse. | Only the publication page was read, not the full book | high | C-ABX-12 | |
| I-ABX-106 | Sexually Transmitted Infections Treatment Guidelines, 2021. Workowski KA et al. | 2021 | PMID 34292926 DOI 10.15585/mmwr.rr7004a1 | Guideline / position statement | Adolescents and adults with or at risk of STIs | A single ceftriaxone injection cures more than 99% of genital gonorrhoea; untreated infection can cause infertility. | US-specific drug choices; resistance patterns vary by country | high | C-ABX-13 |
| I-ABX-107 | Updated recommendations for the treatment of Neisseria gonorrhoeae, Chlamydia trachomatis and Treponema pallidum (syphilis) and new recommendations on syphilis testing and partner services. World Health Organization | 2024 | Guideline / position statement | People with these STIs | WHO publishes antibiotic treatment recommendations for gonorrhoea and partner services. | Only the overview page was read; specific regimens not extracted | high | C-ABX-13 | |
| I-ABX-108 | The Duration of Pharyngeal Gonorrhea: A Natural History Study. Barbee LA et al. | 2021 | PMID 33513222 DOI 10.1093/cid/ciab071 | Cohort study | Men who have sex with men | Without treatment, throat gonorrhoea lasted a median of 16 weeks. | Small number of infections; Pharyngeal site only; one population | moderate | C-ABX-13 |
| I-ABX-109 | The natural history of incident gonococcal infection in adolescent women. Stupiansky NW et al. | 2011 | PMID 21317686 DOI 10.1097/OLQ.0b013e31820ff9a4 | Cohort study | Adolescent women aged 14-17 from urban primary care clinics | Bacterial load stayed level for at least six weeks and did not track symptoms. | Only 16 infections; Adolescents only | moderate | C-ABX-13 |
| I-ABX-11 | Antibiotic-associated Vulvovaginal Candidiasis. Xu J & Sobel JD | 2003 | PMID 14642189 DOI 10.1007/s11908-003-0091-x | Narrative review | Women | Antibiotics may trigger yeast infections, but evidence is limited and conflicting. | Old; Narrative | low | C-ABX-11 |
| I-ABX-110 | Early Antibiotic Exposure and Weight Outcomes in Young Children. Block JP et al. | 2018 | PMID 30381474 DOI 10.1542/peds.2018-0290 | Cohort study | Children with same-day height and weight measurements, 35 US institutions | Children given antibiotics before age 2 were very slightly heavier at age 5. | Observational; confounding by indication (infections) not removed; Small effect | moderate | C-ABX-05 |
| I-ABX-111 | The impact of antibiotics on growth in children in low and middle income countries: systematic review and meta-analysis of randomised controlled trials. Gough EK et al. | 2014 | PMID 24735883 DOI 10.1136/bmj.g2267 | Meta-analysis | Children aged 1 month-12 years in LMICs | In randomised trials, children given antibiotics gained about 24 g more per month. | LMIC, often undernourished, infection-burdened children; Growth, not obesity | high | C-ABX-05 |
| I-ABX-112 | Early-life antibiotic use and children with overweight and obesity: a Dutch twin cohort study. Feil RS et al. | 2026 | PMID 42457938 DOI 10.1038/s41366-026-02164-6 | Cohort study | Twins aged 4.5-15.4 years in the Netherlands Twin Register | Among 34,142 Dutch twins, early antibiotics were not linked to overweight or obesity. | Parent-reported antibiotic use (retrospective); Low obesity prevalence limits power for obesity | moderate | C-ABX-05 |
| I-ABX-113 | Early-life antibiotic exposure and the risk of overweight and obesity in children. Ainonen S et al. | 2026 | PMID 41792341 DOI 10.1038/s41390-026-04841-8 | Cohort study | Vaginally delivered children | Antibiotics in the first 2 years were linked to a 20% higher relative risk of obesity by age 12. | Observational; no sibling control; Country not explicit in abstract | moderate | C-ABX-05 |
| I-ABX-114 | Use of antibiotics in early life and development of diseases in childhood: nationwide registry study. Brandt S et al. | 2025 | PMID 40519361 DOI 10.1136/bmjmed-2024-001064 | Cohort study | Children born in Denmark 1998-2006 resident in their first year | Comparing siblings, the link with overweight vanished and the link with asthma halved. | Overweight captured only by hospital diagnosis (underestimated); Sibling design does not control confounding by indication within families | high | C-ABX-05 C-ABX-06 |
| I-ABX-115 | Association of infant antibiotic exposure and risk of childhood asthma: A meta-analysis. Zhang Z et al. | 2021 | PMID 34934469 DOI 10.1016/j.waojou.2021.100607 | Meta-analysis | Infants and children | Pooled data: about 37% higher odds, 19% when bias is addressed. | Observational; heterogeneity; Short-lag subgroup shows strongest effect, typical of reverse causation | moderate | C-ABX-06 |
| I-ABX-116 | Recovery of gut microbiota of healthy adults following antibiotic exposure. Palleja A et al. | 2018 | PMID 30349083 DOI 10.1038/s41564-018-0257-9 | Other | Healthy young men | After a 4-day strong antibiotic course, gut bacteria largely recovered in 6 weeks; some species were still gone at 6 months. | 12 men; last-resort antibiotic cocktail not typical outpatient therapy | moderate | C-ABX-04 |
| I-ABX-117 | The effect of antibiotics on the composition of the intestinal microbiota - a systematic review. Zimmermann P & Curtis N | 2019 | PMID 31629863 DOI 10.1016/j.jinf.2019.10.008 | Systematic review | Humans given systemic antibiotics | Across 129 studies, many antibiotics reduced gut diversity; some changes lasted up to 4 years. | No meta-analysis; Mostly small heterogeneous studies | moderate | C-ABX-04 |
| I-ABX-118 | Systematic review and meta-analysis of childhood exposure to antibiotics and the subsequent risk of IBD. Størdal K et al. | 2026 | PMID 41617205 DOI 10.1093/ibd/izaf324 | Meta-analysis | Children exposed <1 to 17 years | Pooled studies show about 59% higher relative risk of Crohn's disease after childhood antibiotics. | Observational studies only; Few studies | moderate | C-ABX-07 |
| I-ABX-119 | Early-Life Infections, Antibiotics and Later Risk of Childhood and Early Adult-Onset Inflammatory Bowel Disease: Pooled Analysis of Two Scandinavian Birth Cohorts. Mårild K et al. | 2025 | PMID 39450871 DOI 10.1111/apt.18358 | Cohort study | Children followed from birth (ABIS Sweden, MoBa Norway) | Antibiotics in the first year were linked to 33% higher relative risk of IBD after accounting for infections. | Few cases; wide CIs; Parent-reported exposures | moderate | C-ABX-07 |
| I-ABX-120 | Use of azithromycin and death from cardiovascular causes. Svanström H et al. | 2013 | PMID 23635050 DOI 10.1056/NEJMoa1300799 | Cohort study | Danish adults aged 18-64 | Compared with penicillin, azithromycin showed no extra cardiovascular deaths in Danish adults aged 18-64. | Younger, lower-risk population than Ray; Few events | high | C-ABX-08 |
| I-ABX-121 | Systematic Review, Meta-analysis, and Network Meta-analysis of the Cardiovascular Safety of Macrolides. Gorelik E et al. | 2018 | PMID 29610207 DOI 10.1128/AAC.00438-18 | Meta-analysis | Subjects exposed to macrolides | Across 33 studies, macrolides were not linked to cardiovascular death; a small MI signal was found. | Observational inputs; Heterogeneous designs | moderate | C-ABX-08 |
| I-ABX-122 | Fluoroquinolones and the risk of tendon injury: a systematic review and meta-analysis. Alves C et al. | 2019 | PMID 31270563 DOI 10.1007/s00228-019-02713-1 | Meta-analysis | Patients treated with fluoroquinolones | Pooled studies show about 2.5-fold odds of Achilles tendon rupture. | High heterogeneity for rupture; Observational | moderate | C-ABX-09 |
| I-ABX-123 | Association Between Fluoroquinolone Use and Hospitalization With Aortic Aneurysm or Aortic Dissection. Brown JP et al. | 2023 | PMID 37585175 DOI 10.1001/jamacardio.2023.2418 | Cohort study | Adults prescribed fluoroquinolones or cephalosporins; cases hospitalised with AA/AD | Compared with other antibiotics, fluoroquinolones were not linked to aortic aneurysm or dissection. | Observational; Outcome = hospitalisation | high | C-ABX-09 |
| I-ABX-124 | Risk of aortic aneurysm or dissection following use of fluoroquinolones: a retrospective multinational network cohort study. Janetzki JL et al. | 2025 | PMID 39975698 DOI 10.1016/j.eclinm.2025.103096 | Cohort study | Patients >=35 years starting outpatient antibiotics for UTI | In 13.6 million patients, fluoroquinolones did not raise aortic aneurysm/dissection risk versus other antibiotics. | UTI indication only; Non-European data | high | C-ABX-09 |
| I-ABX-125 | Is antibiotic use a risk factor for breast cancer? A meta-analysis. Sergentanis TN et al. | 2010 | PMID 20845408 DOI 10.1002/pds.1986 | Meta-analysis | Women | Pooling 5 studies gave a slightly raised but not statistically significant risk. | Only 5 case-control studies; CI includes 1 | moderate | C-ABX-10 |
| I-ABX-126 | Use of antibiotics and risk of breast cancer. García Rodríguez LA et al. | 2005 | PMID 15781950 DOI 10.1093/aje/kwi087 | Case-control study | Women aged 30-79 in UK primary care | A UK replication found no rise in breast cancer with antibiotic use. | Observational | moderate | C-ABX-10 |
| I-ABX-127 | Association between Antibiotic Use and Subsequent Risk of Breast Cancer: A Nationwide Retrospective Cohort Study in South Korea. Hong J et al. | 2025 | PMID 39648494 DOI 10.1158/1940-6207.CAPR-24-0154 | Cohort study | Women in the Korean National Health Insurance database | Women with over a year of total antibiotic use had a 15% higher relative risk. | Residual confounding (healthcare use, detection); Small effect | moderate | C-ABX-10 |
| I-ABX-128 | Effect of lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial. Pirotta M et al. | 2004 | PMID 15333452 DOI 10.1136/bmj.38210.494977.DE | Randomised controlled trial | Non-pregnant women 18-50 needing a short oral antibiotic course for a non-gynaecological infection | 23% of women developed vaginal yeast infection after a short antibiotic course. | Trial stopped early; Women only | high | C-ABX-11 |
| I-ABX-129 | CDC: 1 in 3 antibiotic prescriptions unnecessary (press release, 3 May 2016). Centers for Disease Control and Prevention | 2016 | Guideline / position statement | US outpatients | CDC estimated 47 million unnecessary prescriptions a year, mostly for viral respiratory illnesses. | Press release; methods in the JAMA paper | high | C-ABX-01 | |
| I-ABX-130 | Appropriateness of outpatient antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study. Chua KP et al. | 2019 | PMID 30651273 DOI 10.1136/bmj.k5092 | Cross-sectional study | Privately insured enrollees aged 0-64 | 23% of outpatient antibiotic fills had no diagnosis justifying them. | Claims coding; Privately insured only | moderate | C-ABX-01 |
| I-ABX-131 | AWaRe antibiotic prescribing for common acute infections in private primary care in low-middle-income countries: a patient-level analysis using IQVIA prescriber surveys from Pakistan, Egypt and Indonesia. Nguyen N et al. | 2026 | PMID 42097706 DOI 10.1136/bmjgh-2025-021139 | Cross-sectional study | Infection-related consultations, mostly private sector | In Egypt, 81% of infection consultations ended with an antibiotic, half from the 'Watch' group. | Commercial survey data; private sector; Appropriateness not directly classified | moderate | C-ABX-01 |
| I-ABX-132 | Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019. GBD 2019 HIV Collaborators | 2021 | PMID 34592142 DOI 10.1016/S2352-3018(21)00152-1 | Other | Global population | The GBD study estimated 864,000 HIV deaths worldwide in 2019. | Model estimates | high | C-ABX-03 |
| I-ABX-133 | Trends of the Global, Regional and National Incidence, Mortality, and Disability-Adjusted Life Years of Malaria, 1990-2019: An Analysis of the Global Burden of Disease Study 2019. Shi D et al. | 2023 | PMID 37396933 DOI 10.2147/RMHP.S419616 | Other | Global population | GBD-based estimate of 643,000 malaria deaths worldwide in 2019. | Secondary analysis; no UI given in abstract for deaths; Lower-tier journal | moderate | C-ABX-03 |
| I-AUTO-101 | A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. Canadian Hydroxychloroquine Study Group | 1991 | PMID 1984192 DOI 10.1056/NEJM199101173240303 | Randomised controlled trial | Patients with clinically stable SLE taking HCQ | In stable lupus, people switched to placebo had far more flares (73%) than those who kept taking hydroxychloroquine (36%). | Small; 24 weeks; Severe exacerbation estimate imprecise | high | C-AUTO-01 |
| I-AUTO-102 | Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis. Gonzalez-Lorenzo M et al. | 2024 | PMID 38174776 DOI 10.1002/14651858.CD011381.pub3 | Meta-analysis | Adults with RRMS | Several MS drugs cut relapses roughly in half over two years compared with placebo. | Mostly industry-sponsored trials; Little evidence beyond 2 years | high | C-AUTO-01 |
| I-AUTO-103 | ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Montalban X et al. | 2018 | PMID 29353550 DOI 10.1177/1352458517751049 | Guideline / position statement | People with MS | European neurology societies recommend disease-modifying drugs for MS. | 2018; newer drugs since; Abstract only read | high | C-AUTO-01 |
| I-AUTO-104 | The effect of dietary interventions on peripheral markers of inflammation among people with multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials. Pingel WR et al. | 2026 | PMID 41422672 DOI 10.1016/j.msard.2025.106913 | Meta-analysis | People with MS | Some diets may lower inflammation markers in MS, but the evidence is weak and does not show effects on relapses or disability. | Surrogate markers only; no relapse or disability outcomes; Small trials; COI | low | C-AUTO-01 |
| I-BAR-01 | Association of metabolic-bariatric surgery with long-term survival in adults with and without diabetes: a one-stage meta-analysis of matched cohort and prospective controlled studies with 174 772 participants. Syn NL et al. | 2021 | PMID 33965067 DOI 10.1016/S0140-6736(21)00591-2 | Meta-analysis | Adults with severe obesity | Across 174,772 people, surgery was linked to about half the risk of death and about 6 more years of median life expectancy; sleeve showed similar effects to bypass. | Observational primary studies (confounding, healthy-patient selection); Reconstructed IPD | moderate | C-BAR-01 C-BAR-09 C-BAR-10 |
| I-BAR-02 | Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes. Courcoulas AP et al. | 2024 | PMID 38411644 DOI 10.1001/jama.2024.0318 | Randomised controlled trial | T2D, mean BMI 36.4 | Blood sugar control stayed better after surgery; full remission was uncommon in both groups but more frequent after surgery (12.7% vs 0%). | 86% enrolment into follow-up; Crossover 25% | moderate | C-BAR-05 C-BAR-06 C-BAR-08 |
| I-BAR-03 | Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Mingrone G et al. | 2021 | PMID 33485454 DOI 10.1016/S0140-6736(20)32649-0 | Randomised controlled trial | T2D >5 years, BMI>=35 | More than half of those in remission at 2 years relapsed, but their sugar control stayed good (HbA1c 6.7%) and complications were fewer than with medicines alone. | Very small; Single centre | moderate | C-BAR-08 C-BAR-14 |
| I-BAR-04 | Risk of De Novo Barrett's Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Chandan S et al. | 2025 | PMID 39059544 DOI 10.1016/j.cgh.2024.06.041 | Meta-analysis | SG patients | About 5.6% developed new Barrett's esophagus; reflux and acid-medication use were about 3 times more frequent after sleeve. | Mostly observational, heterogeneous; Pre-post comparison, no non-surgical control | moderate | C-BAR-02 C-BAR-03 C-BAR-04 C-BAR-12 |
| I-BAR-05 | Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial. Peterli R et al. | 2018 | PMID 29340679 DOI 10.1001/jama.2017.20897 | Randomised controlled trial | Morbid obesity, mean BMI 43.9 | Reflux got worse in about 32% after sleeve vs 6% after bypass. | Reflux exploratory endpoint | high | C-BAR-02 C-BAR-03 C-BAR-14 |
| I-BAR-06 | Risk of Suicide and Self-harm Is Increased After Bariatric Surgery-a Systematic Review and Meta-analysis. Castaneda D et al. | 2019 | PMID 30343409 DOI 10.1007/s11695-018-3493-4 | Meta-analysis | Bariatric patients | Self-harm attempts were about twice as common after surgery as before; suicides occurred in about 2.7 per 1000 patients. | Observational studies; Overlap with Bhatti/Neovius | moderate | C-BAR-07 |
| I-BAR-07 | Change in fracture risk and fracture pattern after bariatric surgery: nested case-control study. Rousseau C et al. | 2016 | PMID 27814663 DOI 10.1136/bmj.i3794 | Case-control study | Severely obese adults undergoing bariatric surgery in Quebec (72.3% women, mean age 42.6 years), matched by age (+-3 years) and sex 1:3 to obese and 1:10 to non-obese controls | Fractures were about 38% more frequent than in obese controls, clearly so only after biliopancreatic diversion. | Obese controls not BMI-matched; bariatric group had more comorbidities and baseline fractures (authors); Administrative data; no information on medications, physical activity, smoking, alcohol, trauma level, weight loss (authors) | moderate | C-BAR-06 |
| I-BAR-08 | Fracture Risk After Gastric Bypass Surgery: A Retrospective Cohort Study. Axelsson KF et al. | 2018 | PMID 30011091 DOI 10.1002/jbmr.3553 | Cohort study | Swedish obese patients | Fracture risk was about 26-32% higher than in similar people without surgery. | Median follow-up 3.1 years | moderate | C-BAR-06 C-BAR-14 |
| I-BAR-09 | Clinical Practice Guidelines for the Perioperative Nutrition, Metabolic, and Nonsurgical Support of Patients Undergoing Bariatric Procedures - 2019 Update (Executive Summary). Mechanick JI et al. | 2019 | PMID 31682518 DOI 10.4158/GL-2019-0406 | Guideline / position statement | Nutrition and metabolic follow-up is a mandatory part of bariatric care. | Many low-grade recommendations; Detailed supplement doses not in abstract | moderate | C-BAR-05 | |
| I-BAR-10 | Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Global BMI Mortality Collaboration | 2016 | PMID 27423262 DOI 10.1016/S0140-6736(16)30175-1 | Meta-analysis | Adults aged 20-90 years, BMI 15-<60, in 32 countries (Asia, Australia/New Zealand, Europe, North America); primary analysis restricted to never-smokers without known chronic disease at baseline who survived 5 years | Severe obesity (BMI 40+) was linked to nearly 3 times the death risk of normal weight. | Observational; BMI is the only adiposity measure (authors); Study results generally not adjusted for ethnicity or socioeconomic status (authors) | high | C-BAR-01 C-BAR-09 |
| I-BAR-101 | Association of Bariatric Surgery Using Laparoscopic Banding, Roux-en-Y Gastric Bypass, or Laparoscopic Sleeve Gastrectomy vs Usual Care Obesity Management With All-Cause Mortality. Reges et al. | 2018 | PMID 29340677 DOI 10.1001/jama.2017.20513 | Cohort study | Adults >=24 y with obesity (median BMI 40.6) undergoing surgery 2005-2014 and matched nonsurgical patients | People who had surgery, including sleeve, died less often over about 4 years than similar people with obesity who did not (sleeve 0.8% vs 1.3%). | Observational; residual confounding (more low-SES patients among controls); Short sleeve follow-up (median ~3 y) | moderate | C-BAR-01 C-BAR-10 |
| I-BAR-102 | Reduction in Long-term Mortality After Sleeve Gastrectomy and Gastric Bypass Compared to Nonsurgical Patients With Severe Obesity. Courcoulas et al. | 2023 | PMID 34387200 DOI 10.1097/SLA.0000000000005155 | Cohort study | Adults 19-79 y, BMI >=35, primary SG or RYGB 2005-2015, and up to 3 matched controls each | Over 5 years, people who had a sleeve died about 70% less often than similar people who did not have surgery (1.0% vs 2.7%). | 29-35% lost to follow-up at 5 y; State death indices only | moderate | C-BAR-01 C-BAR-10 C-BAR-12 |
| I-BAR-103 | Perioperative mortality in bariatric surgery: meta-analysis. Robertson et al. | 2021 | PMID 34297806 DOI 10.1093/bjs/znab245 | Meta-analysis | Patients undergoing bariatric surgery in large studies, registries and RCTs | About 1 in 2,000 sleeve operations ends in death around the time of surgery. | Under-reporting possible in some sources; High-volume settings over-represented | moderate | C-BAR-01 |
| I-BAR-104 | Effects of Obesity Surgery on Overall and Disease-Specific Mortality in a 5-Country Population-Based Study. Kauppila et al. | 2019 | PMID 30940524 DOI 10.1053/j.gastro.2019.03.048 | Cohort study | Persons with an obesity diagnosis in Nordic national registries, 1980-2012 | Operated people died less often than non-operated people with obesity, but more often than the general population; suicide deaths were more frequent. | Registry diagnosis of obesity (selection); Few sleeve operations in 1980-2012 | moderate | C-BAR-01 C-BAR-09 C-BAR-12 C-BAR-07 |
| I-BAR-105 | Perioperative Morbidity and Mortality of Laparoscopic Sleeve Gastrectomy (LSG) in a Single-Surgeon Experience on 892 Patients Over 11 Years. El Masry et al. | 2023 | PMID 37548678 DOI 10.1007/s00268-023-07123-0 | Case series / case report | Patients undergoing LSG by one surgeon in Cairo | 2 of 892 patients died within 30 days (0.22%). | Single surgeon, no control group; Retrospective | low | C-BAR-01 |
| I-BAR-106 | Long-term all-cause and cause-specific mortality for four bariatric surgery procedures. Adams et al. | 2023 | PMID 36695060 DOI 10.1002/oby.23646 | Cohort study | Utah bariatric patients 1982-2021 and matched non-surgical persons | Overall deaths were 16% lower after surgery, but suicide was about 2.4 times more frequent, mostly in young patients. | Controls from driver licences with self-reported BMI; No clinical data or weight follow-up | moderate | C-BAR-07 C-BAR-09 |
| I-BAR-107 | Overweight and obesity management (NICE guideline NG246; replaces CG189) NICE | 2025 | Guideline / position statement | Adults with obesity in England | NICE recommends considering surgery for people with severe obesity and requires lifelong yearly checks of nutrition. | UK health-system context | high | C-BAR-01 C-BAR-05 | |
| I-BAR-109 | Does Sleeve Gastrectomy Expose the Distal Esophagus to Severe Reflux?: A Systematic Review and Meta-analysis. Yeung et al. | 2020 | PMID 30921053 DOI 10.1097/SLA.0000000000003275 | Meta-analysis | Patients after primary sleeve gastrectomy | About 23 in 100 developed new reflux after sleeve, 28 in 100 had oesophagitis at long-term endoscopy, and 4 in 100 needed a second operation for reflux. | Observational, heterogeneous; Uncontrolled pre-post designs | moderate | C-BAR-02 C-BAR-03 C-BAR-04 |
| I-BAR-11 | 2022 American Society of Metabolic and Bariatric Surgery (ASMBS) and International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) Indications for Metabolic and Bariatric Surgery. Eisenberg D et al. | 2023 | PMID 36336720 DOI 10.1007/s11695-022-06332-1 | Guideline / position statement | Surgical societies recommend it for BMI above 35 and consider it from BMI 30 with metabolic disease. | Surgical societies (professional interest); Abstract only | moderate | C-BAR-10 | |
| I-BAR-110 | Meta-analysis of Long-term De Novo Acid Reflux-Related Outcomes Following Sleeve Gastrectomy: Evidence Against the Need for Routine Postoperative Endoscopic Surveillance. Hajibandeh et al. | 2023 | PMID 37535236 DOI 10.1007/s13679-023-00521-4 | Meta-analysis | Patients after primary SG followed >=4 y | About 1 in 4 developed new reflux and about 7 in 100 had Barrett changes; authors think the Barrett figure may be too high. | Observational only; Reporting bias acknowledged by authors | moderate | C-BAR-03 C-BAR-04 |
| I-BAR-111 | Prevalence of Severe Erosive Esophagitis After Sleeve Gastrectomy: A Systematic Review and Meta-Analysis. Alqasem et al. | 2026 | PMID 41964778 DOI 10.1007/s11695-026-08605-5 | Meta-analysis | Adults after primary SG with postoperative endoscopy | About 3 in 100 sleeve patients had severe inflammation of the gullet at endoscopy. | Small total sample; Observational | moderate | C-BAR-03 C-BAR-02 |
| I-BAR-112 | Incidence of Post-operative Gastro-esophageal Reflux Disorder in Patients Undergoing Laparoscopic Sleeve Gastrectomy: A Systematic Review and Meta-analysis. Trujillo et al. | 2024 | PMID 38483740 DOI 10.1007/s11695-024-07163-y | Meta-analysis | Patients after LSG | About 1 in 3 patients developed reflux disease after sleeve (about 6 in 10 in trials with systematic testing). | Extreme heterogeneity (I2 98%); Definitions vary | low | C-BAR-02 C-BAR-03 |
| I-BAR-113 | Gastroesophageal Reflux and Laparoscopic Sleeve Gastrectomy: Results of the First International Consensus Conference. Assalia et al. | 2020 | PMID 32533520 DOI 10.1007/s11695-020-04749-0 | Guideline / position statement | 50 bariatric experts from 25 countries | Experts agreed that reflux is probably the main drawback of sleeve and that bypass is preferable when severe reflux exists. | Expert opinion, not systematic evidence grading | low | C-BAR-02 C-BAR-14 |
| I-BAR-114 | International Federation for Surgery for Obesity and Metabolic Disorders Position Statement on the role of Upper Gastrointestinal Endoscopy Before and After Metabolic Bariatric Surgery. Brown et al. | 2025 | PMID 41108366 DOI 10.1007/s11695-025-08206-8 | Guideline / position statement | People undergoing MBS | Barrett changes were found in about 2.4 in 100 people after weight-loss surgery, but data were weak and short-term. | Heterogeneous data, short follow-up; Pooled across all MBS types | moderate | C-BAR-04 |
| I-BAR-115 | Incidence of Barrett's esophagus and esophageal cancer following sleeve gastrectomy versus liraglutide therapy. Butt et al. | 2026 | PMID 42164611 DOI 10.20524/aog.2026.1058 | Cohort study | Adults with obesity treated with SG or liraglutide | Barrett changes were diagnosed in 0.3% after sleeve vs 0.1% with liraglutide; cancer did not differ. | Coded diagnoses depend on endoscopy being done (surveillance bias); Two-author study, abstract only | low | C-BAR-04 C-BAR-12 |
| I-BAR-116 | Effect of gastric bypass versus sleeve gastrectomy on the remission of type 2 diabetes, weight loss, and cardiovascular risk factors at 5 years (Oseberg): secondary outcomes of a single-centre, triple-blind, randomised controlled trial. Wågen Hauge et al. | 2025 | PMID 40185112 DOI 10.1016/S2213-8587(24)00396-6 | Randomised controlled trial | Adults with type 2 diabetes and obesity (mean BMI 42.3) | After 5 years, diabetes was in remission in 50% after bypass vs 20% after sleeve; acid reflux was more common after sleeve, but Barrett changes were similar. | Single centre, small; Secondary outcomes | high | C-BAR-14 C-BAR-02 C-BAR-04 C-BAR-08 |
| I-BAR-117 | Risk assessment for esophageal cancer after bariatric surgery: a comparative cohort study between sleeve gastrectomy and gastric bypass. Lazzati et al. | 2025 | PMID 39799019 DOI 10.1016/j.soard.2024.12.002 | Cohort study | Adults undergoing SG or GB in France 2007-2020 | Oesophageal cancer was rare after both operations (about 4 per 100,000 per year after sleeve) and not significantly different. | Administrative coding; Point estimate leans toward higher risk after SG (HR 1.60) with borderline CI | moderate | C-BAR-12 C-BAR-04 |
| I-BAR-118 | Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity. Aminian et al. | 2022 | PMID 35657620 DOI 10.1001/jama.2022.9009 | Cohort study | Adults BMI >=35 at a US health system (Cleveland Clinic), 2004-2017 | Over 10 years, obesity-related cancer occurred in 2.9% after surgery vs 4.9% without; cancer deaths 0.8% vs 1.4%. | Single health system; Healthy-user and screening differences | moderate | C-BAR-12 |
| I-BAR-119 | Upper gastrointestinal cancer risk following bariatric surgery: meta-analysis. Cooke et al. | 2025 | PMID 41947341 DOI 10.1093/bjsopen/zrag006 | Meta-analysis | Patients with obesity with or without bariatric surgery | People who had surgery had about 40% fewer upper digestive cancers, including cancer of the gullet. | Observational studies; Procedure types not separated | moderate | C-BAR-12 |
| I-BAR-12 | Ursodeoxycholic acid for the prevention of gallstones and subsequent cholecystectomy after bariatric surgery: a meta-analysis of randomized controlled trials. Mulliri A et al. | 2022 | PMID 35704084 DOI 10.1007/s00535-022-01886-4 | Meta-analysis | Bariatric patients | A bile-acid drug cut new gallstones by about 75% after surgery, including sleeve. | Control incidence not in abstract | moderate | C-BAR-11 |
| I-BAR-120 | Prevalence of anemia and related nutrient deficiencies after sleeve gastrectomy: A systematic review and meta-analysis. Nie et al. | 2023 | PMID 36323610 DOI 10.1111/obr.13516 | Meta-analysis | Patients after SG | About 1 in 5 sleeve patients had anaemia 4-5 years after surgery, mostly from iron deficiency; B12 and folate deficiency stayed rare. | Observational, heterogeneous; Supplement adherence varies | moderate | C-BAR-05 C-BAR-10 |
| I-BAR-121 | Comparative risk of anemia and related micronutrient deficiencies after Roux-en-Y gastric bypass and sleeve gastrectomy in patients with obesity: An updated meta-analysis of randomized controlled trials. Kwon et al. | 2022 | PMID 35048495 DOI 10.1111/obr.13419 | Meta-analysis | Patients with obesity randomised to RYGB or SG | Anaemia and iron deficiency were similar after bypass and sleeve, but B12 deficiency was about twice as common after bypass. | Few trials, deficiency definitions vary | high | C-BAR-05 C-BAR-14 |
| I-BAR-122 | American Society for Metabolic and Bariatric Surgery Integrated Health Nutritional Guidelines for the Surgical Weight Loss Patient 2016 Update: Micronutrients. Parrott et al. | 2017 | PMID 28392254 DOI 10.1016/j.soard.2016.12.018 | Guideline / position statement | Patients undergoing LAGB, RYGB, LSG, BPD, BPD/DS | Experts recommend screening before surgery and preventive vitamin and mineral supplements afterwards. | Dated (2016); US perspective | moderate | C-BAR-05 |
| I-BAR-123 | Gastric Bypass But Not Sleeve Gastrectomy Increases Risk of Major Osteoporotic Fracture: French Population-Based Cohort Study. Paccou et al. | 2020 | PMID 32187759 DOI 10.1002/jbmr.4012 | Cohort study | Patients 40-65 y with BMI >=40, 2010-2014, and matched controls | Serious osteoporotic fractures increased after gastric bypass (about 70% more) but not after sleeve. | Administrative data; inpatient-coded fractures; Age 40-65 only | moderate | C-BAR-06 C-BAR-14 |
| I-BAR-124 | Fracture risk following bariatric surgery: a systematic review and meta-analysis. Saad et al. | 2022 | PMID 34988627 DOI 10.1007/s00198-021-06206-9 | Meta-analysis | Adults after bariatric surgery | Fractures were about 45% more frequent after bypass-type operations, but not after restrictive ones such as sleeve. | Moderate-high heterogeneity; Trials of unclear-high risk of bias | moderate | C-BAR-06 |
| I-BAR-125 | Changes in bone mineral density and bone metabolism after sleeve gastrectomy: a systematic review and meta-analysis. Jaruvongvanich et al. | 2019 | PMID 31311755 DOI 10.1016/j.soard.2019.06.006 | Meta-analysis | Adults with obesity after SG (>=6 mo follow-up) | Bone density at the hip fell after sleeve, while the spine did not change significantly. | DXA artefacts with large weight loss; No control group | moderate | C-BAR-06 |
| I-BAR-126 | Bone Mineral Density and Turnover After Sleeve Gastrectomy and Gastric Bypass: A Randomized Controlled Trial (Oseberg). Hofsø et al. | 2021 | PMID 33150385 DOI 10.1210/clinem/dgaa808 | Randomised controlled trial | Patients with severe obesity and type 2 diabetes | Hip and spine bone density fell more after bypass than after sleeve. | Small; 1-year only; Secondary outcome | high | C-BAR-06 C-BAR-14 |
| I-BAR-127 | Alcohol use disorder and alcohol-related mortality after metabolic bariatric surgery: prospective controlled cohort study. Sjöholm et al. | 2025 | PMID 41066138 DOI 10.1093/bjs/znaf211 | Cohort study | SOS participants with severe obesity (surgery vs matched usual care) | Alcohol use disorder and alcohol-related deaths were several times more frequent after surgery, especially after gastric bypass. | No sleeve gastrectomy patients; Non-randomised allocation | high | C-BAR-07 |
| I-BAR-128 | Risk of suicide after metabolic bariatric surgery: a meta-analysis of matched cohort studies and population-based studies. Cui et al. | 2025 | PMID 39516067 DOI 10.1016/j.soard.2024.10.014 | Meta-analysis | Adults with obesity | Suicide was about twice as frequent after surgery, though still rare (about 2 in 1000). | Few studies; Overlap with A-BAR-16 and I-BAR-104 data | moderate | C-BAR-07 |
| I-BAR-129 | Bariatric Surgery and Suicide Risk in Patients With Obesity. Hung et al. | 2023 | PMID 36805965 DOI 10.1097/SLA.0000000000005825 | Cohort study | Veterans with severe obesity (78.7% men) | Suicide attempts were about 60% more frequent after bypass or sleeve than in similar veterans without surgery. | Mostly male veterans; Procedure-specific estimates not in abstract | moderate | C-BAR-07 |
| I-BAR-130 | Rates of de novo alcohol use disorder and de novo high-risk alcohol use after bariatric surgery: a systematic review and meta-analysis. Cheloff et al. | 2026 | PMID 42191444 DOI 10.1016/j.soard.2026.03.030 | Meta-analysis | Patients after MBS | About 2.5 in 100 developed new alcohol problems; the increase was clear after bypass but uncertain after sleeve. | Heterogeneous outcomes; Mostly retrospective | moderate | C-BAR-07 |
| I-BAR-131 | Meta-analysis of Long-Term Relapse Rate of Type 2 Diabetes Following Initial Remission After Roux-en-Y Gastric Bypass. Yu et al. | 2021 | PMID 34505971 DOI 10.1007/s11695-021-05692-4 | Meta-analysis | Patients with T2D in remission after RYGB | About 3 in 10 people whose diabetes went into remission after bypass later relapsed; relapse was less common than after sleeve. | Observational; definitions vary; Follow-up lengths differ | moderate | C-BAR-08 C-BAR-14 |
| I-BAR-132 | Metabolic bariatric surgery as a therapeutic option for patients with type 2 diabetes: A meta-analysis and network meta-analysis of randomized controlled trials. De Luca et al. | 2023 | PMID 37272316 DOI 10.1111/dom.15117 | Meta-analysis | Patients with T2D in RCTs | Across 36 trials, weight-loss operations led to more diabetes remission and lower blood sugar than medical treatment. | Mostly 1-5 y follow-up; Effect sizes not in abstract | high | C-BAR-08 |
| I-BAR-133 | Benefits of bariatric surgery on microvascular outcomes in adult patients with type 2 diabetes: a systematic review and meta-analysis. Obeso-Fernández et al. | 2023 | PMID 37169666 DOI 10.1016/j.soard.2023.02.024 | Meta-analysis | Adults with T2D | People with diabetes who had surgery had fewer eye and kidney complications than those treated with medicines alone. | Mostly observational; Wide CIs | moderate | C-BAR-08 |
| I-BAR-134 | Comparing the 5-Year Diabetes Outcomes of Sleeve Gastrectomy and Gastric Bypass: The National Patient-Centered Clinical Research Network (PCORNet) Bariatric Study. McTigue et al. | 2020 | PMID 32129809 DOI 10.1001/jamasurg.2020.0087 | Cohort study | Adults with T2D undergoing RYGB or SG 2005-2015 | Diabetes remission was slightly more common and relapse less common after bypass; still, about 1 in 3 remitted bypass patients relapsed within 5 years. | Observational; EHR-defined remission; Median follow-up 2.7 y | moderate | C-BAR-08 C-BAR-14 |
| I-BAR-135 | Comparative survival of sleeve gastrectomy versus Roux-en-Y gastric bypass in adults with obesity: a systematic review and meta-analysis. Sakurai et al. | 2025 | PMID 39732586 DOI 10.1016/j.soard.2024.11.016 | Meta-analysis | Adults with morbid obesity undergoing SG or RYGB | Sleeve was associated with about 15% lower death risk than bypass over about 3 years, but needed more revision operations. | Dominated by observational data; Short median follow-up | moderate | C-BAR-14 |
| I-BAR-136 | Cholelithiasis after bariatric surgery, incidence, and prophylaxis: randomized controlled trial. Talha et al. | 2020 | PMID 31858245 DOI 10.1007/s00464-019-07323-7 | Randomised controlled trial | Morbidly obese patients undergoing OAGB, SG or greater curve plication | Without preventive medicine, about 22 in 100 patients formed gallstones within a year; a bile-acid medicine lowered this to about 6 in 100. | Abstract numbers internally inconsistent (overall 9.7% vs 22%/6.5%; "RR is 3.4%"); Procedure shares among stone formers do not give procedure-specific incidence | moderate | C-BAR-11 |
| I-BAR-137 | Comparative Risk of Gallstone Formation After Sleeve Gastrectomy and Roux-En-Y Gastric Bypass: A Systematic Review and Meta-Analysis. Silva-Chavez et al. | 2025 | PMID 41251897 DOI 10.1007/s11695-025-08388-1 | Meta-analysis | Patients after SG or RYGB | Gallstones formed after both operations; in the short term they were somewhat less common after sleeve. | Fragile to one study; Observational | moderate | C-BAR-11 |
| I-BAR-138 | The risk of inflammatory bowel disease after bariatric surgery. Kiasat et al. | 2022 | PMID 35012883 DOI 10.1016/j.soard.2021.12.014 | Cohort study | Swedish adults with primary RYGB or SG 2007-2018 and matched general-population controls | Ulcerative colitis was diagnosed more often after sleeve (and Crohn disease after bypass) than in the general population. | Controls not matched for obesity (obesity itself may raise IBD risk); Surveillance bias after surgery (more endoscopy) | moderate | C-BAR-13 |
| I-BAR-139 | The Impact of Metabolic Bariatric Surgery on Inflammatory Bowel Disease Risk and Outcomes in Adults With Obesity: a Propensity-matched, Nationwide, Analysis. Pusateri et al. | 2026 | PMID 42082785 DOI 10.1007/s11695-026-08714-1 | Cohort study | Adults with severe obesity with or without RYGB/VSG | Bowel inflammation was less common in the first 3 years after surgery but more common afterwards, especially after sleeve; it remained rare. | Claims data; Late-period estimate imprecise (CI 1.02-5.06) | moderate | C-BAR-13 |
| I-BAR-140 | The association between bariatric surgery and incident rheumatoid arthritis. Jeries et al. | 2026 | PMID 41908723 DOI 10.1093/rap/rkag025 | Cohort study | Patients with bariatric surgery 2010-2015 and age/sex-matched controls | Rheumatoid arthritis appeared equally rarely in operated and non-operated people (9 cases each). | Very few events; underpowered; Controls matched only on age and sex | low | C-BAR-13 |
| I-BAR-141 | Compared with Controls, Bariatric Surgery Prevents Long-Term Mortality in Persons with Obesity Only Above Median Age of Cohorts: a Systematic Review and Meta-Analysis. Pontiroli et al. | 2020 | PMID 32152843 DOI 10.1007/s11695-020-04530-3 | Meta-analysis | Persons with obesity with or without surgery in studies reporting median age | Surgery was linked to fewer deaths in older patients, but in younger patients no clear survival benefit was shown. | Ecological stratification by cohort median age; Abstract only | moderate | C-BAR-01 |
| I-BAR-142 | Long-Term Outcomes of Laparoscopic Roux-en-Y Gastric Bypass vs Laparoscopic Sleeve Gastrectomy for Obesity: The SM-BOSS Randomized Clinical Trial. Kraljevic et al. | 2025 | PMID 39969869 DOI 10.1001/jamasurg.2024.7052 | Randomised controlled trial | Patients with severe obesity (mean BMI 43.9) | After more than 10 years, 3 in 10 sleeve patients needed a conversion operation (for reflux or weight) vs about 1 in 20 after bypass; new reflux was more common after sleeve. | 34.6% incomplete 10-y follow-up; Small trial | high | C-BAR-02 C-BAR-14 C-BAR-03 |
| I-BAR-143 | Metabolic and bariatric surgery in adults with obesity and diabetes mellitus: a network meta-analysis. Kiesswetter et al. | 2026 | PMID 42610488 DOI 10.1002/14651858.CD015622.pub2 | Meta-analysis | Adults with obesity and type 2 diabetes | Trials show more weight loss and better blood sugar after surgery, but long-term data on complete diabetes remission, serious harms and deaths are very uncertain. | Few RCT participants and events; Cohorts not GRADE-rated | high | C-BAR-08 C-BAR-01 |
| I-BAR-144 | Use of proton pump inhibitors after laparoscopic gastric bypass and sleeve gastrectomy: a nationwide register-based cohort study. Gormsen et al. | 2024 | PMID 39043831 DOI 10.1038/s41366-024-01593-5 | Cohort study | All patients with L-RYGB or L-SG in Denmark 2008-2018 | Sleeve patients were much more likely to start acid-reducing medicines and to keep taking them than bypass patients. | Different follow-up lengths; Small SG group | moderate | C-BAR-03 C-BAR-02 |
| I-BAR-145 | Long-term effect of Roux-en-Y gastric bypass versus sleeve gastrectomy on reflux and Barrett's oesophagus: a randomized controlled trial. Lee et al. | 2025 | PMID 39829211 DOI 10.1111/ans.19369 | Randomised controlled trial | Participants of an RCT for T2D remission; 48 of 109 took part | Barrett changes were found in 8 of 26 examined sleeve patients and 3 of 22 bypass patients; the difference was not statistically certain. | Only 44% of randomised patients examined (selection); Very small; underpowered | low | C-BAR-04 C-BAR-03 |
| I-BAR-146 | Postoperative micronutrient changes in bariatric surgery patients compliant with nutritional supplementation. Sandhu et al. | 2023 | PMID 37775602 DOI 10.1007/s00464-023-10421-2 | Cross-sectional study | Consecutive adults after RYGB or VSG who reported supplement adherence | Patients who took their supplements did not show worse vitamin or mineral levels after surgery. | Very small, retrospective; Self-reported adherence | very low | C-BAR-05 |
| I-BAR-147 | Effect of Sleeve Gastrectomy on Ghrelin, GLP-1, PYY, and GIP Gut Hormones: A Systematic Review and Meta-analysis. McCarty et al. | 2020 | PMID 31592891 DOI 10.1097/SLA.0000000000003614 | Meta-analysis | Patients undergoing SG | After sleeve the hunger hormone ghrelin fell and satiety hormones GLP-1 and PYY rose. | Short follow-up; High heterogeneity | moderate | C-BAR-10 |
| I-BAR-148 | Adaptations in gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass. Steenackers et al. | 2021 | PMID 33581761 DOI 10.1016/S2468-1253(20)30302-2 | Narrative review | Preclinical and clinical studies | After sleeve, food leaves the stomach faster and bile acids rise; many other effects are still unknown. | Narrative, not systematic | low | C-BAR-10 |
| I-BAR-149 | Long-term prevalence of vitamin deficiencies after bariatric surgery: a meta-analysis. Chen et al. | 2024 | PMID 39030449 DOI 10.1007/s00423-024-03422-9 | Meta-analysis | Patients after bariatric surgery (RYGB, SG, BPD-DS and others) | Years after surgery, about 1 in 3 people lacked vitamin D and about 1 in 12 lacked vitamin B12. | Heterogeneous definitions and supplementation; Preoperative prevalence not subtracted | moderate | C-BAR-05 |
| I-CAN-01 | Mortality in relation to smoking: 50 years' observations on male British doctors. Doll R et al. | 2004 | PMID 15213107 DOI 10.1136/bmj.38142.554479.AE | Cohort study | Male British doctors | Smoking tripled death rates; stopping at 30 avoided almost all the excess risk. | Men, doctors only | high | C-CAN-02 C-CAN-01 C-SYS-01 C-SYS-03 C-SRC-62 |
| I-CAN-02 | Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States, 2019. Islami F et al. | 2024 | PMID 38990124 DOI 10.3322/caac.21858 | Risk assessment | US adults >=30 y | Smoking accounted for 19% of cancers and 29% of cancer deaths; excess weight and alcohol followed. | Assumes causal RRs; US-specific prevalence | moderate | C-CAN-02 C-CAN-01 C-CAN-07 C-CAN-08 C-CAN-06 C-SYS-03 C-SRC-62 |
| I-CAN-03 | The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019. GBD 2019 Cancer Risk Factors Collaborators | 2022 | PMID 35988567 DOI 10.1016/S0140-6736(22)01438-6 | Risk assessment | Global population; 204 countries and territories, by age, sex, region and Socio-demographic Index (SDI) | 44% of cancer deaths worldwide in 2019 were attributable to known risk factors, smoking first; diet accounted for about 5-6% of cancer burden. | Model-based; sparse registry and exposure data in many low-SDI countries, with greater uncertainty (authors); Residual exposure measurement bias likely despite adjustment; exposure model performance not formally assessed (authors) | moderate | C-CAN-01 C-CAN-02 C-CAN-07 C-CAN-08 C-SYS-02 C-SRC-62 |
| I-CAN-04 | Familial Risk and Heritability of Cancer Among Twins in Nordic Countries. Mucci LA et al. | 2016 | PMID 26746459 DOI 10.1001/jama.2015.17703 | Cohort study | Same-sex monozygotic and dizygotic twins from the national twin registries of Denmark, Finland, Norway and Sweden (birth cohorts 1870-2004) | Heritability of cancer overall was 33% in 200,000 Nordic twins. | Equal-environment assumption of twin models cannot be tested (authors); Incomplete registry coverage and survival-to-age-6 requirement in early birth cohorts (selection) | high | C-CAN-01 C-SYS-03 |
| I-CAN-05 | Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. de Martel C et al. | 2020 | PMID 31862245 DOI 10.1016/S2214-109X(19)30488-7 | Risk assessment | Global | H. pylori, HPV and hepatitis B/C viruses cause most infection-related cancers. | Model-based fractions | moderate | C-CAN-01 C-SYS-03 |
| I-CAN-06 | Definition and classification of cancer cachexia: an international consensus. Fearon K et al. | 2011 | PMID 21296615 DOI 10.1016/S1470-2045(10)70218-7 | Guideline / position statement | Cancer patients | Experts define cachexia as muscle loss driven by the tumour's effects on metabolism and appetite, not fully reversible by food. | Expert opinion | moderate | C-CAN-05 C-SYS-01 C-SRC-32 |
| I-CAN-07 | Dietary sugar consumption and health: umbrella review. Huang Y et al. | 2023 | PMID 37019448 DOI 10.1136/bmj-2022-071609 | Systematic review | Humans free of disease at baseline | Evidence for weight gain is moderate; links with cancers are mostly low quality. | Mostly observational, low-quality evidence for cancer outcomes | moderate | C-CAN-06 |
| I-CAN-101 | Use of Complementary and Alternative Medicine in the Management of Breast Cancer. Ayoade OF et al. | 2026 | PMID 41770560 DOI 10.1001/jamanetworkopen.2026.0337 | Cohort study | Women with stage I-IV breast cancer in the NCDB (about 70% of new US cancer diagnoses) | Using alternative medicine instead of standard treatment was linked to a 3.7-fold higher risk of death; skipping parts of treatment also raised risk. | Observational; residual confounding (no adjustment for receptor/HER2 status or grade; criticised in I-CAN-128); NCDB captures only registry-coded treatment by non-medical personnel (construct narrower than CAM in general; I-CAN-128) | moderate | C-CAN-04 C-SYS-01 C-SYS-06 |
| I-CAN-102 | Complementary and alternative medicine use: impact on survival among patients with gastrointestinal cancers. Ekenze SO et al. | 2026 | PMID 42607749 DOI 10.1016/j.gassur.2026.102552 | Cohort study | Adults with gastrointestinal cancers in the NCDB | Patients who used only alternative medicine had an 86% higher risk of death; those who combined it with standard care did not. | Very small CAM groups; Observational; residual confounding | moderate | C-CAN-04 |
| I-CAN-103 | Impact of ketogenic diets on cancer patient outcomes: a systematic review and meta-analysis. Zhang M et al. | 2025 | PMID 40756563 DOI 10.3389/fnut.2025.1535921 | Meta-analysis | Cancer patients assigned to ketogenic or standard diet | Ketogenic diets lowered body fat, insulin and glucose and improved some symptoms; survival was not shown to improve. | Outcomes are surrogate/metabolic, not survival; Abstract does not give number of studies or certainty | low | C-CAN-04 C-CAN-06 |
| I-CAN-104 | Effects of ketogenic diets on cancer-related variables: A systematic review and meta-analysis of randomised controlled trials. Salido-Bueno B et al. | 2024 | PMID 38923748 DOI 10.1111/nbu.12693 | Meta-analysis | Adults with cancer in RCTs | In 7 small randomised trials, a ketogenic diet lowered blood glucose but did not clearly improve other cancer-related measures. | Few, small, short trials; No survival outcomes | moderate | C-CAN-04 C-CAN-06 |
| I-CAN-105 | Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline. Ligibel JA et al. | 2022 | PMID 35576506 DOI 10.1200/JCO.22.00687 | Guideline / position statement | Adults receiving cancer treatment | ASCO found that exercise helps during cancer treatment but that evidence for specific diets is very limited. | Evidence base for diet thin; Abstract only | high | C-CAN-04 C-CAN-06 |
| I-CAN-106 | Complementary and Alternative Medicine (CAM) for cancer - patient information page National Cancer Institute | 2024 | Guideline / position statement | Cancer patients | The NCI states that no special diet has been proven to slow or cure cancer. | Patient-level summary, not a systematic review | moderate | C-CAN-04 | |
| I-CAN-108 | Why do patients with cancer die? Boire A et al. | 2024 | PMID 38898221 DOI 10.1038/s41568-024-00708-4 | Narrative review | Patients with advanced cancer | Death in cancer usually results from several organ problems caused by the cancer, including wasting; tumour size alone does not explain it. | Narrative, not systematic; Few quantitative data | moderate | C-CAN-05 |
| I-CAN-109 | Cancer- and endotoxin-induced cachexia require intact glucocorticoid signaling in skeletal muscle. Braun TP et al. | 2013 | PMID 23733748 DOI 10.1096/fj.13-230375 | Animal study | Mice (muscle-specific glucocorticoid receptor knockout) with LPS or tumour | Mice lacking glucocorticoid receptors in muscle lost 77% less muscle when they had tumours. | Mouse model; Does not address cause of death in humans | moderate | C-CAN-05 |
| I-CAN-110 | Why do cancer patients die? A decade of experience on trends, profile, causes, and timing of deaths in India. Doshi A et al. | 2026 | PMID 42830814 DOI 10.5588/pha.26.0040 | Cohort study | Inpatients of a medical oncology department, South India | Most deaths were due to cancer progression (57%), organ failure (21%) or sepsis (15%). | Single centre; Cachexia not recorded as a separate category | low | C-CAN-05 |
| I-CAN-111 | Postdiagnosis dietary and lifestyle factors and mortality outcomes among colorectal cancer patients: a meta-analysis. Chen QY et al. | 2025 | PMID 40317134 DOI 10.1093/jnci/djaf098 | Meta-analysis | Colorectal cancer survivors | Bowel cancer survivors who ate more whole grains, milk and calcium lived longer; more refined grains and high-fat dairy was linked to shorter survival. | Observational; Many exposures tested | moderate | C-CAN-06 C-CAN-08 |
| I-CAN-112 | Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort. Chazelas E et al. | 2019 | PMID 31292122 DOI 10.1136/bmj.l2408 | Cohort study | French adults | Each extra 100 mL of sugary drinks per day was linked to 18% higher cancer risk. | Short follow-up; Observational | moderate | C-CAN-06 C-CAN-07 C-CAN-08 |
| I-CAN-113 | European Code Against Cancer, 5th edition - diet, excess body weight, physical activity, sedentary behavior, breastfeeding, and cancer. Leitzmann MF et al. | 2026 | PMID 41542809 DOI 10.1002/1878-0261.70201 | Guideline / position statement | General EU population | Europe's cancer code advises eating whole grains, vegetables, legumes and fruit and limiting processed meat, sugary drinks and ultra-processed food. | Consensus; underlying evidence mostly observational | high | C-CAN-07 C-CAN-08 C-SYS-02 |
| I-CAN-114 | Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project. Vieira AR et al. | 2017 | PMID 28407090 DOI 10.1093/annonc/mdx171 | Meta-analysis | Adults in 111 prospective cohorts | More red/processed meat and alcohol raised bowel cancer risk; whole grains and dairy lowered it; poultry and legumes showed no link. | Observational; Search to 2015 | high | C-CAN-08 C-CAN-07 |
| I-CAN-115 | Our Cancer Prevention Recommendations (WCRF/AICR) World Cancer Research Fund International | 2018 (page accessed 2026) | Guideline / position statement | General population and cancer survivors | Eat wholegrains, vegetables, fruit and beans; limit fast food, red/processed meat, sugary drinks and alcohol; no supplements for prevention. | Web summary | high | C-CAN-07 C-CAN-08 | |
| I-CAN-116 | Ultra-Processed Food Consumption and Cancer Risk: An Umbrella Review of Systematic Reviews and Meta-Analyses. Bao J et al. | 2026 | PMID 42619402 DOI 10.1111/1750-3841.71367 | Systematic review | Observational study populations | Eating more ultra-processed food may be linked to some cancers, but the evidence is of low certainty. | Low-quality underlying reviews; Observational evidence | moderate | C-CAN-08 C-CAN-07 |
| I-CAN-117 | Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Tomasetti C et al. | 2017 | PMID 28336671 DOI 10.1126/science.aaf9011 | Ecological study | 17 cancer types in 69 countries; cancer genome data | About two-thirds of cancer mutations may come from random errors when cells divide; preventable causes still matter. | Mutation share is not the same as share of cases preventable; Contested methodology | moderate | C-CAN-01 C-SYS-03 |
| I-CAN-118 | Cancer - WHO fact sheet World Health Organization | 2026 | Guideline / position statement | Global | About 38% of cancers can be prevented by avoiding risk factors, and many can be cured with early, effective treatment. | Summary without methods | moderate | C-CAN-01 C-CAN-02 C-CAN-04 | |
| I-CAN-119 | Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Grulich AE et al. | 2007 | PMID 17617273 DOI 10.1016/S0140-6736(07)61050-2 | Meta-analysis | People with HIV/AIDS (n=444,172) and solid-organ transplant recipients (n=31,977) | People with HIV/AIDS or on transplant drugs had higher rates of 20 of 28 cancer types. | Mainly infection-related cancers increased; Confounding by other exposures possible | high | C-CAN-03 |
| I-CAN-120 | Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Galon J et al. | 2006 | PMID 17008531 DOI 10.1126/science.1129139 | Cohort study | Patients with colorectal cancer (large cohorts plus two validation populations) | Patients whose tumours contained more of certain immune cells survived longer. | Prognostic association, not intervention | moderate | C-CAN-03 |
| I-CAN-121 | p53 Antibodies in the sera of patients with various types of cancer: a review. Soussi T | 2000 | PMID 10766157 | Narrative review | Cancer patients and high-risk individuals | About 30% of cancer patients have antibodies against the tumour protein p53. | Narrative review; older | low | C-CAN-03 |
| I-CAN-122 | Hallmarks of cancer: the next generation. Hanahan D et al. | 2011 | PMID 21376230 DOI 10.1016/j.cell.2011.02.013 | Narrative review | not applicable | Cancers acquire the ability to escape immune destruction; this is why they can grow despite immunity. | Conceptual | moderate | C-CAN-03 C-CAN-01 |
| I-CAN-123 | Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009. Grant EJ et al. | 2017 | PMID 28319463 DOI 10.1667/RR14492.1 | Cohort study | Atomic bomb survivors and unexposed residents of Hiroshima and Nagasaki | Radiation raised solid cancer risk even at doses of 0-100 mGy; most cancers in survivors were due to other causes. | Dose-response shape uncertain at low doses | high | C-CAN-02 C-CAN-01 |
| I-CAN-124 | Epidemiology of bladder cancer in Alexandria, Egypt: tobacco smoking. Bedwani R et al. | 1997 | PMID 9334811 DOI 10.1002/(sici)1097-0215(19970926)73:1<64::aid-ijc11>3.0.co;2-5 | Case-control study | Men in Alexandria, Egypt | Egyptian men who smoked had 4-7 times the odds of bladder cancer; risk fell after quitting. | Small; Hospital controls | moderate | C-CAN-02 |
| I-CAN-125 | A randomized phase II trial of gemcitabine, nab-paclitaxel, cisplatin with or without a medically supervised ketogenic diet for patients with metastatic pancreatic cancer. Jameson GS et al. | 2026 | PMID 41817106 DOI 10.1002/cncr.70343 | Randomised controlled trial | Treatment-naive metastatic pancreatic ductal adenocarcinoma | In 32 patients, adding a supervised ketogenic diet to chemotherapy showed a trend toward longer survival that was not statistically confirmed. | Very small (n=32); One-sided alpha 0.20 screening design | moderate | C-CAN-04 C-CAN-06 |
| I-CAN-126 | The mortality burden of cachexia or weight loss in patients with colorectal or pancreatic cancer: A systematic literature review. Dunne RF et al. | 2024 | PMID 39095951 DOI 10.1002/jcsm.13510 | Systematic review | Adults with colorectal or pancreatic cancer (studies with >=100 patients) | In about two-thirds of studies, cancer patients with wasting or weight loss lived shorter. | Observational; heterogeneous definitions; Industry funding | moderate | C-CAN-05 |
| I-CAN-127 | Consumption of sugar-sweetened and artificially sweetened beverages and breast cancer survival. Farvid MS et al. | 2021 | PMID 33945630 DOI 10.1002/cncr.33461 | Cohort study | Women with stage I-III breast cancer | Women who drank sugary drinks after a breast cancer diagnosis had a 31-35% higher risk of dying from breast cancer. | Observational; residual confounding; Self-reported diet | moderate | C-CAN-06 |
| I-CAN-128 | When "CAM" is not CAM: Interpreting national cancer database analyses in breast cancer. Jeitler M et al. | 2026 | PMID 42135607 DOI 10.1093/oncolo/oyag187 | Other | not applicable | Experts note that the US registry studies capture people who used non-medical alternatives as cancer treatment, not complementary therapies in general. | Commentary; no new data | moderate | C-CAN-04 |
| I-CAN-129 | Refusal of cancer-directed treatment by colon cancer patients: Risk factors and survival outcomes. Kaltenmeier C et al. | 2020 | PMID 32680623 DOI 10.1016/j.amjsurg.2020.04.022 | Cohort study | Patients with potentially treatable colon cancer | Patients who refused recommended surgery lived a median of 6.8 months vs 24 months. | Observational; confounding by health status; Reasons for refusal unknown | moderate | C-CAN-04 |
| I-CAN-130 | Substantial contribution of extrinsic risk factors to cancer development. Wu S et al. | 2016 | PMID 26675728 DOI 10.1038/nature16166 | Other | Tissue-specific cancer risk data | Modelling suggests that internal 'bad luck' explains only about 10-30% of lifetime cancer risk; the rest depends on external factors. | Model-based; contested (opposes I-CAN-117) | moderate | C-CAN-01 C-SYS-03 |
| I-CAN-131 | Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study. Chlebowski RT et al. | 2006 | PMID 17179478 DOI 10.1093/jnci/djj494 | Randomised controlled trial | Women with resected early-stage breast cancer receiving conventional cancer management | Women who cut dietary fat while receiving standard treatment had somewhat fewer relapses (9.8% vs 12.4%), but the result was borderline. | Interim analysis after funding stopped; Log-rank P not significant | moderate | C-CAN-04 |
| I-CHK-01 | Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis. Tang KL et al. | 2017 | PMID 29387833 DOI 10.1016/S2542-5196(17)30141-9 | Meta-analysis | Food-producing animals; humans | Restricting antibiotics in livestock reduced resistant bacteria in animals and, in fewer studies, in people. | Underlying studies mostly cross-sectional with few adjusting for confounders; Extreme heterogeneity (I2 up to 99.4%; human 97.4%) | high | C-CHK-05 |
| I-CHK-02 | Regulation (EC) No 1831/2003 on additives for use in animal nutrition (original text, Article 11 and recitals 25-26) European Parliament and Council | 2003 | Guideline / position statement | EU animal feed | Since 2006, antibiotics may not be used as growth-promoting feed additives in the EU. | Therapeutic and prophylactic veterinary use regulated separately (not covered) | not applicable | C-CHK-05 C-CHK-07 | |
| I-CHK-03 | Arsenic-based Animal Drugs and Poultry (FDA web page, last updated 29 April 2022) US Food and Drug Administration | 2022 | Guideline / position statement | US poultry | Arsenic-based poultry drugs were withdrawn in the US between 2013 and 2015. | Page does not cover other countries | not applicable | C-CHK-07 | |
| I-CHK-04 | The European Union summary report on antimicrobial resistance in zoonotic and indicator bacteria from humans, animals and food in 2021-2022. EFSA, ECDC | 2024 | PMID 38419967 DOI 10.2903/j.efsa.2024.8583 | Other | EU MSs | Resistance in poultry-linked bacteria is common and varies by country, but key indicators improved in several countries. | Country variation in sampling | high | C-CHK-05 |
| I-CHK-05 | Update and review of control options for Campylobacter in broilers at primary production. EFSA BIOHAZ Panel | 2020 | PMID 32874298 DOI 10.2903/j.efsa.2020.6090 | Risk assessment | EU broiler production | Farm measures could reduce human Campylobacter infections from chicken meat substantially. | Wide, overlapping probability intervals make ranking uncertain; Relies on risk-factor studies with Nordic over-representation and on an outdated 2008 baseline survey | high | C-CHK-09 C-CHK-08 |
| I-CHK-06 | Carcinogenicity of consumption of red and processed meat. Bouvard V et al. | 2015 | PMID 26514947 DOI 10.1016/S1470-2045(15)00444-1 | Guideline / position statement | Human evidence base | Processed meat causes cancer and red meat probably does; poultry was not evaluated; cooking method evidence was insufficient. | Poultry not evaluated | high | C-CHK-01 C-CHK-10 |
| I-CHK-07 | Meat consumption and risk of 25 common conditions: outcome-wide analyses in 475,000 men and women in the UK Biobank study. Papier K et al. | 2021 | PMID 33648505 DOI 10.1186/s12916-021-01922-9 | Cohort study | UK Biobank participants aged ~40-69 at recruitment (2006-2010) from 22 assessment centres, excluding prevalent cancer | More poultry was linked to slightly more reflux, gastritis and diabetes, partly explained by body weight, and to less anaemia. | Residual confounding, especially by adiposity and energy intake (total energy not measured); Meat types not mutually adjusted | high | C-CHK-01 C-CHK-04 |
| I-CHK-08 | Association between total, processed, red and white meat consumption and all-cause, CVD and IHD mortality: a meta-analysis of cohort studies. Abete I et al. | 2014 | PMID 24932617 DOI 10.1017/S000711451400124X | Meta-analysis | 13 cohorts | Processed and red meat were linked to higher death risk, white meat (including poultry) was not. | High heterogeneity; Older | moderate | C-CHK-01 |
| I-CHK-09 | Antimicrobial resistance profiles and virulence genotyping of Salmonella enterica serovars recovered from broiler chickens and chicken carcasses in Egypt. Elkenany R et al. | 2019 | PMID 31029108 DOI 10.1186/s12917-019-1867-z | Cross-sectional study | Five small-scale broiler farms (birds at 3 weeks of the growing cycle; farm environment incl. water, feed, litter, fans, workers' hands) and five retail shops (freshly dressed whole carcasses, outer skin) | About 29% of retail chicken carcasses and 32% of farm chickens in one Egyptian province had Salmonella, mostly multidrug-resistant. | Only 5 farms and 5 shops in one province, single summer season; small clusters (34 carcasses per shop) not accounted for; Selection of farms and shops not described | moderate | C-CHK-05 C-CHK-08 C-CHK-09 |
| I-CHK-10 | Avian Influenza A(H5N1) Virus in Egypt. Kayali G et al. | 2016 | PMID 26886164 DOI 10.3201/eid2203.150593 | Narrative review | Poultry in commercial/semicommercial farms, abattoirs, backyard flocks and live bird markets across Egyptian governorates; human H5N1 cases in Egypt | Bird flu is established in Egyptian poultry and has caused many human infections. | Non-random bird selection; uneven sampling across governorates; Human case data from official reports; true burden uncertain | moderate | C-CHK-13 |
| I-CHK-101 | Association of poultry consumption with cardiovascular diseases and all-cause mortality: a systematic review and dose response meta-analysis of prospective cohort studies. Papp RE et al. | 2023 | PMID 34542332 DOI 10.1080/10408398.2021.1975092 | Meta-analysis | Adults in 24 prospective cohorts | Across 24 cohort studies, people eating the most poultry did not die earlier; the risk was slightly lower (RR 0.96). | Observational data; residual confounding; Authors rate certainty very low to low | moderate | C-CHK-01 |
| I-CHK-102 | Associations of Processed Meat, Unprocessed Red Meat, Poultry, or Fish Intake With Incident Cardiovascular Disease and All-Cause Mortality. Zhong VW et al. | 2020 | PMID 32011623 DOI 10.1001/jamainternmed.2019.6969 | Cohort study | US adults, mean age 53.7 y | Two extra servings a week were linked to 4% more cardiovascular events (about 1 extra case per 100 people over 30 years), but not to more deaths. | Single baseline diet assessment; Preparation methods (frying, skin) not separated in abstract | moderate | C-CHK-01 |
| I-CHK-103 | Associations of unprocessed and processed meat intake with mortality and cardiovascular disease in 21 countries [Prospective Urban Rural Epidemiology (PURE) Study]: a prospective cohort study. Iqbal R et al. | 2021 | PMID 33787869 DOI 10.1093/ajcn/nqaa448 | Cohort study | Adults in 21 countries | In 134,297 people from 21 countries, poultry intake was not related to death or major heart disease. | Poultry results only qualitatively in abstract; Observational | moderate | C-CHK-01 |
| I-CHK-104 | Poultry Consumption and Human Health: How Much Is Really Known? A Systematically Searched Scoping Review and Research Perspective. Connolly G et al. | 2022 | PMID 36351778 DOI 10.1093/advances/nmac074 | Systematic review | Published studies of any design | A map of 525 studies found little direct research on poultry itself and no randomised trials. | Scoping review: no effect estimates or quality rating; Funding not stated in abstract (PubMed: non-US government support) | moderate | C-CHK-01 C-CHK-02 |
| I-CHK-105 | Red and White Meat Intake in Relation to Mental Disorders in Iranian Adults. Kazemi S et al. | 2021 | PMID 34386515 DOI 10.3389/fnut.2021.710555 | Cross-sectional study | Adults aged 18-55 y, Isfahan (Iran) | In 3,362 Iranian adults, eating more white meat was not linked to anxiety or depression. | Cross-sectional; reverse causation possible; White meat includes fish | low | C-CHK-02 |
| I-CHK-106 | Meat and mental health: A meta-analysis of meat consumption, depression, and anxiety. Dobersek U et al. | 2023 | PMID 34612096 DOI 10.1080/10408398.2021.1974336 | Meta-analysis | Adults in 20 studies | Pooling 20 studies, meat eaters had slightly lower anxiety and depression than meat avoiders. | Mostly cross-sectional; Not poultry-specific | low | C-CHK-02 |
| I-CHK-107 | Updated trends in the global prevalence and burden of mental disorders, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. GBD 2023 Mental Disorder Collaborators | 2026 | PMID 42167272 DOI 10.1016/S0140-6736(26)00519-2 | Systematic review | Global population, 204 countries and territories | Age-standardised prevalence of anxiety disorders increased between 1990 and 2023. | Modelled estimates, sparse data in many countries; No information on causes of trends | moderate | C-CHK-02 |
| I-CHK-108 | Prevalence of breast muscle myopathies (spaghetti meat, woody breast, white striping) and associated risk factors in broiler chickens from Ontario Canada. Che S et al. | 2022 | PMID 35427383 DOI 10.1371/journal.pone.0267019 | Cross-sectional study | Commercial broiler flocks (2 processing plants) | Severe woody breast affected 11.8% of fillets, and almost all fillets had white striping. | One province; CIs do not appear to account for clustering by flock (stats/C-CHK-03_woody_breast.py) | moderate | C-CHK-03 |
| I-CHK-109 | Research note: Influence of growing systems (conventional, organic, raised-without-antibiotics) on myopathies of broiler breast fillets. Barbut S et al. | 2026 | PMID 42096902 DOI 10.1016/j.psj.2026.106997 | Cross-sectional study | Fast-growing broilers from three production systems | Woody breast and related defects occurred in conventional, antibiotic-free and organic broilers; heavier fillets were more affected. | Sample size not in abstract; Inconsistent results between years | low | C-CHK-03 |
| I-CHK-11 | Breast muscle myopathies: twists and turns in modern broilers. Greene ES et al. | 2025 | PMID 40658058 DOI 10.1080/03079457.2025.2533454 | Narrative review | Modern broilers | Muscle disorders such as woody breast are widespread in fast-growing broilers. | Narrative | moderate | C-CHK-03 C-CHK-06 |
| I-CHK-110 | Bacitracin, Bacillus subtilis, and Eimeria spp. challenge exacerbates woody breast incidence and severity in broilers. Jia L et al. | 2022 | PMID 34788711 DOI 10.1016/j.psj.2021.101512 | Animal study | Ross x Ross 708 broiler chicks | Bacitracin, a probiotic and a parasite challenge each increased woody breast in some conditions. | Sample size not in abstract; WB assessed by palpation | low | C-CHK-03 |
| I-CHK-111 | True Digestibility of Tryptophan in Plant and Animal Protein. Kashyap S et al. | 2024 | PMID 39307282 DOI 10.1016/j.tjnut.2024.09.014 | Other | Healthy adults (n = 5-7 per protein) | In a human tracer study, 95.9% of tryptophan from chicken meat was digested, the highest of all foods tested. | Small n per protein; One amino acid reported here | moderate | C-CHK-04 |
| I-CHK-112 | Impact of Wooden Breast myopathy on in vitro protein digestibility, metabolomic profile, and cell cytotoxicity of cooked chicken breast meat. Trithavisup T et al. | 2024 | PMID 37992618 DOI 10.1016/j.psj.2023.103261 | Laboratory / cell study | Cooked breasts with and without severe WB | In simulated digestion, woody breast protein was digested as well as normal breast. | In vitro; n = 6 per group; Cell findings of unclear relevance | low | C-CHK-04 |
| I-CHK-113 | Estimating In Vitro Protein Digestion and Protein Digestibility Corrected Amino Acid Score of Chicken Breasts Affected by White Striping and Wooden Breast Abnormalities. Srimarut Y et al. | 2024 | PMID 38201187 DOI 10.3390/foods13010159 | Laboratory / cell study | Cooked chicken breasts: normal, WS, WS+WB | Breast with wooden breast and white striping was broken down more, not less, in simulated digestion. | In vitro only; Sample size not in abstract | low | C-CHK-04 |
| I-CHK-114 | Effect of the Consumption of Lean Red Meat from Beef (Pirenaica Breed) Versus Lean White Meat (Chicken) on the Gut Microbiota: A Randomized Cross-Over Study in Healthy Young Adults. Rueda-De Torre I et al. | 2025 | PMID 40711376 DOI 10.1002/mnfr.70189 | Randomised controlled trial | Healthy young adults (mean age 20.1 y) | In 16 young adults, chicken and beef diets changed gut bacteria only modestly and similarly. | Very small sample; Short duration | low | C-CHK-04 |
| I-CHK-115 | Attributable sources of community-acquired carriage of Escherichia coli containing beta-lactam antibiotic resistance genes: a population-based modelling study. Mughini-Gras L et al. | 2019 | PMID 31439317 DOI 10.1016/S2542-5196(19)30130-5 | Risk assessment | Dutch population; gene data from humans, animals, food, water, wild birds | Food accounted for about 19% of community carriage of ESBL E. coli; human-to-human spread for about 60%. | Model assumptions; Food not split by type in abstract | moderate | C-CHK-05 |
| I-CHK-116 | The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2023-2024 EFSA and ECDC | 2026 | DOI 10.2903/j.efsa.2026.9887 | Measurement / residue study | Isolates from humans, broilers, laying hens, turkeys, pigs, calves and meat | Resistance to common antibiotics is frequent in Salmonella and Campylobacter, and ciprofloxacin resistance is rising in poultry-associated strains in humans. | Abstract only (read via Crossref); No PMID located | high | C-CHK-05 |
| I-CHK-117 | Antimicrobial use in animal farms in Egypt: rates, patterns, and determinants. ElSayed N et al. | 2025 | PMID 39828782 DOI 10.1186/s42506-024-00180-w | Cross-sectional study | Personnel of poultry, cattle and mixed farms in 15 governorates | All 111 farms used antibiotics; 65% also used them for prevention or growth. | Self-report; Farms selected from a private platform list | low | C-CHK-05 C-RES-05 C-RES-04 |
| I-CHK-118 | World Health Organization (WHO) guidelines on use of medically important antimicrobials in food-producing animals. Aidara-Kane A et al. | 2018 | PMID 29375825 DOI 10.1186/s13756-017-0294-9 | Guideline / position statement | Food-producing animals; global policy | WHO recommends ending antibiotic use for growth promotion and for prevention in healthy animals. | Recommendations rest partly on low-certainty evidence | high | C-CHK-05 C-RES-05 |
| I-CHK-119 | FDA: Steroid Hormone Implants Used for Growth in Food-Producing Animals (content current as of 24 October 2024) U.S. Food and Drug Administration | 2024 | Guideline / position statement | US food-producing animals | FDA approves hormone implants for beef cattle and sheep, but none for poultry or pigs. | US-specific | high | C-CHK-06 C-RES-04 | |
| I-CHK-12 | Health risk assessment of enrofloxacin, oxytetracycline, and sulfadimidine residues in broiler chicken carcasses marketed in Mit Ghamr, Egypt. Noah SM et al. | 2026 | PMID 42527435 DOI 10.1038/s41598-026-63227-2 | Measurement / residue study | Broiler carcass tissues (breast, thigh, liver; carcass ~1.25 kg) purchased from poultry shops in Mit Ghamr City, Dakahlia, Egypt | Many chicken samples had antibiotic residues above legal limits, especially in liver, but estimated health risk was low. | One city; number of shops and sampling procedure unclear; small n per tissue (60); HPLC-PDA without confirmatory LC-MS/MS (acknowledged by authors) | moderate | C-EGG-10 C-CHK-05 C-CHK-12 |
| I-CHK-120 | Chickens Do Not Receive Growth Hormones: So Why All the Confusion? (Mississippi State University Extension, Publication P2767) Tabler T, Wells J, Zhai W | 2023 (date not stated; code POD-05-23) | Narrative review | US broiler industry | US extension experts state that hormones have been banned in poultry since the 1950s and would not work in feed. | Extension (non-peer-reviewed) text; Possible industry-friendly framing | low | C-CHK-06 | |
| I-CHK-121 | Effect of oestrogenic compounds on performance and biochemical parameters of chickens in Egypt. Badr MO et al. | 2009 | PMID 20391405 | Animal study | 15-day-old chickens | In 60 chickens, oral contraceptive hormones increased weight and liver enzymes and left residues. | Small; methods for residues not described in abstract; PubMed labels it 'Duplicate Publication' | very low | C-CHK-06 |
| I-CHK-122 | Role of steroid growth promoter on growth performance and meat quality traits in broiler. Islam R et al. | 2022 | PMID 35523031 DOI 10.1016/j.psj.2022.101904 | Animal study | Day-old broiler chicks | Dexamethasone reduced weight gain and feed efficiency in broilers. | Small; TLC residue method; Country of practice not stated in abstract | low | C-CHK-06 |
| I-CHK-123 | Prevalence of Non-typhoidal Salmonellae in the Retail Chicken Meat in Alexandria, Egypt. Barac D et al. | 2024 | PMID 39678989 DOI 10.1007/s12088-024-01210-z | Cross-sectional study | Retail chicken carcasses/parts | 33% of carcass samples from Alexandria markets were contaminated; a supermarket sample set was free. | Small convenience sample from one city; Not nationally representative | low | C-CHK-08 C-CHK-09 |
| I-CHK-124 | Occurrence, genetic characterization and antimicrobial resistance of Salmonella isolated from chicken meat and giblets. Abd-Elghany SM et al. | 2015 | PMID 25004116 DOI 10.1017/S0950268814001708 | Cross-sectional study | Retail chicken carcasses/parts | Whole carcasses 16%, gizzards 60%, overall 34%; most isolates were multidrug resistant. | Small convenience sample from one city; Not nationally representative | low | C-CHK-08 C-CHK-09 |
| I-CHK-125 | Colistin-, cefepime-, and levofloxacin-resistant Salmonella enterica serovars isolated from Egyptian chicken carcasses. El-Saeed BA et al. | 2024 | PMID 38965586 DOI 10.1186/s12941-024-00713-3 | Cross-sectional study | Retail chicken carcasses/parts | 18% of native chicken carcasses carried Salmonella, often highly resistant to antibiotics. | Small convenience sample from one city; Not nationally representative | low | C-CHK-08 C-CHK-09 C-CHK-12 |
| I-CHK-126 | Arsanilic acid contributes more to total arsenic than roxarsone in chicken meat from Chinese markets. Zhao D et al. | 2020 | PMID 31525688 DOI 10.1016/j.jhazmat.2019.121178 | Measurement / residue study | Raw and cooked chicken meat | Organoarsenical drugs were detected in over 90% of tested Chinese chicken samples and raised inorganic arsenic. | Risk estimate model-based; Ecological comparison between cities | moderate | C-CHK-07 |
| I-CHK-127 | Public Health Risk of Arsenic Species in Chicken Tissues from Live Poultry Markets of Guangdong Province, China. Hu Y et al. | 2017 | PMID 28219238 DOI 10.1021/acs.est.6b06258 | Measurement / residue study | Chicken tissues (liver, breast, drumstick) and commercial feeds | Where roxarsone was used, chicken and especially liver contained more arsenic; estimated cancer risk was above priority levels for many adults. | Regional; Risk model assumptions; sample size not in abstract | moderate | C-CHK-07 |
| I-CHK-128 | A combined case-control and molecular source attribution study of human Campylobacter infections in Germany, 2011-2014. Rosner BM et al. | 2017 | PMID 28698561 DOI 10.1038/s41598-017-05227-x | Case-control study | Notified cases and controls; human and animal/food isolates | About three quarters of human C. jejuni isolates were attributed to chickens; kitchen handling of raw poultry was a risk factor. | Attribution models assign reservoirs, not exposure route; Sample size not in abstract | moderate | C-CHK-09 |
| I-CHK-129 | A pilot study revealing host-associated genetic signatures for source attribution of sporadic Campylobacter jejuni infection in Egypt. Saif NA et al. | 2022 | PMID 34033263 DOI 10.1111/tbed.14165 | Other | C. jejuni isolates from clinical cases, retail chicken and dairy products | Half to two thirds of patient isolates matched retail chicken; the rest matched cattle/dairy. | Pilot; small sample; Only two candidate sources | low | C-CHK-09 |
| I-CHK-13 | Overview of Colistin Resistance in the Middle East and North Africa (MENA) Region. Saniour R et al. | 2026 | PMID 42655038 DOI 10.3390/microorganisms14081693 | Narrative review | Humans, animals, food, environment | Resistance to the last-resort antibiotic colistin is reported in Egypt and other countries, including in poultry. | Narrative; heterogeneous sources | low | C-CHK-05 |
| I-CHK-130 | WHO fact sheet: Campylobacter (1 May 2020) World Health Organization | 2020 | Guideline / position statement | General population | WHO names undercooked poultry as a major source and says thorough cooking kills the bacteria. | Fact sheet from 2020 | moderate | C-CHK-09 | |
| I-CHK-131 | USDA FoodData Central, SR Legacy: Chicken, broilers or fryers, breast, meat only, cooked, roasted (FDC 171477) and meat and skin, cooked, roasted (FDC 171450) U.S. Department of Agriculture, Agricultural Research Service | 2019 | Other | US broiler meat samples (analytical dates not given in API record) | With skin, energy from fat (1.12 x protein) slightly exceeds protein; skinless breast is lean (0.26). The n-6:n-3 ratio is high in both. | Older US analyses; not modern EU/Egyptian birds; 18:3 undifferentiated; AA and DPA not retrieved | moderate | C-CHK-11 | |
| I-CHK-132 | Fatty acid composition of cooked chicken meat and chicken meat products as influenced by price range at retail. Gibbs RA et al. | 2013 | PMID 23411307 DOI 10.1016/j.foodchem.2012.11.002 | Measurement / residue study | Retail chicken products | Nuggets and burgers had much more fat than chicken meat; organic and conventional meat were similar. | Sample size not in abstract; UK only | moderate | C-CHK-11 |
| I-CHK-133 | A Prospective Pooled Analysis of Meat Mutagens and Colorectal Adenoma and Cancer in the US and EPIC Studies: Findings with an Emphasis on Improving Exposure Measurements. Nguyen LC et al. | 2022 | PMID 35901325 DOI 10.31557/APJCP.2022.23.7.2215 | Meta-analysis | Participants of 7 prospective cohorts | PhIP was associated with bowel polyps (HR 1.19) but not with bowel cancer (HR 1.00). | Simple pooling of published estimates; Exposure estimates vary widely | low | C-CHK-10 |
| I-CHK-134 | Salmonella enterica isolated from pigeon (Columba livia) in Egypt. Osman KM et al. | 2013 | PMID 23531124 DOI 10.1089/fpd.2012.1347 | Cross-sectional study | Pigeons in Cairo | Pigeons in Cairo carried multidrug-resistant Salmonella, including S. Typhimurium. | Prevalence and n not in abstract; Faecal samples, not meat | low | C-CHK-12 |
| I-CHK-135 | Natural infection with highly pathogenic avian influenza virus H5N1 in domestic pigeons (Columba livia) in Egypt. Mansour SM et al. | 2014 | PMID 24861170 DOI 10.1080/03079457.2014.926002 | Outbreak report | Domestic pigeons (1-18 months) | An outbreak killed half of a pigeon flock; pigeons shed H5N1 virus. | Single outbreak | low | C-CHK-12 C-CHK-13 |
| I-CHK-136 | WHO fact sheet: Influenza (avian and other zoonotic) (21 January 2026) World Health Organization | 2026 | Guideline / position statement | General population | WHO says infection comes from contact with live or dead infected birds and home slaughter; there is no evidence of spread through properly cooked poultry. | Fact sheet | moderate | C-CHK-13 | |
| I-CHK-137 | Risk of pneumonia among residents living near goat and poultry farms during 2014-2016. Post PM et al. | 2019 | PMID 31609989 DOI 10.1371/journal.pone.0223601 | Cross-sectional study | Residents of a livestock-dense area (Noord-Brabant/Limburg), GP records | In 90,183 residents, living near poultry farms was not linked to pneumonia in 2014-2016; living near goat farms was. | No individual confounder data (smoking, SES); Distance as exposure proxy | moderate | C-CHK-13 |
| I-CHK-138 | Increased Number of Human Cases of Influenza Virus A(H5N1) Infection, Egypt, 2014-15. Refaey S et al. | 2015 | PMID 26584397 DOI 10.3201/eid2112.150885 | Case series / case report | Human H5N1 cases | 99% of 165 Egyptian cases had contact with poultry; 51 died. | Descriptive; no control group | moderate | C-CHK-13 |
| I-CHK-139 | Poultry rearing and slaughtering practices in rural Egypt: an exploration of risk factors for H5N1 virus human transmission. Lohiniva AL et al. | 2013 | PMID 23145955 DOI 10.1111/irv.12023 | Other | 56 households with flocks | Observations in 56 rural households showed close contact with birds and home slaughter without protection. | Qualitative; small | moderate | C-CHK-13 C-CHK-12 |
| I-CHK-14 | Dietary Intake of Meat Cooking-Related Mutagens (HCAs) and Risk of Colorectal Adenoma and Cancer: A Systematic Review and Meta-Analysis. Chiavarini M et al. | 2017 | PMID 28524104 DOI 10.3390/nu9050514 | Meta-analysis | Observational studies | Higher intake of cooking-related mutagens was linked to more colorectal polyps and cancer. | Mutagen intake estimated from questionnaires; Heterogeneity | moderate | C-CHK-10 |
| I-CHK-140 | WHO fact sheet: Anxiety disorders (15 September 2026) World Health Organization | 2026 | Guideline / position statement | General population | WHO names effective psychological and drug treatments and does not list any food as a cause. | Fact sheet, not a systematic review | moderate | C-CHK-02 | |
| I-CHK-141 | WHO fact sheet: Salmonella (non-typhoidal) (20 February 2018) World Health Organization | 2018 | Guideline / position statement | General population | WHO names poultry among the main food sources of Salmonella and recommends thorough cooking. | Fact sheet from 2018 | moderate | C-CHK-09 | |
| I-CHK-15 | Salmonella enterica serotypes isolated from squabs reveal multidrug resistance and a distinct pathogenicity gene repertoire. Osman KM et al. | 2014 | PMID 25812222 DOI 10.20506/rst.33.3.2336 | Cross-sectional study | Squabs (young pigeons) | About one in eight squabs carried Salmonella, often multidrug-resistant. | Small sample | low | C-CHK-12 |
| I-CHM-01 | Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. EBCTCG | 2012 | PMID 22152853 DOI 10.1016/S0140-6736(11)61625-5 | Meta-analysis | Women with early breast cancer | In 123 trials with 100,000 women, modern regimens cut breast-cancer deaths by about one-third, and overall deaths fell too. | Chemotherapy-vs-none trials are old (median start 1986), half without endocrine therapy, suboptimal supportive care; 3 taxane trials (n~7000) unavailable; taxane follow-up short (mostly <=8 years) | high | C-CHM-09 C-CHM-10 C-CHM-12 C-CHM-13 C-SYS-06 |
| I-CHM-02 | Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. EBCTCG | 2011 | PMID 22019144 DOI 10.1016/S0140-6736(11)61629-2 | Meta-analysis | Women after breast-conserving surgery | Recurrence within 10 years fell from 35% to 19%, and breast-cancer deaths within 15 years from 25% to 21%. | Older radiotherapy, surgery, pathology and systemic therapy (trials 1976-99); margins would differ with modern pathology (authors); Risk-prediction categories derived from the same data, not externally validated (authors) | high | C-CHM-09 C-CHM-02 C-CHM-10 C-CHM-12 C-CHM-13 |
| I-CHM-03 | Use of Alternative Medicine for Cancer and Its Impact on Survival. Johnson SB et al. | 2018 | PMID 28922780 DOI 10.1093/jnci/djx145 | Cohort study | Nonmetastatic breast, prostate, lung or colorectal cancer | Risk of death was 2.5 times higher overall and 5.7 times higher for breast cancer. | Small AM group; Observational; residual confounding | moderate | C-CHM-09 C-CHM-10 C-CHM-12 C-CAN-04 C-SYS-01 C-SYS-06 C-SRC-32 C-SRC-45 |
| I-CHM-04 | Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients With Curable Cancers. Johnson SB et al. | 2018 | PMID 30027204 DOI 10.1001/jamaoncol.2018.2487 | Cohort study | Nonmetastatic breast, prostate, lung, colorectal cancer 2004-2013 | Users of complementary medicine refused chemotherapy or radiotherapy far more often and had about twice the risk of death. | Observational; CM recording incomplete | moderate | C-CHM-12 C-CHM-09 C-CAN-04 C-SRC-32 |
| I-CHM-05 | Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. Hunger SP et al. | 2012 | PMID 22412151 DOI 10.1200/JCO.2011.37.8018 | Cohort study | Children/adolescents 0-22 y with ALL | 5-year survival in childhood ALL rose to 90.4% by 2000-2005. | Trial participants only | high | C-CHM-06 C-CHM-09 C-CHM-11 C-CHM-12 C-CHM-13 C-SYS-06 |
| I-CHM-06 | Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials. Taylor C et al. | 2017 | PMID 28319436 DOI 10.1200/JCO.2016.72.0722 | Meta-analysis | Women randomised to RT vs no RT | About 0.3% risk of radiation-related heart death or lung cancer in non-smokers, higher in smokers. | Smoking status unavailable in trials (modelled) | high | C-CHM-02 C-CHM-01 C-CHM-03 C-CAN-02 |
| I-CHM-07 | Mortality due to cancer treatment delay: systematic review and meta-analysis. Hanna TP et al. | 2020 | PMID 33148535 DOI 10.1136/bmj.m4087 | Meta-analysis | Patients receiving curative, neoadjuvant or adjuvant surgery, systemic treatment or radiotherapy for bladder, breast, colon, rectum, lung, cervix, head and neck cancer | For example, every 4-week delay of breast surgery was linked to 8% higher mortality. | All primary studies retrospective observational: residual confounding by comorbidity/performance status (authors' main limitation); Single database (Medline) plus reference lists/Google; English only; no registered protocol reported | moderate | C-CHM-10 C-CHM-12 C-CAN-04 |
| I-CHM-08 | Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. Larkin J et al. | 2019 | PMID 31562797 DOI 10.1056/NEJMoa1910836 | Randomised controlled trial | Previously untreated advanced melanoma | 5-year survival 52% with combined immunotherapy vs 26% with the older drug. | Industry funded; Active comparator | high | C-CAN-03 C-CHM-13 C-CAN-01 |
| I-CHM-09 | Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius. Arcamone F et al. | 1969 | PMID 5365804 DOI 10.1002/bit.260110607 | Other | not applicable | The 1969 discovery paper names Streptomyces peucetius as the source. | Only title read | moderate | C-CHM-14 |
| I-CHM-10 | Platinum compounds: a new class of potent antitumour agents. Rosenberg B et al. | 1969 | PMID 5782119 DOI 10.1038/222385a0 | Other | not applicable | Its anticancer action was discovered in platinum compounds, not fungi. | Only title read | moderate | C-CHM-14 |
| I-CHM-101 | Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) | 2023 | PMID 37061269 DOI 10.1016/S0140-6736(23)00285-4 | Meta-analysis | Women with early-stage operable breast cancer in randomised adjuvant or neoadjuvant trials begun before 2012 | Anthracycline-taxane chemotherapy lowered recurrence and breast-cancer death; it caused about one extra leukaemia per 700 women and no measurable excess heart deaths within about 5 years. | Median follow-up only 5.4 years for the taxane +/- anthracycline comparison (late cardiac effects underestimated); Patients with high cardiovascular risk often excluded | high | C-CHM-01 C-CHM-03 C-CHM-09 C-CHM-10 C-CHM-12 |
| I-CHM-102 | Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. EBCTCG; McGale P et al. | 2014 | PMID 24656685 DOI 10.1016/S0140-6736(14)60488-8 | Meta-analysis | Women after mastectomy and axillary surgery in randomised trials | In women with cancer in the lymph nodes, radiotherapy prevented about 1 in 10 recurrences and about 1 in 12 breast-cancer deaths; in low-risk women with old techniques it did more harm than good. | Old trials (1964-86) with outdated radiotherapy techniques and higher heart doses; Systemic therapy mostly CMF | high | C-CHM-09 C-CHM-10 C-CHM-12 |
| I-CHM-103 | Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. NSCLC Meta-Analyses Collaborative Group | 2008 | PMID 18678835 DOI 10.1200/JCO.2008.17.7162 | Meta-analysis | Patients with advanced non-small-cell lung cancer | Chemotherapy raised 1-year survival from 20% to 29%. | Older chemotherapy regimens; most trials unblinded; Quality of life not pooled in abstract | high | C-CHM-07 C-CHM-13 |
| I-CHM-104 | Early palliative care for adults with advanced cancer. Haun MW et al. | 2017 | PMID 28603881 DOI 10.1002/14651858.CD011129.pub2 | Meta-analysis | Adults with advanced cancer | Early palliative care slightly improved quality of life and symptoms; any survival effect is uncertain. | Few trials; heterogeneous interventions; Lack of blinding | high | C-CHM-07 |
| I-CHM-105 | Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update. Ferrell BR et al. | 2017 | PMID 28034065 DOI 10.1200/JCO.2016.70.1474 | Guideline / position statement | Patients with advanced cancer and their caregivers | Patients with advanced cancer should get palliative care early, together with active treatment. | Partly expert opinion; US health-system focus | moderate | C-CHM-07 |
| I-CHM-106 | Are increasing 5-year survival rates evidence of success against cancer? Welch HG et al. | 2000 | PMID 10865276 DOI 10.1001/jama.283.22.2975 | Ecological study | US population (SEER), 20 most common solid tumours | Survival gains over time matched rising diagnosis rates, not falling death rates. | Ecological; 20 data points; Does not assess treatment effects directly | moderate | C-CHM-13 |
| I-CHM-107 | Reduced lung-cancer mortality with low-dose computed tomographic screening. National Lung Screening Trial Research Team; Aberle DR et al. | 2011 | PMID 21714641 DOI 10.1056/NEJMoa1102873 | Randomised controlled trial | 53,454 persons at high risk for lung cancer (heavy smokers) | Screening heavy smokers with low-dose CT cut lung-cancer deaths by 20% and deaths from any cause by 6.7%. | High false-positive rate; Some overdiagnosis (higher incidence) | high | C-CHM-13 |
| I-CHM-108 | Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Swain SM et al. | 2003 | PMID 12767102 DOI 10.1002/cncr.11407 | Cohort study | Patients with breast cancer or small-cell lung cancer receiving doxorubicin | About 5% of 630 patients developed heart failure; risk rose steeply at high cumulative doses (26% estimated at 550 mg/m2). | Retrospective analysis; mostly advanced (metastatic) disease with high cumulative doses; Old dosing practices | moderate | C-CHM-01 |
| I-CHM-109 | Dexrazoxane for preventing or reducing cardiotoxicity in adults and children with cancer receiving anthracyclines. de Baat EC et al. | 2022 | PMID 36162822 DOI 10.1002/14651858.CD014638.pub2 | Meta-analysis | Adults (mostly breast cancer) and children receiving anthracyclines | Dexrazoxane cut heart failure in adults by about four-fifths without lowering cancer control. | Heterogeneous outcome definitions; Low-quality paediatric evidence | high | C-CHM-01 |
| I-CHM-11 | Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Olive KP et al. | 2009 | PMID 19460966 DOI 10.1126/science.1171362 | Animal study | KPC mice with autochthonous pancreatic ductal adenocarcinoma; mice with transplanted (xenograft, orthotopic, syngeneic) tumours; 18 human PDA specimens vs normal pancreas (5) and chronic pancreatitis (5) | Reducing the tumour's supporting tissue briefly let more drug reach the tumour. | Mouse model; one tumour type (PDA); Small groups; randomisation, blinding and sample-size planning not reported | moderate | C-CHM-11 |
| I-CHM-110 | Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience. Wolff AC et al. | 2015 | PMID 25534386 DOI 10.1200/JCO.2013.54.6119 | Cohort study | Patients with stage I-III breast cancer at US academic centres | About 5 in 1000 treated women developed a marrow cancer within 10 years. | Observational; few events (wide CIs); Academic centres only | moderate | C-CHM-03 |
| I-CHM-111 | Longitudinal Trajectory and Characterization of Cancer-Related Cognitive Impairment in a Nationwide Cohort Study. Janelsins MC et al. | 2018 | PMID 30240328 DOI 10.1200/JCO.2018.78.6624 | Cohort study | Women with stage I-IIIC breast cancer receiving chemotherapy and matched controls | Patients' memory scores fell during chemotherapy and were still lower 6 months later, unlike controls. | Follow-up only 6 months; Controls without cancer (cancer itself may contribute) | moderate | C-CHM-04 |
| I-CHM-112 | Association of chemotherapy and subjective cognitive impairment in breast cancer patients: Meta-analysis of longitudinal prospective cohort studies. Kim HJ et al. | 2022 | PMID 35255262 DOI 10.1016/j.ejon.2022.102099 | Meta-analysis | Breast cancer patients with and without chemotherapy; healthy controls | Patients reported more thinking problems mainly in the first month after chemotherapy; the difference was small compared with patients who had no chemotherapy. | Few data sets; Subjective outcomes only | moderate | C-CHM-04 |
| I-CHM-113 | Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. Brock PR et al. | 2018 | PMID 29924955 DOI 10.1056/NEJMoa1801109 | Randomised controlled trial | Children 1 month to 18 years with standard-risk hepatoblastoma | Hearing loss fell from 63% to 33% with sodium thiosulfate, and survival stayed above 90%. | Small; open-label; Paediatric hepatoblastoma only | high | C-CHM-05 |
| I-CHM-114 | Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970-99: a report from the Childhood Cancer Survivor Study cohort. Gibson TM et al. | 2018 | PMID 30416076 DOI 10.1016/S1470-2045(18)30537-0 | Cohort study | 5-year survivors of childhood cancer diagnosed before age 21, 1970-1999, and siblings | Severe long-term conditions fell from 33% to 28% across three decades, but stayed far above siblings (5%). | Self-reported conditions; Treatment eras end in 1999 | high | C-CHM-06 |
| I-CHM-115 | The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE). Bhakta N et al. | 2017 | PMID 28890157 DOI 10.1016/S0140-6736(17)31610-0 | Cohort study | 10-year survivors treated at St Jude, aged >=18, and community controls | By age 50, survivors had on average 4.7 serious health conditions vs 2.3 in people without childhood cancer. | Single institution; 45.5% not clinically evaluable (imputed) | high | C-CHM-06 |
| I-CHM-116 | The financial toxicity of cancer: unveiling global burden and risk factors - a systematic review and meta-analysis. Kitaw TA et al. | 2025 | PMID 39929536 DOI 10.1136/bmjgh-2024-017133 | Meta-analysis | Patients with cancer worldwide | More than half of cancer patients in the pooled studies faced catastrophic health costs. | Heterogeneity not reported in abstract; CHE definitions vary between studies | moderate | C-CHM-08 |
| I-CHM-117 | Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Rhim AD et al. | 2014 | PMID 24856585 DOI 10.1016/j.ccr.2014.04.021 | Animal study | Mouse model of pancreatic ductal adenocarcinoma | In mice, removing the scar-like stroma around pancreatic tumours made them more aggressive. | Mouse model; one tumour type | moderate | C-CHM-11 |
| I-CHM-118 | Randomized Phase III Trial of Pegvorhyaluronidase Alfa With Nab-Paclitaxel Plus Gemcitabine for Patients With Hyaluronan-High Metastatic Pancreatic Adenocarcinoma. Van Cutsem E et al. | 2020 | PMID 32706635 DOI 10.1200/JCO.20.00590 | Randomised controlled trial | Adults with untreated metastatic hyaluronan-high PDA | A drug that degrades pancreatic tumour stroma, added to chemotherapy, did not prolong survival (11.2 vs 11.5 months). | Metastatic setting only; Sponsor details not read (abstract only) | high | C-CHM-11 |
| I-CHM-119 | Environment-mediated drug resistance: a major contributor to minimal residual disease. Meads MB et al. | 2009 | PMID 19693095 DOI 10.1038/nrc2714 | Narrative review | Not applicable | Signals between cancer cells and their surroundings can make some cells resist treatment at first. | Narrative, not systematic; Largely preclinical evidence | low | C-CHM-11 |
| I-CHM-12 | Cancer statistics, 2024. Siegel RL et al. | 2024 | PMID 38230766 DOI 10.3322/caac.21820 | Other | US population | More than 4 million cancer deaths averted since 1991 thanks to less smoking, earlier detection and better treatment. | Attribution to causes is not quantified per cause in abstract | moderate | C-CHM-09 C-CHM-13 C-CAN-02 |
| I-CHM-120 | Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. Oettle H et al. | 2013 | PMID 24104372 DOI 10.1001/jama.2013.279201 | Randomised controlled trial | Patients after macroscopically complete resection of pancreatic cancer | Chemotherapy after surgery doubled 5-year survival (21% vs 10%) compared with surgery alone. | Open-label; Modest sample | high | C-CHM-10 C-CHM-11 C-CHM-12 |
| I-CHM-121 | Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Stierle A et al. | 1993 | PMID 8097061 DOI 10.1126/science.8097061 | Laboratory / cell study | Fungal isolate Taxomyces andreanae | A fungus living in yew bark produced small amounts of the cancer drug taxol in the lab. | Single fungal isolate, laboratory culture only; Does not address drug supply or clinical use | low | C-CHM-14 |
| I-CHM-122 | Validation and Modification of a Prediction Model for Acute Cardiac Events in Patients With Breast Cancer Treated With Radiotherapy Based on Three-Dimensional Dose Distributions to Cardiac Substructures. van den Bogaard VA et al. | 2017 | PMID 28095159 DOI 10.1200/JCO.2016.69.8480 | Cohort study | 910 consecutive women irradiated after breast-conserving surgery | Risk of acute heart events rose by about 16.5% per Gy of heart dose; the typical heart dose was low (2.4 Gy). | Few events; wide CI; Single region | moderate | C-CHM-02 |
| I-CHM-123 | The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Morgan G et al. | 2004 | PMID 15630849 DOI 10.1016/j.clon.2004.06.007 | Other | All newly diagnosed adult cancer patients (22 malignancies) | Across all adult cancer patients, the authors estimated that about 2% are alive at 5 years because of chemotherapy alone. | Denominator includes all cancer patients, most of whom are not chemotherapy candidates; Counts only 5-year survival gains attributable solely to chemotherapy (excludes palliation, life extension <5 years, combined-modality gains) | low | C-CHM-09 C-CHM-13 |
| I-CHM-124 | Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. Davis C et al. | 2017 | PMID 28978555 DOI 10.1136/bmj.j4530 | Other | 48 cancer drugs, 68 indications approved by EMA | Of 68 new cancer-drug approvals in Europe, only about half showed a survival or quality-of-life benefit after 5 years. | Concerns new drugs, mostly for advanced disease, not established curative regimens | moderate | C-CHM-09 C-CHM-13 |
| I-CHM-125 | Temporal trends in childhood cancer survival in Egypt, 2007 to 2017: A large retrospective study of 14 808 children with cancer from the Children's Cancer Hospital Egypt. Soliman RM et al. | 2021 | PMID 32997796 DOI 10.1002/ijc.33321 | Cohort study | Children 0-18 years with cancer treated at Children's Cancer Hospital Egypt | At Egypt's main children's cancer hospital, 72% of children were alive 5 years after diagnosis, and survival improved over time. | Single institution (though very large); No untreated comparator; survival not causal proof of treatment effect | moderate | C-CHM-12 C-CHM-13 |
| I-CHM-126 | Family strategies for managing childhood cancer: Using traditional and complementary medicine in Southern Egypt. Farrag A et al. | 2024 | PMID 39289855 DOI 10.1002/pbc.31326 | Cross-sectional study | Children with cancer and caregivers at the South Egypt Cancer Institute | 60% of families used traditional or complementary remedies; some used them instead of treatment and some came late. | Small single-centre sample; No outcome data | low | C-CHM-12 |
| I-CHM-127 | Early elemental diet supplementation during chemotherapy improves treatment response and survival in advanced pancreatic cancer: A single-center randomized controlled trial. Uemura S et al. | 2026 | PMID 41794391 DOI 10.1016/j.clnesp.2026.103106 | Randomised controlled trial | Patients with advanced pancreatic cancer starting chemotherapy | In a small trial, patients who took a special nutrition formula during chemotherapy lived longer (21.4 vs 12.8 months). | Very small single-centre trial; open-label; Large effect from a small trial is likely to be overestimated | low | C-CHM-12 |
| I-CHM-128 | Impact of Interdisciplinary Outpatient Specialty Palliative Care on Survival and Quality of Life in Adults With Advanced Cancer: A Meta-Analysis of Randomized Controlled Trials. Hoerger M et al. | 2019 | PMID 30265282 DOI 10.1093/abm/kay077 | Meta-analysis | Adults with advanced cancer | In three good-quality trials, patients with palliative care alongside cancer treatment were more often alive after one year (56% vs 42%). | Only 3 studies for survival; Small pooled sample | moderate | C-CHM-07 |
| I-CHM-129 | Tumor-Stroma Proportion to Predict Chemoresistance in Patients With Ovarian Cancer. Lou E et al. | 2024 | PMID 38411963 DOI 10.1001/jamanetworkopen.2024.0407 | Cohort study | Patients with high-grade serous ovarian carcinoma | In a German cohort, tumours with much stroma resisted platinum chemotherapy more often; a US cohort showed no such link. | Not replicated in TCGA cohort (contradicts 'consistent'); Retrospective; confounding by stage/residual disease possible | moderate | C-CHM-11 |
| I-DIAB-101 | Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial. Taheri S et al. | 2020 | PMID 32445735 DOI 10.1016/S2213-8587(20)30117-0 | Randomised controlled trial | Adults 18-50 with T2D <=3 years, BMI >=27, from the MENA region | 61% of young adults with recent type 2 diabetes reached remission after an intensive diet programme, versus 12% with usual care. | Open label; 12-month follow-up | high | C-DIAB-03 |
| I-DIAB-102 | Association of an intensive lifestyle intervention with remission of type 2 diabetes. Gregg EW et al. | 2012 | PMID 23288372 DOI 10.1001/jama.2012.67929 | Randomised controlled trial | Overweight/obese adults with T2D | About 1 in 9 people reached remission in the first year with an intensive lifestyle programme, but only 3.5% stayed in remission for 4 years. | Exploratory ancillary analysis; Longer diabetes duration than DiRECT | high | C-DIAB-03 |
| I-DIAB-103 | Type 2 Diabetes Remission: A Systematic Review and Meta-analysis of Nonsurgical Randomized Controlled Trials. Sherifali DT et al. | 2025 | PMID 40982327 DOI 10.2337/dc25-0562 | Meta-analysis | Adults with T2D in RCTs (11 countries) | Structured diet and lifestyle programmes made remission about six times more likely, mainly in people with recently diagnosed type 2 diabetes. | Heterogeneous interventions and definitions; Short follow-up | high | C-DIAB-03 |
| I-DIAB-104 | Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes. Riddle MC et al. | 2021 | PMID 34462270 DOI 10.2337/dci21-0034 | Guideline / position statement | People with T2D | Remission means HbA1c below 6.5% at least 3 months after stopping diabetes drugs; it is not called a cure and needs ongoing checks. | Consensus elements; partly expert opinion | high | C-DIAB-03 |
| I-DIAB-105 | Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial. Athinarayanan SJ et al. | 2019 | PMID 31231311 DOI 10.3389/fendo.2019.00348 | Other | Adults with T2D | Many participants reduced or stopped diabetes medicines, including insulin, while doctors adjusted doses remotely; the study was not randomised. | Not randomised; Self-selected participants | low | C-INS-10 |
| I-DIAB-106 | Translating the A1C assay into estimated average glucose values. Nathan DM et al. | 2008 | PMID 18540046 DOI 10.2337/dc08-0545 | Other | 268 T1D, 159 T2D, 80 without diabetes | In 507 people with about 2,700 glucose readings each, HbA1c closely matched the 3-month average blood sugar. | Few people with haemoglobin variants/anaemia; Industry support possible (not stated) | high | C-DIAB-01 |
| I-DIAB-107 | Stress hyperglycemia: an essential survival response! Marik PE, Bellomo R | 2013 | PMID 23470218 DOI 10.1186/cc12514 | Narrative review | Critically ill patients | Critical-care experts argue that a short-term rise in sugar during severe illness may be a survival response; this does not apply to long-term diabetes. | Narrative, opinion-based; Concerns acute critical illness only, not chronic diabetes | low | C-DIAB-01 |
| I-DIAB-108 | The limitations and fallacies of relying on glycosylated hemoglobin for diagnosing and monitoring diabetes in Indian populations. Samajdar SS et al. | 2026 | PMID 41743216 DOI 10.1016/j.lansea.2026.100724 | Narrative review | People with or at risk of diabetes in India | Anaemia, inherited haemoglobin disorders and G6PD deficiency can distort HbA1c, so it should be combined with direct glucose measurements. | Narrative review; India-specific | low | C-DIAB-01 |
| I-DIAB-109 | Sick day management using blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: a randomized clinical trial. Laffel LM et al. | 2006 | PMID 16492211 DOI 10.1111/j.1464-5491.2005.01771.x | Randomised controlled trial | Children, adolescents and young adults 3-22 with T1D | Young people who checked blood ketones when sick needed hospital or emergency care about half as often as those using urine strips. | Small; Borderline significance | moderate | C-DIAB-02 |
| I-DIAB-110 | Evidence of a strong association between frequency of self-monitoring of blood glucose and hemoglobin A1c levels in T1D exchange clinic registry participants. Miller KM et al. | 2013 | PMID 23378621 DOI 10.2337/dc12-1770 | Cross-sectional study | People with T1D >=1 year not using CGM | Among 20,555 people with type 1 diabetes, those who checked blood sugar more often had lower HbA1c. | Cross-sectional; reverse causation and residual confounding possible | moderate | C-DIAB-02 |
| I-DIAB-111 | Glucose Self-monitoring in Non-Insulin-Treated Patients With Type 2 Diabetes in Primary Care Settings: A Randomized Trial. Young LA et al. | 2017 | PMID 28600913 DOI 10.1001/jamainternmed.2017.1233 | Randomised controlled trial | Adults >30 with non-insulin-treated T2D, HbA1c 6.5-9.5% | For people with type 2 diabetes not using insulin, daily self-testing did not improve HbA1c or quality of life over one year. | Moderate HbA1c range only; 1 year | high | C-DIAB-02 |
| I-DIAB-112 | Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. Emdin CA et al. | 2015 | PMID 25668264 DOI 10.1001/jama.2014.18574 | Meta-analysis | Participants with diabetes in BP-lowering RCTs | In 40 trials with 100,354 people, each 10 mmHg lower systolic pressure reduced deaths by 13% and strokes by 27%. | Fixed-effects model; Search to 2014 | high | C-DIAB-02 |
| I-DIAB-113 | 8. Obesity and Weight Management for the Prevention and Treatment of Diabetes: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes | 2026 | PMID 41358882 DOI 10.2337/dc26-S008 | Guideline / position statement | People with T2D and overweight/obesity | Losing more than 10% of body weight can lead to remission of type 2 diabetes and reduce the need for insulin. | Consensus elements; partly expert opinion | high | C-DIAB-03 C-BAR-08 C-BAR-01 |
| I-DIAB-114 | 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes | 2026 | PMID 41358899 DOI 10.2337/dc26-S010 | Guideline / position statement | People with diabetes | Blood pressure should be measured at every visit, and people with diabetes and hypertension should check it at home. | Consensus elements; partly expert opinion | high | C-DIAB-02 |
| I-DIAB-115 | NICE guideline NG28: Type 2 diabetes in adults: management National Institute for Health and Care Excellence (NICE) | 2015 | Guideline / position statement | Adults with T2D | Low-energy diet remission programmes are part of standard UK care for type 2 diabetes. | Consensus elements; partly expert opinion | high | C-INS-11 | |
| I-DRY-01 | Associations of dairy intake with risk of mortality in women and men: three prospective cohort studies. Ding M et al. | 2019 | PMID 31776125 DOI 10.1136/bmj.l6204 | Cohort study | 168,153 women (NHS 74,805; NHS II 93,348) and 49,602 men (HPFS), US health professionals (~95% European ancestry), free of CVD and cancer at baseline (1984 NHS, 1989 NHS II, 1986 HPFS) | Only the highest intake (about 4.2 servings/day) showed 7% higher mortality. | Observational; residual confounding acknowledged (whole milk may mark unhealthy lifestyle); Mostly white US health professionals; limited generalisability | high | C-DRY-03 C-DRY-04 |
| I-DRY-02 | Milk and dairy consumption and risk of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies. Guo J et al. | 2017 | PMID 28374228 DOI 10.1007/s10654-017-0243-1 | Meta-analysis | 938,465 participants in 29 cohorts | No association for milk or total dairy; fermented dairy slightly inverse. | Dairy-industry funding/COI declared by several authors; High heterogeneity (I2 up to 94%) | moderate | C-DRY-03 |
| I-DRY-03 | Dairy product consumption and risk of hip fracture: a systematic review and meta-analysis. Bian S et al. | 2018 | PMID 29357845 DOI 10.1186/s12889-018-5041-5 | Meta-analysis | Adults in cohort and case-control studies | Yogurt RR 0.75 and cheese RR 0.68 in 3 cohort studies each; milk RR 0.91 (not significant), though the cohort dose curve rose up to about 600 g/day. | Yogurt and cheese estimates rest on only 3 cohort studies each, cream on 1; no subgroup or heterogeneity analysis possible for them; High heterogeneity for milk (I2 75-87%) | moderate | C-DRY-03 C-DRY-11 |
| I-DRY-04 | Milk A1 β-casein and health-related outcomes in humans: a systematic review. Küllenberg de Gaudry D et al. | 2019 | PMID 30722004 DOI 10.1093/nutrit/nuy063 | Systematic review | Humans in 15 RCTs, 2 case-control, 8 ecological studies | Moderate certainty for digestive symptoms; low/very low for other outcomes. | Few, small, often industry-funded primary trials; Ecological data weak | high | C-DRY-07 C-DRY-10 |
| I-DRY-05 | Systematic Review of the Gastrointestinal Effects of A1 Compared with A2 β-Casein. Brooke-Taylor S et al. | 2017 | PMID 28916574 DOI 10.3945/an.116.013953 | Systematic review | Rodents and humans (39 studies) | Human evidence limited to a few studies. | Authors consulted for / received support from A2 companies; Mainly animal data | low | C-DRY-07 |
| I-DRY-06 | A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk. Travis RC et al. | 2016 | PMID 26921328 DOI 10.1158/0008-5472.CAN-15-1551 | Meta-analysis | Men in 19 studies | Top vs bottom fifth: OR 1.29. | Does not address diet; Observational | high | C-DRY-04 C-DRY-06 |
| I-DRY-07 | Dairy foods intake and risk of Parkinson's disease: a dose-response meta-analysis of prospective cohort studies. Jiang W et al. | 2014 | PMID 24894826 DOI 10.1007/s10654-014-9921-4 | Meta-analysis | 304,193 subjects; 1,083 PD cases | Absolute risk: 2-4 extra cases per 100,000 person-years per 200 g milk a day. | Few studies; Observational | moderate | C-DRY-09 C-DRY-11 |
| I-DRY-08 | Dairy intake and acne development: A meta-analysis of observational studies. Aghasi M et al. | 2019 | PMID 29778512 DOI 10.1016/j.clnu.2018.04.015 | Meta-analysis | Observational study participants | Total milk OR 1.48. | Observational, heterogeneous; Sample sizes not in abstract | moderate | C-DRY-08 C-DRY-11 |
| I-DRY-09 | Dairy Intake and Acne Vulgaris: A Systematic Review and Meta-Analysis of 78,529 Children, Adolescents, and Young Adults. Juhl CR et al. | 2018 | PMID 30096883 DOI 10.3390/nu10081049 | Meta-analysis | Children, adolescents, young adults | Any dairy OR 1.25; cheese 1.22; yogurt 1.36. | Publication bias; Unadjusted estimates | moderate | C-DRY-08 |
| I-DRY-10 | Dairy consumption and risk of type 2 diabetes: 3 cohorts of US adults and an updated meta-analysis. Chen M et al. | 2014 | PMID 25420418 DOI 10.1186/s12916-014-0215-1 | Cohort study | US men (HPFS) and women (NHS, NHS II) | Each daily serving of yogurt: about 18% lower risk of type 2 diabetes in the meta-analysis. | Observational; residual confounding acknowledged, especially for yogurt (marker of healthy lifestyle); Health professionals of mainly European ancestry (91-99% white); limited generalisability | high | C-DRY-11 |
| I-DRY-101 | Dietary Guidelines for Americans, 2025-2030 U.S. Department of Agriculture; U.S. Department of Health and Human Services | 2026 | Guideline / position statement | US general population incl. infants, children, adolescents, pregnant and lactating women, older adults | Three servings of dairy a day, including milk and yogurt, for children and adults; olive oil first, butter as an option, saturated fat at most 10% of calories. | Policy document; the evidence review behind it was not read; Departs from earlier US guidance on full-fat dairy and animal fats; scientific basis contested (not assessed here) | moderate | C-DRY-01 C-DRY-11 C-FAT-01 C-FAT-03 | |
| I-DRY-102 | Meat, fish and dairy products and the risk of cancer (Continuous Update Project Expert Report 2018) World Cancer Research Fund / American Institute for Cancer Research | 2018 | Guideline / position statement | Prospective cohort studies worldwide | 13% lower colorectal cancer risk per 400 g dairy a day; evidence for higher prostate cancer risk judged limited. | Observational data; 2018 cut-off | high | C-DRY-04 | |
| I-DRY-103 | The Effects of Dairy Product Supplementation on Bone Health Indices in Children Aged 3 to 18 Years: A Meta-Analysis of Randomized Controlled Trials. Hidayat K et al. | 2023 | PMID 37414219 DOI 10.1016/j.advnut.2023.06.010 | Meta-analysis | Children and adolescents 3-18 y | In 21 trials, children given extra dairy gained about 2-4% more bone mineral and grew slightly taller. | Dairy-industry-employed co-authors; Surrogate outcomes (BMC), not fractures | moderate | C-DRY-01 C-DRY-11 C-DRY-06 |
| I-DRY-104 | A Systematic Review on the Impact of Plant-Based Milk Consumption on Growth and Nutrition in Children and Adolescents. Soczynska I et al. | 2024 | PMID 39332772 DOI 10.1016/j.tjnut.2024.09.010 | Systematic review | Children 1-18 y | Six small studies; fortified soy milk may be an adequate alternative for bone. | Only 6 studies, mostly observational; Confounding likely | low | C-DRY-01 |
| I-DRY-105 | Effect of dietary sources of calcium and protein on hip fractures and falls in older adults in residential care: cluster randomised controlled trial. Iuliano S et al. | 2021 | PMID 34670754 DOI 10.1136/bmj.n2364 | Randomised controlled trial | Permanent residents of Australian aged-care facilities, mean age 86, 68% women, vitamin D replete, low calcium/protein intake | Hip fractures 42 v 93 (HR 0.54) over two years; deaths not different. | Dairy-industry funding; Cluster design with few clusters per arm | moderate | C-DRY-03 |
| I-DRY-106 | Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study. Dehghan M et al. | 2018 | PMID 30217460 DOI 10.1016/S0140-6736(18)31812-9 | Cohort study | Adults 35-70 y in 21 countries (high-, middle- and low-income) | More than 2 servings/day: 17% lower mortality, 34% lower stroke risk than no dairy. | Single baseline FFQ; Residual confounding (dairy intake marks affluence in poorer countries) | moderate | C-DRY-03 C-DRY-02 |
| I-DRY-107 | The dose-response relationship between dairy product intake and all-cause and cardiovascular mortality risk: a systematic review and meta-analysis of prospective cohort studies. Hu X et al. | 2026 | PMID 41660415 DOI 10.3389/fnut.2026.1731841 | Meta-analysis | Healthy adults in prospective cohorts | 200 g yogurt/day: 11% lower all-cause mortality; total dairy U-shaped (optimum ~250-300 g/day). | Overlaps with earlier meta-analyses (e.g. I-DRY-02); Observational | moderate | C-DRY-03 C-DRY-11 |
| I-DRY-108 | Dairy foods, calcium intakes, and risk of incident prostate cancer in Adventist Health Study-2. Orlich MJ et al. | 2022 | PMID 35672028 DOI 10.1093/ajcn/nqac093 | Cohort study | Seventh-day Adventist men, USA and Canada (6389 Black men) | About 27% higher risk at 430 g/day v 20 g/day; also for advanced cancer. | Observational; Health-conscious population | moderate | C-DRY-04 |
| I-DRY-109 | Genetically proxied milk consumption and risk of colorectal, bladder, breast, and prostate cancer: a two-sample Mendelian randomization study. Larsson SC et al. | 2020 | PMID 33261611 DOI 10.1186/s12916-020-01839-9 | Other | UK Biobank, FinnGen, BCAC, PRACTICAL (European ancestry) | Prostate OR 1.01 (0.99-1.02) per milk allele; colorectal 0.95. | Single-variant instrument; effect per allele, not per glass; Pleiotropy cannot be fully excluded | moderate | C-DRY-04 C-DRY-06 |
| I-DRY-11 | Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies. Aune D et al. | 2012 | PMID 21617020 DOI 10.1093/annonc/mdr269 | Meta-analysis | Adults in 19 cohorts | Total dairy RR 0.83 per 400 g/day. | Observational | high | C-DRY-04 |
| I-DRY-110 | Circulating insulin-like growth factor-I, total and free testosterone concentrations and prostate cancer risk in 200 000 men in UK Biobank. Watts EL et al. | 2021 | PMID 33252839 DOI 10.1002/ijc.33416 | Cohort study | Men in UK Biobank; PRACTICAL consortium | Per 5 nmol/L IGF-I: 9% higher diagnosis risk; genetic analysis OR 1.34. | Does not examine diet; MR instrument assumptions | high | C-DRY-06 |
| I-DRY-111 | Effects of dairy products, calcium and vitamin D on ovarian cancer risk: a meta-analysis of twenty-nine epidemiological studies. Liao MQ et al. | 2020 | PMID 32189606 DOI 10.1017/S0007114520001075 | Meta-analysis | Women in 29 studies | Whole milk linked to higher risk (RR 1.35), low-fat milk and cheese to lower risk. | Mixes case-control (recall bias) and cohort; Opposite directions for similar foods suggest confounding | low | C-DRY-05 |
| I-DRY-112 | Dairy Intake and Parkinson's Disease: A Mendelian Randomization Study. Domenighetti C et al. | 2022 | PMID 34997937 DOI 10.1002/mds.28902 | Other | 23 studies of European ancestry | OR 1.70 per daily serving; 2.50 in men. | Single variant; Effect restricted to men | moderate | C-DRY-09 |
| I-DRY-113 | Dairy and Milk Intake and Risk for Parkinson's Disease in Women and Men: A Systematic Review and Meta-Analysis. Warz SI et al. | 2026 | PMID 41792943 DOI 10.1002/mdc3.70575 | Meta-analysis | 8 cohorts, 7 countries | Men HR 1.28; women 1.02. | Few cohorts; Overlaps with I-DRY-07 | moderate | C-DRY-09 |
| I-DRY-114 | Comparative effects of conventional cow's milk versus milk free of A1-type beta-casein on gastrointestinal physiology and symptoms of digestive discomfort in participants intolerant to conventional cow's milk: a pilot randomised controlled trial. Greenway FL et al. | 2026 | PMID 41634798 DOI 10.1186/s12937-026-01288-9 | Randomised controlled trial | Non-regular milk drinkers aged 18-68 with self-reported cow's milk intolerance (USA) | No differences in symptoms, gut transit or immune markers. | Pilot, no power calculation; Self-reported intolerance | moderate | C-DRY-07 |
| I-DRY-115 | Tolerance of protein-hydrolyzed lactose-free A1 milk and A2 milk in lactose-tolerant and lactose-intolerant volunteers: A randomized crossover trial with 2 parallel groups. Mannila E et al. | 2025 | PMID 40614809 DOI 10.3168/jds.2025-26712 | Randomised controlled trial | Self-reported milk-sensitive volunteers | No difference between A2 and A1 milk in lactose-tolerant people; no rise in inflammation markers. | Very short (3 days); Small | moderate | C-DRY-07 C-DRY-02 |
| I-DRY-116 | Comparison of the impact of bovine milk beta-casein variants on digestive comfort in females self-reporting dairy intolerance: a randomized controlled trial. Milan AM et al. | 2020 | PMID 31773165 DOI 10.1093/ajcn/nqz279 | Randomised controlled trial | Women 25 y with varying self-reported dairy tolerance (New Zealand) | Fewer symptoms with A2 milk in 10 lactose-intolerant women; no difference in others. | Single meals; Very small subgroups | moderate | C-DRY-07 |
| I-DRY-117 | Effects of fermented dairy products on inflammatory biomarkers: A meta-analysis. Zhang X et al. | 2023 | PMID 36710113 DOI 10.1016/j.numecd.2022.12.014 | Meta-analysis | Adults in trials | CRP slightly lower (SMD -0.21) across 14 trials. | Small number of trials; Surrogate markers | moderate | C-DRY-02 C-DRY-10 |
| I-DRY-118 | Assessment of some chemical residues in Egyptian raw milk and traditional cheese. Ibrahim AA et al. | 2024 | PMID 38549581 DOI 10.5455/OVJ.2024.v14.i2.4 | Measurement / residue study | Market samples | No raw milk sample exceeded pesticide limits; 7% exceeded the aflatoxin M1 limit; some Ras and Domiati cheeses exceeded pesticide limits. | Single season, four governorates; Heavy-metal units/figures inconsistent | low | C-DRY-01 C-DRY-11 |
| I-DRY-119 | Tolerance to extensively heated milk in children with cow's milk allergy. Nowak-Wegrzyn A et al. | 2008 | PMID 18620743 DOI 10.1016/j.jaci.2008.05.043 | Case series / case report | Children with cow's milk allergy (mean age 7.5 y) | 75% of reactive children tolerated extensively heated milk. | No control group; Baked milk (e.g. in muffins) differs from cheese | moderate | C-DRY-10 |
| I-DRY-12 | Milk consumption and multiple health outcomes: umbrella review of systematic reviews and meta-analyses in humans. Zhang X et al. | 2021 | PMID 33413488 DOI 10.1186/s12986-020-00527-y | Systematic review | Humans in included meta-analyses | Milk was linked more often to benefits (heart, stroke, bowel cancer, diabetes, bones) than to harms (prostate cancer, Parkinson's, acne); most evidence was rated low certainty. | No registered protocol reported; English-language only; screening process by two reviewers not clearly described; list of excluded studies not given; Only one (newest/largest) meta-analysis per outcome selected; overlap of primary studies between meta-analyses not assessed | low | C-DRY-01 C-DRY-03 C-DRY-04 C-DRY-11 |
| I-DRY-120 | Food Consumption and Risk of Islet Autoimmunity and Type 1 Diabetes in Children at Increased Genetic Susceptibility for Type 1 Diabetes. Virtanen SM et al. | 2024 | PMID 39313195 DOI 10.1016/j.tjnut.2024.09.018 | Cohort study | Finnish children with HLA-conferred susceptibility, born 1996-2004 | Fermented dairy linked to one autoimmunity marker; not in the final type 1 diabetes model. | Many foods tested (multiplicity); Genetically selected population | moderate | C-DRY-12 |
| I-DRY-121 | Meat, fish, dairy products and risk of hematological malignancies in adults - a systematic review and meta-analysis of prospective studies. Sergentanis TN et al. | 2019 | PMID 30912696 DOI 10.1080/10428194.2018.1563693 | Meta-analysis | Adults in cohort studies | No association with non-Hodgkin lymphoma in 13 cohorts. | Numbers not in abstract; Abstract only | moderate | C-DRY-12 |
| I-DRY-122 | Milk and dairy products - a scoping review for Nordic Nutrition Recommendations 2023. Bjorklund Holven K et al. | 2024 | PMID 39781268 DOI 10.29219/fnr.v68.10486 | Systematic review | Adults and children | No increased heart disease risk; lower bowel cancer; limited prostate signal. | Scoping (not graded); Literature to 2022 | moderate | C-DRY-02 |
| I-DRY-123 | Dairy and alternatives in your diet (NHS) NHS (England) | 2026 | Guideline / position statement | General population, pregnant women, children | Milk, cheese and yogurt provide calcium needed for the baby's bones; pasteurised products only in pregnancy. | Consumer guidance; evidence base not cited on page | moderate | C-DRY-11 | |
| I-DRY-124 | Cheese consumption and multiple health outcomes: an umbrella review and updated meta-analysis of prospective studies. Zhang M et al. | 2023 | PMID 37328108 DOI 10.1016/j.advnut.2023.06.007 | Systematic review | Prospective cohorts | About 5-8% lower mortality and CVD in high cheese eaters. | Observational; Possible healthy-user effects | moderate | C-DRY-11 |
| I-DRY-125 | Inflammatory Cytokine Responses to 6 Wks of Increased Dairy Intake in Individuals with Overweight and Obesity-A Randomized Crossover Trial. Prowting JL et al. | 2026 | PMID 41176279 DOI 10.1016/j.tjnut.2025.10.040 | Randomised controlled trial | Adults with overweight/obesity and cardiometabolic risk factors (Canada) | IL-6 unchanged; TNF-alpha down; men showed some opposite changes. | Small, short; Dairy-industry links | moderate | C-DRY-02 |
| I-DRY-126 | Estimation and Human Health Risk Assessment of Organochlorine Pesticides in Raw Milk Marketed in Zagazig City, Egypt. Raslan AA et al. | 2018 | PMID 30158973 DOI 10.1155/2018/3821797 | Risk assessment | Raw milk marketed in Zagazig (Sharkia, Egypt) | 50-75% of samples contaminated, mostly within limits; 10% of goat milk exceeded limits. | Single city; sample size not in abstract; Reported means appear high relative to 'within limits' (units/lipid basis unclear) | low | C-DRY-01 |
| I-DRY-13 | Lactose Residual Content in PDO Cheeses: Novel Inclusions for Consumers with Lactose Intolerance. Facioni MS et al. | 2021 | PMID 34574346 DOI 10.3390/foods10092236 | Measurement / residue study | 25 PDO soft, semi-hard and hard cheeses bought in Italian supermarkets (incl. Cheddar, Brie, Emmentaler, Le Gruyere); Mozzarella di Bufala Campana PDO as positive control. Survey: 1,398 lactose-intolerant consumers (91.2% female, mean age 35) recruited via the AILI patients' association on Facebook; 57 nutrition professionals. | All but one of 25 PDO cheeses (even some aged only 20-35 days) had lactose below 10 mg/kg; fresh mozzarella had about 3,500 mg/kg. | Industry funding and authors' financial interest in lactose-free certification; conclusions promote the authors' trademark; Fresh cheeses, yogurt, processed cheese and Egyptian products (romi, processed triangles) not analysed | moderate | C-DRY-10 C-DRY-11 |
| I-DRY-14 | Nutritional management of lactose intolerance: the importance of diet and food labelling. Facioni MS et al. | 2020 | PMID 32590986 DOI 10.1186/s12967-020-02429-2 | Narrative review | Lactose-intolerant people | Most adults worldwide produce less lactase, but most lactose-intolerant people tolerate small amounts of lactose and usually yogurt; avoiding all dairy may harm bones. | Narrative review without search strategy, selection criteria or quality appraisal; Funded by and partly authored by a lactose-free certification company; promotes its own trademark (Lfree) | low | C-DRY-02 C-DRY-10 C-DRY-11 |
| I-DRY-15 | Cheese consumption and risk of cardiovascular disease: a meta-analysis of prospective studies. Chen GC et al. | 2017 | PMID 27517544 DOI 10.1007/s00394-016-1292-z | Meta-analysis | Adults in 15 prospective studies | High vs low cheese: CVD RR 0.90. | Observational; Erratum published | moderate | C-DRY-11 |
| I-DRY-16 | The prevalence of aflatoxin M1 in milk of Middle East region: A systematic review, meta-analysis and probabilistic health risk assessment. Rahmani J et al. | 2018 | PMID 29902498 DOI 10.1016/j.fct.2018.06.016 | Risk assessment | Milk samples from Middle-East countries | Egyptian raw milk: 38% of samples positive; estimated hazard index 0.84 for children. | Heterogeneous sampling; Hazard-index approach for a genotoxic carcinogen is debatable | moderate | C-DRY-01 |
| I-DRY-17 | Hormones in Dairy Foods and Their Impact on Public Health - A Narrative Review Article. Malekinejad H et al. | 2015 | PMID 26258087 | Narrative review | n/a | Milk contains small amounts of hormones (more in butter and cream than in milk); the authors raise a cancer concern but provide no new human outcome data. | Narrative, non-systematic; no selection or appraisal of evidence; Abstract conclusion ('important risk factor for various cancers') is stronger than the body text, which calls the cancer evidence 'very controversial' and notes low bioavailability for several hormones | very low | C-DRY-01 C-DRY-11 |
| I-DRY-18 | Effects of dairy products consumption on inflammatory biomarkers among adults: A systematic review and meta-analysis of randomized controlled trials. Moosavian SP et al. | 2020 | PMID 32409275 DOI 10.1016/j.numecd.2020.01.011 | Meta-analysis | 663 participants in 11 RCTs | CRP slightly lower (-0.24 mg/L) with more dairy; no effect in cross-over trials. | Small trials, short duration; Surrogate markers | moderate | C-DRY-02 |
| I-DRY-19 | Dairy products and inflammation: A review of the clinical evidence. Bordoni A et al. | 2017 | PMID 26287637 DOI 10.1080/10408398.2014.967385 | Systematic review | Participants of 52 trials | Overall anti-inflammatory score; pro-inflammatory only in allergic people. | Ad hoc scoring method; Heterogeneous trials | moderate | C-DRY-02 C-DRY-10 |
| I-EGG-01 | Egg consumption and risk of cardiovascular disease: three large prospective US cohort studies, systematic review, and updated meta-analysis. Drouin-Chartier JP et al. | 2020 | PMID 32132002 DOI 10.1136/bmj.m513 | Meta-analysis | US women and men free of CVD, diabetes and cancer; meta-analysis of global cohorts | Eating up to one egg a day was not linked to heart disease or stroke. | Observational data; higher egg eaters were less healthy (higher BMI, more red meat, more T2D), so residual confounding possible; Health-professional cohorts may limit generalisability | high | C-EGG-02 C-EGG-04 C-EGG-05 C-EGG-11 |
| I-EGG-02 | Association of egg intake with blood lipids, cardiovascular disease, and mortality in 177,000 people in 50 countries. Dehghan M et al. | 2020 | PMID 31965140 DOI 10.1093/ajcn/nqz348 | Cohort study | PURE general population (21 countries) and patients with vascular disease (ONTARGET/TRANSCEND) | Eating an egg a day was not linked to cholesterol levels, heart disease or death. | Single FFQ; Few very high consumers | high | C-EGG-02 C-EGG-04 C-EGG-05 C-EGG-11 |
| I-EGG-03 | Associations of egg consumption with cardiovascular disease in a cohort study of 0.5 million Chinese adults. Qin C et al. | 2018 | PMID 29785957 DOI 10.1136/heartjnl-2017-312651 | Cohort study | Adults 30-79 from 10 regions, free of cancer, CVD, diabetes | Daily egg eaters had a lower risk of heart disease and stroke. | Low intake range; Reverse causation possible | high | C-EGG-04 |
| I-EGG-04 | Egg consumption and cardiovascular risk: a dose-response meta-analysis of prospective cohort studies. Godos J et al. | 2021 | PMID 32865658 DOI 10.1007/s00394-020-02345-7 | Meta-analysis | 39 studies, ~2 million individuals | Moderate egg intake was not linked to more heart disease; a possible higher heart failure risk at 1+ egg/day. | Overlap with other meta-analyses; Low certainty | moderate | C-EGG-04 |
| I-EGG-05 | Egg Consumption and Risk of All-Cause and Cause-Specific Mortality: A Systematic Review and Dose-Response Meta-analysis of Prospective Studies. Mousavi SM et al. | 2022 | PMID 35396834 DOI 10.1093/advances/nmac040 | Meta-analysis | General population | Egg intake was not linked to overall or heart deaths; a small link with cancer deaths was found. | Overlap with other meta-analyses; Heterogeneity | moderate | C-EGG-02 C-EGG-04 C-EGG-11 |
| I-EGG-06 | Dietary Cholesterol and Cardiovascular Risk: A Science Advisory From the American Heart Association. Carson JAS et al. | 2020 | PMID 31838890 DOI 10.1161/CIR.0000000000000743 | Guideline / position statement | General population | Studies do not show a clear link between dietary cholesterol and heart disease, but high intakes can raise LDL; focus on overall diet. | Not a formal systematic review | moderate | C-EGG-04 C-EGG-11 C-SRC-05 |
| I-EGG-07 | Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol. Vincent MJ et al. | 2019 | PMID 30596814 DOI 10.1093/ajcn/nqy273 | Meta-analysis | Trial participants | More dietary cholesterol modestly raises LDL cholesterol. | Surrogate endpoint | moderate | C-EGG-04 |
| I-EGG-08 | Egg consumption and risk of type 2 diabetes: findings from 3 large US cohort studies of men and women and a systematic review and meta-analysis of prospective cohort studies. Drouin-Chartier JP et al. | 2020 | PMID 32453379 DOI 10.1093/ajcn/nqaa115 | Meta-analysis | US cohorts; global cohorts | No overall link; higher risk only in US studies. | Heterogeneity | high | C-EGG-07 |
| I-EGG-09 | Egg intake and cancers of the breast, ovary and prostate: a dose-response meta-analysis of prospective observational studies. Keum N et al. | 2015 | PMID 26293984 DOI 10.1017/S0007114515002135 | Meta-analysis | Participants of prospective cohorts, nested case-control/case-cohort and pooled cohort studies (North America, Europe, Asia) | A possible link with fatal prostate cancer, but small studies may exaggerate it; no link with prostate cancer overall. | Fatal prostate estimate based on only 4 studies and 609 cases, with small-study effects (P Egger 0.04); Fatal prostate association loses significance under the alternative serving-size assumption (RR 1.23, 0.97-1.55) | low | C-EGG-06 |
| I-EGG-10 | Dietary Choline Supplements, but Not Eggs, Raise Fasting TMAO Levels in Participants with Normal Renal Function: A Randomized Clinical Trial. Wilcox J et al. | 2021 | PMID 33872583 DOI 10.1016/j.amjmed.2021.03.016 | Randomised controlled trial | Healthy volunteers from the Cleveland, Ohio area with normal renal function (median age 28.0 [IQR 24.0-38.8]; 41.5% male; 81.7% Caucasian; median BMI 26.9) | Eating four eggs a day for four weeks did not raise fasting TMAO; choline pills did. | Small arms (10-20); no power calculation; non-significance for eggs (P=0.20) does not exclude a small rise; Fifth (PC) arm enrolled later, i.e. not concurrently randomised | moderate | C-EGG-05 |
| I-EGG-101 | Timing of Allergenic Food Introduction and Risk of Immunoglobulin E-Mediated Food Allergy: A Systematic Review and Meta-analysis. Scarpone R et al. | 2023 | PMID 36972063 DOI 10.1001/jamapediatrics.2023.0142 | Meta-analysis | Infants in 23 trials (13,794 randomized participants); egg analysis: 9 trials, 4,811 participants | In 9 trials, babies who were given egg from 3-6 months were 40% less likely to develop egg allergy (RR 0.60). | Trials mostly from high-income settings; Adherence and withdrawal problems in multi-food interventions | high | C-EGG-11 C-EGG-02 |
| I-EGG-102 | EAACI guideline: Preventing the development of food allergy in infants and young children (2020 update). Halken S et al. | 2021 | PMID 33710678 DOI 10.1111/pai.13496 | Guideline / position statement | Infants (up to 1 year) and young children (up to 5 years), regardless of allergy risk | The EAACI guideline suggests introducing well-cooked egg during complementary feeding and advises against avoiding allergenic foods in pregnancy. | Moderate certainty; mostly trials from high-income countries | high | C-EGG-11 |
| I-EGG-103 | WHO Guideline for complementary feeding of infants and young children 6-23 months of age World Health Organization | 2023 | Guideline / position statement | Infants and young children 6-23 months in low-, middle- and high-income countries | WHO recommends daily animal-source foods such as meat, fish or eggs for children aged 6-23 months. | Low or very low certainty for most outcomes; Only relevant sections (Recommendation 4, evidence summary on animal source foods, certainty, allergy remarks) were read, not the full 96-page document | high | C-EGG-11 C-MEAT-03 | |
| I-EGG-104 | Maternal dietary antigen avoidance during pregnancy or lactation, or both, for preventing or treating atopic disease in the child. Kramer MS, Kakuma R | 2012 | PMID 22972039 DOI 10.1002/14651858.CD000133.pub3 | Systematic review | Pregnant or lactating women, mostly at high risk of atopic offspring | Trials found no protection against eczema and a slightly lower weight gain in pregnancy. | Few and small trials; old evidence; Not specific to egg alone | high | C-EGG-11 |
| I-EGG-105 | Eggs in Early Complementary Feeding and Child Growth: A Randomized Controlled Trial. Iannotti LL et al. | 2017 | PMID 28588101 DOI 10.1542/peds.2016-3459 | Randomised controlled trial | Children aged 6-9 months, Cotopaxi Province, Ecuador | Babies given an egg daily for 6 months had less stunting (PR 0.53) and no reported allergic reactions. | Not blinded; small sample; Single region; larger effect than the later Malawi trial | moderate | C-EGG-02 |
| I-EGG-106 | The effect of eggs on early child growth in rural Malawi: the Mazira Project randomized controlled trial. Stewart CP et al. | 2019 | PMID 31386106 DOI 10.1093/ajcn/nqz163 | Randomised controlled trial | Children aged 6-9 months, rural Malawi | No overall effect on length or weight after 6 months. | Low baseline stunting; Adherence declined | high | C-EGG-02 |
| I-EGG-107 | Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches. Mitchell N et al. | 2011 | PMID 21835022 DOI 10.1186/1475-2891-10-85 | Randomised controlled trial | UK community volunteers with migraine-like headaches and at least one IgG-detected food 'intolerance' | No significant difference at 12 weeks; small effect at 4 weeks. | IgG food testing is not a validated diagnostic method for food allergy; Individual foods eliminated varied; eggs not analysed separately | moderate | C-EGG-01 |
| I-EGG-108 | The Interconnection Between Systemic Lupus Erythematosus and Diet: Unmet Needs, Available Evidence, and Guidance-A Patient-Driven, Multistep-Approach Study. Sciascia S et al. | 2024 | PMID 39683527 DOI 10.3390/nu16234132 | Systematic review | People with SLE at an Italian referral centre (surveys); published systematic reviews | A review of 28 systematic reviews found no consistent evidence that a specific diet reduces lupus activity. | Single-database (PubMed) search; Overview level, no new meta-analysis | moderate | C-EGG-03 |
| I-EGG-109 | Associations of Dietary Cholesterol, Serum Cholesterol, and Egg Consumption With Overall and Cause-Specific Mortality: Systematic Review and Updated Meta-Analysis. Zhao B et al. | 2022 | PMID 35360933 DOI 10.1161/CIRCULATIONAHA.121.057642 | Meta-analysis | ATBC: 27,078 Finnish male smokers aged 50-69; meta-analysis: 49 risk estimates, 3,601,401 participants | Each extra egg per day: 4% higher CVD risk overall (RR 1.04), 8% in US studies, none in Asian studies. | Cohort limited to male smokers; High heterogeneity (I2 80%) | moderate | C-EGG-04 |
| I-EGG-11 | Prevalence estimates of eight big food allergies in Europe: Updated systematic review and meta-analysis. Spolidoro GCI et al. | 2023 | PMID 37405695 DOI 10.1111/all.15801 | Meta-analysis | European populations, all ages | Confirmed egg allergy affects about 0.8% of people; 2.4% believe they have it. | Most studies moderate risk of bias | high | C-EGG-01 C-SRC-05 |
| I-EGG-110 | Association Between Egg Consumption and Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. Krittanawong C et al. | 2021 | PMID 32653422 DOI 10.1016/j.amjmed.2020.05.046 | Meta-analysis | 23 prospective studies, 1,415,839 individuals | HR 0.99 (0.93-1.06) for cardiovascular events in 1.4 million people. | Comparator category includes 1 egg/day; crude high vs low comparison; Overlaps with other meta-analyses | moderate | C-EGG-04 |
| I-EGG-111 | Egg consumption and risk of cardiovascular events among Iranians: results from Isfahan Cohort Study (ICS). Mohammadifard N et al. | 2022 | PMID 35347253 DOI 10.1038/s41430-022-01118-1 | Cohort study | 6,504 adults aged >=35 years without CVD at baseline, Isfahan, Iran | Eating eggs 3+ times a week was not linked to heart attacks, strokes or CVD over 12 years. | Moderate size; wide CIs; Highest category only >=3/week | moderate | C-EGG-04 |
| I-EGG-112 | Association of Egg Consumption with Risk of All-Cause and Cardiovascular Disease Mortality: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies. Ma W et al. | 2022 | PMID 35524693 DOI 10.1093/jn/nxac105 | Meta-analysis | 24 articles, 48 reports, 11,890,695 participants | Each extra egg per day was linked to 6% higher all-cause mortality, but only in some subgroups. | Subgroup-driven associations (multiplicity); Overlaps with Mousavi 2022 (I-EGG-05) and Zhao 2022 | moderate | C-EGG-04 |
| I-EGG-113 | Effect of egg consumption on circulating choline, betaine, and trimethylamine n-oxide in adults: a systematic review and meta-analysis of randomized controlled trials. Aryaeian N et al. | 2025 | PMID 41146117 DOI 10.1186/s12937-025-01227-0 | Meta-analysis | Adults in 6 RCTs (5 for TMAO) | Pooled trials found no change in TMAO after egg consumption (WMD -0.08 umol/L). | Few, small, short trials | moderate | C-EGG-05 |
| I-EGG-114 | Gut microbe-generated metabolite trimethylamine-N-oxide as cardiovascular risk biomarker: a systematic review and dose-response meta-analysis. Schiattarella GG et al. | 2017 | PMID 29020409 DOI 10.1093/eurheartj/ehx342 | Meta-analysis | 17 clinical studies, 26,167 subjects | People with high TMAO had more cardiovascular events (HR 1.67) and deaths (HR 1.91). | Very high heterogeneity for mortality; Mostly patient cohorts; confounding by kidney function | moderate | C-EGG-05 |
| I-EGG-115 | Assessment of Causal Direction Between Gut Microbiota-Dependent Metabolites and Cardiometabolic Health: A Bidirectional Mendelian Randomization Analysis. Jia J et al. | 2019 | PMID 31167879 DOI 10.2337/db19-0153 | Other | GWAS summary data (European-ancestry consortia; details not in abstract) | Genetically higher TMAO was not linked to heart attack or stroke; kidney disease raised TMAO. | Weak instruments for metabolites possible; Power for some outcomes unclear | moderate | C-EGG-05 |
| I-EGG-116 | Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies. Wu K et al. | 2016 | PMID 26685908 DOI 10.1002/ijc.29973 | Cohort study | 842,149 men in 15 cohorts (North America, Europe, Japan, Australia) | Fatal prostate cancer RR 1.14 (1.00-1.30) for about 3.5+ eggs/week; no link outside North America. | Baseline diet only; Residual confounding | high | C-EGG-06 |
| I-EGG-117 | Postdiagnostic Red Meat, Poultry, and Egg Intake and Risk of Prostate Cancer Progression and Mortality: A Systematic Review. Sandhu S et al. | 2026 | PMID 42607142 DOI 10.1097/JU.0000000000005263 | Systematic review | Men with prostate cancer in 6 cohorts (>10,000 men) | Most studies found no link at around 2.5-3 eggs per week; one found a link at about 5.5 per week. | Few studies; no pooling; Postdiagnostic population differs from the claim (incidence of lethal cancer) | moderate | C-EGG-06 |
| I-EGG-118 | Egg consumption, overall diet quality, and risk of type 2 diabetes and coronary heart disease: A pooling project of US prospective cohorts. Djoussé L et al. | 2021 | PMID 33932789 DOI 10.1016/j.clnu.2021.03.003 | Cohort study | 103,811 adults in 9 US cohorts (median age 25-72 years) | Eating 7+ eggs a week was linked to 27% higher type 2 diabetes risk; under 2 eggs a week was not. | US only; Funding from American Egg Board (result nevertheless unfavourable to eggs) | high | C-EGG-07 |
| I-EGG-119 | Effect of a high-egg diet on cardiometabolic risk factors in people with type 2 diabetes: the Diabetes and Egg (DIABEGG) Study-randomized weight-loss and follow-up phase. Fuller NR et al. | 2018 | PMID 29741558 DOI 10.1093/ajcn/nqy048 | Randomised controlled trial | Adults with prediabetes or type 2 diabetes | Over 12 months, a high-egg diet had no adverse effect on glucose, HbA1c or lipids compared with a low-egg diet. | Small; surrogate outcomes; Background diet emphasised unsaturated fats | moderate | C-EGG-07 |
| I-EGG-12 | Dreams of the Rarebit Fiend: food and diet as instigators of bizarre and disturbing dreams. Nielsen T, Powell RA | 2015 | PMID 25741294 DOI 10.3389/fpsyg.2015.00047 | Cross-sectional study | Undergraduate students in first-year psychology courses at a Canadian university, receiving partial course credit; 130 males (mean age 21.6), 264 females (mean age 21.4), 2 unspecified | About one in six students thought food affected their dreams, mostly dairy. | Convenience sample of young psychology students receiving course credit; Self-reported, retrospective perceptions; in-house unvalidated dream and food items | low | C-EGG-01 C-CHK-02 |
| I-EGG-120 | Egg, cholesterol and protein intake and incident type 2 diabetes mellitus: Results of repeated measurements from a prospective cohort study. Yuan S et al. | 2021 | PMID 33593662 DOI 10.1016/j.clnu.2021.01.041 | Cohort study | Chinese adults (7,312 in 2004 wave) | People eating 3+ eggs a day reported diabetes more often (OR 3.76), but the study had few cases. | Few cases (209); Self-reported diabetes | low | C-EGG-07 |
| I-EGG-121 | Evaluation of Heavy Metal Content in Feed, Litter, Meat, Meat Products, Liver, and Table Eggs of Chickens. Korish MA, Attia YA | 2020 | PMID 32331361 DOI 10.3390/ani10040727 | Measurement / residue study | Commercial chicken products and table eggs (4 brands) in Saudi Arabia | Commercial table eggs had no detectable lead, cadmium or arsenic; chicken liver had the most metals. | Small sample; few brands; Detection limits not in abstract | low | C-EGG-08 C-MEAT-02 |
| I-EGG-122 | Risk assessment of lead and cadmium concentrations in hen's eggs using Monte Carlo simulations. Hoseini H et al. | 2023 | PMID 37324917 DOI 10.1002/fsn3.3268 | Risk assessment | Commercial hen eggs from 17 major brands, Iranian supermarkets | Lead and cadmium in eggs from 17 brands were below permitted levels; no health risk was estimated. | Small sample size; Single country | moderate | C-EGG-08 |
| I-EGG-123 | Risk Factors Associated With Salmonella in Laying Hen Farms: Systematic Review of Observational Studies. Denagamage T et al. | 2015 | PMID 26473681 DOI 10.1637/10997-120214-Reg | Systematic review | Commercial laying hen farms | Cage housing, large flocks, rodents and poor cleaning were linked to Salmonella on layer farms. | Observational, mostly cross-sectional; Cage effect confounded with flock size and age of systems | moderate | C-EGG-09 |
| I-EGG-124 | Occurrence, antimicrobial resistance, and whole-genome characterization of Salmonella in retail eggs in the United Arab Emirates: Evidence of a clonal dominance of serovar Braenderup. Habib I et al. | 2026 | PMID 41963064 DOI 10.1016/j.fm.2026.105092 | Cross-sectional study | 380 retail egg packs (4,560 eggs) from supermarkets in three UAE cities | 11.6% of cage-egg packs had Salmonella on the shell vs none of 60 cage-free packs; egg contents were clean. | Few cage-free packs (60); Shell, not contents, contamination | moderate | C-EGG-09 |
| I-EGG-125 | Evaluation of Biosecurity Measures and Microbiological Quality of Table Eggs in Egyptian Layer Farms. Hafez E et al. | 2025 | PMID 40232862 DOI 10.12834/VetIt.3466.29418.2 | Cross-sectional study | Seven Egyptian layer farms with different housing systems and biosecurity levels | Closed battery-cage farms with strong biosecurity had fewer bacteria on eggs than open deep-litter and backyard systems. | Very small (7 farms, 70 samples); Housing confounded with biosecurity | low | C-EGG-09 |
| I-EGG-126 | Antimicrobial Resistance of Salmonella enteritidis and Salmonella typhimurium Isolated from Laying Hens, Table Eggs, and Humans with Respect to Antimicrobial Activity of Biosynthesized Silver Nanoparticles. Abou Elez RMM et al. | 2021 | PMID 34944331 DOI 10.3390/ani11123554 | Cross-sectional study | Laying hen faecal swabs, retail table eggs and human stool samples, Sharkia Governorate | 3.6% of retail table egg contents in Sharkia carried Salmonella, often drug-resistant. | Single governorate; Housing system not compared | low | C-EGG-09 |
| I-EGG-127 | Monitoring antimicrobial residues in table eggs in Aswan governorate markets and their impact on egg quality and public health. Zakaria AM et al. | 2023 | PMID 37304600 DOI 10.5455/OVJ.2023.v13.i5.4 | Measurement / residue study | Brown table eggs from retail stores, Aswan governorate | 12% of conventional egg yolks tested positive in a screening test; organic eggs were all negative. | Disc diffusion is a qualitative screen: no concentrations, no MRL comparison, no exposure assessment; Single governorate | low | C-EGG-10 |
| I-EGG-128 | Dietary exposure to antimicrobial residues in eggs: Traceability-driven risk heterogeneity and national monitoring optimization in China. Wang Z et al. | 2026 | PMID 41833166 DOI 10.1016/j.jhazmat.2026.141724 | Risk assessment | China's poultry egg supply chain (11 antimicrobials) | 0.8-2.2% of eggs were contaminated; intakes were mostly below toxic thresholds, but one antibiotic exceeded the limit for resistance effects in some regions. | Modelling assumptions; China-specific | moderate | C-EGG-10 |
| I-EGG-129 | Risk factors associated with Salmonella prevalence, its antibiotic resistance, and egg antibiotic residues in the layer farming environment. Sornplang P et al. | 2022 | PMID 35497971 DOI 10.14202/vetworld.2022.543-550 | Cross-sectional study | One laying farm with battery-cage closed housing (country not stated in abstract) | On a single farm, streptomycin residues were found in 36% of egg yolks by screening test. | Single farm; Screening test (Four Plate Test), no concentrations | low | C-EGG-10 |
| I-EGG-13 | More dreams of the rarebit fiend: food sensitivity and dietary correlates of sleep and dreaming. Nielsen T et al. | 2025 | PMID 40667395 DOI 10.3389/fpsyg.2025.1544475 | Cross-sectional study | Undergraduate psychology students at MacEwan University, Canada (mean age 20.3 +/- 3.68, range 17-54; 721 women, 338 men, 23 other/undisclosed; 46.4% White, 22.2% Asian, 7.9% Black, 6.3% Arab); course credit (2% of final grade) | Only 5.5% of students thought food affected their dreams, mostly sweets and dairy; eggs were rarely named. People with food allergy or lactose intolerance reported more nightmares. | Student convenience sample with course credit; All exposures and outcomes self-reported; food sensitivities not clinically verified | low | C-EGG-01 C-CHK-02 |
| I-EGG-130 | Effect of egg consumption on health outcomes: An updated umbrella review of systematic reviews and meta-analysis of observational and intervention studies. Formisano E et al. | 2025 | PMID 39934049 DOI 10.1016/j.numecd.2025.103849 | Systematic review | 14 meta-analyses (10 observational, 4 interventional) | Across 14 meta-analyses, eggs were not linked to heart disease or overall death; a few weak signals remain uncertain. | Restricted to meta-analyses since 2020; Included meta-analyses of critically low quality | moderate | C-EGG-02 C-EGG-11 |
| I-EGG-131 | Comparative Analysis of Lupus Nephritis Guidelines: ACR 2025, EULAR 2025, and Kdigo 2024. Xipell M et al. | 2026 | PMID 42101868 DOI 10.1093/ndt/gfag106 | Narrative review | Patients with lupus nephritis (guideline scope) | ACR 2025, EULAR 2025 and KDIGO 2024 recommend early combination drug treatment, including biologic drugs, for lupus nephritis. | Narrative review; guidelines themselves not fetched | moderate | C-EGG-03 |
| I-EGG-132 | Prevalence of Salmonella in Eggs from Conventional and Cage-Free Egg Production Systems and the Role of Consumers in Reducing Household Contamination. Solís D et al. | 2023 | PMID 38231772 DOI 10.3390/foods12234300 | Cross-sectional study | Eggs from conventional and alternative systems | Salmonella Enteritidis was found in 2 of 186 cage-free egg samples and none of 240 conventional samples. | Very few positives (2); Single country | moderate | C-EGG-09 |
| I-EGG-133 | Dietary exclusions for established atopic eczema. Bath-Hextall F et al. | 2008 | PMID 18254073 DOI 10.1002/14651858.CD005203.pub2 | Systematic review | People with doctor-diagnosed atopic eczema; 9 RCTs, 421 participants | Avoiding eggs did not help eczema in general, but may help infants with eczema who are sensitised to egg. | Small, poor-quality trials; Old search (2006) | moderate | C-EGG-11 C-EGG-03 |
| I-EGG-134 | Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study. Miller CA et al. | 2014 | PMID 24944063 DOI 10.3945/ajcn.114.087692 | Randomised controlled trial | 6 healthy volunteers | Eating 2 or more egg yolks raised TMAO in blood and urine over the next day, without changes in inflammation markers. | Only 6 participants; Acute (24-h) effects only | moderate | C-EGG-05 |
| I-EGG-14 | The European Union One Health 2024 Zoonoses Report. EFSA, ECDC | 2025 | PMID 41377167 DOI 10.2903/j.efsa.2025.9759 | Other | 27 EU Member States, UK (NI), 8 non-MS | Campylobacter and Salmonella are the most common food-borne infections in the EU; about 5% of fresh chicken samples and 0.3% of egg samples had Salmonella. | Reporting differences between countries; Operator vs official sampling differ | high | C-EGG-09 C-CHK-08 C-CHK-09 |
| I-EGG-15 | Salmonella control in poultry flocks and its public health impact. EFSA BIOHAZ Panel | 2019 | PMID 32626222 DOI 10.2903/j.efsa.2019.5596 | Risk assessment | EU poultry flocks | Overall, laying-hen flocks kept outside cages tend to have less Salmonella, but studies conflict; crowding, large farms and stress clearly increase it. | Housing evidence largely from studies before the 2012 EU ban on conventional cages; Cage effect confounded by flock size, stocking density, cleaning and infection history (EFSA states the cause is unclear) | high | C-EGG-09 |
| I-EGG-16 | Risk to human health related to the presence of perfluoroalkyl substances in food. EFSA CONTAM Panel | 2020 | PMID 32994824 DOI 10.2903/j.efsa.2020.6223 | Risk assessment | European population | EFSA set a safe weekly intake for PFAS and named fish, fruit and eggs as main dietary sources. | Lower-bound vs upper-bound uncertainty | high | C-EGG-08 |
| I-EGG-17 | Council Directive 1999/74/EC laying down minimum standards for the protection of laying hens (as summarised by the European Commission) European Commission | 1999 | Guideline / position statement | EU laying hens | The EU banned barren battery cages in 2012; enriched cages and cage-free systems remain. | Enriched cages still permitted | not applicable | C-EGG-09 | |
| I-FAST-01 | Fuel metabolism in starvation. Cahill GF | 2006 | PMID 16848698 DOI 10.1146/annurev.nutr.26.061505.111258 | Narrative review | Humans in starvation (historical studies) | During long fasting the brain uses ketones from fat, which allows survival. | Narrative; No quantitative data in abstract | moderate | C-FAST-01 C-FAST-02 C-FAST-03 C-FAST-04 C-SYS-04 |
| I-FAST-02 | Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. Trepanowski JF et al. | 2017 | PMID 28459931 DOI 10.1001/jamainternmed.2017.0936 | Randomised controlled trial | Sedentary obese/overweight adults aged 18-65 (BMI 25.0-39.9; mean 34), 86% women, mean age 44; primarily metabolically healthy; excluded CVD, diabetes, smokers, weight-affecting medication. | Both approaches gave similar weight loss after a year; fasting had more dropouts and higher LDL. | Small sample (100); power fell to 60% for the primary comparison; High and differential dropout (38% ADF), more ADF withdrawals for diet dissatisfaction - possible selection bias | moderate | C-FAST-02 C-FAST-04 C-FAST-05 C-SRC-22 |
| I-FAST-03 | Calorie Restriction with or without Time-Restricted Eating in Weight Loss. Liu D et al. | 2022 | PMID 35443107 DOI 10.1056/NEJMoa2114833 | Randomised controlled trial | Adults with obesity | Adding an 8-hour eating window to calorie restriction did not significantly improve weight loss. | Single country | high | C-FAST-02 C-FAST-04 C-FAST-05 C-SRC-22 |
| I-FAST-04 | Effects of Time-Restricted Eating on Weight Loss and Other Metabolic Parameters in Women and Men With Overweight and Obesity: The TREAT Randomized Clinical Trial. Lowe DA et al. | 2020 | PMID 32986097 DOI 10.1001/jamainternmed.2020.4153 | Randomised controlled trial | Adults with BMI 27-43 | No more weight loss than three meals a day, and slightly more muscle-related lean mass loss. | Short; Self-reported adherence | moderate | C-FAST-02 C-FAST-05 |
| I-FAST-05 | Metabolic Effects of Intermittent Fasting. Patterson RE et al. | 2017 | PMID 28715993 DOI 10.1146/annurev-nutr-071816-064634 | Narrative review | Rodent models (mostly male mice) and adults in small human trials (n=8-107) and observational studies. | Fasting regimens seem to help weight loss and may improve metabolism; much is still hypothesis. | Non-systematic narrative review: single database, no protocol, no risk-of-bias assessment, no pooling; Human evidence consists of small, short trials, many uncontrolled; much mechanistic reasoning extrapolated from male rodents | low | C-FAST-01 C-FAST-02 C-FAST-05 |
| I-FAST-06 | Similar weight loss with low-energy food combining or balanced diets. Golay A et al. | 2000 | PMID 10805507 DOI 10.1038/sj.ijo.0801185 | Randomised controlled trial | Obese patients | Separating food groups did not add weight loss. | Short; Small | moderate | C-FAST-06 |
| I-FAST-07 | Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. Bauer J et al. | 2013 | PMID 23867520 DOI 10.1016/j.jamda.2013.05.021 | Guideline / position statement | Adults >65 | People over 65 should eat at least 1.0-1.2 g protein per kg body weight every day. | Expert consensus | moderate | C-FAST-04 C-FAST-05 C-FAST-07 C-FAST-08 |
| I-FAST-08 | "Drink at least eight glasses of water a day." Really? Is there scientific evidence for "8 x 8"? Valtin H | 2002 | PMID 12376390 DOI 10.1152/ajpregu.00365.2002 | Narrative review | Healthy adults | No proof for 8 glasses in healthy adults in mild climates, but more is needed in heat, hard work and some diseases. | Narrative; Old | moderate | C-FAST-09 C-FAST-10 C-GUT-08 |
| I-FAST-09 | Urinary volume, water and recurrences in idiopathic calcium nephrolithiasis: a 5-year randomized prospective study. Borghi L et al. | 1996 | PMID 8583588 | Randomised controlled trial | First-episode idiopathic calcium stone formers (plus 101 controls) | Over five years, stones came back in 12% of those drinking a lot vs 27% without advice. | Not blinded; Single centre | moderate | C-FAST-09 C-FAST-10 C-GUT-08 |
| I-FAST-10 | A population-based study of diabetes and its characteristics during the fasting month of Ramadan in 13 countries: results of the epidemiology of diabetes and Ramadan 1422/2001 (EPIDIAR) study. Salti I et al. | 2004 | PMID 15451892 DOI 10.2337/diacare.27.10.2306 | Cross-sectional study | Muslims with type 1 or type 2 diabetes | Severe low blood sugar was 4.7 times (type 1) and 7.5 times (type 2) more common during Ramadan. | Retrospective, recall | moderate | C-FAST-03 C-FAST-05 C-FAST-07 |
| I-FAST-101 | Glucagon levels and metabolic effects in fasting man. Marliss EB et al. | 1970 | PMID 5480852 DOI 10.1172/JCI106445 | Other | Adults undergoing supervised prolonged fasts (obese volunteers; details not in abstract) | During fasts of up to six weeks, insulin fell to a low plateau by the third day and stayed there; glucagon rose. | Small, old, uncontrolled study; numbers not in abstract; Mostly obese subjects under supervision | moderate | C-FAST-01 |
| I-FAST-102 | Impact of prolonged fasting on insulin secretion, insulin action, and hepatic versus whole body insulin secretion disposition indices in healthy young males. Jørgensen SW et al. | 2021 | PMID 33284087 DOI 10.1152/ajpendo.00433.2020 | Other | Healthy young men | In 13 healthy men, a 36-hour fast only slightly reduced early insulin release; the body became more insulin resistant for a while. | Very small sample, men only; Full text not open; numbers not available | moderate | C-FAST-01 C-FAST-03 |
| I-FAST-103 | Reference intervals for glucose, beta-cell polypeptides, and counterregulatory factors during prolonged fasting. Højlund K et al. | 2001 | PMID 11120658 DOI 10.1152/ajpendo.2001.280.1.E50 | Other | Healthy adults | In 33 healthy adults fasting 72 hours, glucose and insulin went down while stress hormones went up. | Absolute values not in abstract (full text not accessed); Small sample | moderate | C-FAST-01 |
| I-FAST-104 | Efficacy and safety of time-restricted eating in metabolic dysfunction-associated steatotic liver disease. Oh JH et al. | 2025 | PMID 40543603 DOI 10.1016/j.jhep.2025.06.005 | Randomised controlled trial | Adults with overweight/obesity and MASLD | Eating within a time window cut liver fat by about a quarter in 16 weeks, the same as simply eating fewer calories. | 16 weeks only; no histology; Open-label dietary intervention | high | C-FAST-02 |
| I-FAST-105 | EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). European Association for the Study of the Liver (EASL) et al. | 2024 | PMID 38851997 DOI 10.1016/j.jhep.2024.04.031 | Guideline / position statement | Adults with MASLD | European liver, diabetes and obesity societies recommend weight loss through diet change and exercise, plus drugs or surgery for some patients. | Abstract only accessed; specific statements on intermittent fasting not verified; Industry relationships of some authors | high | C-FAST-02 |
| I-FAST-106 | Intermittent fasting for rheumatic diseases: a systematic review and meta-analysis of conflicting evidence from observational studies and randomized controlled trials. Liu R et al. | 2026 | PMID 42079723 DOI 10.7717/peerj.21185 | Meta-analysis | Adults with rheumatoid arthritis (RA) or spondyloarthritis (SpA) | In small studies, fasting slightly lowered rheumatoid arthritis activity scores; the evidence is weak. | Only 2 independent RCTs (94 people); Abstract says 'three RCTs' while full text says two independent RCTs in three publications | low | C-FAST-02 |
| I-FAST-107 | Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Kjeldsen-Kragh J et al. | 1991 | PMID 1681264 DOI 10.1016/0140-6736(91)91770-u | Randomised controlled trial | Patients with rheumatoid arthritis | People with RA who fasted and then ate a vegetarian diet had fewer painful joints and lower inflammation over a year than controls. | Small; Single-blind; different settings (health farm vs convalescent home) | moderate | C-FAST-02 |
| I-FAST-108 | Diabetes and Ramadan: Practical Guidelines 2021 (IDF-DAR), International Diabetes Federation and DAR International Alliance International Diabetes Federation and DAR International Alliance (ed. Hassanein M) | 2021 | Guideline / position statement | People with type 1 and type 2 diabetes who fast in Ramadan | People with diabetes who fast must stop fasting if blood sugar goes above 300 mg/dL or below 70 mg/dL. | Largely consensus-based; observational evidence | moderate | C-FAST-03 C-FAST-10 | |
| I-FAST-109 | Assessment of the IDF-DAR Fasting Risk Assessment Tool to Predict Type 1 Diabetes-Related Complications During Ramadan in a Real-World Setting. Alguwaihes AM et al. | 2025 | PMID 41001082 DOI 10.1177/11795514251376888 | Cross-sectional study | Adults with type 1 diabetes in Saudi Arabia who observed Ramadan 2022 | Among 963 Saudi adults with type 1 diabetes, those rated high risk had more complications and emergency visits when fasting. | Self-reported online survey; recall and selection bias; No objective confirmation of DKA | low | C-FAST-03 |
| I-FAST-11 | Diabetes and Ramadan: Practical guidelines 2021. Hassanein M et al. | 2022 | PMID 35016991 DOI 10.1016/j.diabres.2021.109185 | Guideline / position statement | People with diabetes who fast | People with diabetes who fast need individual risk assessment and medical guidance. | Abstract only read | moderate | C-FAST-03 C-FAST-10 |
| I-FAST-110 | Ramadan fasting among adolescents with type 1 diabetes: a systematic review and meta-analysis. Safari O et al. | 2025 | PMID 39966830 DOI 10.1186/s12902-025-01835-1 | Meta-analysis | Adolescents with type 1 diabetes who fasted Ramadan | Low blood sugar was very common and high sugar and ketoacidosis also occurred in fasting teenagers with type 1 diabetes. | Small observational studies; high heterogeneity; DKA rates not quantified in abstract | low | C-FAST-03 |
| I-FAST-111 | Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects. Wilhelmi de Toledo F et al. | 2019 | PMID 30601864 DOI 10.1371/journal.pone.0209353 | Cohort study | Clinic guests aged 18-99 without contraindications (e.g. cachexia, anorexia nervosa, advanced kidney/liver/cerebrovascular insufficiency, dementia, pregnancy, lactation) | In 1,422 clinic guests, supervised fasting with small amounts of juice and soup was mostly well tolerated; blood sugar fell to the low-normal range. | No control group; Selected, paying, health-conscious clientele; contraindications excluded | low | C-FAST-04 C-FAST-03 |
| I-FAST-112 | Is fasting safe? A chart review of adverse events during medically supervised, water-only fasting. Finnell JS et al. | 2018 | PMID 29458369 DOI 10.1186/s12906-018-2136-6 | Case series / case report | Adults >=21 years water-only fasting >=2 days at a residential facility | Among 768 supervised water-only fasts, about one in four had a severe (grade 3) side effect; two people needed hospital care. | Retrospective, single centre, single abstractor; Conflicts of interest | low | C-FAST-04 C-FAST-10 |
| I-FAST-113 | Intermittent fasting strategies and their effects on body weight and other cardiometabolic risk factors: systematic review and network meta-analysis of randomised clinical trials. Semnani-Azad Z et al. | 2025 | PMID 40533200 DOI 10.1136/bmj-2024-082007 | Meta-analysis | Adults (720 healthy, 5862 with health conditions) | Across 99 trials, fasting diets led to weight loss similar to simply eating less every day; differences were small and short-term. | Short median follow-up; Religious fasting excluded | high | C-FAST-05 C-FAST-02 |
| I-FAST-114 | Intermittent fasting for adults with overweight or obesity. Garegnani LI et al. | 2026 | PMID 41692034 DOI 10.1002/14651858.CD015610.pub2 | Systematic review | Adults with overweight or obesity | Intermittent fasting led to about the same weight loss as standard diet advice over up to 12 months. | No studies from low/middle-income Arab countries; Short-term only | high | C-FAST-05 |
| I-FAST-115 | A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults. Stote KS et al. | 2007 | PMID 17413096 DOI 10.1093/ajcn/85.4.981 | Randomised controlled trial | Healthy normal-weight middle-aged adults | Eating the same calories in one meal reduced body fat slightly but raised blood pressure, LDL cholesterol and hunger. | Small pilot; short; Evening meal timing may confound lipid/BP measurements | moderate | C-FAST-05 |
| I-FAST-116 | Meal Skipping and Shorter Meal Intervals Are Associated with Increased Risk of All-Cause and Cardiovascular Disease Mortality among US Adults. Sun Y et al. | 2023 | PMID 35964910 DOI 10.1016/j.jand.2022.08.119 | Cohort study | US adults aged >=40 | US adults who ate only one meal a day had a higher death rate, but this type of study cannot prove the meal pattern caused it. | Single 24-h recall; misclassification; Residual confounding (illness, poverty, smoking) | moderate | C-FAST-05 |
| I-FAST-117 | Systematic review of diet quality scores including diet diversity in relation to major chronic diseases, obesity and mortality in healthy adults. Nickel DV et al. | 2026 | PMID 42047829 DOI 10.1007/s00394-026-03907-x | Systematic review | Healthy adults in high-income Western countries | Studies on diet variety and disease gave inconsistent results. | Heterogeneous definitions of diversity; Only PubMed/NCBI searched | moderate | C-FAST-06 |
| I-FAST-118 | Effects of mindfulness and mindful eating on food intake and appetite: a systematic review and meta-analysis. Ahmadyar K et al. | 2026 | PMID 42341365 DOI 10.1016/j.cpr.2026.102780 | Meta-analysis | Adults and children | Paying attention while eating slightly reduced how much people ate in experiments. | Mostly short laboratory studies; No intuitive eating trials found | moderate | C-FAST-07 |
| I-FAST-119 | Relationships between intuitive eating and health indicators: literature review. Van Dyke N, Drinkwater EJ | 2014 | PMID 23962472 DOI 10.1017/S1368980013002139 | Systematic review | Adults (mostly women, Western countries) | People who eat according to hunger and fullness tend to have lower BMI and better well-being; trials show weight maintenance. | Mostly cross-sectional; no formal quality assessment; no meta-analysis | low | C-FAST-07 |
| I-FAST-12 | Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lean ME et al. | 2018 | PMID 29221645 DOI 10.1016/S0140-6736(17)33102-1 | Randomised controlled trial | Age 20-65, T2D <6 years, BMI 27-45, not on insulin | 46% of people in the programme were free of diabetes and medication after one year. | Open-label; Selected population | high | C-INS-10 C-DIAB-03 C-INS-01 C-SUG-07 |
| I-FAST-120 | Quantity of dietary protein intake, but not pattern of intake, affects net protein balance primarily through differences in protein synthesis in older adults. Kim IY et al. | 2015 | PMID 25352437 DOI 10.1152/ajpendo.00382.2014 | Randomised controlled trial | Healthy older adults aged 52-75 | In older adults, eating more protein improved protein balance, while how it was spread across meals made no difference. | Very small; Only 4 days; within-day distribution, not alternate days | moderate | C-FAST-08 |
| I-FAST-121 | Systematic review and meta-analysis of protein intake to support muscle mass and function in healthy adults. Nunes EA et al. | 2022 | PMID 35187864 DOI 10.1002/jcsm.12922 | Meta-analysis | Healthy non-obese adults | Eating more protein each day slightly increased muscle mass in people doing strength training. | Most trials with resistance exercise; Industry COI | moderate | C-FAST-08 |
| I-FAST-122 | Water for preventing urinary stones. Bao Y et al. | 2020 | PMID 32045491 DOI 10.1002/14651858.CD004292.pub4 | Systematic review | People with or without history of stones | People who had kidney stones and drank enough to pass 2 litres of urine a day had fewer new stones. | Single trial (same as I-FAST-09); Low certainty | high | C-FAST-09 C-FAST-10 |
| I-FAST-123 | Outcomes in Randomized Clinical Trials Testing Changes in Daily Water Intake: A Systematic Review. Hakam N et al. | 2024 | PMID 39585691 DOI 10.1001/jamanetworkopen.2024.47621 | Systematic review | Various adult populations | Only 18 trials exist; drinking more water helped with kidney stones and weight loss in some. | Heterogeneous small trials; no meta-analysis | moderate | C-FAST-09 |
| I-FAST-124 | Scientific Opinion on Dietary Reference Values for water. EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) | 2010 | DOI 10.2903/j.efsa.2010.1459 | Guideline / position statement | EU population by age group | European experts set adequate total water intake at 2.0 L/day for women and 2.5 L/day for men, including water in food. | AIs, not requirements; based on observed intakes; Only moderate temperatures covered | moderate | C-FAST-09 C-FAST-10 |
| I-FAST-125 | Hypoglycemia compensation mechanisms in dry fasting. Papagiannopoulos-Vatopaidinos IE et al. | 2025 | PMID 40585323 DOI 10.1016/j.metop.2025.100363 | Case series / case report | Adults without medication, normal glucose metabolism, no diabetes, no cardiovascular disease, recruited from a medical office | Ten healthy people under supervision coped with a five-day dry fast, but the researchers say medical supervision is essential. | 10 participants, no control; No prospective ethics committee approval | very low | C-FAST-10 |
| I-FAST-13 | Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lean MEJ et al. | 2019 | PMID 30852132 DOI 10.1016/S2213-8587(19)30068-3 | Randomised controlled trial | As DiRECT | 36% were still in remission after two years. | Open-label | high | C-DIAB-03 |
| I-FAST-14 | 5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study. Lean ME et al. | 2024 | PMID 38423026 DOI 10.1016/S2213-8587(23)00385-6 | Randomised controlled trial | Adults aged 20-65 with type 2 diabetes diagnosed within 6 years (mean duration 3.0 years), BMI 27-45 kg/m2 (mean ~34-35), NOT receiving insulin, in Scotland and Tyneside. | Only 13% of those continuing support were still in remission at 5 years; people with long diabetes or on insulin were not studied. | Extension group self-selected (engaged participants) - non-randomised comparison; Large missing data, especially controls (45% without year-5 weight) | moderate | C-DIAB-03 |
| I-FAT-01 | Reduction in saturated fat intake for cardiovascular disease. Hooper L et al. | 2020 | PMID 32827219 DOI 10.1002/14651858.CD011737.pub3 | Meta-analysis | Adults with or without CVD (15 RCTs, 16 comparisons) | 17% fewer combined cardiovascular events (RR 0.83); no clear effect on deaths. | Old trials with heterogeneous interventions; Heterogeneity (I2 67%) | high | C-FAT-01 C-FAT-02 C-MEAT-04 |
| I-FAT-02 | Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Ference BA et al. | 2017 | PMID 28444290 DOI 10.1093/eurheartj/ehx144 | Guideline / position statement | Totality of evidence (>2 million participants) | Genetic studies, cohorts and drug trials agree: more LDL over time means more atherosclerosis. | Not a systematic review: no protocol, selection of meta-analyses partly by panel discussion, no formal risk-of-bias or GRADE assessment; Extensive financial ties of panel members to manufacturers of LDL-lowering drugs; meeting logistics funded by MSD and Amgen | moderate | C-FAT-01 C-FAT-02 C-FAT-05 C-SYS-07 |
| I-FAT-03 | Is Butter Back? A Systematic Review and Meta-Analysis of Butter Consumption and Risk of Cardiovascular Disease, Diabetes, and Total Mortality. Pimpin L et al. | 2016 | PMID 27355649 DOI 10.1371/journal.pone.0158118 | Meta-analysis | Adults (mean age 44-71 years) in general-population cohorts in the USA, Netherlands, Sweden, Finland (incl. one cohort of male smokers, ATBC) and 8 European EPIC countries. | Per tablespoon/day: CVD RR 1.00; mortality RR 1.01. | Observational only; no RCTs; residual confounding acknowledged (butter eaters have worse diets/lifestyles); Few independent cohorts per outcome (CVD 4, CHD 3, mortality 2 publications); subgroup analyses not possible; Egger's test underpowered | moderate | C-FAT-01 |
| I-FAT-04 | Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. Estruch R et al. | 2018 | PMID 29897866 DOI 10.1056/NEJMoa1800389 | Randomised controlled trial | 7,447 adults aged 55-80 at high CV risk | HR 0.69; events 3.8% vs 4.4%. | Randomisation irregularities at some sites (corrected analysis); Whole-diet intervention, not olive oil alone | moderate | C-FAT-03 C-FAT-04 |
| I-FAT-05 | Dietary linoleic acid and risk of coronary heart disease: a systematic review and meta-analysis of prospective cohort studies. Farvid MS et al. | 2014 | PMID 25161045 DOI 10.1161/CIRCULATIONAHA.114.010236 | Meta-analysis | 310,602 individuals; 12,479 CHD events | CHD events RR 0.85 highest vs lowest intake. | Observational | moderate | C-FAT-04 |
| I-FAT-06 | Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). Ramsden CE et al. | 2016 | PMID 27071971 DOI 10.1136/bmj.i1246 | Randomised controlled trial | 9,423 institutionalised women and men aged 20-97 | No mortality benefit; HR 1.22 death per 30 mg/dL cholesterol drop. | Institutionalised population; short exposure for many; Control diet contained trans-fat margarines | low | C-FAT-04 |
| I-FAT-07 | Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review. Astrup A et al. | 2020 | PMID 32562735 DOI 10.1016/j.jacc.2020.05.077 | Narrative review | n/a | Claims whole-fat dairy and unprocessed meat are not linked to more CVD. | Narrative, non-systematic; Possible COI | low | C-FAT-01 |
| I-FAT-08 | Saturated fatty acid and trans-fatty acid intake for adults and children: WHO guideline World Health Organization | 2023 | Guideline / position statement | Adults and children | Replace with plant oils rich in unsaturated fats. | Population-level guidance | high | C-FAT-01 C-FAT-03 C-FAT-04 | |
| I-FAT-101 | Butter and Plant-Based Oils Intake and Mortality. Zhang Y et al. | 2025 | PMID 40048719 DOI 10.1001/jamainternmed.2025.0205 | Cohort study | US health professionals free of cancer, CVD, diabetes, neurodegenerative disease | Highest v lowest butter HR 1.15; swapping 10 g butter for plant oil linked to 17% lower mortality. | Observational; US health professionals | moderate | C-FAT-01 |
| I-FAT-102 | The effects of replacing ghee with rapeseed oil on liver steatosis and enzymes, lipid profile, insulin resistance and anthropometric measurements in patients with non-alcoholic fatty liver disease: a randomised controlled clinical trial. Maleki Sedgi F et al. | 2024 | PMID 38501177 DOI 10.1017/S0007114524000564 | Randomised controlled trial | Adults with NAFLD who consumed ghee daily (Iran) | Less liver fat, LDL -7.5 mg/dL, triglycerides -40 mg/dL over 12 weeks. | Unblinded advice trial; Weight loss in intervention arm confounds lipid changes | low | C-FAT-01 |
| I-FAT-103 | Longitudinal association of dietary fat intake with cardiovascular events in a prospective cohort study in Eastern Mediterranean region. Sadeghi M et al. | 2021 | PMID 33719857 DOI 10.1080/09637486.2021.1895725 | Cohort study | Iranian adults >=35 y | No association for ghee; HVO top quartile ~68% more MI (borderline). | Frequency-based FFQ; Modest size; limited power | low | C-FAT-01 |
| I-FAT-104 | Intake of saturated and trans unsaturated fatty acids and risk of all cause mortality, cardiovascular disease, and type 2 diabetes: systematic review and meta-analysis of observational studies. de Souza RJ et al. | 2015 | PMID 26268692 DOI 10.1136/bmj.h3978 | Meta-analysis | Adults in cohort studies | SFA and CHD RR 1.06 (0.95-1.17); trans fat and mortality RR 1.34. | Observational; Does not model replacement nutrient (replacement by refined carbohydrate may mask harm) | high | C-FAT-01 |
| I-FAT-105 | Consumption of Olive Oil and Risk of Total and Cause-Specific Mortality Among U.S. Adults. Guasch-Ferre M et al. | 2022 | PMID 35027106 DOI 10.1016/j.jacc.2021.10.041 | Cohort study | US women and men free of CVD and cancer | >7 g/day: 19% lower mortality; similar to other vegetable oils. | Observational; US intakes low | moderate | C-FAT-03 C-FAT-04 |
| I-FAT-106 | Optimization and validation of a rapid LC-MS/MS method for the detection and quantification of illegal dyes in olive oil from Egyptian markets. Ragab M et al. | 2025 | PMID 40446662 DOI 10.1016/j.foodchem.2025.144924 | Measurement / residue study | Olive oil samples from Egyptian local markets | Sudan Yellow in 5% of 870 samples; other dyes rarer. | Only dyes tested (not oil substitution or other fraud); Sampling frame not described in abstract | moderate | C-FAT-04 |
| I-FAT-107 | Omega-6 fats for the primary and secondary prevention of cardiovascular disease. Hooper L et al. | 2018 | PMID 30488422 DOI 10.1002/14651858.CD011094.pub4 | Meta-analysis | Adults with or without CVD | Mortality RR 1.00; possible small reduction in heart attacks. | Few low-risk-of-bias trials; Imprecise | high | C-FAT-04 |
| I-FAT-108 | Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Study and updated meta-analysis. Ramsden CE et al. | 2013 | PMID 23386268 DOI 10.1136/bmj.e8707 | Randomised controlled trial | Men 30-59 y with recent coronary event | Death 17.6% v 11.8% (HR 1.62). | Old trial; margarines of the era contained trans fat (control arm); Small | moderate | C-FAT-04 |
| I-FAT-109 | Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. Ravnskov U et al. | 2016 | PMID 27292972 DOI 10.1136/bmjopen-2015-010401 | Systematic review | Elderly in general-population cohorts | Inverse association in 16 of 28 cohorts. | Single database; Vote counting | low | C-FAT-05 |
| I-FAT-110 | Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Cholesterol Treatment Trialists' Collaboration | 2019 | PMID 30712900 DOI 10.1016/S0140-6736(18)31942-1 | Meta-analysis | 186,854 trial participants; 14,483 aged >75 | 21% fewer major vascular events per 1 mmol/L lower LDL, including older people. | Drug trials (LDL lowering by statins, not diet); Fewer data >75 without CVD | high | C-FAT-05 C-FAT-02 |
| I-FAT-111 | Effect of Isoenergetic Substitution of Cheese with Other Dairy Products on Blood Lipid Markers in the Fasted and Postprandial State: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials in Adults. Pradeilles R et al. | 2023 | PMID 37717700 DOI 10.1016/j.advnut.2023.09.003 | Meta-analysis | Adults in RCTs | LDL 0.19 mmol/L higher on butter than on cheese. | Few trials; Heterogeneity | moderate | C-FAT-01 |
| I-FRU-01 | Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies. Muraki I et al. | 2013 | PMID 23990623 DOI 10.1136/bmj.f5001 | Cohort study | 66,105 + 85,104 women, 36,173 men | Blueberries, grapes and apples linked to lower diabetes risk; juice and cantaloupe to slightly higher risk; glycaemic load did not explain the differences. | US health professionals; Watermelon not regularly measured | high | C-FRU-01 C-FRU-03 C-FRU-04 C-FRU-05 |
| I-FRU-02 | Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. Imamura F et al. | 2015 | PMID 26199070 DOI 10.1136/bmj.h3576 | Meta-analysis | Adults aged >=18 years free of diabetes in 17 prospective cohorts (USA, Finland, Japan, France, Singapore, 8 EPIC countries); PAF in NHANES 2009-10 (n=4729, representing 189.1 million) and UK NDNS 2008-12 (n=1932, representing 44.7 million) | Sugary drinks were linked to more type 2 diabetes. Fruit juice showed at most a small, unstable link (low-quality evidence), so juice is not a proven healthy alternative. | Observational cohorts: residual confounding and reverse causation (health-conscious or high-risk people changing beverages); Protocol not registered; title/abstract screening by one author | high | C-FRU-03 |
| I-FRU-03 | Fruit and vegetable consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of prospective studies. Halvorsen RE et al. | 2021 | PMID 35028521 DOI 10.1136/bmjnph-2020-000218 | Meta-analysis | Adults free of T2D at baseline in 23 prospective cohort, case-cohort or nested case-control studies (42 publications): 10 from America, 5 Europe, 5 Asia, 3 Australia; follow-up 4-30 years | Eating more fruit was linked to about 7% lower diabetes risk. Grapes/raisins and apples looked favourable; cantaloupe and sweetened fruit drinks were linked to higher risk, but in very few studies. 100% fruit juice showed no clear link. | No registered protocol (stated by authors); Subtype analyses based on 2-6 studies, many from the same US cohorts (NHS, NHS II, HPFS); possible selective reporting | moderate | C-FRU-01 C-FRU-03 C-FRU-05 |
| I-FRU-04 | Glycemic indices of five varieties of dates in healthy and diabetic subjects. Alkaabi JM et al. | 2011 | PMID 21619670 DOI 10.1186/1475-2891-10-59 | Other | 13 healthy volunteers (7 F, 6 M; mean age 40.2 years, BMI 27.4) and 10 adults with type 2 diabetes controlled on diet with or without metformin (HbA1c <=8%; mean HbA1c 6.6%, age 40.8 years, BMI 30.7), recruited by poster advertisement in Al Ain | Five date varieties had GI 46-55. | Very small sample (13 + 10); wide SEMs (up to 8.6 GI units); Test order not randomised (authors' limitation); reference tests all before test foods | moderate | C-FRU-05 C-FRU-01 |
| I-FRU-05 | [Food poisoning by cucurbitacines]. Jung C et al. | 2020 | PMID 32668470 DOI 10.1055/a-1163-9741 | Case series / case report | 1 woman, 66 y | A woman developed severe diarrhoea after eating bitter zucchini; bitter taste is the warning sign. | Single case | low | C-FRU-02 |
| I-FRU-06 | WHO calls on countries to reduce sugars intake among adults and children (news release on WHO Guideline: Sugars intake for adults and children, 2015). World Health Organization | 2015 | Guideline / position statement | Adults and children | WHO advises less than 10% of energy from free sugars, which include fruit juice and honey but not whole fruit. | Press release; full PDF not read | high | C-FRU-03 C-FRU-05 | |
| I-FRU-101 | Consumption of Fruit Juice and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Prospective Cohort Studies. Lee CW et al. | 2025 | PMID 40393612 DOI 10.1016/j.amjmed.2025.05.021 | Meta-analysis | Adults in prospective cohorts | Sweetened (non-100%) fruit juices were linked to a 15% higher diabetes risk; pure juice showed no clear link either way. | Observational; residual confounding; Abstract only | moderate | C-FRU-03 |
| I-FRU-102 | 100 % Fruit juice and measures of glucose control and insulin sensitivity: a systematic review and meta-analysis of randomised controlled trials. Murphy MM et al. | 2017 | PMID 29299307 DOI 10.1017/jns.2017.63 | Meta-analysis | Adults in RCTs (mostly BMI >25) | In 18 short trials, pure fruit juice did not change fasting glucose, insulin or HbA1c; the review was funded by the juice industry. | Industry funding of the review and most trials; Heterogeneous controls (some sugar-matched) | low | C-FRU-03 |
| I-FRU-103 | Consumption of 100% Fruit Juice and Body Weight in Children and Adults: A Systematic Review and Meta-Analysis. Nguyen M et al. | 2024 | PMID 38227336 DOI 10.1001/jamapediatrics.2023.6124 | Meta-analysis | 45,851 children (17 cohorts); 268,095 adults (6 cohorts, 19 RCTs) | Each extra daily glass of 100% juice was linked to slightly more BMI gain in children. | No RCTs in children; Small effect sizes | moderate | C-FRU-03 C-SUG-06 |
| I-FRU-104 | Fruit Juice in Infants, Children, and Adolescents: Current Recommendations. Heyman MB, Abrams SA (AAP) | 2017 | PMID 28562300 DOI 10.1542/peds.2017-0967 | Guideline / position statement | Infants, children, adolescents | Babies under one year should not get juice, and young children should have at most 120-180 ml a day; whole fruit is preferred. | Recommendation details read on the summary page, not the full report | moderate | C-FRU-03 |
| I-FRU-105 | Effect of fruit restriction on glycemic control in patients with type 2 diabetes--a randomized trial. Christensen AS et al. | 2013 | PMID 23497350 DOI 10.1186/1475-2891-12-29 | Randomised controlled trial | 63 overweight adults with newly diagnosed T2D | Telling newly diagnosed patients to eat less fruit did not improve their blood sugar, weight or waist. | Small; 12 weeks; Open-label; self-reported intake | moderate | C-FRU-05 |
| I-FRU-106 | Fresh fruit consumption in relation to incident diabetes and diabetic vascular complications: A 7-y prospective study of 0.5 million Chinese adults. Du H et al. | 2017 | PMID 28399126 DOI 10.1371/journal.pmed.1002279 | Cohort study | 0.5 million adults aged 30-79 in 10 regions of China | Daily fruit eaters had a 12% lower diabetes risk, and people with diabetes who ate more fruit had fewer deaths and complications. | Observational; residual confounding (authors' stated limitation); Reverse causation possible (diagnosed patients avoided fruit) | high | C-FRU-05 C-FRU-01 |
| I-FRU-107 | Effect of Date Fruit Consumption on the Glycemic Control of Patients with Type 2 Diabetes: A Randomized Clinical Trial. Butler AE et al. | 2022 | PMID 36079749 DOI 10.3390/nu14173491 | Randomised controlled trial | Patients with T2D | Eating 60 g of dates a day for 12 weeks did not worsen blood sugar control in people with type 2 diabetes. | 23% dropout; Active comparator (raisins), no no-fruit control | moderate | C-FRU-05 |
| I-FRU-108 | Glycemic indices, glycemic load and glycemic response for seventeen varieties of dates grown in Saudi Arabia. AlGeffari MA et al. | 2016 | PMID 27920411 DOI 10.5144/0256-4947.2016.397 | Other | 19 healthy adults | Dates had an average glycaemic index of 55, but the glycaemic load ranged from 8.5 to 24 depending on the variety. | Healthy subjects only; Tamer stage only | moderate | C-FRU-05 |
| I-FRU-109 | Fruit intake, fruit glycemic load, and type 2 diabetes risk: findings from a community based Korean cohort study. Ha AW | 2026 | PMID 41694466 DOI 10.4162/nrp.2026.20.1.101 | Cohort study | Korean adults in the Ansan and Anseong cohorts | In Korean women, very high fruit intake and higher watermelon and melon intake were weakly linked to diabetes; in men there was no link. | 24 individual-fruit tests without multiplicity correction; Women only | moderate | C-FRU-01 |
| I-FRU-110 | A chromosome-level genome of a Kordofan melon illuminates the origin of domesticated watermelons. Renner SS et al. | 2021 | PMID 34031154 DOI 10.1073/pnas.2101486118 | Other | Citrullus accessions (>400); Egyptian tomb paintings | The watermelon's closest wild relative grows in Sudan, and Egyptian tomb paintings suggest people ate watermelon as a dessert more than 4,000 years ago. | Interpretation of iconography; Abstract only | high | C-FRU-02 |
| I-FRU-111 | Plant science. Biosynthesis, regulation, and domestication of bitterness in cucumber. Shang Y et al. | 2014 | PMID 25430763 DOI 10.1126/science.1259215 | Laboratory / cell study | Cucumber genomes and enzymes | Bitter cucurbitacins are made by wild cucurbits, but domestication selected plants whose fruits do not make them. | Cucumber only; Abstract only | high | C-FRU-02 |
| I-FRU-112 | Gastrointestinal toxicity due to bitter bottle gourd (Lagenaria siceraria)--a report of 15 cases. Puri R et al. | 2011 | PMID 21986853 DOI 10.1007/s12664-011-0110-z | Case series / case report | 15 patients after bitter bottle gourd juice | Fifteen people who drank bitter bottle gourd juice developed vomiting, bleeding stomach lesions and low blood pressure; all recovered. | Case series; bitter juice used as alternative medicine; Abstract only | low | C-FRU-02 |
| I-FRU-113 | Effects of food processing on pesticide residues in fruits and vegetables: a meta-analysis approach. Keikotlhaile BM et al. | 2010 | PMID 19879312 DOI 10.1016/j.fct.2009.10.031 | Meta-analysis | Processing experiments on fruits and vegetables | Washing, peeling and cooking generally lower pesticide residues on fruits and vegetables. | Peeling-specific ratio not given in abstract; Abstract only | moderate | C-FRU-04 |
| I-FRU-114 | Antioxidant activity of apple peels. Wolfe K et al. | 2003 | PMID 12537430 DOI 10.1021/jf020782a | Laboratory / cell study | Four apple varieties (New York State) | Apple peels contain more phenolic compounds and antioxidant activity than the flesh. | In vitro; no human outcomes; Abstract only | moderate | C-FRU-04 |
| I-FRU-115 | 100% Fruit juice intake and cardiovascular risk: a systematic review and meta-analysis of prospective and randomised controlled studies. D'Elia L et al. | 2021 | PMID 33150530 DOI 10.1007/s00394-020-02426-7 | Meta-analysis | Adults | Small daily amounts of pure fruit juice were not linked to higher cardiovascular risk and were linked to slightly lower stroke risk. | Many small RCTs; Abstract only | moderate | C-FRU-03 |
| I-FRU-116 | Genome Sequencing of up to 6,000-Year-Old Citrullus Seeds Reveals Use of a Bitter-Fleshed Species Prior to Watermelon Domestication. Pérez-Escobar OA et al. | 2022 | PMID 35907246 DOI 10.1093/molbev/msac168 | Other | 6,000-year-old (Libya) and 3,300-year-old (Sudan) seeds; 131 accessions | The oldest watermelon seeds came from bitter, seed-used plants; sweet watermelon was eaten in Egypt more than 4,000 years ago. | Two ancient samples; Abstract only | high | C-FRU-02 |
| I-FSH-01 | Impact of sustainable feeds on omega-3 long-chain fatty acid levels in farmed Atlantic salmon, 2006-2015. Sprague M et al. | 2016 | PMID 26899924 DOI 10.1038/srep21892 | Measurement / residue study | Farmed Scottish Atlantic salmon (standard quality cuts supplied year-round by producers and feed manufacturers); comparators: 21 wild (mainly Pacific) salmon from supermarkets and retail mackerel, cod, tuna, sardines, beef, chicken, lamb, pork (2014/2015) | Omega-3 in farmed Scottish salmon roughly halved from 2006 to 2015 (2.74 to 1.36 g per 100 g), but it still had more omega-3 per 100 g than the wild salmon tested (0.76 g) and most other foods. | Convenience samples submitted by industry; representativeness not verified; Wild salmon n=21, mostly Pacific species from supermarkets (not wild Atlantic) | high | C-FSH-04 C-FSH-05 C-FSH-11 C-FSH-13 |
| I-FSH-02 | Lower levels of Persistent Organic Pollutants, metals and the marine omega 3-fatty acid DHA in farmed compared to wild Atlantic salmon (Salmo salar). Lundebye AK et al. | 2017 | PMID 28189073 DOI 10.1016/j.envres.2017.01.026 | Measurement / residue study | Wild and farmed Atlantic salmon | Wild salmon had more dioxins, PCBs and mercury than farmed salmon; both were good omega-3 sources. | Norwegian government institute authors (no COI stated); Sample size not in abstract | moderate | C-FSH-01 C-FSH-02 C-FSH-03 C-FSH-04 C-FSH-05 C-FSH-13 C-FSH-14 |
| I-FSH-03 | Fish intake, contaminants, and human health: evaluating the risks and the benefits. Mozaffarian D & Rimm EB | 2006 | PMID 17047219 DOI 10.1001/jama.296.15.1885 | Systematic review | Adults, women of childbearing age | For adults, the benefits of eating fish 1-2 times a week outweigh risks from contaminants. | Not fully systematic; Observational basis for many outcomes | moderate | C-FSH-02 C-FSH-03 C-FSH-05 C-FSH-14 |
| I-FSH-04 | Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Hibbeln JR et al. | 2007 | PMID 17307104 DOI 10.1016/S0140-6736(07)60277-3 | Cohort study | Pregnant women and children | Children of mothers who ate more seafood in pregnancy had better developmental scores. | Observational; FFQ | moderate | C-FSH-14 |
| I-FSH-05 | Evidence on the human health effects of low-level methylmercury exposure. Karagas MR et al. | 2012 | PMID 22275730 DOI 10.1289/ehp.1104494 | Narrative review | General populations (excluding very high consumers) | Methylmercury is a nerve toxin; at low levels possible effects on babies' early development, unclear effects on heart and immune system. | Not a systematic review: limited search (two databases, keywords), no protocol, no duplicate selection, no study-quality assessment, no quantitative synthesis; Excludes the most informative moderate-exposure cohorts by design | low | C-FSH-14 |
| I-FSH-06 | Global trends in antimicrobial use in aquaculture. Schar D et al. | 2020 | PMID 33318576 DOI 10.1038/s41598-020-78849-3 | Systematic review | Aquaculture species groups | About 10,000 tonnes were used in 2017, mostly in Asia; salmon had the lowest use per kg. | Only 25 surveys from 12 countries; China and carp under-represented; Extremely wide UIs (e.g. catfish 9-2,751 mg/kg) | moderate | C-FSH-08 |
| I-FSH-07 | Occurrence and human health risks of pesticides and antibiotics in Nile tilapia along the Rosetta Nile branch, Egypt. Eissa F et al. | 2020 | PMID 33384941 DOI 10.1016/j.toxrep.2020.03.004 | Measurement / residue study | Wild Nile tilapia (Oreochromis niloticus) caught with local fishermen 1 km upstream of the El-Rahawy (Giza), Sabal (Minoufiya) and Tala (Gharbiya) drain outlets on the Rosetta branch | Most wild river tilapia sampled near drains had pesticide traces (chlorpyrifos above the EU limit in 45%) and a fifth had antibiotic traces, including EU-banned drugs; estimated non-cancer risk was low. | Wild river fish sampled close to drain outlets (worst-case locations), not market or farmed fish; Small n per site-season; antibiotic findings driven by one site-season (Sabal, spring) | moderate | C-FSH-12 C-FSH-16 C-RES-01 C-RES-02 |
| I-FSH-08 | Potential health risk assessment of some bioaccumulated metals in Nile tilapia (Oreochromis niloticus) cultured in Kafr El-Shaikh farms, Egypt. Shaaban NA et al. | 2021 | PMID 34043970 DOI 10.1016/j.envres.2021.111358 | Measurement / residue study | 200 farmed tilapia from 3 farms | Metal levels in muscle were judged safe, though fish tissues showed damage at drainage-water farms. | No mercury; Three farms | moderate | C-FSH-12 |
| I-FSH-09 | Heavy Metals Assessment and Health Risk to Consumers of Two Commercial Fish Species from Polyculture Fishponds in El-Sharkia and Kafr El-Sheikh, Egypt: Physiological and Biochemical Study. Abbas MMM et al. | 2024 | PMID 38129339 DOI 10.1007/s12011-023-04007-1 | Measurement / residue study | Tilapia (bolti) and mullet (topara) | Mostly safe, but cadmium in tilapia from one governorate was a cancer-risk warning for children. | Sample size not in abstract | moderate | C-FSH-12 |
| I-FSH-10 | One health risk assessment of heavy-metal contamination in Nile tilapia (Oreochromis niloticus) from contrasting aquaculture systems in Egypt. Farahat Abdelmawla M et al. | 2026 | PMID 42662802 DOI 10.1016/j.toxrep.2026.102331 | Measurement / residue study | Nile tilapia, 4 sites | Even at a heavily polluted drain, tilapia muscle stayed within limits, but lead margins were narrow. | Few sites | moderate | C-FSH-12 |
| I-FSH-101 | Joint FAO/WHO expert consultation on the risks and benefits of fish consumption: meeting report, Rome, 9-13 October 2023 (Food Safety and Quality Series No. 28) FAO/WHO | 2024 | DOI 10.4060/cd2394en | Risk assessment | General population; pregnancy, childhood, adulthood | Strong evidence for benefits of eating fish in pregnancy, childhood and adulthood; methylmercury can reduce the brain benefit in some populations. | Only summary, conclusion and research-gap chapters read; No species-level consumption limits | high | C-FSH-14 C-FSH-02 |
| I-FSH-102 | Report of the Joint FAO/WHO Expert Consultation on the Risks and Benefits of Fish Consumption, Rome, 25-29 January 2010 (FAO Fisheries and Aquaculture Report No. 978) FAO/WHO | 2011 | Risk assessment | General adults, women of childbearing age, infants and children | Cancer risk from dioxins in fish was judged well below the heart benefit; fish in pregnancy lowered the risk of poor neurodevelopment in most scenarios. | Older (2010); EFSA lowered the dioxin TWI in 2018; Summary read only | high | C-FSH-03 C-FSH-14 | |
| I-FSH-103 | Advice about Eating Fish: For Those Who Might Become or Are Pregnant or Breastfeeding and Children Ages 1-11 Years (FDA/EPA joint advice, revised October 2021; page content current as of 03/05/2024) US FDA and US EPA | 2021 | Guideline / position statement | Pregnant or breastfeeding people, people who might become pregnant, children 1-11 years | Salmon, tilapia, sardines and shrimp are 'Best Choices'; grouper is limited to one serving a week; shark, swordfish, king mackerel and bigeye tuna should be avoided. | Based on US market mercury data; the species mix in Egypt differs | high | C-FSH-14 C-FSH-13 C-FSH-12 C-FSH-15 | |
| I-FSH-104 | Relationships between seafood consumption during pregnancy and childhood and neurocognitive development: Two systematic reviews. Hibbeln JR et al. | 2019 | PMID 31739098 DOI 10.1016/j.plefa.2019.10.002 | Systematic review | Mother-offspring pairs and children | Children of mothers who ate seafood had better neurocognitive development than children of mothers who ate none. | Observational primary studies; residual confounding (socioeconomic status); No RCTs | moderate | C-FSH-14 |
| I-FSH-105 | Global methylmercury exposure from seafood consumption and risk of developmental neurotoxicity: a systematic review. Sheehan MC et al. | 2014 | PMID 24700993 DOI 10.2471/BLT.12.116152 | Systematic review | Women and infants in seafood-consuming populations | High fish eaters in all regions studied had mercury intakes above the FAO/WHO reference; Mediterranean averages approached it. | Heterogeneous studies; pooled medians; no health outcome data | moderate | C-FSH-14 |
| I-FSH-106 | Health hazard assessment and cooking effects on toxic metals in marine fish from the mediterranean sea at the Damietta Coast, Egypt. Makroum AH et al. | 2026 | PMID 41526512 DOI 10.1038/s41598-025-33257-3 | Measurement / residue study | Thinlip grey mullet, sardine, sand smelt | Lead and total arsenic were above limits in many samples; mercury was within limits. | Total arsenic used; most arsenic in marine fish is non-toxic arsenobetaine, so arsenic risk is probably overestimated; Single coastal area; wild or farmed origin of mullet not stated in the abstract | low | C-FSH-14 |
| I-FSH-107 | The nutritional and cardiovascular health benefits of rapeseed oil-fed farmed salmon in humans are not decreased compared with those of traditionally farmed salmon: a randomized controlled trial. de Roos B et al. | 2021 | PMID 33015732 DOI 10.1007/s00394-020-02396-w | Randomised controlled trial | Healthy adults aged 35-75 years, BMI 25-35, Aberdeen | Two portions a week of salmon raised on rapeseed oil raised blood omega-3 almost as much as fish-oil-fed salmon and lowered blood fats; inflammation markers did not rise. | Small (n=51); Open-label | moderate | C-FSH-05 C-FSH-07 |
| I-FSH-108 | Dietary intake of differently fed salmon; the influence on markers of human atherosclerosis. Seierstad SL et al. | 2005 | PMID 15638820 DOI 10.1111/j.1365-2362.2005.01443.x | Randomised controlled trial | Patients with coronary heart disease | Only salmon fed fish oil lowered triglycerides and two inflammation markers compared with the other salmon groups. | Small, 6 weeks; No no-fish control, so it cannot show whether rapeseed-fed salmon raises inflammation | moderate | C-FSH-05 |
| I-FSH-109 | Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials. Johnson GH, Fritsche K | 2012 | PMID 22889633 DOI 10.1016/j.jand.2012.03.029 | Systematic review | Healthy non-infant humans | In 15 controlled trials, more linoleic acid did not increase markers such as CRP or cytokines. | No meta-analysis; Healthy people only | moderate | C-FSH-05 C-FSH-07 |
| I-FSH-11 | Hysterical tetracycline in intensive poultry farms accountable for substantial gene resistance, health and ecological risk in Egypt- manure and fish. Mahmoud MAM & Abdel-Mohsein HS | 2019 | PMID 31521994 DOI 10.1016/j.envpol.2019.113039 | Measurement / residue study | Poultry litter/droppings; tilapia from Nile and aquaculture | Farmed tilapia had more tetracycline residues than river tilapia; poultry litter may spread resistance. | Sample sizes not in abstract; Risk statement for fish not quantified in abstract | moderate | C-FSH-12 |
| I-FSH-110 | Foundation Foods reveals significant changes in farmed Atlantic salmon relative to Standard Reference Legacy data. Bukowski MR et al. | 2026 | PMID 42609372 DOI 10.3389/fnut.2026.1870100 | Measurement / residue study | Retail fillets: farmed Atlantic salmon (Chilean producers), wild sockeye salmon, farmed Nile tilapia, farmed channel catfish, wild cod | In 2023 farmed salmon had 2.4 times more linoleic acid and less than half the EPA+DHA of older database values, but still more EPA+DHA than wild sockeye. | Small convenience samples (n=8); US retail only; farmed salmon from Chile | moderate | C-FSH-04 C-FSH-05 C-FSH-06 C-FSH-07 |
| I-FSH-111 | An Update on the Content of Fatty Acids, Dioxins, PCBs and Heavy Metals in Farmed, Escaped and Wild Atlantic Salmon (Salmo salar L.) in Norway. Jensen IJ et al. | 2020 | PMID 33352671 DOI 10.3390/foods9121901 | Measurement / residue study | Atlantic salmon fillets (farmed from one producer, July 2017; wild from Finnmark, 2017-2018; origin checked by scale analysis) | Dioxins, PCBs and mercury were about three times higher in wild than in farmed salmon, all below EU limits; farmed salmon had a lower omega-3:omega-6 ratio but more EPA+DHA per portion. | Single farm, small n; Single region | moderate | C-FSH-01 C-FSH-02 C-FSH-04 C-FSH-05 C-FSH-13 |
| I-FSH-112 | Poultry manure fertilization of Egyptian aquaculture ponds brings more cons than pros Nyberg O et al. | 2024 | DOI 10.1016/j.aquaculture.2024.741040 | Cross-sectional study | Egyptian tilapia farms (earthen ponds around the Northern Delta Lakes) | In 501 Egyptian tilapia farms, chicken manure did not raise yields or profit, and ponds using it had more antibiotic-resistance genes in the sediment. | Abstract only; Fish flesh contamination and consumer health not measured | moderate | C-FSH-12 C-FSH-16 |
| I-FSH-113 | Assessment of heavy metals and microbial loads in Nile tilapia (Oreochromis niloticus) from different farms and rivers. Suleman R et al. | 2025 | PMID 39934286 DOI 10.1038/s41598-025-87152-y | Measurement / residue study | Nile tilapia from the Ravi and Chenab rivers and nearby farms, Punjab | Tilapia from polluted rivers had more heavy metals and bacteria than tilapia from nearby farms. | Pakistan, polluted rivers; Some chromium values look implausibly high (possible unit problem) | low | C-FSH-02 C-FSH-12 |
| I-FSH-114 | A 20-year retrospective review of global aquaculture. Naylor RL et al. | 2021 | PMID 33762770 DOI 10.1038/s41586-021-03308-6 | Narrative review | Global aquaculture | Fish farms now need less wild fish per kilogram of farmed fish, but still rely on marine feed ingredients. | Narrative; abstract only; no net fish-balance figures read | moderate | C-FSH-11 |
| I-FSH-115 | Ecological Impacts of Emamectin Benzoate, a Sea Lice Therapeutant, on Benthic Communities in the Vicinity of Norwegian Aquaculture Facilities. Arnberg M et al. | 2026 | PMID 41566218 DOI 10.1021/acs.est.5c11181 | Cross-sectional study | Seabed communities near Norwegian farms | Emamectin benzoate was widespread in sediments and had the strongest negative effect on seabed animals, especially crustaceans. | Environmental outcomes only, not consumer health | moderate | C-FSH-10 |
| I-FSH-116 | Prevalence and Severity of Food Allergies Among US Adults. Gupta RS et al. | 2019 | PMID 30646188 DOI 10.1001/jamanetworkopen.2018.5630 | Cross-sectional study | US adults | Shellfish was the most common adult food allergy, at 2.9%. | Self-report, not challenge-confirmed; Low response rates | moderate | C-FSH-15 |
| I-FSH-117 | Steroid hormones in fish, caution for present and future: A review. Islam P et al. | 2024 | PMID 39323426 DOI 10.1016/j.toxrep.2024.101733 | Narrative review | Fish production globally | Hormones are used in some fish farming and residues are poorly monitored; the review's health-harm statements are not well supported. | Narrative review without systematic methods in the abstract; Causal health-harm statements not supported by human outcome data in the abstract; likely overstated | very low | C-FSH-16 |
| I-FSH-118 | A review of the global use of fishmeal and fish oil and the Fish In:Fish Out metric. Majluf P et al. | 2024 | PMID 39413173 DOI 10.1126/sciadv.adn5650 | Narrative review | Global aquaculture feed supply | Farmed carnivorous species such as salmon and shrimp use most of the world's fishmeal and fish oil, made mainly from small wild fish; the usual efficiency metric hides this. | Abstract only; Authors linked to ocean-conservation research; methods not seen | moderate | C-FSH-11 |
| I-FSH-119 | Prevalence of shrimp allergy: a meta-analysis based on different diagnostic methods. Chen J et al. | 2025 | PMID 40958988 DOI 10.3389/falgy.2025.1635274 | Meta-analysis | General populations (children and adults) | Across 40 studies, about 2% reported shrimp allergy and 0.5% were confirmed by food challenge. | Considerable heterogeneity; Abstract only | moderate | C-FSH-15 |
| I-FSH-12 | Comparative analysis of virulence genes, antibiotic resistance and gyrB-based phylogeny of motile Aeromonas species isolates from Nile tilapia and domestic fowl. Abu-Elala N et al. | 2015 | PMID 26280543 DOI 10.1111/lam.12484 | Other | Nile tilapia, domestic fowl isolates | Integrated fish farms often use poultry droppings as feed and fertiliser. | Small microbiological study | low | C-FSH-12 |
| I-FSH-13 | Systems-thinking approach to identify and assess feasibility of potential interventions to reduce antibiotic use in tilapia farming in Egypt. Desbois AP et al. | 2021 | PMID 34276104 DOI 10.1016/j.aquaculture.2021.736735 | Other | Aquaculture stakeholders | Antibiotics enter farms via medicated feed and drainage water. | Qualitative | low | C-FSH-08 C-FSH-12 |
| I-FSH-14 | Carcinogenic and non-carcinogenic health risks associated with heavy metal exposure in commonly consumed marine fish in Egypt. Elshebrawy HA et al. | 2026 | PMID 42632867 DOI 10.1038/s41598-026-67201-w | Measurement / residue study | Flathead grey mullet (Mugil cephalus, n=50), round sardinella (Sardinella aurita, n=100) and Atlantic mackerel (Scomber scombrus, n=100; imported frozen, mainly from Norway and the Netherlands per vendors) from six retail outlets in East Mansoura | Up to a fifth of mullet, sardine and mackerel samples exceeded mercury limits; heavy eaters could exceed safe intake for mercury and lead (arsenic risk is probably overestimated). | Total arsenic used for cancer risk; authors state more than 90% of As in marine fish is organic and only 0.02-11% inorganic, so cancer risk is substantially overestimated; Hg measured as total Hg (treated as MeHg) | moderate | C-FSH-14 |
| I-FSH-15 | Toxic trace elements in fish and seafood from North African coasts: A systematic review and meta-analysis of contamination levels and health risk assessment. Nahal A & Mehouel F | 2026 | PMID 42250752 DOI 10.1016/j.yrtph.2026.106156 | Meta-analysis | Fish and seafood | Mercury and cadmium in seafood signalled potential concern in Egypt and Tunisia. | Heterogeneous studies; Mixed farmed/wild | moderate | C-FSH-14 |
| I-FSH-16 | Prevalence of fish and shellfish allergy: A systematic review. Moonesinghe H et al. | 2016 | PMID 27613460 DOI 10.1016/j.anai.2016.07.015 | Systematic review | General populations | With proper food challenges, under 1% of people were allergic to shellfish. | Heterogeneous diagnostic methods | moderate | C-FSH-15 |
| I-FSH-17 | Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food. EFSA Panel on Contaminants in the Food Chain (CONTAM) et al. | 2018 | PMID 32625737 DOI 10.2903/j.efsa.2018.5333 | Risk assessment | EU population; farm animals | EFSA set a stricter weekly limit for dioxins (2 pg TEQ/kg/week), which many Europeans exceed from their whole diet. | Single critical study | high | C-FSH-02 C-FSH-03 C-EGG-08 |
| I-FSH-18 | Risk to human health related to the presence of perfluoroalkyl substances in food. EFSA Panel on Contaminants in the Food Chain (EFSA CONTAM Panel) et al. | 2020 | PMID 32994824 DOI 10.2903/j.efsa.2020.6223 | Risk assessment | EU population | Fish meat, fruit and eggs were the main dietary PFAS sources; EFSA set a weekly limit of 4.4 ng/kg body weight, which parts of the population exceed. Freshwater fish such as eel had the highest levels; salmon/trout were low. | 92% of results left-censored; large LB-UB gap; Occurrence data concentrated in 3 countries | high | C-FSH-14 |
| I-FSH-19 | Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food. EFSA Panel on Contaminants in the Food Chain (CONTAM) et al. | 2018 | PMID 32625773 DOI 10.2903/j.efsa.2018.5194 | Risk assessment | EU population | Fish and seafood were important dietary sources of PFOS and PFOA; many Europeans exceeded EFSA's 2018 weekly limits (13 and 6 ng/kg). | High left-censoring and insensitive methods; large LB-UB gap; Data dominated by Germany (62%) | high | C-FSH-14 |
| I-FSH-20 | Scientific Opinion on the risk for public health related to the presence of mercury and methylmercury in food (EFSA press release: 'Mercury in food - EFSA updates advice on risks for public health', 20 December 2012) EFSA CONTAM Panel | 2012 | DOI 10.2903/j.efsa.2012.2985 | Risk assessment | EU population | EFSA set a weekly safety limit for methylmercury; tuna, swordfish and pike are among the main sources. | Only the press release was read | high | C-FSH-14 |
| I-FSH-21 | Statement on the benefits of fish/seafood consumption compared to the risks of methylmercury in fish/seafood (EFSA press release 'Fish: scenarios indicate benefits versus risks', 22 January 2015) EFSA Scientific Committee | 2015 | DOI 10.2903/j.efsa.2015.3982 | Risk assessment | EU population groups | Eating fish 1-4 times a week brings benefits; children and women of childbearing age should choose low-mercury species. | Only press release read | high | C-FSH-14 |
| I-GRN-01 | Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity. Skodje GI et al. | 2018 | PMID 29102613 DOI 10.1053/j.gastro.2017.10.040 | Randomised controlled trial | 59 adults on self-instituted gluten-free diet, coeliac excluded | In people who think they react to gluten, a wheat sugar (fructan) caused more symptoms than gluten. | Small; short challenges | high | C-GRN-01 C-WHT-09 |
| I-GRN-02 | European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. Al-Toma A et al. | 2019 | PMID 31210940 DOI 10.1177/2050640619844125 | Guideline / position statement | Adults and children with coeliac disease (CD), dermatitis herpetiformis, non-coeliac gluten sensitivity (NCGS), gluten ataxia and other gluten-related disorders | Coeliac disease needs a strict lifelong gluten-free diet; gluten is in wheat, rye and barley (not in uncontaminated rice, maize or oats); non-coeliac gluten sensitivity is recognised after coeliac disease and wheat allergy are excluded. | Literature search in PubMed only; no systematic review, evidence tables or explicit study selection criteria; Consensus by a small board (8 authors); no patient, dietitian or methodologist involvement reported | moderate | C-GRN-01 C-GRN-02 C-GRN-03 C-WHT-02 |
| I-GRN-03 | White Rice Intake and Incident Diabetes: A Study of 132,373 Participants in 21 Countries. Bhavadharini B et al. | 2020 | PMID 32873587 DOI 10.2337/dc19-2335 | Cohort study | PURE participants aged 35-70 years without baseline diabetes, with complete diet data and >=1 follow-up visit (148,858 with diet data minus 16,485 with baseline diabetes); mean age 50 years; South Asia n=26,419, China n=41,727, rest of world n=64,227 | Very high white rice intake (>=3 cups/day) linked to 20% higher diabetes risk. | Diet measured once at baseline by FFQ; no rice type data (parboiled, basmati, etc.); Residual confounding possible (authors list unmeasured alcohol, air pollution, pesticides; South Asian high consumers differ markedly: lower BMI, fibre 10.8 vs 24.2 g/day, 71% energy from carbohydrate) | high | C-GRN-05 C-SRC-18 |
| I-GRN-04 | Total and specific potato intake and risk of type 2 diabetes: results from three US cohort studies and a substitution meta-analysis of prospective cohorts. Mousavi SM et al. | 2025 | PMID 40769531 DOI 10.1136/bmj-2024-082121 | Cohort study | US female nurses (NHS n=72,712; NHS II n=90,232) and male health professionals (HPFS n=42,163), free of diabetes, CVD and cancer at baseline; >90% of European ancestry. Meta-analysis: 13 cohorts (5 US, 4 Europe, 2 Asia, 2 Australia), 587,081 participants | Eating fries 3 more times a week was linked to 20% higher diabetes risk; boiled, baked or mashed potatoes and potato/corn chips showed no clear link. Swapping potatoes for whole grains was linked to lower risk, swapping for white rice to higher risk. | Observational: residual confounding (high potato/fries consumers had lower diet quality and activity); Health professionals, >90% European ancestry; effect modification by race and BMI | high | C-GRN-07 C-GRN-05 |
| I-GRN-05 | Fried potato consumption is associated with elevated mortality: an 8-y longitudinal cohort study. Veronese N et al. | 2017 | PMID 28592612 DOI 10.3945/ajcn.117.154872 | Cohort study | 4440 adults 45-79 y | Fried potatoes 3+ times/week linked to about double the death risk in a small cohort. | Small number of deaths; Subgroup finding | low | C-GRN-07 |
| I-GRN-06 | Update of the risk assessment of inorganic arsenic in food. EFSA CONTAM Panel | 2024 | PMID 38239496 DOI 10.2903/j.efsa.2024.8488 | Risk assessment | EU population | Arsenic exposure from food, mainly rice, is a health concern; the EU limits arsenic in rice. | Uncertainties acknowledged | high | C-GRN-06 |
| I-GRN-07 | International tables of glycemic index and glycemic load values 2021: a systematic review. Atkinson FS et al. | 2021 | PMID 34258626 DOI 10.1093/ajcn/nqab233 | Systematic review | Foods tested | Fruits usually have a low GI; most potatoes have a high GI. | Abstract only; food-specific values not extracted | high | C-FRU-01 C-GRN-07 C-SRC-18 |
| I-GRN-101 | Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials. Molina-Infante J et al. | 2017 | PMID 27523634 DOI 10.1016/j.cgh.2016.08.007 | Systematic review | Adults with suspected NCGS who responded to a gluten-free diet | Only 16% of 231 people with suspected gluten sensitivity reacted specifically to gluten in blinded challenges. | Short report; no formal risk-of-bias or GRADE assessment in abstract; Very heterogeneous doses, durations and placebos | moderate | C-GRN-01 |
| I-GRN-102 | The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-coeliac gluten sensitivity: a randomised, double-blind, placebo-controlled, international, multicentre study. de Graaf MCG et al. | 2024 | PMID 38040019 DOI 10.1016/S2468-1253(23)00317-5 | Randomised controlled trial | Adults 18-70 years with self-reported NCGS, coeliac disease and wheat allergy excluded, asymptomatic on a gluten-free diet | People with self-reported gluten sensitivity had the most symptoms when they expected and got gluten; gluten given without that expectation caused no extra symptoms. | Single-day challenge; Per-protocol analysis | moderate | C-GRN-01 |
| I-GRN-103 | Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Uhde M et al. | 2016 | PMID 27459152 DOI 10.1136/gutjnl-2016-311964 | Case-control study | People reporting wheat-related symptoms with coeliac disease and wheat allergy excluded; coeliac patients; healthy controls | People who react to wheat without coeliac disease had higher markers of immune activation and gut-cell damage, which improved off wheat in a subgroup. | Not blinded challenge; self-selected cases; Cross-sectional, so cause and effect unclear | moderate | C-GRN-01 |
| I-GRN-104 | Prevalence of celiac disease in Egyptian children disputes the east-west agriculture-dependent spread of the disease. Abu-Zekry M et al. | 2008 | PMID 18664863 DOI 10.1097/MPG.0b013e31815ce5d1 | Cross-sectional study | Egyptian children: general population sample, children with diarrhoea/failure to thrive, children with type 1 diabetes | Screening of 1500 Egyptian children found coeliac disease in 0.53%, and much more often in children with diarrhoea or type 1 diabetes. | Single study; sampling frame details not in abstract; Reported CI is a Wald interval (stats/C-GRN-01) | moderate | C-GRN-01 C-WHT-02 |
| I-GRN-105 | American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease. Rubio-Tapia A et al. | 2023 | PMID 36602836 DOI 10.14309/ajg.0000000000002075 | Guideline / position statement | Children and adults with suspected or confirmed coeliac disease | Coeliac disease is a lifelong immune reaction to gluten from wheat, barley and rye; treatment is a strict gluten-free diet with medical follow-up. | Full text not accessible (publisher block); only abstract read; A correction was published (content not read) | high | C-GRN-01 C-GRN-02 C-GRN-03 C-WHT-02 |
| I-GRN-106 | Coeliac disease: recognition, assessment and management (NICE guideline NG20) - Recommendations National Institute for Health and Care Excellence (NICE) | 2015 | Guideline / position statement | Children and adults in England | People with unexplained iron deficiency, IBS-type symptoms and other signs should be tested, and must keep eating gluten until a specialist confirms the diagnosis. | 2015 guideline; still current on the website | high | C-GRN-01 C-WHT-02 C-GRN-03 | |
| I-GRN-107 | A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease. Catassi C et al. | 2007 | PMID 17209192 DOI 10.1093/ajcn/85.1.160 | Randomised controlled trial | Adults with biopsy-proven coeliac disease on a gluten-free diet for >=2 years | In treated coeliac patients, 50 mg gluten daily for 3 months reduced villus height by about 20%; placebo did not. | Small groups; Only 90 days | moderate | C-GRN-03 C-GRN-02 |
| I-GRN-108 | Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease. Leffler D et al. | 2013 | PMID 22619366 DOI 10.1136/gutjnl-2012-302196 | Randomised controlled trial | Adults with biopsy-proven coeliac disease on a gluten-free diet | In 20 coeliac adults, 3 g gluten daily for 14 days halved villus height ratio; symptoms rose and then went back to baseline by day 28. | Small, no placebo arm; Short duration | moderate | C-GRN-03 |
| I-GRN-109 | Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Lebwohl B et al. | 2013 | PMID 23922062 DOI 10.7326/0003-4819-159-3-201308060-00006 | Cohort study | Patients with coeliac disease who had a follow-up biopsy | Among 7625 Swedish coeliac patients, those whose gut had not healed had about twice the lymphoma risk of those whose gut had healed. | No dietary adherence data; Observational; persistent atrophy may have causes other than gluten | moderate | C-GRN-03 |
| I-GRN-110 | Long-term follow-up of 61 coeliac patients diagnosed in childhood: evolution toward latency is possible on a normal diet. Matysiak-Budnik T et al. | 2007 | PMID 17303598 DOI 10.1136/gut.2006.100511 | Case series / case report | Adults (18-65) diagnosed with coeliac disease in childhood who had resumed a normal diet and were symptom-free | Of 61 symptom-free adults back on a normal diet, 48 had villous atrophy and many had bone loss; 13 had no atrophy, but some of those relapsed later. | Retrospective, selected; Small | low | C-GRN-03 |
| I-GRN-111 | Safety of Adding Oats to a Gluten-Free Diet for Patients With Celiac Disease: Systematic Review and Meta-analysis of Clinical and Observational Studies. Pinto-Sánchez MI et al. | 2017 | PMID 28431885 DOI 10.1053/j.gastro.2017.04.009 | Meta-analysis | Children and adults with coeliac disease | Adding uncontaminated oats for up to 12 months did not change symptoms, gut histology or antibodies, but evidence quality was low. | Low-quality evidence; Few studies per outcome | moderate | C-GRN-02 |
| I-GRN-112 | Naturally gluten-free flours are commonly contaminated, while commercially produced gluten-free flours are relatively safe: a market-based study in Turkey. Öcal HY et al. | 2025 | PMID 41459067 DOI 10.3389/fnut.2025.1707584 | Measurement / residue study | Oat, buckwheat, corn and rice flours on sale | In Turkey, 17% of certified gluten-free flours but 50-85% of unlabelled naturally gluten-free flours exceeded the 20 ppm gluten limit. | One country; No data on time on shelf | moderate | C-GRN-02 |
| I-GRN-113 | The Prevalence of Anti-Zein Antibodies: A Comparative Study between Celiac Disease and Irritable Bowel Syndrome. Sánchez-Vargas LA et al. | 2021 | PMID 33671228 DOI 10.3390/nu13020649 | Cross-sectional study | Newly diagnosed coeliac patients, IBS patients, healthy controls | About a third of newly diagnosed coeliac patients had antibodies to the maize protein zein, rarely seen in others. | In-house ELISA; Small coeliac group | low | C-GRN-02 |
| I-GRN-114 | White rice intake and incidence of type-2 diabetes: analysis of two prospective cohort studies from Iran. Golozar A et al. | 2017 | PMID 28137245 DOI 10.1186/s12889-016-3999-4 | Cohort study | Adults without diabetes or chronic disease at baseline | Eating more than 250 g of white rice a day was linked to about twice the odds of diabetes in Tehran, but not in rural Golestan. | Logistic regression of cumulative incidence (OR, not HR); Few cases in TLGS (81) | moderate | C-GRN-05 |
| I-GRN-115 | Rice consumption and risk of cardiovascular disease: results from a pooled analysis of 3 U.S. cohorts. Muraki I et al. | 2015 | PMID 25527760 DOI 10.3945/ajcn.114.087551 | Cohort study | US women and men free of CVD and cancer | Eating white or brown rice 5 or more times a week was not associated with higher cardiovascular risk. | Low rice intake in US population; FFQ | high | C-GRN-05 C-GRN-06 |
| I-GRN-116 | Rice consumption contributes to arsenic exposure in US women. Gilbert-Diamond D et al. | 2011 | PMID 22143778 DOI 10.1073/pnas.1109127108 | Measurement / residue study | Pregnant women in a US cohort | In 229 pregnant women, rice intake raised urinary arsenic; 0.56 cup of cooked rice per day matched 1 L of water at 10 ug/L. | Small; Exposure only, no health outcomes | moderate | C-GRN-06 |
| I-GRN-117 | Geographical variation in total and inorganic arsenic content of polished (white) rice. Meharg AA et al. | 2009 | PMID 19350943 DOI 10.1021/es802612a | Measurement / residue study | 901 polished rice samples for market sale, 10 countries | Median total arsenic in white rice was 0.04 mg/kg in Egypt versus 0.25-0.28 mg/kg in the USA and France. | 2009 data; Egyptian samples not speciated (inorganic fraction unknown) | moderate | C-GRN-06 |
| I-GRN-118 | Association between rice consumption and risk of cancer incidence in the California Teachers Study. Sanchez TR et al. | 2020 | PMID 32974796 DOI 10.1007/s10552-020-01350-9 | Cohort study | Women in the California Teachers Study | Rice intake was not associated with most arsenic-related cancers; breast cancer showed a borderline 7% higher risk. | Low rice intake; No arsenic biomarker | moderate | C-GRN-06 |
| I-GRN-119 | Potato intake and incidence of hypertension: results from three prospective US cohort studies. Borgi L et al. | 2016 | PMID 27189229 DOI 10.1136/bmj.i2351 | Cohort study | Non-hypertensive US adults | In 187,000 US adults, eating French fries 4+ times a week was linked to 17% higher hypertension risk. | Self-reported hypertension; Observational | moderate | C-GRN-07 |
| I-GRN-120 | Potato Consumption and Risk of Cardiovascular Disease in a Harmonized Analysis of Seven Prospective Cohorts. Djousse L et al. | 2025 | PMID 39940309 DOI 10.3390/nu17030451 | Meta-analysis | Adults in seven cohorts | In seven cohorts, total potato intake was not associated with CVD; fried potatoes 1+ times a week were linked to 10% higher hypertension risk. | Potato-industry related grant; FFQ | moderate | C-GRN-07 |
| I-GRN-121 | Changes in diet and lifestyle and long-term weight gain in women and men. Mozaffarian D et al. | 2011 | PMID 21696306 DOI 10.1056/NEJMoa1014296 | Cohort study | US women and men free of chronic disease and not obese at baseline | In 120,877 US adults, each extra daily serving of potato chips was linked to 0.8 kg and French fries to 1.5 kg more weight gain over 4 years. | Self-reported weight and diet; Observational | moderate | C-GRN-07 C-WHT-06 |
| I-GRN-122 | Green wheat Freekeh: evolution from traditional cereal to sustainable future food. Aluthge S et al. | 2026 | PMID 40622358 DOI 10.1080/10408398.2025.2528741 | Narrative review | not applicable | A review reports 12-19% dietary fibre and 11-15% protein in freekeh, and notes that it contains gluten. | Narrative, not systematic; No outcome studies | low | C-GRN-08 |
| I-GRN-123 | Mycotoxin Prevalence and Microbiological Characteristics of Locally Produced Elected Freekeh Products. Mudalal S | 2024 | PMID 39591254 DOI 10.3390/toxins16110499 | Measurement / residue study | Local freekeh products | In locally produced freekeh, more than 78% of samples exceeded EU limits for aflatoxin and ochratoxin in a screening test. | Lateral-flow screening assay, not confirmatory LC-MS; Small, local sample | low | C-GRN-08 |
| I-GUT-01 | Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Malfertheiner P et al. | 2022 | PMID 35944925 DOI 10.1136/gutjnl-2022-327745 | Guideline / position statement | Global | H. pylori is an infectious disease; infected people should be treated. | Industry COI of several authors; Abstract only read | moderate | C-GUT-06 C-SRC-50 |
| I-GUT-02 | Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive people. Ford AC et al. | 2016 | PMID 27092708 DOI 10.1002/14651858.CD003840.pub5 | Meta-analysis | H. pylori-positive ulcer patients | Duodenal ulcer recurrence fell from 64% without treatment to 13% with eradication. | Low/very low GRADE for some outcomes (older trials) | high | C-GUT-06 C-SOD-12 |
| I-GUT-03 | Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis. Ford AC et al. | 2020 | PMID 32205420 DOI 10.1136/gutjnl-2020-320839 | Meta-analysis | Healthy H. pylori-positive adults; patients after endoscopic resection | Eradication nearly halved gastric cancer incidence in trials. | Mostly East Asian; COI of one author | high | C-GUT-06 |
| I-GUT-04 | Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity. Skodje GI et al. | 2018 | PMID 29102613 DOI 10.1053/j.gastro.2017.10.040 | Randomised controlled trial | Adults on self-instituted gluten-free diet, coeliac disease excluded | In people who felt gluten-sensitive, fructans (wheat sugars) increased bloating and symptoms; gluten did not. | Small; Selected population | moderate | C-GUT-01 |
| I-GUT-05 | ACG Clinical Guideline: Management of Irritable Bowel Syndrome. Lacy BE et al. | 2021 | PMID 33315591 DOI 10.14309/ajg.0000000000001036 | Guideline / position statement | Patients with IBS | A low-FODMAP diet trial is recommended, along with drugs and psychotherapy. | Abstract only | high | C-GUT-01 C-GUT-02 |
| I-GUT-06 | Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Kirkpatrick AW et al. | 2013 | PMID 23673399 DOI 10.1007/s00134-013-2906-z | Guideline / position statement | Critically ill patients | Harmful pressure starts at ≥12 mmHg sustained, in critically ill patients. | Low-quality evidence base | moderate | C-GUT-04 C-UPF-10 |
| I-GUT-07 | Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Reynolds A et al. | 2019 | PMID 30638909 DOI 10.1016/S0140-6736(18)31809-9 | Meta-analysis | Adults without chronic disease | People eating the most fibre had 15–30% lower risk of death and major chronic diseases. | Observational main outcomes; Erratum | high | C-GUT-05 |
| I-GUT-08 | Gut-microbiota-targeted diets modulate human immune status. Wastyk HC et al. | 2021 | PMID 34256014 DOI 10.1016/j.cell.2021.06.019 | Randomised controlled trial | Healthy adults | Fermented foods increased gut bacterial diversity and lowered inflammation markers in a small trial. | Very small; Primary outcome null | low | C-GUT-05 |
| I-GUT-09 | Dietary interventions for multiple sclerosis-related outcomes. Parks NE et al. | 2020 | PMID 32428983 DOI 10.1002/14651858.CD004192.pub4 | Systematic review | Adults with MS | No reliable evidence that diet changes relapses or disability in MS. | Low-certainty evidence; Author COI | high | C-AUTO-01 |
| I-GUT-10 | EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Fanouriakis A et al. | 2024 | PMID 37827694 DOI 10.1136/ard-2023-224762 | Guideline / position statement | Patients with SLE (incl. lupus nephritis, cutaneous, neuropsychiatric, haematological disease, SLE-associated APS) | Hydroxychloroquine for all patients; immunosuppressants and biologics to control disease. | Extensive industry relationships of panel members relevant to recommended biologics; SLR limited to two databases and English language | high | C-AUTO-01 C-EGG-03 |
| I-GUT-102 | Efficacy of dietary interventions in irritable bowel syndrome: a systematic review and network meta-analysis. Cuffe MS et al. | 2025 | PMID 40258374 DOI 10.1016/S2468-1253(25)00054-8 | Meta-analysis | Adults with IBS in 28 RCTs (2338 patients) | A review of 28 trials found that several diets, especially low-FODMAP and a starch- and sugar-reduced diet, improved IBS symptoms more often than usual eating. | Diet trials cannot be blinded well; Starch/sucrose-reduced diet based on only 2 trials | high | C-GUT-01 C-GUT-02 |
| I-GUT-103 | Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet, and the Gluten-Free Diet. Rej A et al. | 2022 | PMID 35240330 DOI 10.1016/j.cgh.2022.02.045 | Randomised controlled trial | Adults with Rome IV non-constipated IBS, UK tertiary centre | In 99 IBS patients, about half improved meaningfully after 4 weeks on a gluten-free, low-FODMAP or standard advice diet. | Small, underpowered for differences; No habitual-diet control arm | moderate | C-GUT-01 C-GUT-02 |
| I-GUT-104 | The placebo response rate in pharmacological trials in patients with irritable bowel syndrome: a systematic review and meta-analysis. Bosman M et al. | 2021 | PMID 33765447 DOI 10.1016/S2468-1253(21)00023-6 | Meta-analysis | Adults with IBS in placebo arms of 73 RCTs | Across 73 trials, about 27% of IBS patients improved overall on dummy pills. | Drug trials, not diet trials; High heterogeneity | high | C-GUT-02 |
| I-GUT-105 | Association of Diet and Lifestyle With the Risk of Gastroesophageal Reflux Disease Symptoms in US Women. Mehta RS et al. | 2021 | PMID 33393976 DOI 10.1001/jamainternmed.2020.7238 | Cohort study | Women aged 42-62 without weekly GERD symptoms or regular PPI/H2RA use at baseline | Women with five healthy habits had half the risk of developing weekly heartburn; normal weight mattered most. | Self-reported symptoms; Mostly White women | moderate | C-GUT-01 C-GUT-02 |
| I-GUT-106 | Lifestyle Intervention in Gastroesophageal Reflux Disease. Ness-Jensen E et al. | 2016 | PMID 25956834 DOI 10.1016/j.cgh.2015.04.176 | Systematic review | Adults with GERD | Weight loss, stopping smoking, not eating late and raising the head of the bed reduced reflux in studies of GERD patients. | Few, small trials; No meta-analysis | moderate | C-GUT-07 C-GUT-01 |
| I-GUT-107 | Association between dinner-to-bed time and gastro-esophageal reflux disease. Fujiwara Y et al. | 2005 | PMID 16393212 DOI 10.1111/j.1572-0241.2005.00354.x | Case-control study | 147 GERD patients and 294 age- and sex-matched controls without reflux symptoms, Japan | People with reflux disease more often went to bed less than 3 hours after dinner than people without reflux. | Case-control; recall bias; reverse causation possible; Self-reported timing | low | C-GUT-07 |
| I-GUT-108 | Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management (NICE guideline CG184) National Institute for Health and Care Excellence (NICE) | 2014 (last updated 18 October 2019) | Guideline / position statement | Adults with dyspepsia, GORD or both | NICE advises lifestyle changes and the lowest effective dose of acid blockers, but long-term full-dose treatment for severe inflammation or a narrowed gullet. | Core recommendations from 2004/2014; Not specific to Egypt | high | C-PPI-10 C-GUT-02 C-GUT-06 C-GUT-07 C-PPI-11 | |
| I-GUT-109 | Suspected cancer: recognition and referral (NICE guideline NG12), section 1.2 upper gastrointestinal tract cancers National Institute for Health and Care Excellence (NICE) | 2015 (last updated 15 April 2026) | Guideline / position statement | Adults in primary care | Difficulty swallowing, vomiting blood, or weight loss with reflux at 55 or older should be checked for cancer. | UK-specific thresholds | high | C-GUT-02 C-PPI-10 | |
| I-GUT-110 | Irritable bowel syndrome in adults: diagnosis and management (NICE guideline CG61) National Institute for Health and Care Excellence (NICE) | 2008 (last updated 04 April 2017) | Guideline / position statement | Adults with IBS | NICE suggests regular meals, plenty of fluids, fewer fizzy drinks and possibly less high-fibre bread, with supervised diets if needed. | Diet advice largely expert-based (2008) | high | C-GUT-01 C-GUT-02 C-GUT-08 | |
| I-GUT-111 | Prevalence of Antibiotic Resistance in Helicobacter pylori: A Systematic Review and Meta-analysis in World Health Organization Regions. Savoldi A et al. | 2018 | PMID 29990487 DOI 10.1053/j.gastro.2018.07.007 | Meta-analysis | H. pylori isolates from 65 countries | In many regions, more than 15% of H. pylori bacteria resist key antibiotics, and resistance makes standard triple therapy fail far more often. | High heterogeneity; Uneven country coverage | moderate | C-GUT-06 |
| I-GUT-112 | Vonoprazan-based therapy versus standard regimen for Helicobacter pylori infection management in Egypt: an open-label randomized controlled trial. Shekeban YM et al. | 2025 | PMID 40341536 DOI 10.1038/s41598-025-98606-8 | Randomised controlled trial | H. pylori-infected adults, Alexandria, Egypt | In an Egyptian trial, standard triple therapy cleared H. pylori in 70% and vonoprazan-based regimens in 76-79% of those who completed treatment. | Open label; Per-protocol only in abstract | low | C-GUT-06 |
| I-GUT-113 | Normal intraabdominal pressure in healthy adults. Cobb WS et al. | 2005 | PMID 16140336 DOI 10.1016/j.jss.2005.06.015 | Cross-sectional study | 20 healthy non-obese adults aged 18-30 without prior abdominal surgery | Coughing and jumping briefly raise pressure inside the abdomen to over 100 mmHg in healthy young adults without harm. | Very small; Upright measurements not comparable with supine ICU standard | low | C-GUT-04 |
| I-GUT-114 | Abdominothoracic mechanisms of functional abdominal distension and correction by biofeedback. Barba E et al. | 2015 | PMID 25500424 DOI 10.1053/j.gastro.2014.12.006 | Other | 45 patients (42 women) with IBS-C, functional bloating or IBS-M and episodes of visible distension | In people with functional bloating, the belly swells because the diaphragm drops and the abdominal wall relaxes, not mainly because of high internal pressure. | Small, selected; No pressure measurement | moderate | C-GUT-04 |
| I-GUT-115 | Review article: insights into colonic protein fermentation, its modulation and potential health implications. Yao CK et al. | 2016 | PMID 26527169 DOI 10.1111/apt.13456 | Narrative review | Clinical and pre-clinical studies | Fermentation of protein in the colon can produce irritating substances, but fermentation of fibre and resistant starch is beneficial and reduces them. | Narrative; largely pre-clinical evidence | low | C-GUT-05 |
| I-GUT-116 | Effect of Increased Daily Water Intake in Premenopausal Women With Recurrent Urinary Tract Infections: A Randomized Clinical Trial. Hooton TM et al. | 2018 | PMID 30285042 DOI 10.1001/jamainternmed.2018.4204 | Randomised controlled trial | Healthy premenopausal women with >=3 cystitis episodes in the past year and fluid intake <1.5 L/day | Women with frequent bladder infections who drank an extra 1.5 litres of water daily had about half as many infections over a year. | Open label; Industry funded | moderate | C-GUT-08 |
| I-GUT-117 | Effect of Coaching to Increase Water Intake on Kidney Function Decline in Adults With Chronic Kidney Disease: The CKD WIT Randomized Clinical Trial. Clark WF et al. | 2018 | PMID 29801012 DOI 10.1001/jama.2018.4930 | Randomised controlled trial | Adults with stage 3 CKD and albuminuria, urine volume <3 L/day | Coaching people with kidney disease to drink about 0.6 L more per day did not change kidney function over a year. | 1 year only; Kidney, not liver, outcomes | high | C-GUT-08 |
| I-GUT-118 | Effect of mastication on lipid bioaccessibility of almonds in a randomized human study and its implications for digestion kinetics, metabolizable energy, and postprandial lipemia. Grundy MM et al. | 2015 | PMID 25527747 DOI 10.3945/ajcn.114.088328 | Randomised controlled trial | 17 healthy adults (15 completed) | After chewing almonds, most cells stayed intact and only about a tenth of the fat was released for digestion. | One food; Small | moderate | C-GUT-09 |
| I-GUT-119 | Bezoar-induced small bowel obstruction: Clinical characteristics and diagnostic value of multi-slice spiral computed tomography. Wang PY et al. | 2015 | PMID 26361425 DOI 10.3748/wjg.v21.i33.9774 | Case series / case report | 35 patients with surgically confirmed bezoar SBO in one Chinese hospital | Among 35 people with bowel blockage from food balls, most had eaten lots of persimmons, half had previous stomach surgery and half had missing back teeth. | No control group; Small, single centre | very low | C-GUT-09 C-GUT-03 |
| I-GUT-120 | Effect of gluten and wheat on symptoms and behaviours in adults with irritable bowel syndrome: a single-centre, randomised, double-blind, sham-controlled crossover trial. Seiler CL et al. | 2025 | PMID 40706614 DOI 10.1016/S2468-1253(25)00090-1 | Randomised controlled trial | Adults with Rome IV IBS who previously reported improvement on a gluten-free diet | IBS patients who believed wheat or gluten made them ill had similar symptom flares after wheat, gluten or a look-alike sham bar. | Small (n=28); Short challenges | high | C-GUT-01 C-GUT-02 |
| I-GUT-122 | Eradication Therapy to Prevent Gastric Cancer in Helicobacterpylori-Positive Individuals: Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies. Ford AC et al. | 2025 | PMID 39824392 DOI 10.1053/j.gastro.2024.12.033 | Meta-analysis | H. pylori-positive adults without neoplasia, or after endoscopic resection of early gastric neoplasia | In randomised trials, clearing H. pylori lowered stomach cancer by about a third and stomach cancer deaths by about a fifth. | Trial regions not detailed in abstract (earlier version mostly East Asian); Overlaps with I-GUT-03 (earlier version) | high | C-GUT-06 |
| I-INS-01 | Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. ADVANCE Collaborative Group; Patel A et al. | 2008 | PMID 18539916 DOI 10.1056/NEJMoa0802987 | Randomised controlled trial | Type 2 diabetes diagnosed at >=30 years, age >=55 (mean 66), with history of major macro- or microvascular disease or >=1 other vascular risk factor; mean diabetes duration 7.9 years, mean HbA1c 7.5%; 91% on oral agents, ~1.5% on insulin; definite indication for long-term insulin excluded. | Fewer kidney complications and no extra deaths, but more severe hypoglycaemia. | Open-label glucose comparison; more visits in intensive arm (31 vs 11) - co-intervention (e.g. lower BP); Mid-trial protocol amendment adding joint primary outcome (stated as blinded to results) | high | C-INS-04 C-ODD-11 |
| I-INS-02 | 10-year follow-up of intensive glucose control in type 2 diabetes. Holman RR et al. | 2008 | PMID 18784090 DOI 10.1056/NEJMoa0806470 | Randomised controlled trial | Newly diagnosed type 2 diabetes from UKPDS | People treated intensively early with sulfonylureas or insulin had 15% fewer heart attacks and 13% fewer deaths years later. | Post-trial therapy not controlled; Questionnaire follow-up | high | C-INS-03 C-INS-04 C-INS-05 C-ODD-01 C-ODD-11 C-DIAB-01 |
| I-INS-03 | The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. Diabetes Control and Complications Trial Research Group; Nathan DM et al. | 1993 | PMID 8366922 DOI 10.1056/NEJM199309303291401 | Randomised controlled trial | Insulin-dependent (type 1) diabetes | Intensive insulin cut the risk of eye damage by three-quarters and nerve damage by 60%, with more low-sugar episodes. | Open-label; Selected young population | high | C-INS-02 C-INS-04 C-INS-07 C-INS-09 C-INS-10 C-ODD-03 C-DIAB-01 C-DIAB-03 |
| I-INS-04 | Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. Stratton IM et al. | 2000 | PMID 10938048 DOI 10.1136/bmj.321.7258.405 | Cohort study | UKPDS patients (white, Asian Indian, Afro-Caribbean) | Each 1% lower HbA1c was linked to 21% fewer diabetes deaths and 37% fewer eye/kidney complications. | Observational | moderate | C-INS-09 C-ODD-06 C-DIAB-01 C-DIAB-02 |
| I-INS-05 | The association of basal insulin glargine and/or n-3 fatty acids with incident cancers in patients with dysglycemia. Bordeleau L et al. | 2014 | PMID 24574355 DOI 10.2337/dc13-1468 | Randomised controlled trial | Dysglycaemia with high CV risk, mean age 63.5 | Cancer rates were identical with glargine and standard care (1.32 per 100 person-years each). | Industry funding; 6 years may be short for some cancers | high | C-INS-05 C-INS-06 |
| I-INS-06 | Insulin glargine and cancer risk in patients with diabetes: a meta-analysis. Tang X et al. | 2012 | PMID 23284776 DOI 10.1371/journal.pone.0051814 | Meta-analysis | Diabetes patients | Glargine was not linked to more cancer, including breast cancer. | Very high heterogeneity (I2 = 93% overall cancer; ~80% breast cancer); No study-level risk-of-bias tool; 3 of 11 studies unadjusted for confounders; few adjusted for metformin or diabetes type | low | C-INS-06 |
| I-INS-07 | Hyperglycemic Crises in Adults With Diabetes: A Consensus Report. Umpierrez GE et al. | 2024 | PMID 39052901 DOI 10.2337/dci24-0032 | Guideline / position statement | Adults with diabetes | Insulin, fluids and potassium are the core treatment; with this, fewer than 1% of adults die. | Consensus, not trial | high | C-INS-02 C-INS-07 C-INS-08 C-INS-09 C-INS-10 C-FAST-03 C-FAST-10 C-DIAB-02 C-SYS-06 C-SUG-07 |
| I-INS-08 | Diabetic ketoacidosis. Dhatariya KK et al. | 2020 | PMID 32409703 DOI 10.1038/s41572-020-0165-1 | Narrative review | Adults and children with diabetes | DKA is an emergency that can kill; it is treated with fluids, insulin and salts, and insulin must not be stopped in type 1 diabetes even when not eating. | Narrative review without systematic search, selection or appraisal methods; Epidemiological figures are cited from heterogeneous primary studies, not pooled | moderate | C-INS-02 C-INS-07 C-INS-08 C-INS-10 C-ODD-03 C-FAST-01 C-FAST-03 C-DIAB-02 |
| I-INS-09 | Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. Hall KD et al. | 2015 | PMID 26278052 DOI 10.1016/j.cmet.2015.07.021 | Randomised controlled trial | Adults with obesity (BMI >30; mean 35.9 +/- 1.1 kg/m2), 10 men and 9 women, weight-stable, non-diabetic per exclusion of interfering disease/medication | Cutting fat led to more fat loss than cutting carbs, even though cutting carbs lowered insulin more. | Very short (6-day) diet periods; long-term inference rests on model simulation; Small sample (19 randomised, 17 complete crossovers) | high | C-INS-01 C-SRC-22 |
| I-INS-10 | 6. Glycemic Goals, Hypoglycemia, and Hyperglycemic Crises: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes* | 2026 | PMID 41358894 DOI 10.2337/dc26-S006 | Guideline / position statement | People with diabetes | Most adults should aim for HbA1c below 7%, avoid low sugar, and measure ketones when at risk. | US-centred; Partially read | high | C-INS-04 C-INS-08 C-INS-11 C-ODD-01 C-ODD-02 C-FAST-01 C-FAST-03 C-DIAB-02 C-SUG-07 |
| I-INS-101 | Why were "starvation diets" promoted for diabetes in the pre-insulin period? Mazur A | 2011 | PMID 21396115 DOI 10.1186/1475-2891-10-23 | Narrative review | People with diabetes (mostly severe, juvenile-onset) treated 1914-1922 in the USA | Before 1922, children with diabetes usually died of diabetic coma within months to a few years, even on strict fasting diets; some starved to death. | Historical, uncontrolled case data; Single author interpretation | low | C-INS-07 C-INS-08 C-INS-10 C-DIAB-03 |
| I-INS-102 | Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study. Gregory GA et al. | 2022 | PMID 36113507 DOI 10.1016/S2213-8587(22)00218-2 | Other | People with type 1 diabetes worldwide | About 8.4 million people had type 1 diabetes in 2021; a 10-year-old diagnosed in a low-income country could expect about 13 more years of life, versus 65 in a high-income country. | Model-based; sparse mortality data (37 countries); Diagnosis rates from expert survey | moderate | C-INS-07 C-INS-10 |
| I-INS-103 | Glycemic control and excess mortality in type 1 diabetes. Lind M et al. | 2014 | PMID 25409370 DOI 10.1056/NEJMoa1408214 | Cohort study | Patients with T1D registered from 1998 and matched population controls | People with type 1 diabetes died about 3.5 times as often as matched controls; with very high HbA1c the risk was about 8.5 times higher. | Observational; Residual confounding | high | C-INS-07 C-DIAB-01 |
| I-INS-104 | Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. Writing Group for the DCCT/EDIC Research Group et al. | 2015 | PMID 25562265 DOI 10.1001/jama.2014.16107 | Randomised controlled trial | 1441 people aged 13-39 with T1D, 1-15 years duration, without major complications | People who received intensive insulin treatment for about 6.5 years had about one third lower death risk 27 years later. | Post-trial period observational; Few deaths; CI near 1 | high | C-INS-09 C-DIAB-01 C-ODD-03 |
| I-INS-105 | Glycemic Control and Adult Height: A Nationwide Swedish Cohort Study on Childhood Type 1 Diabetes. Smew AI et al. | 2025 | PMID 39556501 DOI 10.1210/clinem/dgae809 | Cohort study | All individuals with childhood-onset T1D in the register | Children with poorly controlled type 1 diabetes ended up about 2-3 cm shorter as adults than those with good control. | Observational; Sample size not given in abstract | moderate | C-INS-07 |
| I-INS-106 | The influence of treatment, age at onset, and metabolic control on height in children and adolescents with type 1 diabetes-A SWEET collaborative study. Svensson J et al. | 2018 | PMID 30105887 DOI 10.1111/pedi.12751 | Cross-sectional study | Youth <20 years with T1D >1 year, without coeliac disease | In about 23,000 young people, those on more intensive insulin treatment were taller; major growth problems were virtually absent with modern care. | Cross-sectional; Industry grant | moderate | C-INS-07 |
| I-INS-107 | Mauriac Syndrome in Sudanese Children: An Old Syndrome Still Existing in Resource-Limited Countries. Ismail MM et al. | 2025 | PMID 40904852 DOI 10.1155/pedi/7047312 | Case series / case report | Children and adolescents with T1D (and 2 with neonatal diabetes) and Mauriac syndrome | Children with long-standing poor control were short and had enlarged livers; most improved when their insulin treatment was intensified. | Small, uncontrolled; Clinical diagnosis only | low | C-INS-07 |
| I-INS-108 | Diabetes in urban African-Americans. I. Cessation of insulin therapy is the major precipitating cause of diabetic ketoacidosis. Musey VC et al. | 1995 | PMID 7497857 DOI 10.2337/diacare.18.4.483 | Case series / case report | Consecutive patients with moderate-to-severe DKA | Two out of three ketoacidosis episodes in people with known diabetes followed stopping insulin. | Small, single centre, 3 months; Old data; specific population | low | C-INS-08 C-INS-10 |
| I-INS-109 | Recurrent diabetic ketoacidosis in inner-city minority patients: behavioral, socioeconomic, and psychosocial factors. Randall L et al. | 2011 | PMID 21775761 DOI 10.2337/dc11-0701 | Cross-sectional study | Adults admitted with DKA to Grady Hospital | In 164 adults admitted with ketoacidosis, stopping insulin was the main trigger in 68%. | Single centre; Specific population | moderate | C-INS-08 C-INS-10 |
| I-INS-110 | Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis. Kuppermann N et al. | 2018 | PMID 29897851 DOI 10.1056/NEJMoa1716816 | Randomised controlled trial | Children with DKA | Faster or slower fluids, with more or less salt, gave the same brain outcomes; brain injury was rare (0.9%). | No 'no fluid' arm (would be unethical); Children only | high | C-INS-08 |
| I-INS-111 | Time trends in deaths before age 50 years in people with type 1 diabetes: a nationwide analysis from Scotland 2004-2017. O'Reilly JE et al. | 2020 | PMID 32451572 DOI 10.1007/s00125-020-05173-w | Cohort study | People with T1D aged 1-49 in Scotland | Ketoacidosis or diabetic coma caused about one in five deaths before age 50, and four in five of these deaths happened outside hospital. | DKA and hypoglycaemic coma combined; Single country | high | C-INS-08 |
| I-INS-112 | Differential effects of fasting and dehydration in the pathogenesis of diabetic ketoacidosis. Burge MR et al. | 2001 | PMID 11229425 DOI 10.1053/meta.2001.20194 | Other | Adults with T1D | When insulin was stopped, prior fasting lowered blood sugar but made ketones and acid build up faster; lack of water raised both sugar and ketones. | Small; Short experimental exposure | moderate | C-INS-08 C-DIAB-02 |
| I-INS-113 | Clinical efficacy of dexamethasone on diabetic ketoacidosis complicated with acute pancreatitis: A randomized controlled study. Zhang J et al. | 2023 | PMID 37832092 DOI 10.1097/MD.0000000000035320 | Randomised controlled trial | Adults with DKA plus acute pancreatitis (55 T1D, 51 T2D) | The trial reported better results with dexamethasone, but its numbers are physiologically implausible and it did not replace insulin and fluids. | Single centre, two authors, no trial registration reported; Blinding and allocation concealment not described | very low | C-INS-08 |
| I-INS-114 | Prevalence, Clinical Profile, and Outcomes of Diabetic Ketoacidosis (DKA) in Pediatric ICU Patients in the Middle East: A Systematic Review and Meta-Analysis. Ali NM et al. | 2026 | PMID 41859577 DOI 10.7759/cureus.103735 | Meta-analysis | Children 0-18 with DKA in ICUs | More than a third had severe ketoacidosis, but none died with intensive-care treatment. | Few, small observational studies; Published in a journal with light peer review | low | C-INS-08 |
| I-INS-115 | Presentations, Complications, and Challenges Encountered During Management of Type 1 Diabetes in Egyptian Children During COVID-19 Pandemic: A Single-Center Experience. Abdou M et al. | 2022 | PMID 35360079 DOI 10.3389/fendo.2022.814991 | Cross-sectional study | Children and adolescents with T1D presenting to the emergency department, Abo El Rish Children's Hospital, Cairo University | 43% of 324 children arrived with severe ketoacidosis, often at first diagnosis; delays made it worse. | Single centre; Retrospective | low | C-INS-08 |
| I-INS-116 | Effect of insulin deprivation on muscle mitochondrial ATP production and gene transcript levels in type 1 diabetic subjects. Karakelides H et al. | 2007 | PMID 17660267 DOI 10.2337/db07-0378 | Other | C-peptide-negative adults with T1D | Stopping insulin for about 9 hours reduced the muscle cells' energy (ATP) production and raised ketones and protein breakdown. | Small (n=9); Short deprivation | moderate | C-INS-02 C-INS-09 |
| I-INS-117 | Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Hall KD, Guo J | 2017 | PMID 28193517 DOI 10.1053/j.gastro.2017.01.052 | Meta-analysis | Adults in controlled feeding studies | When calories were fixed, cutting fat led to slightly more fat loss than cutting carbohydrate, even though carbohydrate cuts lower insulin. | Short studies; Small effects | moderate | C-INS-01 C-SRC-22 |
| I-INS-118 | Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. Ebbeling CB et al. | 2018 | PMID 30429127 DOI 10.1136/bmj.k4583 | Randomised controlled trial | Adults with BMI >=25 | People on a low-carbohydrate diet burned about 200 more calories per day than on a high-carbohydrate diet while keeping weight off. | Post-hoc debates about exclusions and measurement; Weight-maintenance phase only | moderate | C-INS-01 C-SRC-22 |
| I-INS-119 | Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake. Hall KD et al. | 2021 | PMID 33479499 DOI 10.1038/s41591-020-01209-1 | Randomised controlled trial | Adults (BMI 27.8) | On a high-carbohydrate low-fat diet people ate about 690 fewer calories per day than on a ketogenic diet. | Small, short; Not a test of long-term weight | moderate | C-INS-01 C-LIFE-01 C-SRC-22 |
| I-INS-120 | Hyperinsulinemia drives diet-induced obesity independently of brain insulin production. Mehran AE et al. | 2012 | PMID 23217255 DOI 10.1016/j.cmet.2012.10.019 | Animal study | Mice | Mice genetically prevented from producing excess insulin were protected from diet-induced obesity. | Animal model; Not transferable as 'only cause' in humans | moderate | C-INS-01 |
| I-INS-121 | Exploring the pathways linking fasting insulin to coronary artery disease: a proteome-wide Mendelian randomization study. Huang X et al. | 2025 | PMID 40442727 DOI 10.1186/s12916-025-04127-6 | Other | GWAS summary data (mostly European ancestry) | People genetically inclined to higher fasting insulin had a higher risk of coronary artery disease. | Fasting-insulin instruments largely reflect insulin resistance/adiposity (pleiotropy); Two authors | moderate | C-INS-03 |
| I-INS-122 | Efficacy and safety of insulin in type 2 diabetes: meta-analysis of randomised controlled trials. Erpeldinger S et al. | 2016 | PMID 27391319 DOI 10.1186/s12902-016-0120-z | Meta-analysis | Adults with T2D in RCTs | In 20 trials with 18,599 people, insulin did not change the risk of death but caused more severe low blood sugar. | Trials to 2013; Heterogeneous comparators | high | C-INS-05 C-INS-03 C-INS-11 C-INS-02 |
| I-INS-123 | Nine-Year Effects of 3.7 Years of Intensive Glycemic Control on Cardiovascular Outcomes. ACCORD Study Group | 2016 | PMID 26822326 DOI 10.2337/dc15-2283 | Randomised controlled trial | High-risk T2D (ACCORD survivors without primary outcome) | Very intensive sugar lowering in high-risk type 2 diabetes still showed more cardiovascular deaths after 9 years, but overall deaths were no longer different. | Post-trial treatment uncontrolled | high | C-INS-04 |
| I-INS-124 | Long-Term Use of Long-Acting Insulin Analogs and Breast Cancer Incidence in Women With Type 2 Diabetes. Wu JW et al. | 2017 | PMID 28953430 DOI 10.1200/JCO.2017.73.4491 | Cohort study | Women >=40 with T2D treated with glargine, detemir or NPH | After more than 5 years, glargine users had about twice the breast-cancer rate of NPH users, mainly among women who had used other insulin before. | Observational; Signal mainly in prevalent (prior) insulin users | moderate | C-INS-06 |
| I-INS-125 | Similar Breast Cancer Risk in Women Older Than 65 Years Initiating Glargine, Detemir, and NPH Insulins. Bradley MC et al. | 2020 | PMID 32075848 DOI 10.2337/dc19-0614 | Cohort study | Female Medicare beneficiaries >=65 initiating insulin | Among more than 300,000 women starting insulin, glargine users did not have more breast cancer, even with longer use or higher doses. | Older women only; Claims data | high | C-INS-06 |
| I-INS-126 | Effect of Long-Acting Insulin Analogs on the Risk of Cancer: A Systematic Review of Observational Studies. Wu JW et al. | 2016 | PMID 26740633 DOI 10.2337/dc15-1816 | Systematic review | People with T1D or T2D | Most studies found no cancer increase; a few suggested more breast cancer, but many studies had design flaws. | No meta-analysis; Search to 2014 | moderate | C-INS-06 |
| I-INS-127 | Insulin glargine use and breast cancer risk: Associations with cumulative exposure. Peeters PJ et al. | 2016 | PMID 27150973 DOI 10.3109/0284186X.2016.1155736 | Cohort study | Women with a first insulin prescription | Women starting with glargine had no extra breast cancer even after 5 years; a raised risk appeared only in women with long prior use of other insulins. | Few cases; Wide CIs | moderate | C-INS-06 |
| I-INS-128 | Phenotype and predictors of insulin independence in adults presenting with diabetic ketoacidosis: a prospective cohort study. Raubenheimer PJ et al. | 2024 | PMID 38240751 DOI 10.1007/s00125-023-06067-3 | Cohort study | Adults newly diagnosed with diabetes presenting with DKA, four public hospitals | In Cape Town, about a quarter of adults could stay off insulin for 5 years, mostly those with a type 2-like profile; people with type 1 antibodies rarely could. | Small; Single region | moderate | C-INS-10 C-DIAB-03 |
| I-INS-129 | Illnesses associated with ketosis including diabetic ketoacidosis during very low carbohydrate and ketogenic diets. Roberts CGP et al. | 2025 | PMID 39996364 DOI 10.1111/dom.16252 | Cohort study | Patients with and without T2D in a VLCKD programme | DKA was rare (about 1 per 1000 patient-years in type 2 diabetes) in a supervised programme, but almost three times higher with SGLT2 inhibitors. | Programme-run data; possible underascertainment; No control group | low | C-INS-10 C-DIAB-02 |
| I-INS-130 | 16. Diabetes Care in the Hospital: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes | 2026 | PMID 41358892 DOI 10.2337/dc26-S016 | Guideline / position statement | Hospitalised people with diabetes | Ketoacidosis must be treated with drip fluids, insulin and salts such as potassium; steroids raise blood sugar. | Consensus elements; partly expert opinion | high | C-INS-08 |
| I-INS-131 | 14. Children and Adolescents: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes | 2026 | PMID 41358890 DOI 10.2337/dc26-S014 | Guideline / position statement | Children and adolescents with diabetes | Insulin is essential for children with type 1 diabetes; in youth with type 2 diabetes, insulin can be reduced when goals are met. | Consensus elements; partly expert opinion | high | C-INS-07 C-INS-11 |
| I-INS-132 | 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes | 2026 | PMID 41358893 DOI 10.2337/dc26-S002 | Guideline / position statement | People with diabetes | Type 1 diabetes is an autoimmune destruction of insulin-producing cells that leads to absolute insulin deficiency. | Consensus elements; partly expert opinion | high | C-INS-07 |
| I-INS-133 | The management of type 1 diabetes in adults. The updated 2026 consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Holt RIG et al. | 2026 | PMID 42747450 DOI 10.1007/s00125-026-06833-z | Guideline / position statement | Adults with T1D | Lifelong insulin is essential in type 1 diabetes, and everyone with type 1 diabetes should be able to test glucose and ketones. | Consensus elements; partly expert opinion | high | C-INS-07 C-INS-09 C-DIAB-02 C-INS-11 |
| I-INS-134 | NICE guideline NG17: Type 1 diabetes in adults: diagnosis and management National Institute for Health and Care Excellence (NICE) | 2015 | Guideline / position statement | People with diabetes in England/Wales | UK guideline: insulin is standard for all adults with T1D; DKA treated with IV saline and IV insulin. | Consensus elements; partly expert opinion | high | C-INS-08 C-INS-07 C-ODD-03 | |
| I-INS-135 | NICE guideline NG18: Diabetes (type 1 and type 2) in children and young people: diagnosis and management National Institute for Health and Care Excellence (NICE) | 2015 | Guideline / position statement | People with diabetes in England/Wales | UK paediatric guideline: insulin from diagnosis; DKA needs urgent hospital IV fluids and insulin; honeymoon phase is temporary. | Consensus elements; partly expert opinion | high | C-INS-08 C-INS-07 C-DIAB-02 | |
| I-INS-136 | The management of diabetic ketoacidosis in adults-An updated guideline from the Joint British Diabetes Society for Inpatient Care. Dhatariya KK et al. (JBDS-IP) | 2022 | PMID 35224769 DOI 10.1111/dme.14788 | Guideline / position statement | Adults with DKA | Treatment starts within the first hour with drip fluids and an insulin infusion, plus potassium. | Consensus elements; partly expert opinion | high | C-INS-08 |
| I-INS-137 | Diabetes (fact sheet) World Health Organization | 2024 | Guideline / position statement | Global | Type 1 diabetes requires daily insulin; long-term high blood sugar damages nerves, blood vessels and organs. | Consensus elements; partly expert opinion | high | C-INS-07 C-DIAB-01 | |
| I-INTA-01 | Association between tea consumption and gastroesophageal reflux disease: A meta-analysis. Cao H et al. | 2019 | PMID 30681584 DOI 10.1097/MD.0000000000014173 | Meta-analysis | Participants of 23 observational studies (30 estimates) published 2004-2017: 17 estimates from East Asia, 5 Europe, 5 Middle East, 2 North America, 1 South Asia | Across 30 studies, tea drinkers did not have significantly more reflux disease overall (OR 1.12, 0.98-1.27). | Mostly cross-sectional and case-control data; only 3 cohort estimates (all null); Majority of included studies did not adjust for confounders (authors' statement) | low | C-SRC-24 |
| I-INTA-02 | Tea consumption and risk of all-cause, cardiovascular disease, and cancer mortality: a meta-analysis of thirty-eight prospective cohort data sets. Kim Y et al. | 2024 | PMID 38938012 DOI 10.4178/epih.e2024056 | Meta-analysis | General adult populations in prospective cohorts (studies restricted to patients with a specific disease excluded); cohorts from Asia, Europe, USA and Oceania; mean follow-up 12.3 years (5-23 years) | Across nearly 2 million people, tea drinkers had about 10% lower death rates than non-drinkers. | Observational cohorts: residual confounding and healthy-user effects; adjustment sets vary; High heterogeneity (I2 75-82%) | moderate | C-SRC-24 |
| I-INTA-03 | Tea Consumption and Health Outcomes: Umbrella Review of Meta-Analyses of Observational Studies in Humans. Yi M et al. | 2019 | PMID 31216091 DOI 10.1002/mnfr.201900389 | Systematic review | All human populations in included meta-analyses | Across 96 meta-analyses, tea showed more benefits than harms; only very hot tea (>55-60 °C) was linked to oesophageal and gastric cancer. | Observational evidence only; Overlapping meta-analyses | moderate | C-SRC-24 |
| I-INTA-04 | The effect of tea on iron absorption. Disler PB et al. | 1975 | PMID 1168162 DOI 10.1136/gut.16.3.193 | Other | Human volunteers | Tea taken with meals reduced absorption of plant (non-haem) iron in volunteers. | Old study; Sample size not given in abstract | moderate | C-SRC-24 |
| I-INTA-05 | Analysis of oxytocin in milk samples and intake pattern in different age groups of Indian population. Mishra M et al. | 2014 | PMID 24712660 DOI 10.3109/15376516.2014.910851 | Measurement / residue study | Milk samples from Lucknow, India; consumers of different age groups | In 55 milk samples from an Indian city, oxytocin was found in milkman samples; the authors report indiscriminate injection of cattle. | Small sample, one city; No health outcomes | low | C-SRC-29 |
| I-INTA-06 | Induction of milk ejection and milk removal in different production systems. Bruckmaier RM et al. | 2008 | PMID 17709779 DOI 10.2527/jas.2007-0335 | Narrative review | Dairy cows | Oxytocin releases the milk stored in the udder during milking; long-term injections make cows respond less to their own oxytocin. | Narrative review; Abstract only | moderate | C-SRC-29 |
| I-INTA-07 | Endocrinology of milk production. Svennersten-Sjaunja K et al. | 2005 | PMID 15876512 DOI 10.1016/j.domaniend.2005.03.006 | Narrative review | Dairy cows | Pregnancy hormones, growth hormone and prolactin build and run milk production; oxytocin only releases the milk. | Narrative review; Abstract only | moderate | C-SRC-29 |
| I-INTA-08 | Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. de Groot S et al. | 2020 | PMID 32576828 DOI 10.1038/s41467-020-16138-3 | Randomised controlled trial | Women >=18 years with HER2-negative stage II/III breast cancer receiving neoadjuvant AC-T or FEC-T chemotherapy at 11 Dutch centres; BMI >19 kg/m2, no diabetes, WHO 0-2, adequate organ function; median age 49-51 years, median BMI about 26 | In 131 women with breast cancer, a fasting-mimicking diet around chemotherapy did not reduce severe side effects or increase complete tumour disappearance (the main outcomes); tumour shrinkage on imaging was more frequent, but this was a secondary result. | Primary endpoint (grade III/IV toxicity) not met; pCR (planned phase III primary) not different; Positive findings are secondary endpoints with P values near 0.05 and wide CIs; pathological benefit only in per-protocol analysis (selection bias acknowledged by authors) | moderate | C-SRC-32 |
| I-INTA-09 | ESPEN guidelines on nutrition in cancer patients. Arends J et al. | 2017 | PMID 27637832 DOI 10.1016/j.clnu.2016.07.015 | Guideline / position statement | Adult cancer patients | European guidelines say cancer patients should be screened for malnutrition and should get enough energy and protein. | Abstract only read; Evidence gaps acknowledged | high | C-SRC-32 |
| I-INTA-10 | Impact of intermittent fasting on patients with cancer undergoing chemotherapy and/or targeted therapies: a systematic review of the literature. Maes J et al. | 2025 | PMID 40970988 DOI 10.1007/s00520-025-09907-7 | Systematic review | Cancer patients undergoing chemotherapy or targeted therapy (mostly breast cancer) | Nine small studies found fasting feasible and safe under supervision but showed no proven effect on treatment results or side effects. | Few, small studies; Mostly breast cancer | moderate | C-SRC-32 |
| I-INTA-11 | Growth, efficiency, and yield of commercial broilers from 1957, 1978, and 2005. Zuidhof MJ et al. | 2014 | PMID 25260522 DOI 10.3382/ps.2014-04291 | Other | Broiler chicks: University of Alberta control strains unselected since 1957 and 1978, and Ross 308 (2005) | Modern broilers grew over four times faster than 1957 birds on the same feed, showing the role of breeding. | Single experiment; Abstract does not mention antibiotic use | moderate | C-RES-05 C-CHK-06 |
| I-INTA-12 | Aetiology and associations of halitosis: A systematic review. Memon MA et al. | 2023 | PMID 35212093 DOI 10.1111/odi.14172 | Systematic review | Studies on people with halitosis | 80-90% of bad breath comes from the mouth itself (tongue coating, gum disease, poor hygiene). | Narrative synthesis; Limited time window | moderate | C-SRC-05 |
| I-INTA-13 | Egg intake and cognitive function in healthy adults: A systematic review of the literature. Sultan N et al. | 2025 | PMID 41061594 DOI 10.1016/j.jnha.2025.100696 | Systematic review | Adults >=18 years without diagnosed chronic metabolic/cardiovascular disease, or cohorts statistically adjusted for chronic disease; mostly older adults; 11 studies (1 pre-post, 6 prospective cohorts, 3 cross-sectional, 1 case-control) from China (6), USA (3), Thailand (1), Finland (1) | Eleven mostly observational studies did not show that eggs cause dementia; several found no link, some found better results with moderate intake, and one cross-sectional study found more mild cognitive impairment at the highest intake. | English-only; small number of heterogeneous studies; no meta-analysis; Mostly observational (cross-sectional and case-control included); residual confounding and reverse causation (cognitive decline may change diet) | moderate | C-SRC-05 |
| I-INTA-14 | Effect of different cooking methods on glycaemic index of Indian and Pakistani basmati rice varieties. Gunathilaka MD et al. | 2015 | PMID 26132185 DOI 10.4038/cmj.v60i2.7545 | Randomised controlled trial | Healthy adults aged 20-30, BMI 18.5-23.5 | Two basmati rices had low (Indian) and medium (Pakistani) glycaemic index in 10 volunteers. | n = 10; Large SD | low | C-SRC-18 |
| I-INTA-15 | Rice variety and processing: contribution to glycaemic response. Nisanka T U et al. | 2016 | PMID 28076944 DOI 10.4038/cmj.v61i4.8381 | Randomised controlled trial | Healthy volunteers | In 11 volunteers, a basmati variety had a high GI (73), while parboiled rice had a low GI (40). | n = 11; Local varieties | low | C-SRC-18 |
| I-INTA-16 | Relationship between Physicochemical and Cooking Quality Parameters with Estimated Glycaemic Index of Rice Varieties. Pereira CL et al. | 2023 | PMID 38201163 DOI 10.3390/foods13010135 | Laboratory / cell study | Commercial rice types | In laboratory tests, basmati and a long-grain rice had the lowest estimated glycaemic index. | In vitro estimate, not human GI | low | C-SRC-18 |
| I-INTA-17 | The Glycemic Index of Rice and Rice Products: A Review, and Table of GI Values. Kaur B et al. | 2016 | PMID 25590950 DOI 10.1080/10408398.2012.717976 | Narrative review | Not applicable | No: the effect of rice on blood sugar depends on the variety, how it is processed and what it is eaten with. | Narrative; Abstract gives no specific values | moderate | C-SRC-18 |
| I-INTA-18 | Impact of Peptide Structure on Colonic Stability and Tissue Permeability. Taherali F et al. | 2023 | PMID 37514143 DOI 10.3390/pharmaceutics15071956 | Laboratory / cell study | Not applicable | Peptide hormones like oxytocin are broken down in the gut and poorly absorbed; that is why they are usually injected. | In vitro/ex vivo; Colon model, not whole-gut digestion of milk | low | C-SRC-29 |
| I-INTB-01 | Mechanisms of Insulin Action and Insulin Resistance. Petersen MC, Shulman GI | 2018 | PMID 30067154 DOI 10.1152/physrev.00063.2017 | Narrative review | Human and animal physiology literature | Insulin resistance in muscle, liver and fat is a central process in type 2 diabetes; some mechanisms are still debated. | Narrative, not systematic; Abstract only read | moderate | C-SRC-37 C-INS-02 C-INS-09 |
| I-INTB-02 | Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Warram JH et al. | 1990 | PMID 2240915 DOI 10.7326/0003-4819-113-12-909 | Cohort study | 155 normoglycaemic offspring of two parents with type 2 diabetes and 186 controls without family history, aged 16-60 | In high-risk offspring, slow glucose clearance with high insulin levels predicted diabetes one to two decades later. | Selected high-risk population (both parents diabetic); IVGTT is an indirect index of insulin sensitivity | moderate | C-SRC-37 |
| I-INTB-03 | Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Shanik MH et al. | 2008 | PMID 18227495 DOI 10.2337/dc08-s264 | Narrative review | Animal and human studies | Evidence suggests high insulin can be both a result and a driver of insulin resistance. | Narrative, selective; Mainly animal and indirect human data | low | C-SRC-37 |
| I-INTB-04 | Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Karagiannis GS et al. | 2017 | PMID 28679654 DOI 10.1126/scitranslmed.aan0026 | Animal study | Mice with early-stage mammary carcinomas (~11 per group planned; up to 25% removed per panel); 20 patients with ER+/HER2- breast cancer and residual disease (RCB 2-3) after neoadjuvant weekly paclitaxel followed by 4 cycles of doxorubicin plus cyclophosphamide; separate fine-needle aspirates from 5 patients before and 1 week after the second paclitaxel dose | In mice and in residual human tumours, chemotherapy increased markers of cancer-cell dissemination. | Primarily animal data; dosing schedules differ from clinical practice; Human analysis: only 20 selected patients with residual disease (non-responders), unblinded TMEM scoring, surrogate markers only, no recurrence or survival analysis (follow-up insufficient) | moderate | C-CHM-10 |
| I-INTB-05 | Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. Fisher B et al. | 2002 | PMID 12192016 DOI 10.1056/NEJMoa020128 | Randomised controlled trial | 1079 women with clinically node-negative and 586 with clinically node-positive breast cancer | Over 25 years, women without routine axillary dissection survived as long as those with radical mastectomy. | Older surgical and systemic-therapy context; Abstract only read | high | C-SRC-45 |
| I-INTB-06 | Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. Giuliano AE et al. | 2017 | PMID 28898379 DOI 10.1001/jama.2017.11470 | Randomised controlled trial | Women with clinical T1-T2 invasive breast cancer, no palpable adenopathy, 1-2 positive sentinel nodes, treated with lumpectomy, whole-breast irradiation and systemic therapy | In women with 1-2 positive sentinel nodes, skipping full axillary dissection did not worsen 10-year survival. | Closed early: 891 of 1900 planned patients and 110 of 500 planned deaths, so underpowered; wide non-inferiority margin (HR 1.3); Adjusted HR upper bound (1.28) close to the margin | high | C-SRC-45 |
| I-INTB-07 | Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. Faries MB et al. | 2017 | PMID 28591523 DOI 10.1056/NEJMoa1613210 | Randomised controlled trial | Patients aged 18-75 years with clinically localised cutaneous melanoma, ECOG 0-1, non-melanoma life expectancy >=10 years and a tumour-positive sentinel node (by standard pathology or multimarker RT-PCR assay); low nodal tumour burden (median largest deposit 0.61-0.67 mm) | Completion dissection did not improve melanoma-specific survival but caused more lymphoedema. | Short median follow-up (43 months) for melanoma-specific survival; results released at an interim analysis; Main text reports per-protocol rather than ITT analysis; 140 patients in dissection group declined surgery (differed in prognostic factors) | high | C-SRC-45 |
| I-INTB-08 | Incidence of unilateral arm lymphoedema after breast cancer: a systematic review and meta-analysis. DiSipio T et al. | 2013 | PMID 23540561 DOI 10.1016/S1470-2045(13)70076-7 | Meta-analysis | Breast-cancer survivors | About 1 in 5 survivors develop arm lymphoedema; risk is about four times higher after full axillary dissection. | Heterogeneous diagnostic methods; Observational studies | moderate | C-SRC-45 |
| I-INTB-09 | Frequency and impact of nonadherence to immunosuppressants after renal transplantation: a systematic review. Butler JA et al. | 2004 | PMID 15021846 DOI 10.1097/01.tp.0000110408.83054.88 | Meta-analysis | Adult kidney-transplant recipients | Not taking immunosuppressants was linked to about seven times higher odds of graft failure. | Adherence measurement mostly self-report; Older studies | moderate | C-SRC-46 |
| I-INTB-10 | A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy. Woodle ES et al. | 2008 | PMID 18936569 DOI 10.1097/SLA.0b013e318187d1da | Randomised controlled trial | Adult deceased and living donor kidney-transplant recipients without delayed graft function, on tacrolimus/MMF/antibody induction | With continued tacrolimus and MMF, early steroid withdrawal gave similar 5-year graft survival but more mild rejection. | Selected low-risk recipients; Abstract only read | high | C-SRC-46 |
| I-INTB-11 | KDIGO clinical practice guideline for the care of kidney transplant recipients. KDIGO Transplant Work Group | 2009 | PMID 19845597 DOI 10.1111/j.1600-6143.2009.02834.x | Guideline / position statement | Adults and children after kidney transplantation | Gives recommendations on immunosuppression and monitoring after kidney transplant. | Abstract only read; specific recommendation text not verified here; 2009 | moderate | C-SRC-46 |
| I-INTB-12 | Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. GBD Chronic Kidney Disease Collaboration | 2020 | PMID 32061315 DOI 10.1016/S0140-6736(20)30045-3 | Risk assessment | Populations of 195 countries and territories (GBD 2017), all ages, both sexes | About 9% of the world's population (698 million people) had CKD in 2017, about 7.1 million of them in Egypt; diabetes caused almost a third of the burden. | Many countries lack primary population-based CKD data; estimates rely on covariates and neighbouring countries; Single eGFR/ACR measurement may overestimate prevalence by 25-50% (authors) | moderate | C-SRC-47 |
| I-INTB-13 | Vaccines for preventing influenza in healthy adults. Demicheli V et al. | 2018 | PMID 29388196 DOI 10.1002/14651858.CD001269.pub6 | Meta-analysis | Healthy adults 16-65 years incl. pregnant women | Vaccination roughly halves confirmed influenza (2.3% to 0.9%); absolute benefit is modest. | Old trials; Seasonal variability | high | C-SRC-47 C-SRC-56 |
| I-INTB-14 | Non-invasive diagnostic tests for Helicobacter pylori infection. Best LM et al. | 2018 | PMID 29543326 DOI 10.1002/14651858.CD012080.pub2 | Meta-analysis | People suspected of H. pylori infection | Breath tests are highly accurate; blood and stool tests somewhat less so; about 46 false positives per 1000 tested in a model scenario. | Indirect comparisons; Variable thresholds | high | C-SRC-50 |
| I-INTB-15 | Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization. Shattock AJ et al. | 2024 | PMID 38705159 DOI 10.1016/S0140-6736(24)00850-X | Risk assessment | Populations of 194 WHO member states, all ages | Vaccines against 14 diseases averted an estimated 154 million deaths since 1974 (about 94 million by measles vaccine alone), mostly in young children. | Counterfactual (no vaccination) cannot be observed; results depend on model structure and assumptions; No interpretable uncertainty intervals for final estimates (authors' statement) | moderate | C-SRC-56 |
| I-INTB-16 | Vaccines for measles, mumps, rubella, and varicella in children. Di Pietrantonj C et al. | 2021 | PMID 34806766 DOI 10.1002/14651858.CD004407.pub5 | Systematic review | Healthy children up to 15 years | One dose prevents about 95% of measles; serious side effects are rare and no link to autism was found. | Mostly observational for effectiveness; Abstract only read | high | C-SRC-56 |
| I-INTB-17 | Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies. Taylor LE, Swerdfeger AL, Eslick GD | 2014 | PMID 24814559 DOI 10.1016/j.vaccine.2014.04.085 | Meta-analysis | Children | In over 1.2 million children, vaccination was not linked to autism. | Observational data; Abstract only read | moderate | C-SRC-56 |
| I-INTB-18 | Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. CTT Collaboration, Baigent C et al. | 2010 | PMID 21067804 DOI 10.1016/S0140-6736(10)61350-5 | Meta-analysis | Participants of 26 randomised statin trials: 5 trials of more vs less intensive statin (8,659 acute coronary syndrome and 30,953 stable coronary disease patients) and 21 trials of statin vs control (incl. primary prevention, diabetes, haemodialysis, heart failure, coronary disease) | Each 1 mmol/L LDL reduction cut major vascular events by about a fifth and deaths by 10%, without more cancer. | Most trials industry-funded; IPD missing for 3 eligible trials (11,342 patients); including their published haemorrhagic stroke data gives a significant excess | high | C-SRC-60 C-FAT-02 C-FAT-05 |
| I-INTB-19 | Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Cholesterol Treatment Trialists' Collaboration | 2022 | PMID 36049498 DOI 10.1016/S0140-6736(22)01545-8 | Meta-analysis | Participants of 19 double-blind statin vs placebo trials (mean age 63 years, 27.9% women, 48.1% previous vascular disease, 18.5% diabetes) and 4 double-blind trials of more vs less intensive statin (all with vascular disease, mean age 62) | Statins cause a small excess of mild muscle pain, mostly in year 1; most muscle complaints are not caused by the statin. | Heterogeneous ascertainment of muscle symptoms across trials (first-year reporting 1.0% to 60.5%); CK measured in <6.2% of symptom reports | high | C-SRC-60 |
| I-INTB-20 | Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Sattar N et al. | 2010 | PMID 20167359 DOI 10.1016/S0140-6736(09)61965-6 | Meta-analysis | Participants of statin endpoint trials | About one extra diabetes case per 255 people treated for 4 years. | Diabetes was not a primary endpoint of trials; Abstract only read | high | C-SRC-60 |
| I-INTB-21 | Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports. Hackshaw A et al. | 2018 | PMID 29367388 DOI 10.1136/bmj.j5855 | Meta-analysis | Generally healthy adults in prospective cohorts (high-risk-only cohorts excluded); for CHD in men about 3.07 million participants and >75,000 cases; stroke in men about 3.53 million and >73,000 cases; CHD in women about 2.56 million and >36,000 cases; stroke in women about 3.78 million and 62,000 cases | One cigarette a day carries about half the heart-disease risk of 20 a day. | Single database (Medline), English only; no registered protocol; Aggregate data only; log-linear modelling of category midpoints; within-study correlation not fully modelled | moderate | C-SRC-62 |
| I-INTB-22 | A longitudinal study of plasma and urinary cortisol in pregnancy and postpartum. Jung C et al. | 2011 | PMID 21367926 DOI 10.1210/jc.2010-2395 | Cohort study | 20 pregnant women, 12 OCP users, 15 controls | Total cortisol rose about threefold and free cortisol 1.6-fold by the third trimester. | Small sample; Abstract only read | moderate | C-SRC-65 |
| I-INTB-23 | Intra-abdominal pressure, intra-abdominal hypertension, and pregnancy: a review. Chun R, Kirkpatrick AW | 2012 | PMID 22873421 DOI 10.1186/2110-5820-2-S1-S5 | Narrative review | Pregnant and peripartum women, particularly critically ill parturients; case of a 16-year-old at about 32 weeks with influenza A ARDS | Abdominal pressure is probably raised near term, but most women adapt to it; any role in pre-eclampsia is only a hypothesis. Cortisol is not discussed. | Narrative review without systematic search or appraisal; Evidence for IAH-pre-eclampsia link limited to hypotheses, two case reports and historical/animal data | low | C-SRC-65 |
| I-INTC-01 | Water, hydration, and health. Popkin BM et al. | 2010 | PMID 20646222 DOI 10.1111/j.1753-4887.2010.00304.x | Narrative review | General population (review) | Water is a critical nutrient; without it a person dies within days. Long-term trials on ideal intake are missing. | Narrative, non-systematic review; Funded by a bottled-water company (Nestlé Waters), with company staff advice | moderate | C-SYS-04 C-SYS-05 C-GUT-08 |
| I-INTC-02 | Risk-benefit analysis of micronutrients. Renwick AG et al. | 2004 | PMID 15500928 DOI 10.1016/j.fct.2004.07.013 | Narrative review | Not applicable (method paper) | Nutrient risk assessment weighs the risk of deficiency against the risk of excess. | Methodological proposal; no empirical outcome data; Micronutrients only | moderate | C-SYS-04 C-SYS-05 |
| I-INTC-03 | 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee | 2026 | PMID 41358898 DOI 10.2337/dc26-S005 | Guideline / position statement | People with prediabetes or diabetes | There is no single diet for diabetes; meals should be individualised with a dietitian, and medicines may need adjustment when the diet changes. | US-focused; Only the nutrition passages quoted here were read in detail | high | C-SYS-08 |
| I-INTC-04 | Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis. Rovin BH et al. | 2024 | PMID 38182299 DOI 10.1016/j.kint.2023.09.001 | Guideline / position statement | Patients with lupus nephritis | Kidney involvement in lupus is treated with specific medicines; the guideline was updated in 2024 after two new drugs were approved. | Only the abstract was read; recommendations themselves not audited | high | C-EGG-03 |
| I-INTC-05 | Bologna guidelines for diagnosis and management of adhesive small bowel obstruction (ASBO): 2017 update of the evidence-based guidelines from the world society of emergency surgery ASBO working group. Ten Broek RPG et al. | 2018 | PMID 29946347 DOI 10.1186/s13017-018-0185-2 | Guideline / position statement | Patients with small bowel obstruction | A blocked bowel is an emergency with pain, vomiting and swelling; it is usually caused by scar tissue after surgery, hernias or tumours. | Some recommendations based on limited evidence | high | C-GUT-03 C-GUT-09 C-UPF-10 |
| I-INTC-06 | Incretin hormones: Their role in health and disease. Nauck MA et al. | 2018 | PMID 29364588 DOI 10.1111/dom.13129 | Narrative review | Humans (physiology and clinical studies) | After eating, gut hormones and rising blood sugar make the pancreas release insulin; oral glucose triggers 2-3 times more insulin than glucose given into a vein. | Narrative review; Abstract only | moderate | C-GUT-03 |
| I-INTC-07 | Saliva and gastrointestinal functions of taste, mastication, swallowing and digestion. Pedersen AM et al. | 2002 | PMID 12108756 DOI 10.1034/j.1601-0825.2002.02851.x | Narrative review | Humans | Chewing and saliva start digestion and help form a swallowable bolus. | Narrative; Abstract without quantitative data | moderate | C-GUT-09 |
| I-INTC-08 | Review of the diagnosis and management of gastrointestinal bezoars. Iwamuro M et al. | 2015 | PMID 25901212 DOI 10.4253/wjge.v7.i4.336 | Narrative review | Patients with bezoars | Bezoars cause 0.4-4.8% of intestinal blockages, mostly in people with stomach surgery or slow stomach emptying. | Narrative; based partly on own small case series | low | C-GUT-09 |
| I-INTC-09 | Bariatric surgery and the incidence of rheumatoid arthritis - a Swedish Obese Subjects study. Maglio C et al. | 2020 | PMID 31321442 DOI 10.1093/rheumatology/kez275 | Cohort study | Adults aged 37-60 years with obesity (BMI >=34 men, >=38 women) without prevalent RA, recruited at 25 surgical departments and 480 primary care centres | Over a median of 21 years, people who had weight-loss surgery did not develop rheumatoid arthritis more often than matched controls. | Not randomised (ethics boards did not allow randomisation in 1987); surgery group had higher BMI, CRP and smoking at baseline; RA was not a predefined SOS endpoint; authors state the study may be underpowered (92 events) | moderate | C-BAR-13 |
| I-INTC-10 | Systematic review: Outcomes of bariatric surgery in patients with inflammatory bowel disease and de-novo IBD development after bariatric surgery. Mian A et al. | 2023 | PMID 35660070 DOI 10.1016/j.surge.2022.04.008 | Systematic review | Patients with or without IBD undergoing bariatric surgery | Some studies report new inflammatory bowel disease after weight-loss surgery, but how often and whether surgery causes it is unknown. | Mostly case reports/series and observational data; No incidence comparison in abstract | low | C-BAR-13 |
| I-INTC-11 | Fibromyalgia and obesity: A comprehensive systematic review and meta-analysis. D'Onghia M et al. | 2021 | PMID 33676126 DOI 10.1016/j.semarthrit.2021.02.007 | Meta-analysis | Patients with fibromyalgia | About one in three people with fibromyalgia has obesity; early studies suggest weight loss, including surgery, may ease symptoms. | High risk of bias in included studies; Few weight-loss studies | moderate | C-BAR-13 |
| I-INTC-12 | Does breast feeding provide protection against acute appendicitis? A case-control study. Alves JG et al. | 2008 | PMID 18820196 DOI 10.1258/td.2008.070404 | Case-control study | Children with histologically confirmed appendicitis and their siblings | Children breastfed for longer had appendicitis less often than their siblings in one small study. | Small; Recall of breastfeeding | low | C-ORG-02 |
| I-INTC-13 | Risk factors of obstructive sleep apnea syndrome in children. Xu Z et al. | 2020 | PMID 32131901 DOI 10.1186/s40463-020-0404-1 | Cross-sectional study | Children aged 2-15 years with snoring undergoing polysomnography at Beijing Children's Hospital sleep centre, mostly referred by ENT or respiratory specialists | Enlarged tonsils and adenoids, obesity and male sex were linked to sleep apnoea; breastfeeding was too, probably due to other factors. | Highly selected referral population (snoring children, 64% OSAS); not generalisable to the general population; Cross-sectional; exposure recalled by parents years later | low | C-ORG-02 |
| I-INTC-14 | Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Victora CG et al. | 2016 | PMID 26869575 DOI 10.1016/S0140-6736(15)01024-7 | Meta-analysis | Children and mothers worldwide | Breastfeeding protects children against infections and has other benefits; it is not shown here to prevent tonsil or appendix surgery. | Observational evidence for many outcomes; Tonsil, adenoid and appendicitis outcomes not mentioned in abstract | high | C-ORG-02 |
| I-INTC-15 | Instant noodle intake and dietary patterns are associated with distinct cardiometabolic risk factors in Korea. Shin HJ et al. | 2014 | PMID 24966409 DOI 10.3945/jn.113.188441 | Cross-sectional study | Adults 19-64 years | Women who ate instant noodles twice a week or more had metabolic syndrome more often (OR 1.68). | Cross-sectional; FFQ-based | moderate | C-UPF-10 |
| I-LEG-01 | Legume Consumption and Risk of All-Cause and Cause-Specific Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies. Zargarzadeh N et al. | 2023 | PMID 36811595 DOI 10.1016/j.advnut.2022.10.009 | Meta-analysis | General adult populations (aged >=18 y) without prior disease; 5 US, 14 European, 10 Asian, 1 Australian and 2 international cohorts | People eating more legumes had about 6% lower risk of death from any cause. | Observational data: residual confounding and healthy-user effects possible; Substantial heterogeneity (I2 ~65% for all-cause) | moderate | C-LEG-01 C-LEG-02 C-LEG-04 C-LEG-07 C-LEG-13 C-VEG-16 |
| I-LEG-02 | Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials. Ha V et al. | 2014 | PMID 24710915 DOI 10.1503/cmaj.131727 | Meta-analysis | Adults in RCTs | About one serving of pulses daily lowered LDL cholesterol in randomised trials. | Short trials; Quality variable | moderate | C-LEG-01 C-LEG-04 C-LEG-07 C-LEG-13 C-VEG-16 |
| I-LEG-03 | Effects of non-soy legume consumption on C-reactive protein: a systematic review and meta-analysis. Salehi-Abargouei A et al. | 2015 | PMID 25837205 DOI 10.1016/j.nut.2014.10.018 | Meta-analysis | Adults in RCTs | Trials found no increase in CRP from eating legumes; levels tended to fall. | Small; Overall not significant | moderate | C-LEG-01 C-LEG-02 |
| I-LEG-04 | Consumption of nuts and legumes and risk of incident ischemic heart disease, stroke, and diabetes: a systematic review and meta-analysis. Afshin A et al. | 2014 | PMID 24898241 DOI 10.3945/ajcn.113.076901 | Meta-analysis | Adults | Eating legumes regularly was linked to 14% lower heart-disease risk. | Few legume studies (5 for IHD) | moderate | C-LEG-01 C-LEG-04 C-LEG-13 |
| I-LEG-05 | Study of Glucose-6-Phosphate Dehydrogenase Deficiency: 5 Years Retrospective Egyptian Study. Hagag AA et al. | 2018 | PMID 28982343 DOI 10.2174/1871530317666171003160350 | Case series / case report | Children with G6PD deficiency anaemia, Tanta University Hospital | In 1,000 Egyptian children with G6PD deficiency, haemolysis was most often triggered by fava beans and falafel. | Retrospective; precipitants from history; Single centre | low | C-LEG-03 C-LEG-05 |
| I-LEG-06 | Prevalence of glucose-6-phosphate dehydrogenase deficiency in jaundiced Egyptian neonates. Abo El Fotoh WM et al. | 2016 | PMID 26866975 DOI 10.3109/14767058.2016.1148133 | Cross-sectional study | Neonates with indirect hyperbilirubinaemia | About 9% of jaundiced newborns had G6PD deficiency. | Selected (jaundiced) sample; not population prevalence | low | C-LEG-03 |
| I-LEG-07 | Glucose-6-phosphate dehydrogenase deficiency and sulfadimidin acetylation phenotypes in Egyptian oases. Hussein L et al. | 1992 | PMID 1590743 DOI 10.1007/BF02399702 | Cross-sectional study | Males from two oases | 5.9% of 1,315 men screened in two oases had G6PD deficiency. | Oases only; old | low | C-LEG-03 |
| I-LEG-08 | Glucose-6-phosphate dehydrogenase deficiency. Luzzatto L et al. | 2020 | PMID 32702756 DOI 10.1182/blood.2019000944 | Narrative review | Global | About 500 million people carry G6PD deficiency; fava beans, some drugs and infections trigger haemolysis. | Narrative | moderate | C-LEG-03 C-LEG-05 |
| I-LEG-09 | The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Nkhoma ET et al. | 2009 | PMID 19233695 DOI 10.1016/j.bcmd.2008.12.005 | Meta-analysis | Populations in 88 countries | About 400 million people have G6PD deficiency worldwide; highest in sub-Saharan Africa. | Heterogeneity; Country figures not in abstract | moderate | C-LEG-03 |
| I-LEG-10 | Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. Strom BL et al. | 2001 | PMID 11497534 DOI 10.1001/jama.286.7.807 | Cohort study | Adults aged 20-34 | No major health differences in young adulthood; slightly longer menstrual bleeding in women. | Self-report; Many outcomes (multiple testing) | moderate | C-LEG-10 |
| I-LEG-101 | Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in Arab Countries: Insights from a Systematic Review. Alangari AS et al. | 2023 | PMID 37892786 DOI 10.3390/jcm12206648 | Systematic review | Primary studies from Arab countries (neonates, children, adults, special groups) | Across 23 studies from Arab countries, 2% to 31% of the people tested had G6PD deficiency, more often males. | No meta-analysis; Mostly hospital-based, non-random samples (authors' own limitation) | moderate | C-LEG-03 |
| I-LEG-102 | Prevalence of glucose-6-phosphate dehydrogenase deficiency in neonates in Egypt. Elella SA et al. | 2017 | PMID 28988250 DOI 10.5144/0256-4947.2017.362 | Cross-sectional study | Infants born in 2015, samples collected with the central laboratories of the Ministry of Health | In 2,782 newborns from Menoufia, 4.3% were G6PD-deficient, including 6.2% of boys. | Single governorate; Low kit cut-off may misclassify heterozygous females | moderate | C-LEG-03 |
| I-LEG-103 | Pattern of Hemolytic Anemia Among Egyptian Pediatric Emergency Department Patients. Badr MSEM et al. | 2020 | PMID 32108744 DOI 10.1097/PEC.0000000000002053 | Cross-sectional study | Children presenting with acute haemolytic crisis, New Children Hospital, Cairo University | Over half of children with sudden red-cell breakdown in a Cairo emergency department had G6PD deficiency. | Single centre, 4 months; Triggers (fava vs other) not reported in abstract | low | C-LEG-03 |
| I-LEG-104 | Glucose-6-phosphate dehydrogenase deficiency in Kuwait, Syria, Egypt, Iran, Jordan and Lebanon. Usanga EA, Ameen R | 2000 | PMID 10686492 DOI 10.1159/000022906 | Cross-sectional study | 3,501 male subjects of Kuwaiti, Egyptian, Iranian, Syrian, Lebanese and Jordanian origin living in Kuwait | Among men tested in Kuwait, 1.0% of Egyptians and 11.6% of Iranians were deficient. | Egyptian subgroup size not given in abstract; Migrant sample not representative of Egypt | low | C-LEG-03 |
| I-LEG-105 | Fava Bean- Versus Non-Fava Bean-Induced Acute Hemolytic Crisis in Children With Glucose-6-Phosphate Dehydrogenase Deficiency: A Prospective Comparative Study. Prashanth GP et al. | 2025 | PMID 39956941 DOI 10.1002/pbc.31609 | Cohort study | Children hospitalised for acute haemolytic episodes due to G6PD deficiency, regional referral hospital | In Oman, about half of children's haemolytic crises followed fava beans, and these were more severe. | Single centre; Trigger attribution from documentation | moderate | C-LEG-03 |
| I-LEG-106 | Favism: Clinical Features at Different Ages. Beretta A et al. | 2023 | PMID 36678214 DOI 10.3390/nu15020343 | Narrative review | Published favism cases (pregnant/breastfeeding, children, adolescents, adults) | Fava beans trigger haemolysis through vicine and convicine, which other legumes do not contain; infants and young children are most at risk. | Narrative, case-based; no systematic search reported in detail; Publication bias towards severe cases | low | C-LEG-05 C-LEG-04 |
| I-LEG-107 | Expanded Clinical Pharmacogenetics Implementation Consortium Guideline for Medication Use in the Context of G6PD Genotype. Gammal RS et al. | 2023 | PMID 36049896 DOI 10.1002/cpt.2735 | Guideline / position statement | People with G6PD deficiency (by genotype/phenotype) | Only a short list of medicines is high risk; aspirin at normal doses and most antibiotics are low risk, and no food other than fava beans is confirmed as a trigger. | Case-report-dominated evidence base; Focus on drugs; food evidence only briefly addressed | high | C-LEG-05 |
| I-LEG-108 | Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Youngster I et al. | 2010 | PMID 20701405 DOI 10.2165/11536520-000000000-00000 | Systematic review | G6PD-deficient patients (literature) | Only seven medicines had solid evidence of causing haemolysis; many others were blamed wrongly. | No formal quality appraisal described in abstract; Abstract only | moderate | C-LEG-05 |
| I-LEG-109 | Quinolones and risk of haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency: a nationwide retrospective active-comparator cohort study. Lavon O et al. | 2026 | PMID 42522747 DOI 10.1093/jac/dkag265 | Cohort study | Patients with an ICD-coded diagnosis of G6PD deficiency receiving outpatient oral quinolone or penicillin | In 465,083 antibiotic courses, coded haemolysis occurred after fewer than 1 in 1,000 courses, with no clear excess for quinolones. | Coded outcomes; Variant severity unknown | moderate | C-LEG-05 |
| I-LEG-11 | Randomized trial of peanut consumption in infants at risk for peanut allergy. Du Toit G et al. | 2015 | PMID 25705822 DOI 10.1056/NEJMoa1414850 | Randomised controlled trial | Infants aged 4 to <11 months with severe eczema, egg allergy or both; skin-prick wheal 0 mm (n=542) or 1-4 mm (n=98); infants with wheals >4 mm (76/834 screened, 9.1%) excluded | Babies at high risk who ate peanut early developed far less peanut allergy than those who avoided it. | Open-label; no placebo; Only high-risk infants; those with SPT >4 mm excluded | high | C-LEG-11 |
| I-LEG-110 | Glucose-6-phosphate dehydrogenase deficiency (favism or G6PD deficiency): Information for parents (leaflet PL296.2) King's College Hospital NHS Foundation Trust | 2022 | Guideline / position statement | Children with G6PD deficiency and their parents | Fava beans are the only food that commonly causes attacks; a list of specific medicines, including some antibiotics, should be avoided. | Local trust leaflet, not a national guideline; More conservative drug list than CPIC (I-LEG-107) | moderate | C-LEG-05 | |
| I-LEG-111 | Legume consumption in adults and risk of cardiovascular disease and type 2 diabetes: a systematic review and meta-analysis. Thorisdottir B et al. | 2023 | PMID 37288088 DOI 10.29219/fnr.v67.9541 | Meta-analysis | Healthy adults | Cohorts showed no clear link with heart disease or diabetes, while trials showed lower cholesterol and glucose with legumes. | Low legume intake in cohorts limits contrast; High heterogeneity | high | C-LEG-13 C-LEG-04 |
| I-LEG-112 | Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions. Pearce M et al. | 2021 | PMID 33693815 DOI 10.1093/jn/nxaa447 | Meta-analysis | 807,785 adults without diabetes in the Americas, Eastern Mediterranean (Golestan, Iran), Europe and Western Pacific | Overall, legume intake showed a very weak positive link with diabetes, seen only in some European cohorts; pulses were not linked. | Heterogeneous FFQs and portion assumptions; Residual confounding | high | C-LEG-13 C-LEG-01 |
| I-LEG-113 | Pulse consumption improves indices of glycemic control in adults with and without type 2 diabetes: a systematic review and meta-analysis of acute and long-term randomized controlled trials. Hafiz MS et al. | 2022 | PMID 34585281 DOI 10.1007/s00394-021-02685-y | Meta-analysis | Normoglycaemic adults and adults with T2D | Eating beans, lentils or chickpeas lowered blood sugar after meals and improved long-term glucose markers. | Very high heterogeneity; Effect sizes reported as ES (units partly unclear in abstract) | moderate | C-LEG-01 C-LEG-13 C-LEG-07 |
| I-LEG-114 | The effects of nonsoy legumes consumption on serum levels of inflammatory biomarkers and Adiponectin in overweight/obese adults: A systematic review and meta-analysis of randomized controlled trials. Mansouri F et al. | 2024 | PMID 39103105 DOI 10.1016/j.jnutbio.2024.109718 | Meta-analysis | Adults in RCTs (mainly overweight/obese) | In trials, eating non-soy legumes did not raise inflammation markers; some markers improved. | Effect sizes not given in abstract; Surrogate markers | moderate | C-LEG-01 C-LEG-02 |
| I-LEG-115 | Dietary Nut and Legume Intake and Risk of Crohn's Disease and Ulcerative Colitis. Lopes EW et al. | 2025 | PMID 40037780 DOI 10.1093/ibd/izaf032 | Cohort study | 223,283 US adults without IBD at baseline | In 223,283 US adults, eating legumes often was not linked to Crohn's disease or ulcerative colitis. | Few cases; wide CIs; US diet context | moderate | C-LEG-02 |
| I-LEG-116 | Diet-induced systemic lupus erythematosus (SLE) in primates. Bardana EJ et al. | 1982 | PMID 6178289 DOI 10.1016/s0272-6386(82)80005-x | Animal study | 10 adult female cynomolgus macaques | Three of five monkeys fed a diet of 45% alfalfa seed developed a lupus-like illness. | Animal study, 10 animals; Extreme dose (45% of diet) of alfalfa seed, not a food legume eaten by humans | low | C-LEG-02 |
| I-LEG-117 | Diet and the risk of rheumatoid arthritis - A systematic literature review. Bäcklund R et al. | 2023 | PMID 36379128 DOI 10.1016/j.semarthrit.2022.152118 | Systematic review | Cohort and case-control studies of RA risk | Studies give no consistent picture; fish, vegetables and Mediterranean diets may protect, and legumes were not identified as a risk. | Heterogeneous exposures; Abstract only | moderate | C-LEG-02 |
| I-LEG-118 | From Foodborne Disease Outbreak (FBDO) to Investigation: The Plant Toxin Trap, Brittany, France, 2018. Watier-Grillot S et al. | 2023 | PMID 37505726 DOI 10.3390/toxins15070457 | Outbreak report | Customers of a military base dining facility (population 1,700) | Chili con carne made with undercooked kidney beans made 200 people ill within hours; the bean lectin was detected. | Few stool samples; Single outbreak | moderate | C-LEG-06 C-LEG-07 |
| I-LEG-119 | Toxicity Assessment of Common Beans (Phaseolus vulgaris L.) Widely Consumed by Tunisian Population. Nciri N et al. | 2015 | PMID 26355953 DOI 10.1089/jmf.2014.0120 | Measurement / residue study | Three Tunisian white bean varieties; imported and local canned beans | Raw white beans contained much lectin, but soaking followed by cooking removed its activity. | No human outcomes; Immunoreactive protein is not the same as toxic activity | moderate | C-LEG-07 C-LEG-06 |
| I-LEG-12 | Food anaphylaxis in the United Kingdom: analysis of national data, 1998-2018. Baseggio Conrado A et al. | 2021 | PMID 33597169 DOI 10.1136/bmj.n251 | Ecological study | Whole UK population (England, Scotland, Wales, Northern Ireland) | Peanut/tree nut caused at least 46% of food-anaphylaxis deaths; cow's milk is now the top single cause in school children. | Administrative coding errors (trigger and diagnosis); ED-only cases excluded; Admissions are a poor surrogate for anaphylaxis incidence (authors) | moderate | C-LEG-11 |
| I-LEG-120 | Is There Such a Thing as "Anti-Nutrients"? A Narrative Review of Perceived Problematic Plant Compounds. Petroski W, Minich DM | 2020 | PMID 32987890 DOI 10.3390/nu12102929 | Narrative review | Human, animal and in-vitro literature | Lectins cause poisoning from raw or undercooked beans, but boiling destroys almost all of their activity. | Narrative, not systematic; Authors' wellness-sector background | low | C-LEG-07 |
| I-LEG-121 | Legume lectin phytohemagglutinin reduces transepithelial electrical resistance by counteracting the chaperone function of heat shock protein-70. Dokladny K et al. | 2025 | PMID 40692554 DOI 10.1017/jns.2025.10017 | Laboratory / cell study | Caco-2 cells; 12 male Sprague-Dawley rats | Active bean lectin weakened gut-cell barriers in the lab and in rats fed raw beans. | Cells and rats; raw beans; Small | low | C-LEG-07 |
| I-LEG-122 | Phytic acid concentration influences iron bioavailability from biofortified beans in Rwandese women with low iron status. Petry N et al. | 2014 | PMID 25332466 DOI 10.3945/jn.114.192989 | Randomised controlled trial | 22 Rwandese women with low iron status | Removing phytate from bean meals almost doubled the iron absorbed by women with low iron. | Small; Single-meal-series absorption, not iron status | high | C-LEG-08 |
| I-LEG-123 | Consuming Iron Biofortified Beans Increases Iron Status in Rwandan Women after 128 Days in a Randomized Controlled Feeding Trial. Haas JD et al. | 2016 | PMID 27358417 DOI 10.3945/jn.115.224741 | Randomised controlled trial | 195 Rwandan women aged 18-27 y with serum ferritin <20 ug/L | Women eating iron-rich beans for 128 days had higher haemoglobin and iron stores than women eating ordinary beans. | Biofortified beans; comparator also beans; Abstract only | high | C-LEG-08 |
| I-LEG-124 | The effect of vegetarian diets on iron status in adults: A systematic review and meta-analysis. Haider LM et al. | 2018 | PMID 27880062 DOI 10.1080/10408398.2016.1259210 | Meta-analysis | Adult vegetarians vs non-vegetarians | Adult vegetarians had lower iron stores than meat eaters. | Cross-sectional data; Whole-diet comparison, not legumes specifically | moderate | C-LEG-08 |
| I-LEG-125 | Perceptions of flatulence from bean consumption among adults in 3 feeding studies. Winham DM, Hutchins AM | 2011 | PMID 22104320 DOI 10.1186/1475-2891-10-128 | Randomised controlled trial | Adults in three bean feeding studies | Fewer than half of adults noticed more gas when they started eating beans daily, and it eased over time. | Self-reported symptoms; Small; secondary analysis | moderate | C-LEG-09 C-LEG-12 |
| I-LEG-126 | Eight weeks of lentil consumption attenuates insulin resistance progression without increased gastrointestinal symptom severity: A randomized clinical trial. Wilson SMG et al. | 2022 | PMID 36122501 DOI 10.1016/j.nutres.2022.08.002 | Randomised controlled trial | Nondiabetic adults with increased waist circumference | Lentil meals improved insulin resistance, and most participants had no or only mild gut symptoms. | Small; Short | moderate | C-LEG-09 C-LEG-13 |
| I-LEG-127 | Anemia in pregnancy: a systematic review and meta-analysis of prevalence, determinants, and health impacts in Egypt. Azzam A et al. | 2025 | PMID 39810098 DOI 10.1186/s12884-024-07111-9 | Meta-analysis | Pregnant women in Egypt | About half of pregnant women in Egyptian studies had anaemia measured by blood tests. | Heterogeneous primary studies; Abstract only | moderate | C-LEG-09 C-SUP-09 C-SUP-10 |
| I-LEG-128 | Anaemia among Egyptian Children between 2000 and 2005: trends and predictors. Austin AM et al. | 2012 | PMID 21951327 DOI 10.1111/j.1740-8709.2011.00339.x | Cross-sectional study | Egyptian children 12-36 months | Measured anaemia in Egyptian children aged 1-3 years rose from 37% in 2000 to over 52% in 2005. | Older data; Ecological interpretation of causes | moderate | C-LEG-09 |
| I-LEG-129 | Compared with feeding infants breast milk or cow-milk formula, soy formula feeding does not affect subsequent reproductive organ size at 5 years of age. Andres A et al. | 2015 | PMID 25761499 DOI 10.3945/jn.114.206201 | Cohort study | 101 children (50 boys, 51 girls) | Children fed soy formula had reproductive organs of the same size and structure as breastfed or cow-milk-fed children. | Small; early age; Abstract only | moderate | C-LEG-10 |
| I-LEG-13 | Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis. Black CJ et al. | 2022 | PMID 34376515 DOI 10.1136/gutjnl-2021-325214 | Meta-analysis | IBS patients | Across 13 trials, a low-FODMAP diet was the most effective diet for IBS symptoms. | Blinding issues; No reintroduction data | moderate | C-LEG-12 C-VEG-01 |
| I-LEG-130 | Soy-based infant formula feeding and menstrual pain in a cohort of women aged 23-35 years. Upson K et al. | 2019 | PMID 30412246 DOI 10.1093/humrep/dey303 | Cohort study | African-American women aged 23-35 y | Women fed soy formula as babies more often reported severe period pain. | Retrospective recall of infant feeding and pain; Multiple pain indicators | moderate | C-LEG-10 |
| I-LEG-131 | Soy-Based Infant Formula Feeding and Ultrasound-Detected Uterine Fibroids among Young African-American Women with No Prior Clinical Diagnosis of Fibroids. Upson K et al. | 2016 | PMID 26565393 DOI 10.1289/ehp.1510082 | Cohort study | African-American women aged 23-34 y without prior fibroid diagnosis | Women fed soy formula as babies did not have more fibroids, but those who had fibroids had larger ones. | Subgroup finding (size) after null main result; Recall | moderate | C-LEG-10 |
| I-LEG-132 | Soy protein infant formulae and follow-on formulae: a commentary by the ESPGHAN Committee on Nutrition. ESPGHAN Committee on Nutrition | 2006 | PMID 16641572 DOI 10.1097/01.mpg.0000189358.38427.cd | Guideline / position statement | Infants | Soy formula has no advantage over cow-milk formula and should be used only for specific reasons because of possible effects of its plant oestrogens. | 2006; may be dated; Abstract only | moderate | C-LEG-10 |
| I-LEG-133 | Use of soy protein-based formulas in infant feeding. Bhatia J, Greer F | 2008 | PMID 18450914 DOI 10.1542/peds.2008-0564 | Guideline / position statement | Infants | The American Academy of Pediatrics says soy formula has very limited indications and reviews possible effects of its plant oestrogens. | Only the abstract was read; recommendations not verified in detail; 2008 | moderate | C-LEG-10 |
| I-LEG-134 | Efficacy and Findings of a Blinded Randomized Reintroduction Phase for the Low FODMAP Diet in Irritable Bowel Syndrome. Van den Houte K et al. | 2024 | PMID 38401741 DOI 10.1053/j.gastro.2024.02.008 | Randomised controlled trial | Tertiary-care IBS patients | In blinded tests, the legume sugars (GOS) triggered symptoms in about a third of IBS patients, while fructans and mannitol were more common triggers. | Tertiary-care population; High 'control' response rate | moderate | C-LEG-12 |
| I-LEG-135 | Addendum guidelines for the prevention of peanut allergy in the United States: Report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel. Togias A et al. | 2017 | PMID 28065278 DOI 10.1016/j.jaci.2016.10.010 | Guideline / position statement | Infants by risk category | Infants, especially those at high risk, should be given peanut-containing foods early (from 4-6 months) to prevent peanut allergy. | Guideline 2 based on extrapolation (low quality of evidence) | high | C-LEG-11 |
| I-LEG-136 | Food-Based Dietary Guidelines in Countries of the Eastern Mediterranean Region: A Comparison and an Update. Al-Jawaldeh A et al. | 2025 | PMID 41464425 DOI 10.3390/ijerph22121790 | Systematic review | 22 EMR countries | Several Arab national dietary guidelines advise eating legumes daily; Egypt had no national guideline in this review. | Descriptive; Egypt lacks an FBDG in this review | moderate | C-LEG-13 C-LEG-04 |
| I-LIFE-101 | Effects of total fat intake on body fatness in adults. Hooper L et al. | 2020 | PMID 32476140 DOI 10.1002/14651858.CD013636 | Systematic review | Adults not trying to lose weight | People who ate less fat weighed about 1.4 kg less on average than those who ate more fat, even without trying to lose weight. | Heterogeneity (explained by subgroups); Small effect size | high | C-LIFE-01 |
| I-LIFE-102 | Effect of low-fat diet interventions versus other diet interventions on long-term weight change in adults: a systematic review and meta-analysis. Tobias DK et al. | 2015 | PMID 26527511 DOI 10.1016/S2213-8587(15)00367-8 | Meta-analysis | Adults | Over a year or more, low-fat diets did not cause more weight loss than other diets of similar intensity. | Heterogeneity in some comparisons; Overlaps with Hooper 2020 in some trials | high | C-LIFE-01 |
| I-LIFE-104 | Energy expenditure and obesity across the economic spectrum. McGrosky A et al. | 2025 | PMID 40658837 DOI 10.1073/pnas.2420902122 | Cross-sectional study | Adults from hunter-gatherer, pastoralist, farming and industrialised populations | People in industrialised countries burn about as much energy as hunter-gatherers; eating more, not moving less, explains most weight gain. | Cross-sectional; Intake estimated, not measured | high | C-LIFE-02 |
| I-LIFE-105 | Trends over 5 decades in U.S. occupation-related physical activity and their associations with obesity. Church TS et al. | 2011 | PMID 21647427 DOI 10.1371/journal.pone.0019657 | Ecological study | US workforce | US jobs became less active since 1960, and models suggest this could explain much of the weight gain. | Ecological; modelled, not measured expenditure; Ignores compensation in leisure activity and intake | low | C-LIFE-02 |
| I-LIFE-106 | World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Bull FC et al. | 2020 | PMID 33239350 DOI 10.1136/bjsports-2020-102955 | Guideline / position statement | All age groups incl. pregnancy and chronic conditions | WHO recommends adults do 150-300 minutes of moderate activity each week and sit less. | Abstract read only | high | C-LIFE-03 |
| I-LIFE-107 | Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. Consensus Conference Panel, Watson NF et al. | 2015 | PMID 25979105 DOI 10.5664/jcsm.4758 | Guideline / position statement | Adults 18-60 | Sleep experts recommend at least 7 hours of sleep per night; regularly sleeping less is linked to many health problems. | Consensus, partly based on observational evidence; US panel | moderate | C-LIFE-03 C-LIFE-04 |
| I-LIFE-108 | The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Van Dongen HP et al. | 2003 | PMID 12683469 DOI 10.1093/sleep/26.2.117 | Randomised controlled trial | Healthy adults aged 21-38 | Sleeping 6 hours or less for two weeks impaired thinking as much as up to two nights without sleep, and people did not notice. | Small; cognitive outcomes only; 14 days | high | C-LIFE-04 |
| I-LIFE-109 | Chronotype, Life's Essential 8, and Risk of Cardiovascular Disease: A Prospective Cohort Study in UK Biobank. Kianersi S et al. | 2026 | PMID 41603783 DOI 10.1161/JAHA.125.044189 | Cohort study | UK Biobank participants aged 39-74 without CVD | 'Night owls' had a 16% higher risk of heart attack or stroke, mostly because of less healthy habits. | Chronotype by one question; Observational; UK Biobank healthy-volunteer bias | moderate | C-LIFE-04 |
| I-LIFE-110 | Effect of breathwork on stress and mental health: A meta-analysis of randomised-controlled trials. Fincham GW et al. | 2023 | PMID 36624160 DOI 10.1038/s41598-022-27247-y | Meta-analysis | Adults | Breathing exercises reduced stress, anxiety and low mood by a small to moderate amount. | Self-reported outcomes; unblinded; Author COI | moderate | C-LIFE-05 C-LIFE-03 |
| I-LIFE-111 | Efficacy of device-guided breathing for hypertension in blinded, randomized, active-controlled trials: a meta-analysis of individual patient data. Landman GW et al. | 2014 | PMID 25222103 DOI 10.1001/jamainternmed.2014.4336 | Meta-analysis | Adults with hypertension | When compared fairly with sham devices or music, slow-breathing devices did not lower blood pressure. | IPD missing for 2 of 5 trials; Short follow-up | high | C-LIFE-05 |
| I-MEAT-01 | IARC Monographs Volume 114: Red Meat and Processed Meat (with IARC Q&A and Press Release No. 240) International Agency for Research on Cancer (IARC) | 2018 (evaluation 2015) | Risk assessment | Epidemiological and mechanistic literature | About 18% higher risk per 50 g processed meat a day; red meat about 17% per 100 g if causal. | Hazard identification, not risk magnitude; Red meat evidence limited | high | C-MEAT-01 C-MEAT-04 | |
| I-MEAT-02 | Carcinogenicity of consumption of red and processed meat. Bouvard V et al. | 2015 | PMID 26514947 DOI 10.1016/S1470-2045(15)00444-1 | Risk assessment | n/a | Same conclusions as I-MEAT-01 (no abstract available). | No abstract; full text not accessed | moderate | C-MEAT-01 |
| I-MEAT-03 | Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. Chan DS et al. | 2011 | PMID 21674008 DOI 10.1371/journal.pone.0020456 | Meta-analysis | Adults in 24 prospective studies: 12 North American, EPIC (10 European countries), Finland, Netherlands, Japan (2 each), Australia, Canada, Sweden, China, Singapore; 13 mixed-sex, 3 male, 8 female cohorts. | Fresh red meat RR 1.17 per 100 g/day; processed meat RR 1.18 per 50 g/day. | Observational studies; residual confounding cannot be ruled out (authors); association attenuated in some better-adjusted analyses (e.g. NHS/HPFS); No formal risk-of-bias/quality assessment of included studies | moderate | C-MEAT-01 |
| I-MEAT-04 | Reduction of Red and Processed Meat Intake and Cancer Mortality and Incidence: A Systematic Review and Meta-analysis of Cohort Studies. Han MA et al. | 2019 | PMID 31569214 DOI 10.7326/M19-0699 | Meta-analysis | >6 million participants (56 cohorts) | Very small absolute reductions; low certainty. | Methodological choices debated (comments in literature); Article corrected | high | C-MEAT-01 |
| I-MEAT-05 | Unprocessed Red Meat and Processed Meat Consumption: Dietary Guideline Recommendations From the Nutritional Recommendations (NutriRECS) Consortium. Johnston BC et al. | 2019 | PMID 31569235 DOI 10.7326/M19-1621 | Guideline / position statement | Adults | Weak recommendation to continue current intake. | Controversial; contradicts most guideline bodies; Article corrected | moderate | C-MEAT-01 |
| I-MEAT-06 | Teratogenicity of high vitamin A intake. Rothman KJ et al. | 1995 | PMID 7477116 DOI 10.1056/NEJM199511233332101 | Cohort study | Pregnant women undergoing AFP screening or amniocentesis | Above 15,000 IU/day: 3.5-fold more defects of head/face structures. | Dietary vitamin A self-reported; Few exposed cases | moderate | C-MEAT-03 |
| I-MEAT-07 | Foods to avoid in pregnancy (NHS) NHS (UK National Health Service) | accessed 2026 | Guideline / position statement | Pregnant women | Liver has high vitamin A, which can harm the baby. | UK-specific; no evidence summary on page | high | C-MEAT-03 C-EGG-11 | |
| I-MEAT-08 | Purine-rich foods, dairy and protein intake, and the risk of gout in men. Choi HK et al. | 2004 | PMID 15014182 DOI 10.1056/NEJMoa035700 | Cohort study | 47,150 men without gout | Meat RR 1.41; dairy RR 0.56. | Men only; health professionals; Offal not analysed separately in abstract | moderate | C-MEAT-03 |
| I-MEAT-09 | Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Bastide NM et al. | 2011 | PMID 21209396 DOI 10.1158/1940-6207.CAPR-10-0113 | Meta-analysis | 566,607 individuals; 4,734 cases | Highest vs lowest heme intake RR 1.18. | Observational; heme estimates from FFQ | moderate | C-MEAT-01 |
| I-MEAT-10 | Well-done meat intake, heterocyclic amine exposure, and cancer risk. Zheng W et al. | 2009 | PMID 19838915 DOI 10.1080/01635580802710741 | Narrative review | Epidemiological studies | Studies suggest higher cancer risk with well-done meat and HCAs. | Narrative; exposure assessment of doneness uncertain | low | C-MEAT-04 |
| I-MEAT-101 | Red meat consumption, cardiovascular diseases, and diabetes: a systematic review and meta-analysis. Shi W et al. | 2023 | PMID 37264855 DOI 10.1093/eurheartj/ehad336 | Meta-analysis | 43 observational studies for CVD (4,462,810 participants); 27 for diabetes (1,760,774) | Each 100 g/day of unprocessed red meat was linked to 11% higher CVD risk; each 50 g/day of processed meat to 26%. | Observational; Residual confounding by lifestyle | moderate | C-MEAT-01 |
| I-MEAT-102 | Health effects associated with consumption of unprocessed red meat: a Burden of Proof study. Lescinsky H et al. | 2022 | PMID 36216940 DOI 10.1038/s41591-022-01968-z | Meta-analysis | Prospective studies (number not in abstract) | Links between unprocessed red meat and bowel cancer, diabetes and heart disease were rated weak; no link with stroke. | Conservative method may understate true effects; Does not address processed meat | high | C-MEAT-01 |
| I-MEAT-103 | Health effects associated with consumption of processed meat, sugar-sweetened beverages and trans fatty acids: a Burden of Proof study. Haile D et al. | 2025 | PMID 40588677 DOI 10.1038/s41591-025-03775-8 | Meta-analysis | Prospective studies (number not in abstract) | Processed meat was linked to at least 11% higher diabetes risk and 7% higher colorectal cancer risk. | Two-star evidence; Observational inputs | high | C-MEAT-01 |
| I-MEAT-104 | Limit consumption of red and processed meat (WCRF/AICR Cancer Prevention Recommendation) World Cancer Research Fund | 2018 (page accessed 2026) | Guideline / position statement | General population | WCRF advises no more than about three portions (350-500 g cooked) of red meat a week and very little processed meat. | Goal is a precautionary threshold, not a tested dose | high | C-MEAT-01 | |
| I-MEAT-105 | Scientific opinion on the tolerable upper intake level for preformed vitamin A and β-carotene. EFSA NDA Panel et al. | 2024 | PMID 38846679 DOI 10.2903/j.efsa.2024.8814 | Risk assessment | European population groups including pregnant women | Europeans are unlikely to exceed the vitamin A safety limit if liver and offal are eaten once a month or less; pregnant women should avoid liver products. | Exposure scenarios European | high | C-MEAT-03 |
| I-MEAT-106 | Analysis of retinol concentrations in bovine liver and its habitual consumption by pregnant women. Praxedes de Aquino RC et al. | 2006 | PMID 16809900 DOI 10.1159/000094295 | Measurement / residue study | 60 bovine liver samples; 100 pregnant women, Natal, Brazil | 100 g of beef liver contained about 5,200-17,000 ug of vitamin A, well above the 3,000 ug daily safety limit. | Single region; small sample | moderate | C-MEAT-03 |
| I-MEAT-107 | 2020 American College of Rheumatology Guideline for the Management of Gout. FitzGerald JD et al. | 2020 | PMID 32391934 DOI 10.1002/acr.24180 | Guideline / position statement | Patients with gout | The ACR conditionally recommends that people with gout limit purine intake. | Diet recommendations conditional, low-certainty | high | C-MEAT-03 |
| I-MEAT-108 | Clinical and pharmacological profile in a clenbuterol epidemic poisoning of contaminated beef meat in Italy. Brambilla G et al. | 2000 | PMID 10713468 DOI 10.1016/s0378-4274(99)00270-2 | Outbreak report | 15 people who ate contaminated meat (9 hospitalised) | 15 people developed tremors, palpitations and headache after eating beef with clenbuterol; all recovered in 3-5 days. | Single outbreak; illegal use; Acute adrenergic effects, not neuropathy | low | C-MEAT-02 |
| I-MEAT-109 | Effect of microwave pretreatment on heterocyclic aromatic amine mutagens/carcinogens in fried beef patties. Felton JS et al. | 1994 | PMID 7959444 DOI 10.1016/0278-6915(94)90087-6 | Other | Ground beef patties | Brief pre-cooking before frying reduced cancer-linked heterocyclic amines three- to nine-fold. | Microwave, not boiling; Beef patties, not whole meat | moderate | C-MEAT-04 |
| I-MEAT-110 | Frying oils with lower levels of saturated fatty acids induce less heterocyclic amine formation in meat floss (boiled, shredded and fried pork) Pan T et al. | 2020 | DOI 10.1111/ijfs.14368 | Other | Pork meat floss | Boiled, shredded pork fried in lard or palm oil formed more heterocyclic amines than when fried in soybean oil. | Pork product; ghee not tested; Laboratory only | moderate | C-MEAT-04 |
| I-ODD-01 | Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. UKPDS Group | 1998 | PMID 9742977 | Randomised controlled trial | Overweight newly diagnosed type 2 diabetes, mean age 53 | Metformin reduced deaths from any cause by about a third over 10 years. | Small arms; Open-label | moderate | C-INS-11 C-ODD-01 C-ODD-05 C-ODD-06 C-ODD-07 C-ODD-11 |
| I-ODD-02 | Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. Zinman B et al. | 2015 | PMID 26378978 DOI 10.1056/NEJMoa1504720 | Randomised controlled trial | Type 2 diabetes with high CV risk | Deaths fell from 8.3% to 5.7% over about 3 years. | Industry funded; Selected high-risk population | high | C-ODD-02 C-ODD-05 C-ODD-06 |
| I-ODD-03 | Dapagliflozin in Patients with Chronic Kidney Disease. Heerspink HJL et al. | 2020 | PMID 32970396 DOI 10.1056/NEJMoa2024816 | Randomised controlled trial | Adults with CKD (eGFR 25-75 ml/min/1.73 m2, urinary albumin-to-creatinine ratio 200-5000 mg/g) on stable ACE inhibitor/ARB unless intolerant; 67.5% with type 2 diabetes; mean age 61.8 years; 33.1% female; mean eGFR 43.1; median UACR 949 | Forxiga reduced kidney failure and deaths; the trial was stopped early because the benefit was clear. | Stopped early for benefit (408 of planned 681 events), which can overestimate effect size and reduces power for secondary outcomes; Industry sponsored with sponsor employees among authors | high | C-ODD-02 C-ODD-05 C-ODD-06 |
| I-ODD-04 | Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. McMurray JJV et al. | 2019 | PMID 31535829 DOI 10.1056/NEJMoa1911303 | Randomised controlled trial | HFrEF NYHA II-IV, EF <=40%, with/without diabetes | Fewer heart failure worsenings and deaths with Forxiga. | Industry funded; Selected high-risk population | high | C-ODD-02 C-ODD-05 C-ODD-06 |
| I-ODD-05 | Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. Perkovic V et al. | 2019 | PMID 30990260 DOI 10.1056/NEJMoa1811744 | Randomised controlled trial | Adults >=30 years with type 2 diabetes (HbA1c 6.5-12.0%), eGFR 30 to <90 ml/min/1.73 m2 and UACR >300-5000 mg/g on stable maximum-tolerated ACEi/ARB; mean age 63.0 years, 33.9% women, mean HbA1c 8.3%, mean eGFR 56.2, median UACR 927; 50.4% with cardiovascular disease; 5.3% prior amputation | Kidney failure and heart problems fell by about a third; amputations and fractures were not increased, but rare ketoacidosis was more common (11 vs 1 cases). | Stopped early at interim analysis (may overestimate effect size; reduced power for secondary outcomes), as authors acknowledge; Industry sponsorship and author financial ties | high | C-ODD-05 C-ODD-06 C-ODD-02 |
| I-ODD-06 | Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. Marso SP et al. | 2016 | PMID 27295427 DOI 10.1056/NEJMoa1603827 | Randomised controlled trial | Type 2 diabetes, HbA1c >=7.0%, age >=50 with established CVD/CKD stage >=3/heart failure NYHA II-III, or age >=60 with >=1 CV risk factor; 81.3% had established CVD and/or CKD; mean diabetes duration 12.8 years; mean HbA1c 8.7% | Fewer heart deaths and deaths overall; pancreatitis not increased, but more gallstone disease and a small, non-significant excess of pancreatic cancer. | Industry sponsored; sponsor co-analysed data and four authors are sponsor employees with patents; High-risk population (HbA1c >=7%, mostly established CVD); limited applicability to lower-risk patients | high | C-ODD-04 C-ODD-05 C-ODD-06 |
| I-ODD-07 | Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. Marso SP et al. | 2016 | PMID 27633186 DOI 10.1056/NEJMoa1607141 | Randomised controlled trial | Type 2 diabetes, 83% with CVD/CKD | Fewer heart attacks/strokes, but more diabetic eye complications and stomach side effects. | Industry funded; Selected high-risk population | high | C-ODD-05 C-ODD-06 |
| I-ODD-08 | Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Salpeter SR et al. | 2010 | PMID 20393934 DOI 10.1002/14651858.CD002967.pub4 | Systematic review | Type 2 diabetes in trials/cohorts >=1 month | No lactic acidosis cases in about 70,000 patient-years of metformin use. | Trials often excluded high-risk patients | high | C-ODD-01 |
| I-ODD-09 | Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study. Douros A et al. | 2020 | PMID 32716707 DOI 10.7326/M20-0289 | Cohort study | Type 2 diabetes new users | About 2 per 1,000 users per year developed ketoacidosis, nearly 3 times more than with DPP-4 drugs. | No lab data; Unmeasured confounding | high | C-ODD-02 C-FAST-03 |
| I-ODD-10 | Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Peters AL et al. | 2015 | PMID 26078479 DOI 10.2337/dc15-0843 | Case series / case report | 9 patients (8 women, 1 man; age 26-64) on canagliflozin: 7 with type 1 diabetes (off-label use, insulin pump or MDI) and 2 with type 2 diabetes (both postoperative) | Several patients developed ketoacidosis with near-normal sugar, so it was recognised late. | Incidental, non-systematic case collection; no denominator, so incidence cannot be estimated; 7 of 9 patients used the drug off-label in type 1 diabetes; frequent insulin reduction/omission, alcohol and illness as co-factors | very low | C-ODD-02 C-ODD-03 C-FAST-03 |
| I-ODD-101 | Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function: A Community-Based Cohort Study. Lazarus B et al. | 2018 | PMID 29868840 DOI 10.1001/jamainternmed.2018.0292 | Cohort study | Adults with diabetes in the Geisinger Health System; replication in new metformin and sulfonylurea users from 350 US health systems | In 75,413 people, metformin was not linked to acidosis overall (HR 0.98) but was linked when kidney function was severely reduced (eGFR <30: HR 2.07). | Outcome is an administrative code for acidosis of any cause, not adjudicated metformin-associated lactic acidosis; Observational; residual confounding by indication possible | moderate | C-ODD-01 |
| I-ODD-102 | Metformin in patients with type 2 diabetes and kidney disease: a systematic review. Inzucchi SE et al. | 2014 | PMID 25536258 DOI 10.1001/jama.2014.15298 | Systematic review | People with type 2 diabetes, with and without chronic kidney disease | About 3-10 cases per 100,000 patient-years, similar to the background rate in diabetes. | Narrative synthesis without pooled estimate; No RCT in significantly impaired kidney function | moderate | C-ODD-01 |
| I-ODD-103 | Sodium-Glucose Cotransporter-2 Inhibitors and Risk of Diabetic Ketoacidosis Among Adults With Type 2 Diabetes: A Systematic Review and Meta-Analysis. Colacci M et al. | 2022 | PMID 34116926 DOI 10.1016/j.jcjd.2021.04.006 | Meta-analysis | Adults with type 2 diabetes | RCTs: RR 2.46; absolute risk about 0.6-2.2 cases per 1,000 patient-years. | Only 4 RCTs pooled; Search ended 2019 (before DAPA-CKD/EMPA-KIDNEY) | moderate | C-ODD-02 |
| I-ODD-104 | Clinical characteristics and outcomes of diabetes-related ketoacidosis (DKA) in sodium-glucose co-transporter-2 inhibitor (SGLT2i) users with type 2 diabetes. Sharma A et al. | 2025 | PMID 40919651 DOI 10.1111/dom.70098 | Cohort study | Adults with type 2 diabetes admitted with DKA in 18 UK hospitals; published case reports/series | Published cases had median glucose 10.6 mmol/L despite severe acidosis (pH 7.1). | Case-based: cannot estimate incidence or causality; Publication bias in case reports | moderate | C-ODD-02 |
| I-ODD-105 | Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. Wiviott SD et al. | 2019 | PMID 30415602 DOI 10.1056/NEJMoa1812389 | Randomised controlled trial | Adults with type 2 diabetes and established ASCVD or multiple risk factors (10,186 without ASCVD) | HF hospitalisation HR 0.73; renal events HR 0.76; DKA 0.3% vs 0.1%. | Industry-funded; DKA was a secondary safety outcome with few events | high | C-ODD-02 C-ODD-06 |
| I-ODD-106 | Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Nuffield Department of Population Health Renal Studies Group; SMART-C Consortium | 2022 | PMID 36351458 DOI 10.1016/S0140-6736(22)02074-8 | Meta-analysis | Participants of 13 large SGLT2 inhibitor trials (82.7% with diabetes) | Kidney progression -37%, CV death -14%; DKA risk doubled from about 0.2 per 1,000 patient-years. | Summary-level, not individual data; Trials mostly industry-sponsored | high | C-ODD-02 C-ODD-06 C-ODD-05 |
| I-ODD-107 | Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. Shi Q et al. | 2023 | PMID 37024129 DOI 10.1136/bmj-2022-074068 | Meta-analysis | Adults with type 2 diabetes in RCTs >=24 weeks | SGLT2 inhibitors and GLP-1 agonists reduce death by about 12%; each class has specific side effects. | Low certainty for older drugs (metformin, sulfonylureas); Inconsistency for amputation outcome | high | C-ODD-05 C-ODD-06 C-ODD-02 C-ODD-11 |
| I-ODD-108 | Intensive glucose control and macrovascular outcomes in type 2 diabetes. Control Group (Turnbull FM et al.) | 2009 | PMID 19655124 DOI 10.1007/s00125-009-1470-0 | Meta-analysis | Participants with type 2 diabetes in large glucose-lowering trials | MI -15%, major hypoglycaemia about 2.5 times more frequent; death unchanged. | Group-level data; Trials used older drug strategies | high | C-ODD-03 |
| I-ODD-11 | Glucagon-like peptide-1 receptor agonists and risk of acute pancreatitis in patients with type 2 diabetes. Storgaard H et al. | 2017 | PMID 28105738 DOI 10.1111/dom.12885 | Meta-analysis | Type 2 diabetes | In large blinded trials, pancreatitis was not more frequent with GLP-1 drugs than placebo. | Only 3 trials; Rare outcome | high | C-ODD-04 |
| I-ODD-110 | Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis. Seminer A et al. | 2025 | PMID 40193122 DOI 10.1001/jamaneurol.2025.0360 | Meta-analysis | Participants in RCTs of these drug classes (mean age 64.4) | Dementia OR 1.20 (0.67-2.17) for SGLT2i, not significant; GLP-1 RA OR 0.55. | Dementia not a primary trial outcome; under-ascertainment likely; Wide CI for SGLT2i | moderate | C-ODD-06 |
| I-ODD-111 | Incidence of lower-limb amputation in the diabetic and nondiabetic general population: a 10-year population-based cohort study of initial unilateral and contralateral amputations and reamputations. Johannesson A et al. | 2009 | PMID 19001192 DOI 10.2337/dc08-1639 | Cohort study | General population aged >=45 years in a representative Swedish region | 157 of 290 amputees had no diabetes; risk 8 times higher with diabetes. | Single region; Treatment of diabetes not analysed | moderate | C-ODD-06 |
| I-ODD-112 | Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Sattar N et al. | 2021 | PMID 34425083 DOI 10.1016/S2213-8587(21)00203-5 | Meta-analysis | Patients with type 2 diabetes in cardiovascular outcome trials (>500 patients) | Death HR 0.88; MACE HR 0.86; no increase in pancreatic adverse effects. | Only 8 trials; Pancreatitis results reported qualitatively in abstract | high | C-ODD-04 C-ODD-06 |
| I-ODD-113 | Evaluating the Rates of Pancreatitis and Pancreatic Cancer Among GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Wen J et al. | 2025 | PMID 40988099 DOI 10.1002/edm2.70113 | Meta-analysis | Patients in GLP-1 RA RCTs (any age) | RR 1.44 overall, but not significant in subgroups; events rare. | Fixed-effect model despite clinical heterogeneity; Inconsistent pancreatitis definitions | moderate | C-ODD-04 |
| I-ODD-114 | Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis. Yang W et al. | 2019 | PMID 30615306 DOI 10.1111/1753-0407.12900 | Meta-analysis | Patients with diabetes | RR 2.09; B12 about 64 pmol/L lower. | High heterogeneity; Mostly observational | moderate | C-ODD-07 |
| I-ODD-115 | Vitamin B12 Deficiency in Patients with Diabetes on Metformin: Arab Countries. Alhaji JH | 2022 | PMID 35631186 DOI 10.3390/nu14102046 | Narrative review | Patients with type 2 diabetes in Arab/Middle Eastern countries | 11 regional studies point to more B12 deficiency with longer and higher-dose metformin use. | Single author; No meta-analysis | low | C-ODD-07 |
| I-ODD-116 | Association of Sodium-Glucose Cotransporter 2 Inhibitor Treatment With Risk of Hospitalization for Fournier Gangrene Among Men. Dave CV et al. | 2019 | PMID 31479145 DOI 10.1001/jamainternmed.2019.2813 | Cohort study | Men >=18 years with type 2 diabetes initiating SGLT2i or DPP-4i | 15.0 vs 9.7 cases per 100,000 person-years; HR 1.73 (0.87-3.42). | Very few events; Short follow-up | moderate | C-ODD-08 |
| I-ODD-117 | Updating insights into rosiglitazone and cardiovascular risk through shared data: individual patient and summary level meta-analyses. Wallach JD et al. | 2020 | PMID 32024657 DOI 10.1136/bmj.l7078 | Meta-analysis | Adults in rosiglitazone RCTs >=24 weeks | HF OR 1.54; MI OR 1.17 (not significant). | Sensitivity to continuity corrections and data source; Correction for fatal event counts | moderate | C-ODD-09 |
| I-ODD-118 | Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish-Norwegian cohort study. Simonsen E et al. | 2025 | PMID 40098249 DOI 10.1111/dom.16316 | Cohort study | People with type 2 diabetes initiating semaglutide or SGLT2i | HR 2.81, but only about 1 extra case per 7,000 patient-years. | Only 32 events; NAION coding validity | moderate | C-ODD-10 |
| I-ODD-119 | GLP-1 Receptor Agonists and Risk of Optic Nerve or Vision-Threatening Events in Patients With Type 2 Diabetes or Cardiometabolic Diseases: A Meta-analysis of Randomized Controlled Trials. Li HY et al. | 2026 | PMID 41587563 DOI 10.2337/dc25-1929 | Meta-analysis | Patients with type 2 diabetes or cardiometabolic disease (76.4% with diabetes) | ION OR 1.50 (0.49-4.63), not significant. | Events recorded as adverse events, not prespecified; Very wide CI for ION | moderate | C-ODD-10 |
| I-ODD-12 | Fournier's gangrene and sodium-glucose co-transporter-2 inhibitors: A meta-analysis of randomized controlled trials. Silverii GA et al. | 2020 | PMID 31637829 DOI 10.1111/dom.13900 | Meta-analysis | Type 2 diabetes in RCTs | Across 84 trials Fournier gangrene was not more frequent, but cases were too few to be sure. | Very few events; FG not systematically adjudicated | moderate | C-ODD-05 C-ODD-08 |
| I-ODD-120 | PRAC concludes eye condition NAION is a very rare side effect of semaglutide medicines Ozempic, Rybelsus and Wegovy (EMA news, 6 June 2025) European Medicines Agency (PRAC) | 2025 | Guideline / position statement | Users of semaglutide (Ozempic, Rybelsus, Wegovy) | About 1 extra case per 10,000 person-years; product information updated. | Not a peer-reviewed analysis; methods summarised only | moderate | C-ODD-10 | |
| I-ODD-121 | The Association between Sulfonylurea Use and All-Cause and Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials. Varvaki Rados D et al. | 2016 | PMID 27071029 DOI 10.1371/journal.pmed.1001992 | Meta-analysis | Adults with type 2 diabetes in RCTs | All-cause mortality OR 1.12 (0.96-1.30); MI OR 0.92. | Most trials not designed for safety outcomes; Point estimates above 1 versus active comparators | moderate | C-ODD-11 |
| I-ODD-122 | Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. Rosenstock J et al. | 2019 | PMID 31536101 DOI 10.1001/jama.2019.13772 | Randomised controlled trial | Adults with relatively early type 2 diabetes and elevated CV risk | MACE 12.0% vs 11.8%; hypoglycaemia 37.7% vs 10.6%. | Comparator is a DPP-4 inhibitor, not metformin; Erratum | high | C-ODD-11 |
| I-ODD-123 | Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes. Lewis JD et al. | 2015 | PMID 26197187 DOI 10.1001/jama.2015.7996 | Cohort study | Persons with diabetes aged >=40 | Adjusted HR 1.06 (0.89-1.26). | Observational; Possible detection bias | high | C-ODD-12 |
| I-ODD-124 | Pioglitazone and bladder cancer risk: a systematic review and meta-analysis. Tang H et al. | 2018 | PMID 29476615 DOI 10.1002/cam4.1354 | Meta-analysis | Patients with diabetes | Observational OR 1.13 (1.03-1.25), higher with longer and higher-dose use. | Only 2 RCTs; borderline; Heterogeneity by region and funding | moderate | C-ODD-12 |
| I-ODD-125 | Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using datasets from four European countries. Korhonen P et al. | 2016 | PMID 27530399 DOI 10.1136/bmj.i3903 | Cohort study | Patients with type 2 diabetes in Finland, Netherlands, Sweden, UK | aHR 0.99 (0.75-1.30). | Short follow-up for cancer; Manufacturer-funded | moderate | C-ODD-12 |
| I-ODD-126 | Type 2 diabetes in adults: management (NICE guideline NG28), published 2 December 2015, last updated 18 February 2026 National Institute for Health and Care Excellence (NICE) | 2026 | Guideline / position statement | Adults with type 2 diabetes | Fewer heart events and heart-failure admissions; DKA and Fournier gangrene 1 per 1,000 or fewer. | UK cost context; Only selected chapters read | high | C-ODD-06 C-ODD-02 C-ODD-05 | |
| I-ODD-128 | Ketoacidosis at Hypoglycemic and Low Glucose Levels Associated with SGLT2 Inhibitor Use: A Descriptive Systematic Review of Published Cases. Itagaki H et al. | 2026 | PMID 42882058 DOI 10.3390/jcm15197595 | Case series / case report | Published cases of ketoacidosis with glucose <100 mg/dL during SGLT2 inhibitor use | 15 cases, median glucose 68 mg/dL; fasting or poor intake in 11 of 15. | Only 15 cases; Publication bias | very low | C-ODD-02 |
| I-ODD-129 | First-Time Usage of SGLT2 Inhibitors in Patients With Type 2 Diabetes Who Are Fasting Ramadan: Efficacy and Safety. Khalil HAM et al. | 2025 | PMID 40322737 DOI 10.1155/jdr/4321423 | Cohort study | Egyptian Muslim adults with type 2 diabetes intending to fast at least 15 days of Ramadan | No DKA, hypoglycaemia or dehydration under supervision; study small and uncontrolled. | Small, uncontrolled, single centre; Short follow-up | low | C-ODD-02 |
| I-ODD-13 | Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Home PD et al. | 2009 | PMID 19501900 DOI 10.1016/S0140-6736(09)60953-3 | Randomised controlled trial | Type 2 diabetes on metformin or SU, HbA1c 7.9% | Overall heart outcomes were not worse, but heart failure doubled; heart-attack effect unclear. | Open-label; Manufacturer funded | moderate | C-ODD-05 C-ODD-09 |
| I-ODD-14 | Semaglutide and the Risk of Nonarteritic Ischemic Optic Neuropathy: A Systematic Review and Certainty of Evidence Meta-Analysis. Abdelaal A et al. | 2026 | PMID 41692115 DOI 10.1016/j.ophtha.2026.02.013 | Meta-analysis | Adults on semaglutide or comparators | No consistent overall increase found; possible increase in diabetes patients; evidence weak. | Observational inputs; Extreme heterogeneity | moderate | C-ODD-10 |
| I-ODD-15 | Glucagon-like Peptide-1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy: Systematic Review and Meta-Analysis. Dhivagaran T et al. | 2026 | PMID 42060879 DOI 10.1212/WNL.0000000000214864 | Meta-analysis | GLP-1 RA users vs non-users | Risk about 2.5 times higher, but absolute risk about 1 per 1,000 users. | Observational inputs; Heterogeneous incidence | moderate | C-ODD-10 |
| I-ODD-16 | 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes* | 2026 | PMID 41358900 DOI 10.2337/dc26-S009 | Guideline / position statement | People with type 1 and type 2 diabetes | Insulin is essential in type 1 diabetes; SGLT2/GLP-1 drugs are recommended for heart and kidney protection; side effects listed. | Partially read | high | C-INS-07 C-INS-10 C-INS-11 C-ODD-04 C-ODD-07 C-ODD-08 C-ODD-10 C-DIAB-03 C-ODD-01 C-SUG-07 |
| I-ODD-17 | Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Davies MJ et al. | 2022 | PMID 36148880 DOI 10.2337/dci22-0034 | Guideline / position statement | Adults with type 2 diabetes | Weight management plus heart- and kidney-protective drugs are central to type 2 diabetes care. | Abstract only read | high | C-INS-11 C-ODD-06 |
| I-ORG-01 | Korea's thyroid-cancer "epidemic"--screening and overdiagnosis. Ahn HS, Kim HJ, Welch HG | 2014 | PMID 25372084 DOI 10.1056/NEJMp1409841 | Other | Title indicates screening-driven overdiagnosis; content not verified here. | Content not verified by this project beyond metadata | moderate | C-ORG-14 | |
| I-ORG-02 | Thyroid Cancer Screening in South Korea Increases Detection of Papillary Cancers with No Impact on Other Subtypes or Thyroid Cancer Mortality. Ahn HS et al. | 2016 | PMID 27627550 DOI 10.1089/thy.2016.0075 | Ecological study | Regions that screened more found far more small papillary cancers, without any effect on thyroid cancer deaths. | Ecological fallacy | moderate | C-ORG-14 C-ORG-15 | |
| I-ORG-03 | Screening for Thyroid Cancer: US Preventive Services Task Force Recommendation Statement. US Preventive Services Task Force | 2017 | PMID 28492905 DOI 10.1001/jama.2017.4011 | Guideline / position statement | Screening does more harm than good because it finds many harmless cancers. | Indirect evidence | high | C-ORG-14 C-ORG-15 | |
| I-ORG-04 | Tonsillectomy or adenotonsillectomy versus non-surgical treatment for chronic/recurrent acute tonsillitis. Burton MJ et al. | 2014 | PMID 25407135 DOI 10.1002/14651858.CD001802.pub3 | Systematic review | Surgery reduced sore throats modestly in the first year (about 0.6 episodes fewer in children); many children get better without surgery. | Short follow-up; Few adult data | high | C-ORG-01 C-ORG-03 | |
| I-ORG-05 | Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trial. Wilson JA et al. | 2023 | PMID 37209706 DOI 10.1016/S0140-6736(23)00519-6 | Randomised controlled trial | Adults >=16 years newly referred to secondary-care ENT with recurrent acute tonsillitis meeting UK (SIGN) criteria (>=7 episodes in 1 year, >=5/year for 2 years, or >=3/year for 3 years); median age 23, 78% female, 90% White | Surgery roughly halved sore-throat days over 2 years, but 19% had bleeding complications. | Open label; self-reported primary outcome without swab confirmation; High crossover/non-adherence (35% did not receive allocated intervention) | high | C-ORG-01 C-ORG-15 |
| I-ORG-06 | Clinical Practice Guideline: Tonsillectomy in Children (Update). Mitchell RB et al. | 2019 | PMID 30798778 DOI 10.1177/0194599818801757 | Guideline / position statement | Watchful waiting is recommended unless infections are very frequent; surgery is recommended for documented sleep apnea. | US-specific | high | C-ORG-01 C-ORG-15 C-ORG-02 | |
| I-ORG-07 | A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis. CODA Collaborative; Flum DR et al. | 2020 | PMID 33017106 DOI 10.1056/NEJMoa2014320 | Randomised controlled trial | Antibiotics worked about as well for overall health at 30 days, but 29% still needed surgery within 90 days. | Unblinded; Short primary endpoint | high | C-ORG-15 C-ORG-17 | |
| I-ORG-08 | Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial. Salminen P et al. | 2018 | PMID 30264120 DOI 10.1001/jama.2018.13201 | Randomised controlled trial | About 61% treated with antibiotics never needed their appendix removed in 5 years. | Open appendectomy (not laparoscopic) | high | C-ORG-17 | |
| I-ORG-09 | Laparoscopic cholecystectomy versus conservative management for adults with uncomplicated symptomatic gallstones: the C-GALL RCT. Innes K et al. | 2024 | PMID 38943314 DOI 10.3310/MNBY3104 | Randomised controlled trial | Adults with symptomatic uncomplicated gallstone disease (biliary colic or acute cholecystitis) referred to secondary care; mean age 51, predominantly female, 86% white | Over 18 months general pain scores were similar, but about 30% of the 'wait' group needed surgery, 11.5% had gallstone complications before surgery, and gallstone-specific quality of life was better after surgery. | Unblinded participants and surgeons; all outcomes patient-reported or unblinded (authors); Substantial crossover (29.5% conservative had surgery; 29.5% of surgery group not operated by 24 months) | high | C-ORG-01 C-ORG-07 |
| I-ORG-10 | Long-term outcomes of hysterectomy with bilateral salpingo-oophorectomy: a systematic review and meta-analysis. Hassan H et al. | 2024 | PMID 37364803 DOI 10.1016/j.ajog.2023.06.043 | Meta-analysis | Women with hysterectomy plus BSO for benign indications (excluding cancer treatment, gender affirmation, high ovarian-cancer risk); studies from USA, Europe, Australia, Canada, Asia | Linked to less breast cancer but more heart disease, dementia and other conditions in younger women; effect on death was inconsistent. | Fixed-effect pooling despite substantial heterogeneity for several outcomes (I2 up to 92%); No formal per-study risk-of-bias tool (only GRADE) | moderate | C-ORG-09 C-ORG-11 |
| I-ORG-101 | Tonsillectomy or adenotonsillectomy versus non-surgical management for obstructive sleep-disordered breathing in children. Venekamp RP et al. | 2015 | PMID 26465274 DOI 10.1002/14651858.CD011165.pub2 | Systematic review | Children 2-16 years with obstructive sleep-disordered breathing (oSDB), incl. polysomnography-confirmed mild-moderate OSAS (CHAT trial, 453 children aged 5-9). | Surgery normalised sleep studies in 79% versus 46% with watchful waiting and improved symptoms, but did not improve attention or thinking tests. | Only 3 trials; no pooling; Short follow-up (7-12 months) | high | C-ORG-01 C-ORG-15 |
| I-ORG-102 | Adenotonsillectomy for Snoring and Mild Sleep Apnea in Children: A Randomized Clinical Trial. Redline S et al. | 2023 | PMID 38051326 DOI 10.1001/jama.2023.22114 | Randomised controlled trial | Children 3-12.9 years with habitual snoring and obstructive AHI < 3 | Surgery did not improve thinking or attention after a year but did improve behaviour, symptoms and quality of life. | Unblinded caregivers for subjective outcomes; 14% loss to follow-up | high | C-ORG-01 |
| I-ORG-103 | Adenotonsillectomy vs Watchful Waiting in Pediatric Mild to Moderate Obstructive Sleep Apnea: The KATE Randomized Clinical Trial. Sjölander I et al. | 2025 | PMID 40965870 DOI 10.1001/jamaoto.2025.2831 | Randomised controlled trial | Children aged 2-4 years with obstructive AHI 2 to < 10 | After 3 years, waiting was about as good as surgery on sleep tests, but 42% of the waiting group ended up having surgery. | Very small sample; Per-protocol analysis excluding crossovers | low | C-ORG-01 |
| I-ORG-104 | Restrictive Strategy vs Usual Care for Cholecystectomy in Patients With Abdominal Pain and Gallstones: 5-Year Follow-Up of the SECURE Randomized Clinical Trial. Comes DJ et al. | 2024 | PMID 39167382 DOI 10.1001/jamasurg.2024.3080 | Randomised controlled trial | Adults 18-95 with abdominal pain and ultrasound-proven uncomplicated gallstones referred to surgical outpatient clinics | A stricter selection avoided about 8 in 100 operations without more complications, but about a third of patients still had pain after surgery in both groups. | About 30% protocol deviation in restrictive arm (full text); Only about 70% completed the pain survey | high | C-ORG-07 C-ORG-01 |
| I-ORG-105 | Asymptomatic gallstones: Cumulative incidence proportion, incidence rate, and risk factors for symptoms development: Systematic review and meta-analysis. Alzoubi M et al. | 2026 | PMID 41886405 DOI 10.1371/journal.pone.0345462 | Meta-analysis | Adults with incidentally diagnosed gallstones | About 10% of people with silent gallstones develop symptoms within 5 years and about 19% within 10 years. | Only 8 observational cohorts; Heterogeneous definitions | moderate | C-ORG-07 |
| I-ORG-106 | Appendectomy versus antibiotic treatment for acute appendicitis. Doleman B et al. | 2024 | PMID 38682788 DOI 10.1002/14651858.CD015038.pub2 | Meta-analysis | Mostly adults with uncomplicated/simple acute appendicitis (six trials included adults and children) | About two thirds of adults treated with antibiotics avoided an operation in the first year, but treatment failed more often than with surgery. | Mostly low/very low certainty; Heterogeneous definitions of success | high | C-ORG-17 C-ORG-15 |
| I-ORG-107 | Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: an open-label, international, multicentre, randomised, non-inferiority trial. St Peter SD et al. | 2025 | PMID 39826968 DOI 10.1016/S0140-6736(24)02420-6 | Randomised controlled trial | Children 5-16 years with suspected non-perforated appendicitis | Antibiotics failed in 34% of children versus 7% with surgery, but about two thirds of antibiotic-treated children kept their appendix for a year. | Unblinded; Composite failure definitions differ between arms | high | C-ORG-17 |
| I-ORG-108 | Non-operative treatment strategy versus surgery for children with simple appendicitis: non-inferiority randomised controlled trial. van Amstel P et al. | 2026 | PMID 42157906 DOI 10.1136/bmjmed-2025-002466 | Randomised controlled trial | Children 7-17 years with imaging-confirmed simple appendicitis without faecolith | About 70% of children treated with antibiotics avoided an operation, with similar complication rates, but non-inferiority was not proven. | Moderate size; Unblinded | moderate | C-ORG-17 |
| I-ORG-109 | Diagnosis and Treatment of Acute Appendicitis: 2025 Edition of the World Society of Emergency Surgery Jerusalem Guidelines. Podda M et al. | 2026 | PMID 41604201 DOI 10.1001/jamasurg.2025.6218 | Guideline / position statement | Patients with acute appendicitis | Antibiotics can be used in selected simple cases and better diagnosis reduces unnecessary operations, but surgery remains the standard treatment. | Full text not accessed (2025 edition); Consensus elements | high | C-ORG-17 C-ORG-15 |
| I-ORG-11 | Risk of infection and death among post-splenectomy patients. Bisharat N et al. | 2001 | PMID 11798256 DOI 10.1053/jinf.2001.0904 | Systematic review | About 3% developed serious infections and 1.4% died of them over about 7 years in older studies. | Old literature 1966-96; Pre-modern vaccination | low | C-ORG-12 | |
| I-ORG-110 | WHO Statement on Caesarean Section Rates. Betran AP et al. | 2016 | PMID 26681211 DOI 10.1111/1471-0528.13526 | Guideline / position statement | Women giving birth worldwide (population-level analyses) | Caesareans save lives when medically needed, but rates above about 10% in a population do not further reduce deaths. | Ecological, population-level data; No individual-level outcomes | moderate | C-ORG-15 |
| I-ORG-111 | Trends and projections of caesarean section rates: global and regional estimates. Betran AP et al. | 2021 | PMID 34130991 DOI 10.1136/bmjgh-2021-005671 | Ecological study | Live births in 154 countries | About 1 in 5 births worldwide is by caesarean; in Egypt it is about half of all births, one of the highest rates globally. | Mixed data sources and years; No outcome data | moderate | C-ORG-15 |
| I-ORG-112 | Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974-2013. Lim H et al. | 2017 | PMID 28362912 DOI 10.1001/jama.2017.2719 | Ecological study | Patients diagnosed with thyroid cancer in SEER-9 areas | Thyroid cancer diagnoses tripled; deaths rose only slightly, mainly from advanced cancers. | Ecological; Incidence-based mortality small numbers | moderate | C-ORG-14 |
| I-ORG-113 | Evolving epidemiological patterns of thyroid cancer and estimates of overdiagnosis in 2013-17 in 63 countries worldwide: a population-based study. Li M et al. | 2024 | PMID 39389067 DOI 10.1016/S2213-8587(24)00223-7 | Ecological study | Population cancer registries in 63 countries | About three in four thyroid cancer diagnoses worldwide were estimated to be overdiagnosis, while deaths stayed low. | Model-based estimates; Registry coverage uneven | moderate | C-ORG-14 |
| I-ORG-114 | 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Haugen BR et al. | 2016 | PMID 26462967 DOI 10.1089/thy.2015.0020 | Guideline / position statement | Adults with thyroid nodules or differentiated thyroid cancer | Most benign thyroid nodules can simply be monitored, but surgery is recommended for confirmed cancer and for large or compressing nodules. | 2015 (DTC part updated by ATA 2025); Only selected recommendations read | high | C-ORG-15 |
| I-ORG-115 | Risk for hospital contact with infection in patients with splenectomy: a population-based cohort study. Thomsen RW et al. | 2009 | PMID 19841456 DOI 10.7326/0003-4819-151-8-200910200-00008 | Cohort study | All 3812 persons splenectomised in Denmark 1996-2005 | People without a spleen had more serious infections for years after surgery, although part of the extra risk came from their underlying disease. | Surveillance bias possible (authors); Hospital-contact outcomes only | high | C-ORG-12 C-ORG-16 |
| I-ORG-116 | Spleen Australia guidelines for the prevention of sepsis in patients with asplenia and hyposplenism in Australia and New Zealand. Kanhutu K et al. | 2017 | PMID 27925427 DOI 10.1111/imj.13348 | Guideline / position statement | People with asplenia or hyposplenism | People without a spleen have a higher risk of severe, fast sepsis and need vaccinations and preventive measures. | Abstract only; Regional guideline | moderate | C-ORG-12 |
| I-ORG-117 | Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia. Boyle S et al. | 2013 | PMID 23637127 DOI 10.1182/blood-2012-12-467068 | Cohort study | 9976 patients with ITP, 1762 splenectomised | Patients whose spleen was removed had more blood clots (4.3% vs 1.7%) and more sepsis than similar patients who kept their spleen. | Administrative data; Residual confounding by severity | moderate | C-ORG-13 |
| I-ORG-118 | Splenectomy and increased subsequent cancer risk: a nationwide population-based cohort study. Sun LM et al. | 2015 | PMID 25986002 DOI 10.1016/j.amjsurg.2015.01.017 | Cohort study | 2603 non-traumatic and 2295 traumatic splenectomy patients plus 4 matched controls each | Cancer was more common after splenectomy, especially when the spleen was removed because of disease rather than injury. | CIs not in abstract; Confounding by indication in non-traumatic group | low | C-ORG-13 |
| I-ORG-119 | Breastfeeding and sleep-disordered breathing in children: systematic review and proposal of underlying interaction models. Storari M et al. | 2021 | PMID 35034467 DOI 10.23804/ejpd.2021.22.04.10 | Systematic review | Children and adolescents | A review suggests breastfed children snore less, but the studies are observational and no numbers were pooled. | No pooled estimates in abstract; Observational, confounded studies | low | C-ORG-02 |
| I-ORG-120 | Impact of Breastfeeding Duration on Adenoid Hypertrophy, Snoring and Acute Otitis Media: A Case-Control Study in Preschool Children. Zwierz A et al. | 2023 | PMID 38137751 DOI 10.3390/jcm12247683 | Case-control study | 145 children aged 3-5 years | Longer breastfeeding was linked to less snoring and fewer ear infections, but not to smaller adenoids. | Small clinic sample; Recall of breastfeeding | low | C-ORG-02 |
| I-ORG-121 | Revisiting Diet and Appendicitis: A Systematic Review and Meta-Analysis. Pitesa R et al. | 2025 | PMID 41265933 DOI 10.1002/wjs.70166 | Meta-analysis | Human studies of diet and appendicitis | Low-fibre western diets may be linked to appendicitis, but the evidence is weak and inconsistent. | High risk of bias; Extreme heterogeneity | low | C-ORG-02 |
| I-ORG-122 | Adenotonsillectomy Does not Alter the Risk of Upper Airway Infections in Children. Kim JY et al. | 2021 | PMID 33720418 DOI 10.1002/lary.29506 | Cohort study | Children < 10 years with adenotonsillectomy and matched controls | Over 9 years, children who had the operation had the same number of upper airway infections as similar children who did not. | Claims data; Outcome = visits, not severity | moderate | C-ORG-03 C-ORG-16 |
| I-ORG-123 | Association between childhood tonsillectomy and increased risk of autoimmune disease: a nationwide population-based cohort study. Chang YS et al. | 2026 | PMID 42643288 DOI 10.3389/fmed.2026.1892240 | Cohort study | Children 0-12 years treated for tonsillar or adenoid disease in 2007-2008 | Children who had the surgery later had about 32% more autoimmune diseases than similar children who did not, but this does not prove the surgery caused them. | Claims data; Matching only by age and sex | moderate | C-ORG-04 C-ORG-16 |
| I-ORG-124 | Increased Risk of Inflammatory Bowel Disease in Families with Tonsillectomy: A Danish National Cohort Study. Bager P et al. | 2019 | PMID 30461527 DOI 10.1097/EDE.0000000000000946 | Cohort study | Danish population | Even relatives of people who had their tonsils out had more Crohn's disease, suggesting shared family factors rather than the surgery itself. | IBD only (not all autoimmunity); Register data | high | C-ORG-04 C-ORG-16 |
| I-ORG-125 | Appendectomy and the development of ulcerative colitis: results of a metaanalysis of published case-control studies. Koutroubakis IE et al. | 2000 | PMID 10638578 DOI 10.1111/j.1572-0241.2000.01680.x | Meta-analysis | 2770 UC patients and 3352 controls | People who had their appendix removed were much less likely to develop ulcerative colitis. | Case-control designs (recall/selection bias); Old literature (to 1999) | moderate | C-ORG-05 |
| I-ORG-126 | Appendicectomy plus standard medical therapy versus standard medical therapy alone for maintenance of remission in ulcerative colitis (ACCURE): a pragmatic, open-label, international, randomised trial. ACCURE Study Group | 2025 | PMID 40228513 DOI 10.1016/S2468-1253(25)00026-3 | Randomised controlled trial | Adults with UC in remission but treated for relapse within the preceding 12 months | In people with ulcerative colitis, removing the appendix reduced relapses within a year from 56% to 36%. | Open-label; 1-year outcome | high | C-ORG-05 |
| I-ORG-127 | A review of the function and evolution of the cecal appendix. Smith HF | 2023 | PMID 35363436 DOI 10.1002/ar.24917 | Narrative review | Mammals including humans | The appendix has evolved many times in mammals and may support gut immunity and gut bacteria. | Narrative review; Human functional evidence largely indirect | low | C-ORG-05 |
| I-ORG-128 | A Systematic Review and Meta-Analysis: A Prior Appendectomy Does Not Increase the Risk of Severe Clostridioides difficile Infection or Recurrence. Naga YSE et al. | 2023 | PMID 37402978 DOI 10.1007/s10620-023-07998-y | Meta-analysis | Patients with CDI | People without an appendix did not have more severe or recurrent C. difficile infections. | Few observational studies; Colectomy finding unexplained | low | C-ORG-05 |
| I-ORG-129 | The association between cholecystectomy and the risk of colorectal cancer: an updated systematic review and meta-analysis of cohort studies. Mu L et al. | 2023 | PMID 37434692 DOI 10.21037/tcr-22-2049 | Meta-analysis | Cohorts with and without cholecystectomy | Overall bowel cancer was not increased, but cancer in the right side of the colon was about 20% more common. | Observational, heterogeneous; Overlaps with other meta-analyses (e.g. I-ORG-130) | moderate | C-ORG-06 |
| I-ORG-130 | No association between cholecystectomy and risk of colorectal cancer: a meta-analysis of cohort studies. Yu L et al. | 2023 | PMID 37368048 DOI 10.1007/s00384-023-04463-0 | Meta-analysis | Cohort studies | Overall, gallbladder removal was not linked to bowel cancer. | Inconsistent subgroup results (sigmoid vs right colon); Multiple subgroup testing | moderate | C-ORG-06 |
| I-ORG-131 | Associations of cholecystectomy with the risk of colorectal cancer: a Mendelian randomization study. Chen L et al. | 2023 | PMID 37027252 DOI 10.1097/CM9.0000000000002612 | Other | GWAS summary data | A genetic analysis found no sign that gallbladder removal itself causes bowel cancer, but gallstone disease might. | Weak instruments (1.76% variance); Very wide CIs | moderate | C-ORG-06 C-ORG-16 |
| I-ORG-132 | Effectiveness of diet, psychological, and exercise therapies for the management of bile acid diarrhoea in adults: A systematic review. McKenzie YA et al. | 2022 | PMID 35274385 DOI 10.1111/jhn.13005 | Systematic review | Adults with bile acid diarrhoea (BAD) | Eating less fat seemed to ease bile acid diarrhoea, but the studies were small and of very low certainty. | Very small uncontrolled studies; Mostly ileal-resection BAD, indirect for cholecystectomy | low | C-ORG-08 |
| I-ORG-133 | Diet and faecal lipids following cholecystectomy in men. Brydon WG et al. | 1982 | PMID 7166207 DOI 10.1159/000198840 | Case-control study | Men after cholecystectomy and age-matched controls | Men without a gallbladder lost somewhat more fat in their stools than men with one, though they ate the same diet. | Very small, old, men only; No numbers in abstract | very low | C-ORG-08 |
| I-ORG-134 | Association of bilateral salpingo-oophorectomy with all cause and cause specific mortality: population based cohort study. Cusimano MC et al. | 2021 | PMID 34880044 DOI 10.1136/bmj-2021-067528 | Cohort study | Women aged 30-70 undergoing non-malignant hysterectomy | Removing both ovaries before age 50 was linked to more deaths over 20 years (about 1 extra death per 71 women under 45), but not after 50. | No data on menopausal status, smoking, BMI, family history (full text); Observational | high | C-ORG-09 C-ORG-16 |
| I-ORG-135 | Bilateral oophorectomy is not associated with increased mortality: the California Teachers Study. Duan L et al. | 2012 | PMID 22088205 DOI 10.1016/j.fertnstert.2011.10.004 | Cohort study | CTS participants with surgical (n = 9785) or natural menopause (n = 32,219) | Women whose menopause came from ovary removal did not die more often than women with natural menopause. | Comparator is natural menopause, not ovarian conservation at hysterectomy; Self-reported surgery | moderate | C-ORG-09 |
| I-ORG-136 | Examining the association of hysterectomy with and without oophorectomy on cardiovascular disease and all-cause, cardiovascular or cancer mortality: A systematic review and meta-analysis. Chen Y et al. | 2024 | PMID 38747094 DOI 10.1111/1471-0528.17843 | Meta-analysis | Women in cohort studies | Hysterectomy was linked to about 10% more cardiovascular disease and stroke, but not to more deaths. | High heterogeneity for several outcomes; Observational confounding | moderate | C-ORG-10 |
| I-ORG-137 | Association of Early Hysterectomy With Risk of Cardiovascular Disease in Korean Women. Yuk JS et al. | 2023 | PMID 37307002 DOI 10.1001/jamanetworkopen.2023.17145 | Cohort study | Korean women aged 40-49 | Women who had a hysterectomy in their 40s had about 25% more cardiovascular events, mostly strokes, but the absolute increase was small. | Claims data; Residual confounding (reasons for hysterectomy) | moderate | C-ORG-10 |
| I-ORG-138 | Surgical menopause in association with cognitive function and risk of dementia: A systematic review and meta-analysis. Georgakis MK et al. | 2019 | PMID 30928686 DOI 10.1016/j.psyneuen.2019.03.013 | Meta-analysis | Women in observational studies | Removing both ovaries at 45 or younger was linked to a higher risk of dementia; surgery at any age was not clearly linked. | Only 2 studies for the early-menopause estimate; Observational | moderate | C-ORG-11 |
| I-ORG-139 | Associations of Hysterectomy and Oophorectomy with Dementia Risk: A Systematic Review and Meta-Analysis of Observational Studies. Fu X et al. | 2026 | PMID 42796018 DOI 10.3390/jcm15187247 | Meta-analysis | Women in observational studies | Across all ages, removing the uterus or ovaries was not clearly linked to dementia. | Few studies per pool; High heterogeneity | moderate | C-ORG-11 |
| I-ORG-140 | Oophorectomy and rate of dementia: a prospective cohort study. Uldbjerg CS et al. | 2022 | PMID 35102101 DOI 10.1097/GME.0000000000001943 | Cohort study | 24,851 female nurses followed from age 60 | Nurses who had both ovaries removed had a slightly higher dementia rate, but the result could be due to chance. | CI includes 1; Limited power | moderate | C-ORG-11 |
| I-ORG-141 | Gallstone disease: diagnosis and management (NICE clinical guideline CG188), Recommendations National Institute for Health and Care Excellence (NICE) | 2014 | Guideline / position statement | Adults with suspected or confirmed gallstone disease | Silent gallstones need no treatment, but people with symptoms or gallbladder inflammation should be offered gallbladder removal. | 2014; predates C-GALL (I-ORG-09) and SECURE (I-ORG-104) | high | C-ORG-07 | |
| I-ORG-142 | Opportunistic Salpingectomy as a Strategy for Epithelial Ovarian Cancer Prevention (ACOG Committee Opinion No. 774; reaffirmed 2024) American College of Obstetricians and Gynecologists (ACOG) | 2019 | Guideline / position statement | Women undergoing pelvic surgery for benign disease | Removing both ovaries before menopause may raise risks of heart disease, bone loss, memory problems and death, so it should be discussed carefully. | Only the web abstract read; Not a systematic GRADE guideline | moderate | C-ORG-09 C-ORG-11 | |
| I-PPI-01 | Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin. Moayyedi P et al. | 2019 | PMID 31152740 DOI 10.1053/j.gastro.2019.05.056 | Randomised controlled trial | Adults with stable coronary or peripheral artery disease (aged >=65, or younger with additional criteria) without a clinical need for long-term PPI; mean age 67.6, 78% male; excluded high bleeding risk, severe heart failure, significant renal impairment (GFR <15), dementia, severe COPD | Over three years, only gut infections were more common with pantoprazole (1.4% vs 1.0%). | Not powered for safety outcomes; rare events (C. difficile, gastric atrophy) underpowered; Non-CV outcomes self-reported without adjudication (non-differential misclassification biases to null) | high | C-PPI-01 C-PPI-02 C-PPI-04 C-PPI-05 C-PPI-09 |
| I-PPI-02 | Proton pump inhibitors and risk of all-cause and cause-specific mortality: A cohort study. Brown JP et al. | 2021 | PMID 33393677 DOI 10.1111/bcp.14728 | Cohort study | Adults newly prescribed a PPI or H2RA in CPRD GOLD practices eligible for linkage; secondary cohort of PPI users and age/sex/year/practice-matched non-users of acid suppression | The link between PPIs and death shrank with better adjustment and appeared even for causes PPIs could not plausibly cause. | Observational; unmeasured frailty/disease severity likely; Prescription-based exposure; OTC use and non-adherence unrecorded | high | C-PPI-01 |
| I-PPI-03 | The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Freedberg DE et al. | 2017 | PMID 28257716 DOI 10.1053/j.gastro.2017.01.031 | Guideline / position statement | Long-term PPI users | PPIs are justified for defined indications; risks do not require routine monitoring. | Expert opinion; Abstract only | moderate | C-PPI-01 C-PPI-02 C-PPI-03 C-PPI-05 C-PPI-10 C-PPI-11 |
| I-PPI-04 | AGA Clinical Practice Update on De-Prescribing of Proton Pump Inhibitors: Expert Review. Targownik LE et al. | 2022 | PMID 35183361 DOI 10.1053/j.gastro.2021.12.247 | Guideline / position statement | Ambulatory PPI users | Stop PPIs without a definite indication; keep them in Barrett's, severe oesophagitis and high bleeding risk; expect temporary rebound. | Not a systematic review; no formal evidence grading | moderate | C-PPI-01 C-PPI-06 C-PPI-07 C-PPI-10 C-PPI-11 |
| I-PPI-05 | Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Farrell B et al. | 2017 | PMID 28500192 | Guideline / position statement | Adults on PPIs ≥4 weeks for heartburn/mild–moderate GERD/oesophagitis with resolved symptoms | PPIs can be reduced or stopped in many patients, but not in Barrett's, severe oesophagitis or after bleeding ulcers. | Abstract only read | moderate | C-PPI-07 C-PPI-10 C-PPI-11 |
| I-PPI-06 | Systematic review: symptoms of rebound acid hypersecretion following proton pump inhibitor treatment. Lødrup AB et al. | 2013 | PMID 23311977 DOI 10.3109/00365521.2012.746395 | Systematic review | Volunteers and reflux patients | Volunteers often get mild symptoms for up to 4 weeks; patients' studies show no clear rebound. | Only PubMed; 5 studies; Authors include Reimer (A-PPI-14) – not independent | moderate | C-PPI-06 C-PPI-07 |
| I-PPI-07 | Effect of Oral Ranitidine on Urinary Excretion of N-Nitrosodimethylamine (NDMA): A Randomized Clinical Trial. Florian J et al. | 2021 | PMID 34180947 DOI 10.1001/jama.2021.9199 | Randomised controlled trial | Healthy adults | Ranitidine did not raise NDMA in urine compared with placebo. | Small; Urinary NDMA is an indirect marker | moderate | C-PPI-08 |
| I-PPI-08 | Clopidogrel with or without omeprazole in coronary artery disease. Bhatt DL et al. | 2010 | PMID 20925534 DOI 10.1056/NEJMoa1007964 | Randomised controlled trial | Patients with indication for aspirin + clopidogrel | GI events fell from 2.9% to 1.1% with omeprazole. | Stopped early (loss of funding); Industry-funded (Cogentus) | high | C-PPI-10 |
| I-PPI-09 | Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial. Jankowski JAZ et al. | 2018 | PMID 30057104 DOI 10.1016/S0140-6736(18)31388-6 | Randomised controlled trial | Adults with histologically proven Barrett's oesophagus >=1 cm without high-grade dysplasia or adenocarcinoma and not on NSAIDs; ~80% men (women capped at ~500); median age 58-59; predominantly white | Over about 9 years, high-dose esomeprazole improved a composite of death, cancer and severe dysplasia. | Open-label; no placebo or no-PPI arm (compares doses only); Benefit driven by all-cause mortality and dysplasia; no effect on adenocarcinoma itself | high | C-PPI-10 |
| I-PPI-10 | ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Katz PO et al. | 2022 | PMID 34807007 DOI 10.14309/ajg.0000000000001538 | Guideline / position statement | Patients with GERD | Weight loss, avoiding late meals and trigger foods help; PPIs are best for erosive oesophagitis. | Some recommendations low-quality evidence | high | C-PPI-10 C-GUT-01 C-GUT-02 C-GUT-07 C-WHT-08 C-PPI-06 |
| I-PPI-101 | Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Scally B et al. | 2018 | PMID 29475806 DOI 10.1016/S2468-1253(18)30037-2 | Meta-analysis | Participants of 849 placebo/control-comparison trials (prevention, healing, acute bleeding) | Across 849 randomised trials, acid-suppressing drugs, especially PPIs, strongly reduced ulcers and ulcer bleeding. | Median trial size 78 and duration 1.4 months; Small-study bias acknowledged | high | C-PPI-10 C-PPI-11 |
| I-PPI-102 | Pantoprazole to Prevent Gastroduodenal Events in Patients Receiving Rivaroxaban and/or Aspirin in a Randomized, Double-Blind, Placebo-Controlled Trial. Moayyedi P et al. | 2019 | PMID 31054846 DOI 10.1053/j.gastro.2019.04.041 | Randomised controlled trial | Stable coronary or peripheral artery disease | In 17,598 heart patients on aspirin or a blood thinner, pantoprazole halved bleeding from stomach lesions but did not reduce all stomach problems combined; about 1000 needed treatment to prevent one bleed. | Low-risk population (people needing a PPI excluded); Low event rates; post-hoc analyses | high | C-PPI-10 C-PPI-11 |
| I-PPI-103 | Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Boghossian TA et al. | 2017 | PMID 28301676 DOI 10.1002/14651858.CD011969.pub2 | Systematic review | Adult chronic PPI users (mostly non-erosive reflux or mild LA A/B oesophagitis) | In six trials of people with mild reflux, switching to as-needed PPI cut pill use by about 4 pills a week but more people had uncontrolled symptoms. | Few trials; mild GERD only; Low-quality evidence for symptoms | high | C-PPI-07 C-PPI-11 |
| I-PPI-104 | Dyspeptic symptom development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial. Niklasson A et al. | 2010 | PMID 20332770 DOI 10.1038/ajg.2010.81 | Randomised controlled trial | 48 healthy H. pylori-negative volunteers (24 women) | After 4 weeks of pantoprazole, 44% of healthy volunteers developed indigestion when they stopped, compared with 9% after placebo; it faded within 3 weeks. | Small; Short treatment | high | C-PPI-06 C-PPI-07 |
| I-PPI-105 | Rebound Acid Hypersecretion after Withdrawal of Long-Term Proton Pump Inhibitor (PPI) Treatment-Are PPIs Addictive? Namikawa K et al. | 2024 | PMID 38791497 DOI 10.3390/ijms25105459 | Narrative review | Studies of PPI withdrawal | Stopping PPIs can cause a temporary acid surge that people mistake for their old illness; warning patients helps them stop. | Narrative; no systematic search | low | C-PPI-07 C-PPI-06 |
| I-PPI-106 | An App-Based Proton Pump Inhibitor Discontinuation Tool: A Multicentre, Open-Label, Randomised Superiority Trial. Koggel LM et al. | 2026 | PMID 42894466 DOI 10.1002/ueg2.70297 | Randomised controlled trial | Adults using daily PPI >=4 weeks without chronic indication (Dutch GP guideline), outpatients of 3 Dutch hospitals | Among outpatients without a reason for long-term PPIs, 86% using an app and 64% using a leaflet had stopped after 2 months. | Open label, self-reported outcome; Only 2-month follow-up | moderate | C-PPI-07 C-PPI-11 |
| I-PPI-107 | Association between proton pump inhibitor use and upper gastrointestinal cancer: A matched case-control study accounting for reverse causation and confounding by indication. Sawaid IO et al. | 2026 | PMID 41493925 DOI 10.1371/journal.pmed.1004842 | Case-control study | Members of Leumit Health Services, Israel, incl. Arab sector (12% of cases) | People often start acid blockers because of symptoms of a still-undiagnosed cancer; after accounting for this, long-term PPI use was not linked to more upper GI cancer. | Observational; residual confounding; Over-the-counter PPI not captured | moderate | C-PPI-09 |
| I-PPI-108 | Proton pump inhibitors and risk of gastric cancer: population-based cohort study. Abrahami D et al. | 2022 | PMID 34226290 DOI 10.1136/gutjnl-2021-325097 | Cohort study | New users of PPIs or H2RAs in UK primary care | Compared with H2 blockers, PPI users had a 45% higher relative risk of stomach cancer, but only about 1 extra case per 1,200-2,100 users over 5-10 years. | Observational; H. pylori status incompletely recorded | moderate | C-PPI-09 |
| I-PPI-109 | Proton-pump inhibitor use does not affect semen quality in subfertile men. Keihani S et al. | 2018 | PMID 28879865 DOI 10.4103/aja.aja_35_17 | Cohort study | Subfertile men at a US fertility clinic | Among men at a fertility clinic, those taking PPIs had similar semen results to men taking no medicines. | Retrospective; Only age adjusted | low | C-PPI-09 |
| I-PPI-110 | Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Lo CH et al. | 2022 | PMID 35788344 DOI 10.1053/j.gastro.2022.06.067 | Cohort study | US nurses and health professionals | PPI users died somewhat more often, but when the analysis accounted for illness leading to PPI use, there was no clear extra risk. | Observational; Health professionals, mostly White | high | C-PPI-01 |
| I-PPI-111 | Proton Pump Inhibitor Use and Worsening Kidney Function: A Retrospective Cohort Study Including 122,606 Acid-Suppressing Users. González-Pérez A et al. | 2025 | PMID 39627545 DOI 10.1007/s11606-024-09213-8 | Cohort study | Initiators of PPIs or H2RAs with preserved renal function | In 122,606 new users, kidney function worsened equally often with PPIs and ranitidine after accounting for differences between users. | Small H2RA group; Short follow-up (up to ~6 y) | moderate | C-PPI-01 |
| I-PPI-112 | Association between Proton Pump Inhibitor Use and Risk of Incident Chronic Kidney Disease: Systematic Review and Meta-Analysis. Ang SP et al. | 2024 | PMID 39061988 DOI 10.3390/biomedicines12071414 | Meta-analysis | Adults in 12 observational studies | Pooling 12 observational studies, PPI users had about 26% higher relative risk of developing chronic kidney disease. | Observational studies only; Overlaps with archive-cited cohorts (A-PPI-01/02) | moderate | C-PPI-01 |
| I-PPI-113 | Proton Pump Inhibitor Use for Gastroprotection and Stress Ulcer Prophylaxis Does Not Increase the Risk of Clostridioides difficile Infection or Pneumonia: A Systematic Review and Meta-Analysis of RCTs. Omar MA et al. | 2026 | PMID 41976918 DOI 10.3390/jcm15072617 | Meta-analysis | Participants in 8 RCTs (incl. COMPASS and ICU stress-ulcer trials) | In 8 randomised trials with 30,019 people, PPIs reduced serious stomach bleeding and did not significantly increase pneumonia or C. difficile. | Few trials; CDI imprecise; Follow-up 30 days to 3 years | moderate | C-PPI-05 C-PPI-02 C-PPI-10 |
| I-PPI-114 | The impact of proton pump inhibitor exposure on pneumonia: an updated meta-analysis based on randomized controlled trials. Wu Z et al. | 2025 | PMID 41230098 DOI 10.3389/fphar.2025.1713256 | Meta-analysis | 20 RCTs | Pooling 20 randomised trials, PPI users had a 10% higher pneumonia rate, which was not statistically certain. | Many subgroup analyses; multiplicity; Overlaps with Omar 2026 (I-PPI-113) | moderate | C-PPI-05 |
| I-PPI-115 | Proton pump inhibitor use and risk of pneumonia: a self-controlled case series study. Maret-Ouda J et al. | 2023 | PMID 37314495 DOI 10.1007/s00535-023-02007-5 | Other | Swedish patients with >=1 pneumonia episode | In Sweden, people had 73% more pneumonia episodes during times they took PPIs than during times they did not. | Time-varying confounding (prodromal symptoms, aspiration) possible | moderate | C-PPI-05 |
| I-PPI-116 | Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Lam JR et al. | 2017 | PMID 27890768 DOI 10.1053/j.gastro.2016.11.023 | Case-control study | Members without pre-existing iron-deficiency risk factors | People who took PPIs for 2 years or more had about 2.5 times the odds of iron deficiency, more with higher doses. | Observational; residual confounding (occult bleeding) | moderate | C-PPI-03 C-PPI-04 |
| I-PPI-117 | Ranitidine Use and Incident Cancer in a Multinational Cohort. You SC et al. | 2023 | PMID 37725377 DOI 10.1001/jamanetworkopen.2023.33495 | Cohort study | Adults without prior cancer using H2RAs >30 days | In 1.2 million people from 7 countries, ranitidine users developed cancer no more often than users of similar drugs. | Follow-up length limited; Observational | high | C-PPI-08 |
| I-PPI-118 | In Vitro Analysis of N-Nitrosodimethylamine (NDMA) Formation From Ranitidine Under Simulated Gastrointestinal Conditions. Gao Z et al. | 2021 | PMID 34181009 DOI 10.1001/jamanetworkopen.2021.18253 | Laboratory / cell study | Not applicable (150-mg ranitidine tablets) | FDA tests found NDMA formation only at nitrite levels at least 50 times above normal stomach levels. | In vitro; Erratum (figure captions) | moderate | C-PPI-08 |
| I-PPI-119 | Proton pump inhibitor use: systematic review of global trends and practices. Shanika LGT et al. | 2023 | PMID 37420019 DOI 10.1007/s00228-023-03534-z | Systematic review | Adults >=18 in 23 countries | Data from 23 countries suggest nearly one in four adults uses a PPI, many at high doses and for more than a year. | Simple summing; heterogeneous sources; Few low- and middle-income countries | moderate | C-PPI-11 |
| I-PPI-120 | Knowledge, Attitudes, and Practices of Community Pharmacists Regarding Proton Pump Inhibitor (PPI) Use: A Cross-Sectional Study. Moustafa HAM et al. | 2025 | PMID 40648613 DOI 10.3390/healthcare13131588 | Cross-sectional study | Community pharmacists in Egypt and Iraq | A survey of 527 pharmacists found gaps in knowledge about when PPIs are needed and when to stop them. | Self-reported survey; convenience sample; No prescription data | very low | C-PPI-11 |
| I-RES-01 | Commission Regulation (EU) No 37/2010 of 22 December 2009 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin European Commission | 2010 | Guideline / position statement | The EU sets residue limits (e.g. emamectin 100 µg/kg in fish) and bans some drugs such as chloramphenicol and nitrofurans. | As-adopted version; later amendments not checked | high | C-FSH-10 C-RES-03 C-MEAT-02 | ||
| I-RES-02 | Council Directive 96/22/EC concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of beta-agonists Council of the EU | 1996 | Guideline / position statement | The EU prohibits hormonal growth promoters in farm animals. | Only title/contents page read | high | C-FSH-16 C-RES-04 C-CHK-06 | ||
| I-RES-03 | Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed of plant and animal origin European Parliament and Council | 2005 | Guideline / position statement | EU law sets maximum pesticide residue levels for all foods. | Only title page read | high | C-RES-01 | ||
| I-RES-04 | Regulation (EC) No 1831/2003 on additives for use in animal nutrition, Article 11 European Parliament and Council | 2003 | Guideline / position statement | Since 1 January 2006, antibiotics may not be used as growth promoters in EU animal feed. | high | C-RES-04 C-RES-05 | |||
| I-RES-05 | The 2023 European Union report on pesticide residues in food (EFSA news: 'Pesticides residues in food: what's the situation in the EU?') EFSA | 2025 | DOI 10.2903/j.efsa.2025.9398 | Measurement / residue study | Food samples | About 98% of samples complied with EU limits; EFSA judged consumer risk low. | Risk-based sampling not representative of average diet (MANCP) | high | C-RES-01 C-RES-02 |
| I-RES-06 | The 2024 European Union report on pesticide residues in food (summary: 'EFSA's 2024 pesticide residue report finds 98.8% of tested EU foods compliant') EFSA | 2026 | DOI 10.2903/j.efsa.2026.10054 | Measurement / residue study | Food samples | 98.8% of tested common foods complied with EU limits. | Secondary EU summary page, not EFSA report itself | high | C-RES-01 C-RES-02 C-VEG-13 |
| I-RES-07 | Report for 2023 on the results from the monitoring of veterinary medicinal product residues and other substances in live animals and animal products (EFSA news: 'Veterinary drug residues in food - non-compliance stays low in 2023') EFSA | 2025 | Measurement / residue study | Animals and animal products | Only 0.11% of over half a million samples were non-compliant. | Aquaculture not separately reported on the page read | high | C-FSH-09 C-FSH-16 C-RES-02 C-RES-04 C-MEAT-02 C-EGG-10 | |
| I-RES-08 | Health risk assessment of enrofloxacin, oxytetracycline, and sulfadimidine residues in broiler chicken carcasses marketed in Mit Ghamr, Egypt. Noah SM et al. | 2026 | PMID 42527435 DOI 10.1038/s41598-026-63227-2 | Measurement / residue study | Broiler chicken breast, thigh and liver from different poultry shops in Mit Ghamr City, Egypt | Most chicken samples had antibiotic residues, often above legal limits, but estimated intake was far below harmful levels. | One town; shop-level sampling without documented farm origin; No confirmatory LC-MS/MS (authors' stated limitation); PDA identification by retention time and spectrum only | moderate | C-FSH-16 C-RES-01 C-RES-02 C-RES-03 |
| I-RES-09 | Hormonal residues in chicken and cattle meat: A risk threat the present and future consumer health. Kamaly HF & Sharkawy AA | 2023 | PMID 37956705 DOI 10.1016/j.fct.2023.114172 | Measurement / residue study | 92 chicken, 56 beef samples | A small study reported high hormone levels, but its method cannot tell natural from added hormones. | ELISA cannot distinguish endogenous from administered hormones; Small | low | C-RES-04 C-MEAT-02 C-CHK-06 |
| I-RES-101 | Assessment of antibiotic residues in chicken meat. Kamouh HM et al. | 2024 | PMID 38633178 DOI 10.5455/OVJ.2024.v14.i1.40 | Measurement / residue study | Chicken breast, thigh, gizzard and liver from slaughterhouses in Kafr El-Sheikh markets | 21% of samples contained gentamicin, most often liver and gizzard; boiling removed over 90%. | Small sample from one governorate; Gentamicin MRLs taken from EU bovine/porcine values (EU 37/2010 lists gentamicin MRLs only for bovine and porcine species, I-RES-01) | low | C-RES-03 C-RES-01 C-CHK-05 |
| I-RES-102 | JECFA: Gentamicin - toxicological monograph (WHO Food Additives Series 34) and JECFA evaluation summary (ADI 0-0.02 mg/kg bw, latest evaluation 1998) Joint FAO/WHO Expert Committee on Food Additives (JECFA) | 1998 | Risk assessment | General population | Experts set a safe daily intake of 0.02 mg/kg body weight and note that gentamicin is essentially not absorbed from the gut; kidney and ear damage were seen with injected medical doses. | Older evaluation; MRLs set for cattle and pigs only | high | C-RES-03 | |
| I-RES-103 | Temporal Trends, Multiple Residue Incidence, and Chronic Health Risk of Pesticides in Egyptian Onions: A Four-Year Market Surveillance. Malhat F et al. | 2025 | PMID 41283430 DOI 10.3390/jox15060192 | Measurement / residue study | Onion samples from Egyptian markets | Up to half of onion samples had residues and up to 8% exceeded EU limits, but intake stayed below 2.3% of safe levels. | One commodity; Sampling frame not described in abstract | moderate | C-RES-01 C-RES-02 C-VEG-14 |
| I-RES-104 | Comprehensive multi-residue analysis of 87 pesticides in Egyptian food commodities: Method validation and dietary risk assessment. Ezzat A et al. | 2026 | PMID 41678938 DOI 10.1016/j.jchromb.2026.124960 | Measurement / residue study | Apple, chamomile, caraway, dried mint, fennel, green beans, hibiscus, rice | 55% of 591 samples had residues; calculated risks were below the level of concern. | Sampling not described in abstract; Chlorpyrifos detected despite national ban (from 2022, per jurisdiction data) | moderate | C-RES-01 C-RES-02 |
| I-RES-105 | Cumulative dietary risk characterisation of pesticides that have acute effects on the nervous system. EFSA | 2020 | PMID 32874295 DOI 10.2903/j.efsa.2020.6087 | Risk assessment | 10 European consumer populations | EFSA concluded that combined exposure to residues acting on the nervous system did not exceed the threshold in any of 10 European populations. | Limited to selected effects; EU diets and residue levels only | high | C-RES-01 C-RES-02 |
| I-RES-106 | Intake of fruits and vegetables according to pesticide residue status in relation to all-cause and disease-specific mortality: Results from three prospective cohort studies. Sandoval-Insausti H et al. | 2022 | PMID 34894487 DOI 10.1016/j.envint.2021.107024 | Cohort study | US nurses and health professionals without CVD, cancer or diabetes | Low-residue produce was linked to 36% lower mortality; high-residue produce showed no benefit but also no harm. | Exposure assigned at food level, not measured in individuals; Residual confounding | moderate | C-RES-02 C-RES-01 C-VEG-13 |
| I-RES-107 | Association of Frequency of Organic Food Consumption With Cancer Risk: Findings From the NutriNet-Sante Prospective Cohort Study. Baudry J et al. | 2018 | PMID 30422212 DOI 10.1001/jamainternmed.2018.4357 | Cohort study | French adult volunteers (78% women) | The highest organic consumers had 25% fewer cancers (absolute 0.6%), possibly due to healthier lifestyles. | Volunteers; healthy-consumer bias; Short follow-up | moderate | C-RES-02 |
| I-RES-108 | Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom. Bradbury KE et al. | 2014 | PMID 24675385 DOI 10.1038/bjc.2014.148 | Cohort study | Middle-aged UK women | Among 623,080 women, regular organic eaters had no lower overall cancer risk. | Organic intake self-reported once; No residue measurement | moderate | C-RES-02 |
| I-RES-109 | Organic food consumption and the incidence of cancer in the Danish diet, cancer and health cohort. Andersen JLM et al. | 2023 | PMID 36592285 DOI 10.1007/s10654-022-00951-9 | Cohort study | Danish adults | Over 15 years, organic food consumption was not related to overall cancer risk. | Organic intake reported once; Many site-specific tests | moderate | C-RES-02 |
| I-RES-110 | Anabolic Steroids in Fattening Food-Producing Animals-A Review. Skoupa K et al. | 2022 | PMID 36009705 DOI 10.3390/ani12162115 | Narrative review | Food-producing animals | Anabolic steroids are permitted for fattening in countries such as the USA and Australia but banned in the EU. | Narrative review; non-systematic; Health effects described are those of abuse doses in humans | low | C-RES-04 |
| I-RES-111 | Withdrawal of antibiotic growth promoters from broiler diets: performance indexes and economic impact. Maria Cardinal K et al. | 2019 | PMID 31544941 DOI 10.3382/ps/pez536 | Meta-analysis | Broilers in 183 published experiments (52% Ross) | Across 183 experiments, antibiotic growth promoters increased weight gain and feed efficiency, mainly early in life. | Effect sizes not in abstract; Publication bias possible | moderate | C-RES-05 |
| I-RES-112 | Effect of antibiotic growth promoters (AGPs) on feed conversion ratio (FCR) of broiler chickens: A meta-analysis. El-Fateh M et al. | 2024 | PMID 39504822 DOI 10.1016/j.psj.2024.104472 | Meta-analysis | Broilers in 74 experiments | On average, antibiotics improved feed conversion by 2.8%, with large variation. | Heterogeneous studies; FCR only | moderate | C-RES-05 |
| I-SOD-01 | Systematic review: the effects of carbonated beverages on gastro-oesophageal reflux disease. Johnson T et al. | 2010 | PMID 20055784 DOI 10.1111/j.1365-2036.2010.04232.x | Systematic review | Not stated in abstract | Fizzy drinks briefly lower acidity in the food pipe, but there is no direct evidence that they cause reflux disease. | Old (2010); Limited primary evidence | moderate | C-SOD-12 C-SOD-13 C-SOD-14 |
| I-SOD-02 | Effects of carbonated water on functional dyspepsia and constipation. Cuomo R et al. | 2002 | PMID 12352219 DOI 10.1097/00042737-200209000-00010 | Randomised controlled trial | Patients with dyspepsia and secondary constipation | In a small trial, sparkling water improved indigestion and constipation compared with tap water. | Very small; Short | low | C-SOD-12 C-SOD-14 |
| I-SOD-03 | Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Suez J et al. | 2022 | PMID 35987213 DOI 10.1016/j.cell.2022.07.016 | Randomised controlled trial | Healthy adults | Saccharin and sucralose worsened glucose responses in some people; aspartame and stevia did not significantly. | Short (2 weeks); Clinical relevance unknown | high | C-SOD-07 |
| I-SOD-04 | Effect of fructose on markers of non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of controlled feeding trials. Chiu S et al. | 2014 | PMID 24569542 DOI 10.1038/ejcn.2014.8 | Meta-analysis | Healthy participants | Fructose raised liver fat only when it added large amounts of extra calories. | Few, small, short, poor-quality trials | moderate | C-SOD-04 |
| I-SOD-05 | Fructose intake and risk of gout and hyperuricemia: a systematic review and meta-analysis of prospective cohort studies. Jamnik J et al. | 2016 | PMID 27697882 DOI 10.1136/bmjopen-2016-013191 | Meta-analysis | Predominantly white health professionals | High fructose intake was linked with 62% higher gout risk in two cohorts; certainty low. | Only 2 cohorts; Indirect population | moderate | C-SOD-05 |
| I-SOD-06 | Artificially Sweetened Beverages and Stroke, Coronary Heart Disease, and All-Cause Mortality in the Women's Health Initiative. Mossavar-Rahmani Y et al. | 2019 | PMID 30802187 DOI 10.1161/STROKEAHA.118.023100 | Cohort study | Postmenopausal women 50-79 | Women drinking two or more diet drinks daily had 31% more ischaemic strokes; far less than the 'triple' figure. | Reverse causation; Single population | high | C-SOD-06 |
| I-SOD-07 | Sugar-sweetened beverage consumption and bone health: a systematic review and meta-analysis. Ahn H, Park YK | 2021 | PMID 33952276 DOI 10.1186/s12937-021-00698-1 | Meta-analysis | Children and adults | Higher sugary and fizzy drink intake was linked with lower bone density in adults. | Observational; Small meta-analysed sample | moderate | C-SOD-08 |
| I-SOD-08 | WHO advises not to use non-sugar sweeteners for weight control in newly released guideline (Use of non-sugar sweeteners: WHO guideline, 2023) — news release World Health Organization | 2023 | Guideline / position statement | All people except those with pre-existing diabetes | WHO advises not to use sweeteners for weight control, because no long-term benefit was shown; possible harms may be confounded. | Conditional; observational evidence for harms | high | C-SOD-06 C-SOD-10 | |
| I-SOD-09 | Aspartame hazard and risk assessment results released (IARC and WHO/FAO JECFA, 14 July 2023) — news release WHO / IARC / JECFA | 2023 | Risk assessment | General population | IARC said 'possibly carcinogenic' on limited evidence; JECFA kept the safe daily limit of 40 mg/kg. | Limited evidence base | high | C-UPF-07 C-UPF-08 | |
| I-SOD-101 | Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review. Diaz C et al. | 2023 | PMID 37187453 DOI 10.1016/j.advnut.2023.05.010 | Systematic review | Adults in cohort and case-control studies | Across many studies, regular diet-drink consumers had more obesity, diabetes, hypertension, heart disease and deaths; stroke and heart-death links were weak. | Observational associations only; reverse causation not addressed by grading; Underlying reviews of limited quality | moderate | C-SOD-10 C-SOD-06 |
| I-SOD-102 | Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Choi JH et al. | 2026 | PMID 41531289 DOI 10.4093/dmj.2025.0848 | Guideline / position statement | Adults | Korean experts found that swapping sugary drinks for diet drinks lowered weight slightly in trials, but long-term observational links to disease mean water is the better goal. | Consensus process; abstract only reviewed; Korean focus of recommendations | moderate | C-SOD-10 |
| I-SOD-103 | Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis. McGlynn ND et al. | 2022 | PMID 35285920 DOI 10.1001/jamanetworkopen.2022.2092 | Meta-analysis | Adults with overweight or obesity at risk for or with diabetes | In 17 randomised trials, replacing sugary drinks with low- or no-calorie drinks lowered weight by about 1 kg, similar in direction to water. | Short to moderate duration; Industry links of several authors | high | C-SOD-10 |
| I-SOD-104 | Sweetened Beverages and Incident All-Cause Dementia Among Older Adults. Chen H et al. | 2025 | PMID 40531522 DOI 10.1001/jamapsychiatry.2025.1230 | Cohort study | US adults aged >=65 (HRS, ARIC, CHAP, MAP, Framingham original and offspring) | Across six US cohorts with about 11,000 older adults, diet drinks were not linked to dementia (HR 1.00). | Late-life exposure only; Alzheimer subtype not separately reported in abstract | high | C-SOD-06 |
| I-SOD-105 | The association between sugar- and artificially sweetened beverages and risk of Alzheimer's disease: systematic review and dose-response meta-analysis of prospective cohort studies. Jouni N et al. | 2025 | PMID 40511662 DOI 10.1080/13607863.2025.2512215 | Meta-analysis | Adults in prospective cohorts | Pooling seven cohort studies, diet drinks were linked to 42% higher Alzheimer's risk, far less than a tripling. | Few studies; probably includes Pase 2017; Observational | moderate | C-SOD-06 |
| I-SOD-106 | High-dose saccharin supplementation does not induce gut microbiota changes or glucose intolerance in healthy humans and mice. Serrano J et al. | 2021 | PMID 33431052 DOI 10.1186/s40168-020-00976-w | Randomised controlled trial | Healthy men and women; chow-fed wild-type and sweet-receptor knockout mice | In a placebo-controlled trial, two weeks of saccharin at the maximum acceptable dose changed neither gut bacteria nor glucose tolerance. | Two weeks only; Capsules rather than beverages | high | C-SOD-07 |
| I-SOD-107 | Effect of Sucralose Consumption on Gut Microbiota: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Wulandari DT et al. | 2026 | PMID 42794802 DOI 10.3390/ijms27188377 | Meta-analysis | Healthy adults | A 2026 meta-analysis of 10 small trials found no significant effect of sucralose on gut bacteria diversity, fasting glucose or insulin resistance. | Small trials, wide CIs; Short durations | moderate | C-SOD-07 |
| I-SOD-108 | Association Between Beverage Intake and Incidence of Gastroesophageal Reflux Symptoms. Mehta RS et al. | 2020 | PMID 31786327 DOI 10.1016/j.cgh.2019.11.040 | Cohort study | US women aged 42-62 without regular GER symptoms, cancer or acid-suppressant use | In 48,000 US nurses, women drinking the most soda developed weekly heartburn or regurgitation about 29% more often; switching soda for water was linked to lower risk. | Self-reported symptoms; Women only, mostly white health professionals | high | C-SOD-12 |
| I-SOD-109 | Sweetened beverage intake and incident gastroesophageal reflux disease in a prospective cohort study. Ma C et al. | 2025 | PMID 40498344 DOI 10.1007/s00394-025-03707-9 | Cohort study | UK Biobank participants free of GERD | Among 167,574 UK adults, drinking more than one sugary or diet soft drink a day was linked to a 7-12% higher risk of reflux disease. | Small effect sizes; Residual confounding | high | C-SOD-12 |
| I-SOD-110 | Peptic ulcer disease. Lanas A, Chan FKL | 2017 | PMID 28242110 DOI 10.1016/S0140-6736(16)32404-7 | Narrative review | Not applicable | A Lancet review describes Helicobacter pylori infection and anti-inflammatory painkillers as the central causes of stomach and duodenal ulcers. | Narrative; abstract only reviewed; Does not address soft drinks explicitly | moderate | C-SOD-12 |
| I-SOD-111 | Randomized trial of carbonated water consumption on snacking behavior, alcohol intake, and health indices in healthy Japanese adults. Hashimoto H et al. | 2026 | PMID 42106408 DOI 10.1038/s41598-026-51479-x | Randomised controlled trial | Healthy Japanese adults aged 20-64, BMI 23.0-<30.0 | In a 12-week trial in 45 Japanese adults, drinking 500 mL of sparkling water daily caused no adverse effects and was linked to less snacking. | Small; Open-label | moderate | C-SOD-14 |
| I-SOD-112 | Investigation of mineral waters and soft drinks in relation to dental erosion. Parry J et al. | 2001 | PMID 11556958 DOI 10.1046/j.1365-2842.2001.00795.x | Laboratory / cell study | Extracted human teeth; powdered hydroxyapatite | In laboratory tests, sparkling mineral waters dissolved tooth enamel about 100 times less than soft drinks. | In vitro; no saliva or clinical outcomes; Funding not stated in abstract | moderate | C-SOD-14 |
| I-SOD-113 | [Effects of carbonated water intake on constipation in elderly patients following a cerebrovascular accident]. Mun JH, Jun SS | 2011 | PMID 21551998 DOI 10.4040/jkan.2011.41.2.269 | Randomised controlled trial | Bed-ridden elderly patients after cerebrovascular accident | In a small Korean trial, elderly stroke patients drinking carbonated water for two weeks had more frequent bowel movements than those drinking tap water. | Very small; Short | low | C-SOD-14 |
| I-SOD-114 | The pH of beverages in the United States. Reddy A et al. | 2016 | PMID 26653863 DOI 10.1016/j.adaj.2015.10.019 | Measurement / residue study | Not applicable (beverages) | Measured pH: Pepsi 2.39 and Coca-Cola 2.37 (strongly acidic), plain sparkling mineral water 5.25. | pH is only one determinant of erosion; US products; formulations may differ elsewhere | moderate | C-SOD-13 C-SOD-11 C-SOD-14 |
| I-SOD-115 | Ethanol as a Probe for the Mechanism of Bubble Nucleation in the Diet Coke and Mentos Experiment. Kuntzleman TS, Kuntzleman JT | 2021 | PMID 33802982 DOI 10.3390/molecules26061691 | Other | Not applicable | Chemistry research states that carbonated soft drinks generally contain about 6 g of carbon dioxide per litre. | CO2 content given as a general approximation, not measured per brand | moderate | C-SOD-13 |
| I-SOD-116 | Review of carbon dioxide removal and recycling in space. O'Sullivan C et al. | 2026 | PMID 42120392 DOI 10.1038/s41526-026-00608-x | Narrative review | Not applicable | Space life-support engineering uses about 1 kg of carbon dioxide per crew member per day as the design value. | Indirect source for human physiology; Approximate per-person figure | moderate | C-SOD-13 |
| I-SOD-117 | No influence of carbonation on glycemic response, gastric emptying, and satiety of sweetened drinks. Lau ERL, Henry CJ | 2017 | PMID 28606564 DOI 10.1016/j.nut.2017.02.001 | Randomised controlled trial | Healthy adults | Adding carbonation to a sugary drink did not change blood sugar, stomach emptying or fullness in 15 healthy adults. | Very small; Single exposure | moderate | C-SOD-13 |
| I-SOD-118 | A trial of sugar-free or sugar-sweetened beverages and body weight in children. de Ruyter JC et al. | 2012 | PMID 22998340 DOI 10.1056/NEJMoa1203034 | Randomised controlled trial | Primarily normal-weight children aged 4 years 10 months to 11 years 11 months | In an 18-month blinded trial, Dutch children given one sugary drink a day gained about 1 kg more than children given an identical-tasting sugar-free drink. | 26% discontinued; Sensitivity analysis borderline (P=0.06) | high | C-SOD-02 |
| I-SOD-119 | A randomized trial of sugar-sweetened beverages and adolescent body weight. Ebbeling CB et al. | 2012 | PMID 22998339 DOI 10.1056/NEJMoa1203388 | Randomised controlled trial | Overweight and obese adolescents who regularly drank SSB | Overweight teenagers who replaced sugary drinks gained less weight during the one-year programme, but the difference was gone a year later. | Primary outcome null; Open intervention | high | C-SOD-02 |
| I-SOD-120 | Association of Consumption of Sugar-Sweetened Beverages or Artificially Sweetened Beverages with Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. Zhang YB et al. | 2021 | PMID 33786594 DOI 10.1093/advances/nmaa110 | Meta-analysis | General, diseased or occupational populations in cohorts | Pooled cohorts: each daily sugary drink was linked to 8% higher overall and cardiovascular mortality; diet drinks were linked at 1.5 or more per day. | Observational; Overlap with included single cohorts (e.g. Malik 2019, EPIC) | high | C-SOD-03 C-SOD-10 |
| I-SOD-121 | Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial. Geidl-Flueck B et al. | 2021 | PMID 33684506 DOI 10.1016/j.jhep.2021.02.027 | Randomised controlled trial | Healthy lean men | In a 7-week trial, men drinking 80 g/day of fructose or table sugar in drinks doubled their liver's fat production; glucose did not. | Healthy young men only; Surrogate outcome (lipogenesis), not liver disease | high | C-SOD-04 |
| I-SOD-122 | Important Food Sources of Fructose-Containing Sugars and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials. Lee D et al. | 2022 | PMID 35889803 DOI 10.3390/nu14142846 | Meta-analysis | Predominantly healthy younger adults, mixed weight | Across 51 trials, fructose-containing sugars raised liver fat only when they added extra calories, most clearly from sugary drinks. | Short trials; Author industry links | high | C-SOD-04 |
| I-SOD-123 | Soda consumption and risk of hip fractures in postmenopausal women in the Nurses' Health Study. Fung TT et al. | 2014 | PMID 25099544 DOI 10.3945/ajcn.114.083352 | Cohort study | Postmenopausal US women (Nurses' Health Study) | In 73,572 US nurses, each daily soda was linked to 14% more hip fractures; colas were not worse than other sodas. | Observational; Women only | high | C-SOD-08 |
| I-SOD-124 | Carbonated beverages and urinary calcium excretion. Heaney RP, Rafferty K | 2001 | PMID 11522558 DOI 10.1093/ajcn/74.3.343 | Randomised controlled trial | Women aged 20-40 who habitually drank >=680 mL carbonated beverages daily | In a controlled test, cola-type acid did not increase calcium in the urine; only caffeine did, and only slightly. | Acute (5-h) outcome; Small; women only | moderate | C-SOD-08 |
| I-SOD-125 | Sweetened Beverage Intake and Incident Chronic Kidney Disease in the UK Biobank Study. Heo GY et al. | 2024 | PMID 38416492 DOI 10.1001/jamanetworkopen.2023.56885 | Cohort study | UK Biobank participants without CKD | Among 127,830 UK adults, drinking more than one sugary or diet soft drink a day was linked to 19-26% higher risk of chronic kidney disease. | Observational; Cola not analysed separately | high | C-SOD-09 |
| I-SOD-126 | Sugar- and artificially-sweetened beverages and the risks of chronic kidney disease: a systematic review and dose-response meta-analysis. Lo WC et al. | 2021 | PMID 33502726 DOI 10.1007/s40620-020-00957-0 | Meta-analysis | Adults | A meta-analysis found a non-significant 30% higher kidney-disease risk with high sugary-drink intake, with risk rising above seven drinks per week. | Few, small studies; Imprecise | moderate | C-SOD-09 |
| I-SOD-127 | Burdens of type 2 diabetes and cardiovascular disease attributable to sugar-sweetened beverages in 184 countries. Lara-Castor L et al. | 2025 | PMID 39762424 DOI 10.1038/s41591-024-03345-4 | Risk assessment | Adults in 184 countries | A global model estimated that sugary drinks accounted for about 10% of new type 2 diabetes cases in 2020, with high burdens in the Middle East and North Africa. | Model assumes causal relative risks from cohorts; Intake data partly modelled | moderate | C-SOD-01 |
| I-SOD-128 | The potential health effects of taxing sugar-sweetened drinks in Egypt: An epidemiologic-economic modelling study. Dalugoda Y et al. | 2026 | PMID 42058140 DOI 10.1016/j.puhip.2026.100786 | Risk assessment | Egyptian population (2019) | A 2026 model estimated that a 20% tax on sugary drinks in Egypt could prevent about 250,000 cases of type 2 diabetes over 25 years. | Model based on assumed causal effects and price elasticities; Uses international and Egyptian data of variable quality | moderate | C-SOD-01 |
| I-SOD-129 | Parental Feeding Styles, Sugary Drinks Intake, and Early Childhood Caries in Egyptian Children: A Mediation Analysis. Taha A et al. | 2025 | PMID 40468570 DOI 10.1111/ipd.13324 | Cross-sectional study | Children aged 2-6 years at an Egyptian hospital | In 412 Egyptian children aged 2-6, 84% drank sugary drinks daily and 81% had tooth decay; sugary drinks helped explain links between feeding styles and decay. | Cross-sectional; Hospital sample | low | C-SOD-11 |
| I-SRC-101 | Steroid avoidance or withdrawal for kidney transplant recipients. Oliveras L et al. | 2026 | PMID 42187003 DOI 10.1002/14651858.CD005632.pub4 | Meta-analysis | Kidney-transplant recipients (adults; three trials in children) | Across 53 trials, stopping or avoiding steroids did not clearly change graft loss in the first year; avoiding steroids slightly raised acute rejection in some regimens. | Overall certainty low (risk of bias, imprecision); Only 5 of 53 studies blinded | high | C-SRC-46 |
| I-SRC-102 | Adverse Outcomes of Tacrolimus Withdrawal in Immune-Quiescent Kidney Transplant Recipients. Hricik DE et al. | 2015 | PMID 25925687 DOI 10.1681/ASN.2014121234 | Randomised controlled trial | Non-sensitised first living-donor kidney recipients without de novo DSA, rejection or inflammation on 6-month protocol biopsy | In a trial of carefully selected low-risk patients, stopping tacrolimus led to rejection in 4 of 14 and new antibodies in 5 of 14; the trial was stopped. | Very small number in withdrawal arm (14); Stopped early; primary endpoint not assessed | moderate | C-SRC-46 |
| I-SRC-103 | Low protein diets for non-diabetic adults with chronic kidney disease. Hahn D et al. | 2020 | PMID 33118160 DOI 10.1002/14651858.CD001892.pub5 | Meta-analysis | Adults with non-diabetic CKD stages 3-5, not on dialysis | Under supervision, very low protein diets reduced the number reaching kidney failure over 1-4 years; ordinary low protein diets made little difference. | Open-label trials; Adherence and malnutrition data limited | high | C-SRC-47 |
| I-SRC-104 | Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study. Hviid A et al. | 2019 | PMID 30831578 DOI 10.7326/M18-2101 | Cohort study | All children born in Denmark 1999-2010 | Among 657,461 Danish children, vaccinated children did not have more autism than unvaccinated ones. | Observational; No chart review | high | C-SRC-56 |
| I-SRC-105 | Measles and Rubella Elimination Trends in the WHO Eastern Mediterranean Region, 2023-2024: Progress and Recent Epidemiological Shifts. Farid M et al. | 2026 | PMID 42646678 DOI 10.3390/vaccines14080659 | Ecological study | 22 EMR countries including Egypt | Egypt, with about 96% of children vaccinated twice, had no measles in 2024, while low-coverage neighbours had large outbreaks. | Descriptive, ecological; Under-reporting acknowledged | moderate | C-SRC-56 |
| I-SRC-106 | Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial. Reimer T et al. | 2025 | PMID 39665649 DOI 10.1056/NEJMoa2412063 | Randomised controlled trial | Clinically node-negative T1-T2 invasive breast cancer, breast-conserving surgery | Women with small breast cancers who had no lymph-node surgery did as well over 6 years as those who had a sentinel-node biopsy, with less arm swelling. | Per-protocol primary analysis; Mostly small T1 tumours | high | C-SRC-45 |
| I-SRC-107 | Refusal of Cancer-Directed Surgery by Breast Cancer Patients: Risk Factors and Survival Outcomes. Gaitanidis A et al. | 2018 | PMID 28784267 DOI 10.1016/j.clbc.2017.07.010 | Cohort study | US breast-cancer patients in SEER | Patients who refused recommended surgery had a 2.4 times higher risk of death; the groups also differed in other ways. | Observational; refusers differ (age, stage, insurance); Hazard ratio given without CI in abstract | low | C-SRC-45 |
| I-SRC-108 | Cancer cachexia in adult patients: ESMO Clinical Practice Guidelines☆. Arends J et al. (ESMO Guidelines Committee) | 2021 | PMID 34144781 DOI 10.1016/j.esmoop.2021.100092 | Guideline / position statement | Adults with cancer | Cancer patients on treatment should be screened for malnutrition and get at least 25-30 kcal per kg body weight per day. | Evidence levels for nutrition mostly low (V) | moderate | C-SRC-32 C-CAN-05 |
| I-SRC-109 | Dietary restriction during active cancer therapy is associated with improved treatment response: a systematic review and meta-analysis. Agrawal K et al. | 2026 | PMID 42444194 DOI 10.20892/j.issn.2095-3941.2025.0841 | Meta-analysis | Patients with solid tumours during chemotherapy/radiotherapy; malnourished or cachectic patients generally excluded | In three small studies, patients who restricted food during chemotherapy had better tumour shrinkage on scans; survival was not studied. | Response analysis from only 3 small studies; Our recalculation from the paper's Table 1 gives a Mantel-Haenszel OR of 3.50, not 4.80, and the pooled OR exceeds two of the three study ORs - the pooled figure could not be reproduced | low | C-SRC-32 |
| I-SRC-110 | Assessment of adverse effects attributed to statin therapy in product labels: a meta-analysis of double-blind randomised controlled trials. Cholesterol Treatment Trialists' (CTT) Collaboration | 2026 | PMID 41655587 DOI 10.1016/S0140-6736(25)01578-8 | Meta-analysis | Participants in 19 statin-vs-placebo trials (>=1000 participants, >=2 years) and 4 intensity trials | In blinded trials with 124,000 people, only a few listed side effects (mainly liver-test changes) were more common on statins, and only slightly. | Trials not designed for rare adverse events; Authors' group conducted many included trials | high | C-SRC-60 |
| I-SRC-111 | Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis. Byrne P et al. | 2022 | PMID 35285850 DOI 10.1001/jamainternmed.2022.0134 | Meta-analysis | Adults in 21 large statin trials | Statins lowered death by 0.8, heart attacks by 1.3 and strokes by 0.4 percentage points over the trials. | Mixed primary/secondary prevention; Significant heterogeneity | moderate | C-SRC-60 |
| I-SRC-112 | Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. Lillioja S et al. | 1993 | PMID 8247074 DOI 10.1056/NEJM199312303292703 | Cohort study | Non-diabetic Pima Indians (mean age 26 years) | People whose bodies responded poorly to insulin in a clamp test were much more likely to develop diabetes. | Single population with very high diabetes risk; Small | moderate | C-SRC-37 |
| I-SRC-113 | 21st-century hazards of smoking and benefits of cessation in the United States. Jha P et al. | 2013 | PMID 23343063 DOI 10.1056/NEJMsa1211128 | Cohort study | US adults aged 25+ interviewed 1997-2004 | In over 200,000 US adults, smokers died at about three times the rate of never-smokers; quitting before 40 removed about 90% of the excess risk. | Self-reported smoking; Observational | high | C-SRC-62 |
| I-SRC-117 | Egg Intake and the Incidence of Alzheimer's Disease in the Adventist Health Study-2 Cohort Linked with Medicare Data. Oh J et al. | 2026 | PMID 42002260 DOI 10.1016/j.tjnut.2026.101541 | Cohort study | US Seventh-day Adventists aged >=65 in Medicare fee-for-service | People who ate eggs had a lower, not higher, rate of Alzheimer's disease; the study was funded by an egg industry body and cannot prove cause. | Industry (egg board) funding of analysis; Single baseline FFQ | moderate | C-SRC-05 |
| I-SRC-118 | The natural history of clinical operational tolerance after kidney transplantation through twenty-seven cases. Brouard S et al. | 2012 | PMID 22974211 DOI 10.1111/j.1600-6143.2012.04249.x | Case series / case report | European kidney recipients with operational tolerance (off immunosuppression with stable function), plus comparison cohorts | 27 rare patients had stable kidneys off drugs, but almost a third later lost function slowly. | Highly selected survivors; the number of patients who stopped drugs and lost their graft is not the denominator; No prospective withdrawal protocol | low | C-SRC-46 |
| I-SRC-119 | The association between maternal intra-abdominal pressure and hypertension in pregnancy. Jayasundara S et al. | 2023 | PMID 37851647 DOI 10.1371/journal.pone.0284230 | Cross-sectional study | Women with singleton pregnancies undergoing non-emergency caesarean delivery | Pressure inside the abdomen was high at term, and somewhat higher in women with high blood pressure; the study was small. | Small (15 hypertensive); Cross-sectional; cannot show cause | low | C-SRC-65 |
| I-SRC-120 | Diagnostic Accuracy of Serum Antibody, Urine Antibody, and Stool Antigen Tests for Helicobacter pylori in Japan: A Systematic Review and Meta-Analysis. Ichita C et al. | 2026 | PMID 42604577 DOI 10.1111/hel.70157 | Meta-analysis | Japanese participants tested for H. pylori | Blood and stool tests were about 92-97% accurate for current infection; blood tests were less specific in people infected before. | Japan-specific test kits and populations | high | C-SRC-50 |
| I-SRC-121 | Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Hooi JKY et al. | 2017 | PMID 28456631 DOI 10.1053/j.gastro.2017.04.022 | Meta-analysis | Populations in 62 countries | About 70% of people in Africa carry H. pylori, so most positive tests there are correct. | Heterogeneous methods; Egypt-specific estimate not in abstract | moderate | C-SRC-50 |
| I-SRC-122 | Association Between Caffeine Intake and Stool Frequency- or Consistency-Defined Constipation: Data From the National Health and Nutrition Examination Survey 2005-2010. Li Y et al. | 2025 | PMID 40205901 DOI 10.5056/jnm23181 | Cross-sectional study | US adults | In 13,941 US adults, caffeine intake was not linked to constipation. | Cross-sectional; Caffeine from all sources, not tea specifically | moderate | C-SRC-24 |
| I-SRC-123 | Habitual tea consumption is associated with a low prevalence of gastroesophageal reflux disease in a Taiwanese population study. Kuo CM et al. | 2026 | PMID 42807308 DOI 10.7150/ijms.139922 | Cross-sectional study | Taiwanese adults | Habitual drinkers of green or oolong tea had somewhat less reflux; black tea showed no link. | Cross-sectional; self-reported GERD; Mostly green/oolong tea, unlike Egyptian black tea | moderate | C-SRC-24 |
| I-SRC-124 | Prevalence and risk factors of gastro-oesophageal reflux disease in Saudi Arabia: a systematic review and meta-analysis. Alhafid IA et al. | 2026 | PMID 42303406 DOI 10.1136/bmjopen-2026-118665 | Meta-analysis | Adults in Saudi Arabia | Painkillers and smoking were linked to reflux; frequent tea or coffee drinking was not. | Extreme heterogeneity; Coffee and tea combined; self-reported | moderate | C-SRC-24 |
| I-SRC-125 | Safety of vaccines used for routine immunization of U.S. children: a systematic review. Maglione MA et al. | 2014 | PMID 25086160 DOI 10.1542/peds.2014-1079 | Systematic review | Children receiving routine vaccines | Some vaccines have rare serious side effects (e.g. febrile seizures after MMR); these are very rare compared with the benefits. | No pooling; US formulations only | moderate | C-SRC-56 |
| I-SRC-126 | What Is the Real Impact of Smoking on Diseases Alleged to Benefit from It? Yılmaz M et al. | 2025 | PMID 41129423 DOI 10.1159/000549064 | Narrative review | Studies on 8 conditions | A few conditions such as ulcerative colitis and Parkinson's disease are less common in smokers, but this does not outweigh the harms of smoking. | Narrative review, not systematic | low | C-SRC-62 |
| I-SRC-127 | Effect of sustained physiologic hyperinsulinaemia and hyperglycaemia on insulin secretion and insulin sensitivity in man. Del Prato S et al. | 1994 | PMID 7851681 DOI 10.1007/BF00400466 | Randomised controlled trial | Healthy young adults | Four days of raised insulin reduced the body's response to insulin by 20-40% in healthy volunteers. | Very small; Short duration | moderate | C-SRC-37 |
| I-SRC-128 | Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Tabák AG et al. | 2009 | PMID 19515410 DOI 10.1016/S0140-6736(09)60619-X | Cohort study | British civil servants without diabetes at baseline | In 6538 British adults, those who later got diabetes showed falling insulin sensitivity in the 5 years before diagnosis. | HOMA indices, not clamp; Mostly white men | high | C-SRC-37 |
| I-SRC-129 | Adrenal insufficiency in pregnancy: Physiology, diagnosis, management and areas for future research. Lee JH et al. | 2023 | PMID 35816262 DOI 10.1007/s11154-022-09745-6 | Narrative review | Pregnant women | Normal pregnancy raises cortisol, including the free active form; true adrenal insufficiency is a separate, rare disease. | Narrative | moderate | C-SRC-65 |
| I-SRC-130 | Perinatal physiology and welfare in water buffalo: calving, mother-calf bonding, lactation, and postpartum disorders. Mota-Rojas D et al. | 2026 | PMID 42707960 DOI 10.3389/fvets.2026.1913756 | Narrative review | Water buffalo | Most buffalo milk is stored deep in the udder and released only when oxytocin is released, for example by suckling. | Narrative review | moderate | C-SRC-29 |
| I-SRC-131 | Comprehensive quality profiling and multivariate analysis of rice (Oryza sativa L.) cultivars: integrating physical, cooking, nutritional, and micronutrient characteristics for enhanced varietal selection. Abdelsalam KMH et al. | 2025 | PMID 40247171 DOI 10.1186/s12870-025-06438-5 | Other | Rice cultivars Giza 178, Sakha 108, Sakha Super 300, Egyptian Yasmin | Four common Egyptian rice varieties differed clearly in starch (amylose) and nutrient content; blood-sugar effects were not tested. | No glycaemic index or health outcomes; Agronomic study | moderate | C-SRC-18 |
| I-SRC-132 | Deprescribing statins for adults 65 years of age and older: Evidence-based clinical practice guideline. Thompson W et al. | 2026 | PMID 42728062 DOI 10.46747/cfp.7209534 | Guideline / position statement | Adults >=65 years taking statins | A 2026 guideline suggests stopping statins near the end of life but continuing them in other older adults. | Abstract only | moderate | C-SRC-60 |
| I-SRC-133 | The National Burden of Influenza-Associated Respiratory Illness Across Levels of Severity in Egypt, 2016-2019. Fahim M et al. | 2024 | PMID 39722214 DOI 10.1111/irv.70061 | Measurement / residue study | Egyptian population; SARI patients at 8 sentinel hospitals | Egypt has an estimated 16 million mild flu illnesses and thousands of flu deaths per season. | Very wide CIs; Extrapolation from two governorates | moderate | C-SRC-47 |
| I-SRC-134 | KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. KDIGO CKD Work Group | 2024 | PMID 38490803 DOI 10.1016/j.kint.2023.10.018 | Guideline / position statement | Adults and children with CKD | Recommends supervised diet changes and kidney-protective drugs for chronic kidney disease. | Only selected recommendations read | high | C-SRC-47 |
| I-SUG-01 | Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. Te Morenga L et al. | 2012 | PMID 23321486 DOI 10.1136/bmj.e7492 | Meta-analysis | Adults and children | Eating more sugar increased body weight and eating less reduced it, through extra calories. | Heterogeneity in one analysis; Child trials low compliance | high | C-SOD-02 C-SUG-01 |
| I-SUG-02 | Dietary sugar consumption and health: umbrella review. Huang Y et al. | 2023 | PMID 37019448 DOI 10.1136/bmj-2022-071609 | Systematic review | Humans free of acute or chronic disease (children and adults) | Across 73 meta-analyses, high sugar intake was linked to 45 adverse outcomes; authors advise under 25 g/day of added sugar. | Evidence dominated by SSB (58/73 meta-analyses); few data on solid sugars, honey or sugars in foods; Mostly observational; nearly all outcomes low or very low quality; no class I evidence | high | C-SOD-01 C-SOD-03 C-SOD-05 C-SUG-01 |
| I-SUG-03 | Tolerable upper intake level for dietary sugars. EFSA NDA Panel et al. | 2022 | PMID 35251356 DOI 10.2903/j.efsa.2022.7074 | Risk assessment | General European population (children, adults, pregnant women) | EFSA found no safe intake level and advises keeping added and free sugars as low as possible. | RCT evidence on surrogate endpoints only, mostly at intakes >=10% of energy; Cohort analyses mostly isocaloric, which limits detection of energy-mediated effects | high | C-SOD-01 C-SUG-01 C-SUG-05 C-DIAB-01 C-SRC-22 C-SOD-03 C-SOD-05 C-SOD-11 |
| I-SUG-04 | Systematic Review of the Effect on Caries of Sugars Intake: Ten-Year Update. Moores CJ et al. | 2022 | PMID 35302414 DOI 10.1177/00220345221082918 | Systematic review | Children and adults | Most studies link more sugar with more tooth decay; keeping sugar below 10% of energy lowers decay. | Vote counting; Mostly observational | moderate | C-SOD-11 C-SUG-01 |
| I-SUG-05 | WHO calls on countries to reduce sugars intake among adults and children (Guideline: Sugars intake for adults and children, 2015) — news release World Health Organization | 2015 | Guideline / position statement | Adults and children | WHO recommends keeping free sugars, including honey and juice sugars, below 10% of energy. | Conditional recommendation for <5% | high | C-SOD-02 C-SOD-11 C-SUG-01 C-SUG-02 C-SUG-05 C-SUG-06 | |
| I-SUG-06 | USDA FoodData Central: Honey (FDC 169640) and Sugars, granulated (FDC 169655), SR Legacy US Department of Agriculture | SR Legacy | Measurement / residue study | Not applicable | Honey is about 82% sugar and 17% water; white sugar is almost 100% sugar. | US samples; honey composition varies by origin | high | C-SUG-02 C-SUG-03 | |
| I-SUG-07 | Enteroendocrine hormonal response after the ingestion of cola beverages with sucrose and non-nutritive sweeteners in healthy adults: A randomized crossover trial. Galicia-Ayala C et al. | 2026 | PMID 41016269 DOI 10.1016/j.nut.2025.112938 | Randomised controlled trial | Healthy adults | Sugar-sweetened cola raised blood sugar and insulin most; diet cola and sparkling water did not. | Small; Acute only | moderate | C-SUG-04 C-SUG-07 |
| I-SUG-101 | Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake. Tey SL et al. | 2017 | PMID 27956737 DOI 10.1038/ijo.2016.225 | Randomised controlled trial | Healthy men | A drink with 65 g of table sugar caused large rises in blood sugar and insulin within the first hour in 30 healthy men. | Small sample of healthy men only; Single test day per beverage | moderate | C-SUG-04 |
| I-SUG-102 | Postprandial glucose and insulin responses to meals containing different carbohydrates in normal and diabetic subjects. Bantle JP et al. | 1983 | PMID 6343873 DOI 10.1056/NEJM198307073090102 | Other | Healthy adults, adults with type 1 diabetes, adults with type 2 diabetes | In 1983, meals containing table sugar raised blood sugar about as much as meals with potato or wheat starch, in healthy people and people with diabetes. | Single-meal acute study; Small groups | moderate | C-SUG-07 C-SUG-04 |
| I-SUG-103 | Association between added sugar intake and mortality is nonlinear and dependent on sugar source in 2 Swedish population-based prospective cohorts. Ramne S et al. | 2019 | PMID 30590448 DOI 10.1093/ajcn/nqy268 | Cohort study | Swedish adults (Malmö Diet and Cancer Study; Northern Swedish Health and Disease Study) | In two Swedish cohorts, people eating more than 20% of their calories as added sugar had about 30% higher mortality; the lowest risk was at 7.5-10%. | Observational; residual confounding and reverse causation possible for low intakes; Single baseline diet measurement | moderate | C-SUG-01 |
| I-SUG-104 | The oral und systemic health risks of sugar consumption: an umbrella review. Woelber JP et al. | 2026 | PMID 42814269 DOI 10.1007/s00784-026-07191-1 | Systematic review | Systematic reviews of human studies | A 2026 review of 228 systematic reviews found sugar intake consistently linked with 18 harmful health outcomes, mostly from sugary-drink studies. | Narrative synthesis without pooled estimates; Most included reviews low quality | moderate | C-SUG-01 |
| I-SUG-105 | Dietary Sugar Intake and Incident Type 2 Diabetes Risk: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. Della Corte KA et al. | 2025 | PMID 40122386 DOI 10.1016/j.advnut.2025.100413 | Meta-analysis | Healthy adults in prospective cohorts | Each daily serving of sugary drinks was linked to 25% higher diabetes risk and fruit juice to 5%; total sugar from foods was not linked to higher risk. | Observational data; Inverse associations for total sugar/sucrose may reflect fruit/dairy sources and residual confounding | high | C-SOD-01 C-SUG-01 C-SUG-06 |
| I-SUG-106 | Effect of honey on cardiometabolic risk factors: a systematic review and meta-analysis. Ahmed A et al. | 2023 | PMID 36379223 DOI 10.1093/nutrit/nuac086 | Meta-analysis | Trial participants (healthy and with metabolic conditions) | Trials suggest honey may slightly lower blood sugar and blood fats compared with usual diet, but the certainty is low and few trials compared honey directly with sugar. | Most comparisons against usual diet, not against equal amounts of sugar; Small trials, low certainty | moderate | C-SUG-02 |
| I-SUG-107 | The UN Decade of Nutrition, the NOVA food classification and the trouble with ultra-processing. Monteiro CA et al. | 2018 | PMID 28322183 DOI 10.1017/S1368980017000234 | Narrative review | Not applicable | The NOVA classification places table sugar with oils, butter, salt and honey as processed culinary ingredients made by refining; soft drinks and sweets are ultra-processed. | Classification reliability debated (I-UPF-02); Commentary, not empirical study | moderate | C-SUG-05 |
| I-SUG-109 | Important food sources of fructose-containing sugars and incident gout: a systematic review and meta-analysis of prospective cohort studies. Ayoub-Charette S et al. | 2019 | PMID 31061018 DOI 10.1136/bmjopen-2018-024171 | Meta-analysis | Adults in prospective cohorts (mostly US health professionals) | Pooled data from three large cohorts linked high sugary-drink intake with about twice the gout risk; fruit juice was also linked, but whole fruit was not. | Only three cohorts; Overlap with Choi 2008 (A-SOD-06) | moderate | C-SOD-05 C-SUG-06 |
| I-SUP-01 | Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. MRC Vitamin Study Research Group | 1991 | PMID 1677062 | Randomised controlled trial | Women with a previous NTD-affected pregnancy | Folic acid cut neural tube defects by 72%. | High-risk population (recurrence, not first occurrence); Folic acid dose not given in abstract | high | C-SUP-10 |
| I-SUP-02 | Effects and safety of periconceptional oral folate supplementation for preventing birth defects. De-Regil LM et al. | 2015 | PMID 26662928 DOI 10.1002/14651858.CD007950.pub3 | Meta-analysis | Women of reproductive age | Folic acid lowered neural tube defects by about 69%. | Only one trial low risk of bias; Author COI (NGO) | high | C-SUP-10 |
| I-SUP-03 | Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement. US Preventive Services Task Force et al. | 2023 | PMID 37526713 DOI 10.1001/jama.2023.12876 | Guideline / position statement | Persons planning or able to become pregnant | All who could become pregnant should take 400–800 µg folic acid daily (grade A). | US context | high | C-SUP-10 |
| I-SUP-04 | Daily oral iron supplementation during pregnancy. Peña-Rosas JP et al. | 2015 | PMID 26198451 DOI 10.1002/14651858.CD004736.pub5 | Meta-analysis | Pregnant women | Daily iron reduced anaemia at term by 70%. | Heterogeneity; Low-quality evidence for main outcomes | high | C-SUP-09 C-SUP-10 |
| I-SUP-05 | Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. Demay MB et al. | 2024 | PMID 38828931 DOI 10.1210/clinem/dgae290 | Guideline / position statement | General population by age group, pregnancy, prediabetes | Suggests vitamin D for children, pregnancy, people ≥75 and high-risk prediabetes. | Conditional recommendations; Errata | high | C-SUP-07 C-SUP-10 |
| I-SUP-06 | Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Chung M et al. | 2016 | PMID 27776363 DOI 10.7326/M16-1165 | Meta-analysis | Generally healthy adults | No link between calcium intake within upper limits and heart disease. | CVD secondary outcomes; Funded by National Osteoporosis Foundation (potential interest) | moderate | C-SUP-04 |
| I-SUP-07 | Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Vollset SE et al. | 2013 | PMID 23352552 DOI 10.1016/S0140-6736(12)62001-7 | Meta-analysis | Participants of 10 cardiovascular-prevention trials (n=46,969; people with or at high risk of CVD, incl. one renal trial) and 3 colorectal-adenoma trials (n=2652); two-thirds men, mean age 64 | No significant effect of folic acid on cancer over about 5 years. | Only in-trial follow-up (~5 years); late effects not addressed; Search limited to PubMed and reference lists | high | C-SUP-06 |
| I-SUP-08 | Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. O'Connor EA et al. | 2022 | PMID 35727272 DOI 10.1001/jama.2021.15650 | Systematic review | Adults without CVD, cancer or known deficiency | Supplements gave little or no protection; beta-carotene harmful; multivitamins slightly fewer cancers. | Excludes deficiency, pregnancy | high | C-SUP-01 C-SUP-02 C-SUP-03 C-SUP-06 C-SUP-10 |
| I-SUP-09 | Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. Bhatt DL et al. | 2019 | PMID 30415628 DOI 10.1056/NEJMoa1812792 | Randomised controlled trial | Statin-treated with CVD or diabetes + risk factors, TG 135–499 mg/dL | High-dose purified EPA reduced cardiovascular events by 25% in high-risk patients; more AF. | Industry-funded (Amarin); Placebo choice debated (not in abstract) | high | C-SUP-01 C-SUP-05 |
| I-SUP-10 | Liver injury from herbal and dietary supplements. Navarro VJ et al. | 2017 | PMID 27677775 DOI 10.1002/hep.28813 | Narrative review | US cases of hepatotoxicity | Mainly bodybuilding steroids, green tea extract and multi-ingredient products. | Narrative review without systematic search, selection or appraisal methods; Case-series/registry proportions only; no denominator of users, so no risk per user | moderate | C-SUP-08 |
| I-SUP-101 | Daily oral iron supplementation during pregnancy. Finkelstein JL et al. | 2024 | PMID 39145520 DOI 10.1002/14651858.CD004736.pub6 | Meta-analysis | Pregnant women of any age and parity | In 57 trials with almost 49,000 pregnant women, daily iron reduced iron-deficiency anaemia at term from 18.4% to 5.0% and slightly reduced low birthweight. | Mainly preventive supplementation in mixed populations, not treatment of diagnosed anaemia; High heterogeneity; low certainty for some outcomes | high | C-SUP-09 C-SUP-10 |
| I-SUP-102 | Anaemia, prenatal iron use, and risk of adverse pregnancy outcomes: systematic review and meta-analysis. Haider BA et al. | 2013 | PMID 23794316 DOI 10.1136/bmj.f3443 | Meta-analysis | Pregnant women | Iron tablets halved anaemia in pregnancy, and anaemia early in pregnancy was linked to more low-birthweight and preterm babies. | Search ends 2012; Cohort part observational (anaemia-outcome associations may be confounded) | moderate | C-SUP-09 |
| I-SUP-104 | The benefits and harms of oral iron supplementation in non-anaemic pregnant women: a systematic review and meta-analysis. Watt A et al. | 2025 | PMID 39834271 DOI 10.1093/fampra/cmae079 | Meta-analysis | Non-anaemic pregnant women | Iron tablets halved the risk of becoming anaemic (1 in 10 women helped), but did not change birthweight or preterm birth in women who started without anaemia. | Small total sample; High heterogeneity for haemoglobin | moderate | C-SUP-09 |
| I-SUP-105 | Daily iron and folic acid supplementation during pregnancy (WHO e-Library of Evidence for Nutrition Actions, intervention page, last updated 26 July 2024) World Health Organization | 2024 | Guideline / position statement | Pregnant women | WHO recommends that pregnant women take daily iron (30-60 mg) and folic acid (0.4 mg), starting folic acid ideally before conception. | Web summary; full guideline PDF and GRADE tables not read here; Evidence base cited is the 2015 Cochrane version | high | C-SUP-09 C-SUP-10 | |
| I-SUP-106 | Multivitamins in the prevention of cancer and cardiovascular disease: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Sesso HD et al. | 2022 | PMID 35294969 DOI 10.1093/ajcn/nqac056 | Randomised controlled trial | Older US adults (women >=65, men >=60) without major CVD or recent cancer | Over 3.6 years a daily multivitamin neither reduced nor increased cancer, heart disease or deaths. | Median follow-up only 3.6 years; Older, mostly well-nourished US population | high | C-SUP-01 C-SUP-06 |
| I-SUP-107 | Multivitamin Use and Mortality Risk in 3 Prospective US Cohorts. Loftfield E et al. | 2024 | PMID 38922615 DOI 10.1001/jamanetworkopen.2024.18729 | Cohort study | US adults without cancer or other chronic diseases at baseline | People who took multivitamins did not live longer; their risk of death was about 4% higher, which may reflect who takes supplements rather than the pills. | Observational; self-reported exposure; Residual confounding possible in either direction | moderate | C-SUP-01 C-SUP-06 |
| I-SUP-108 | Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Bjelakovic G et al. | 2012 | PMID 22419320 DOI 10.1002/14651858.CD007176.pub2 | Meta-analysis | Adults, healthy or with various diseases in a stable phase | In 78 trials, antioxidant pills did not lower death rates; beta-carotene and vitamin E slightly increased them in the best trials. | Mixed populations and doses; Overlaps with A-SUP-24 (same group, 2007) | high | C-SUP-01 C-SUP-02 C-SUP-03 |
| I-SUP-109 | Treatments for iron-deficiency anaemia in pregnancy. Reveiz L et al. | 2011 | PMID 21975735 DOI 10.1002/14651858.CD003094.pub3 | Systematic review | Pregnant women with anaemia attributed to iron deficiency (Hb <11 g/dL) | Iron tablets improved blood counts in anaemic pregnant women but often upset the stomach; good trials on outcomes for mother and baby are scarce. | Small, poor-quality trials; Few clinical outcomes | moderate | C-SUP-09 |
| I-SUP-11 | International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Kreider RB et al. | 2017 | PMID 28615996 DOI 10.1186/s12970-017-0173-z | Narrative review | Athletes and patient groups | Creatine reported safe up to 30 g/day for 5 years in healthy people. | Narrative; Authors with industry links (sports nutrition) | low | C-SUP-08 |
| I-SUP-110 | Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials. Myung SK et al. | 2021 | PMID 33530332 DOI 10.3390/nu13020368 | Meta-analysis | Adults in double-blind RCTs of calcium supplements (mainly postmenopausal women) | Pooling 13 placebo-controlled trials, calcium pills were linked to about 15% more cardiovascular disease, mainly in healthy postmenopausal women. | CVD mostly secondary outcomes in included trials; Overlaps with Bolland analyses | moderate | C-SUP-04 |
| I-SUP-111 | The Evidence and Controversy Between Dietary Calcium Intake and Calcium Supplementation and the Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Cohort Studies and Randomized Controlled Trials. Yang C et al. | 2020 | PMID 31625814 DOI 10.1080/07315724.2019.1649219 | Meta-analysis | Adults in cohorts and RCTs | Calcium from food was not linked to heart disease, but calcium pills were linked to about 14% more heart attacks in trials. | The CHD estimate 1.08 (1.02-1.22) is not log-symmetric, suggesting a reporting error (stats/C-SUP-04_calcium.py); Overlapping trials with other meta-analyses | moderate | C-SUP-04 |
| I-SUP-112 | Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis. Sim MG et al. | 2023 | PMID 37743221 DOI 10.1016/j.hlc.2023.07.008 | Meta-analysis | Adults in RCTs of calcium supplementation | A 2023 review of 12 trials found no link between calcium pills and heart attacks, strokes or deaths. | Effect sizes not in abstract; Overlapping trials with I-SUP-110 | moderate | C-SUP-04 |
| I-SUP-113 | Effect of Omega-3 Dosage on Cardiovascular Outcomes: An Updated Meta-Analysis and Meta-Regression of Interventional Trials. Bernasconi AA et al. | 2021 | PMID 32951855 DOI 10.1016/j.mayocp.2020.08.034 | Meta-analysis | Participants in EPA/DHA intervention trials | Pooling 40 trials, omega-3 lowered heart attacks by about 13%; one heart attack was prevented per 272 people treated. | First author affiliated with GOED (omega-3 industry association); Includes high-dose prescription EPA (REDUCE-IT) and open-label trials | moderate | C-SUP-05 |
| I-SUP-114 | Omega-3 supplementation and cardiovascular disease: formulation-based systematic review and meta-analysis with trial sequential analysis. Rizos EC et al. | 2021 | PMID 32820013 DOI 10.1136/heartjnl-2020-316780 | Meta-analysis | Participants in double-blind omega-3 RCTs | At the usual dose of one capsule a day, omega-3 had no effect on heart outcomes; higher doses might help, but evidence is weak. | Few trials at high dose; Formulations differ (EPA vs EPA+DHA) | high | C-SUP-05 |
| I-SUP-115 | Effects of intermittent or single high-dose vitamin D supplementation on risk of falls and fractures: a systematic review and meta-analysis. Myung SK et al. | 2023 | PMID 37120684 DOI 10.1007/s00198-023-06761-3 | Meta-analysis | Adults in RCTs | Large doses given monthly or yearly did not prevent falls or fractures and might slightly increase falls. | Heterogeneity; Reported P=0.051 is inconsistent with the 95% CI 0.99-1.15 (recomputed P about 0.13; stats/C-SUP-07_harms.py) | moderate | C-SUP-07 |
| I-SUP-116 | Total, Dietary, and Supplemental Vitamin C Intake and Risk of Incident Kidney Stones. Ferraro PM et al. | 2016 | PMID 26463139 DOI 10.1053/j.ajkd.2015.09.005 | Cohort study | US nurses and health professionals | Men taking 1,000 mg or more of vitamin C a day had about 19% more kidney stones; no link was seen in women. | FFQ-based exposure; Stone composition not known for all | moderate | C-SUP-07 |
| I-SUP-117 | Selenium for preventing cancer. Vinceti M et al. | 2018 | PMID 29376219 DOI 10.1002/14651858.CD005195.pub4 | Meta-analysis | Adults | Selenium pills did not prevent cancer, and trials hinted at more type 2 diabetes. | Diabetes outcome not quantified in abstract; Mostly male participants | high | C-SUP-07 C-SUP-01 |
| I-SUP-118 | Subgroup analyses of the effectiveness of oral glucosamine for knee and hip osteoarthritis: a systematic review and individual patient data meta-analysis from the OA trial bank. Runhaar J et al. | 2017 | PMID 28754801 DOI 10.1136/annrheumdis-2017-211149 | Meta-analysis | People with hip or knee osteoarthritis | Using raw data from five independent trials, glucosamine was no better than a dummy pill for pain or function. | Only 6 of 21 eligible trials shared data; Industry trials not included (may differ) | high | C-SUP-07 C-SUP-01 |
| I-SUP-119 | Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Navarro VJ et al. | 2014 | PMID 25043597 DOI 10.1002/hep.27317 | Case series / case report | Patients with suspected drug/HDS liver injury at 8 US referral centres | About one in six drug-related liver injuries in a US network were caused by supplements, mainly bodybuilding and multi-ingredient products. | Referral-centre case series; no denominator of users; Overlaps with data summarised in I-SUP-10 | moderate | C-SUP-08 |
| I-SUP-120 | The Contents of Herbal and Dietary Supplements Implicated in Liver Injury in the United States Are Frequently Mislabeled. Navarro V et al. | 2019 | PMID 31168513 DOI 10.1002/hep4.1346 | Measurement / residue study | Products collected from DILIN patients | Half of the supplements taken by US patients with liver injury did not contain what their labels said. | Selected products (from injury cases); Whether mislabelling caused injury not established | moderate | C-SUP-08 |
| I-SUP-121 | The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. Goodman GE et al. | 2004 | PMID 15572756 DOI 10.1093/jnci/djh320 | Randomised controlled trial | Smokers, former smokers and asbestos-exposed workers | Six years after stopping the pills, lung cancer and deaths were still somewhat higher in the beta-carotene group. | Post-intervention phase; self-reported endpoints confirmed by records; Subgroup findings by sex | high | C-SUP-02 |
| I-SUP-122 | Baseline selenium status and effects of selenium and vitamin e supplementation on prostate cancer risk. Kristal AR et al. | 2014 | PMID 24563519 DOI 10.1093/jnci/djt456 | Randomised controlled trial | SELECT participants (men) | Vitamin E pills raised prostate cancer risk mainly in men who had low selenium levels. | Post-hoc subgroup analysis by baseline status; Multiple comparisons | moderate | C-SUP-03 |
| I-SUP-123 | Effectiveness of Dietary Interventions in Prevention and Treatment of Iron-Deficiency Anemia in Pregnant Women: A Systematic Review of Randomized Controlled Trials. Skolmowska D et al. | 2022 | PMID 35893877 DOI 10.3390/nu14153023 | Systematic review | Anaemic or mixed pregnant women | Seven small trials suggest that diet changes, fortified foods or counselling can raise haemoglobin in pregnancy, but the evidence is weak. | Only 7 heterogeneous trials; Several interventions used iron-fortified products, i.e. added iron | low | C-SUP-09 |
| I-SUP-124 | A systematic review and meta-analysis of functional vitamin B12 status among adult vegans. Niklewicz A et al. | 2024 | PMID 39373282 DOI 10.1111/nbu.12712 | Meta-analysis | Adult vegans, vegetarians and omnivores | Adult vegans had lower B12 and signs of B12 deficiency; those taking B12 supplements had much better values. | Observational; heterogeneous assays; No clinical outcomes | moderate | C-SUP-10 |
| I-SUP-125 | Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Dror DK et al. | 2008 | PMID 18454811 DOI 10.1111/j.1753-4887.2008.00031.x | Narrative review | Infants of mothers with untreated pernicious anaemia or strict vegetarian diets | Babies of mothers with low B12 can develop serious brain and development problems, which improve quickly with B12. | Case reports; no denominator; Narrative | low | C-SUP-10 |
| I-SYS-01 | Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. GBD 2017 Diet Collaborators | 2019 | PMID 30954305 DOI 10.1016/S0140-6736(19)30041-8 | Risk assessment | Adults >=25 y, 195 countries | 11 million deaths in 2017 were attributed to dietary risks, mainly too much salt and too few whole grains and fruits. | Mostly observational RR inputs; Mixed dietary data sources | moderate | C-SYS-02 C-SYS-03 C-CAN-08 C-CAN-07 |
| I-SYS-02 | Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. GBD 2019 Risk Factors Collaborators | 2020 | PMID 33069327 DOI 10.1016/S0140-6736(20)30752-2 | Risk assessment | Global | In 2019, high blood pressure was linked to 10.8 million and tobacco to 8.7 million deaths. | Model-based; sparse and self-reported exposure data in many locations (authors); Uncertainty intervals do not reflect differences in evidence strength or risk of bias across risk-outcome pairs (authors) | moderate | C-SYS-02 C-SYS-03 C-SYS-07 |
| I-SYS-03 | Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Cappuccio FP et al. | 2010 | PMID 20469800 DOI 10.1093/sleep/33.5.585 | Meta-analysis | General populations | Short sleepers had 12% and long sleepers 30% higher death risk. | Self-reported sleep; Observational; reverse causation possible for long sleep | moderate | C-LIFE-04 C-LIFE-03 |
| I-SYS-04 | Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis. Ekelund U et al. | 2019 | PMID 31434697 DOI 10.1136/bmj.l4570 | Meta-analysis | Middle-aged and older adults | The most active quarter had about a quarter of the death risk of the least active. | Observational; reverse causation | moderate | C-LIFE-03 C-LIFE-02 |
| I-SYS-05 | Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial. Gardner CD et al. | 2018 | PMID 29466592 DOI 10.1001/jama.2018.0245 | Randomised controlled trial | Adults 18-50, BMI 28-40, no diabetes | After a year, weight loss was 5.3 kg vs 6.0 kg - no real difference. | Free-living adherence variation | high | C-LIFE-01 C-INS-01 C-SRC-22 |
| I-SYS-06 | Isolated aerobic exercise and weight loss: a systematic review and meta-analysis of randomized controlled trials. Thorogood A et al. | 2011 | PMID 21787904 DOI 10.1016/j.amjmed.2011.02.037 | Meta-analysis | Overweight/obese adults | 6-12 months of aerobic exercise reduced weight by about 1.6-1.7 kg. | Few trials; Moderate exercise doses | moderate | C-LIFE-02 |
| I-SYS-07 | Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans. Pontzer H et al. | 2016 | PMID 26832439 DOI 10.1016/j.cub.2015.12.046 | Cross-sectional study | Adults aged 25-45 years (55% female) from five populations: Ghana, South Africa, Seychelles, Jamaica, United States. | Daily energy use levels off at higher activity. | Cross-sectional (authors' main limitation); between-person comparison cannot show within-person adaptation over time; Accelerometry is an imperfect measure of activity energy cost | moderate | C-LIFE-02 C-SRC-22 |
| I-SYS-08 | How Breath-Control Can Change Your Life: A Systematic Review on Psycho-Physiological Correlates of Slow Breathing. Zaccaro A et al. | 2018 | PMID 30245619 DOI 10.3389/fnhum.2018.00353 | Systematic review | Healthy subjects | Small studies show more relaxation and heart-rate variability. | Few small studies; Healthy subjects; no hard outcomes | low | C-LIFE-05 C-LIFE-03 |
| I-SYS-101 | Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. GBD 2021 Risk Factors Collaborators | 2024 | PMID 38762324 DOI 10.1016/S0140-6736(24)00933-4 | Risk assessment | 204 countries and 811 subnational locations | Air pollution, high blood pressure and smoking were the top single risks; poor diet as a group ranked fifth. | Model-based; depends on RR assumptions; Diet assessed with error | high | C-SYS-02 C-SYS-03 C-SYS-07 |
| I-SYS-102 | Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023. GBD 2023 Disease and Injury and Risk Factor Collaborators | 2025 | PMID 41092926 DOI 10.1016/S0140-6736(25)01637-X | Risk assessment | 204 countries and territories | About half of all ill health is linked to known risk factors; high blood pressure, air pollution, high blood sugar and smoking lead. | Model-based | high | C-SYS-02 C-SYS-03 |
| I-SYS-103 | Integrating the environmental and genetic architectures of aging and mortality. Argentieri MA et al. | 2025 | PMID 39972219 DOI 10.1038/s41591-024-03483-9 | Cohort study | UK Biobank participants | Lifestyle and living conditions explained 17% of variation in mortality, genes less than 2%; smoking and social factors led. | Healthy-volunteer cohort; Self-reported exposures | moderate | C-SYS-03 C-SYS-02 |
| I-SYS-104 | Genetic Factors Are Not the Major Causes of Chronic Diseases. Rappaport SM | 2016 | PMID 27105432 DOI 10.1371/journal.pone.0154387 | Other | Western European monozygotic twins; mortality statistics | Genetic factors explained a median of 18.5% of the risk of 28 chronic diseases. | Assumptions about twin data; Non-genetic share includes chance and all environmental factors | moderate | C-SYS-03 |
| I-SYS-105 | Antibiotics for treatment of sore throat in children and adults. Spinks A et al. | 2021 | PMID 34881426 DOI 10.1002/14651858.CD000023.pub5 | Meta-analysis | Children and adults with sore throat | 82% of people without antibiotics were symptom-free within a week; antibiotics still prevented some complications. | Most trials from the 1950s | high | C-SYS-01 C-SYS-06 |
| I-SYS-106 | Efficacy and safety of prolonged water fasting: a narrative review of human trials. Ezpeleta M et al. | 2024 | PMID 37377031 DOI 10.1093/nutrit/nuad081 | Narrative review | Human trial participants | Fasting 5-20 days lowered weight and blood pressure, but two-thirds of weight lost was lean mass and benefits faded. | Narrative; Small trials | low | C-SYS-04 |
| I-SYS-107 | Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study. Commissati S et al. | 2025 | PMID 40268190 DOI 10.1016/j.molmet.2025.102152 | Other | Middle-aged volunteers; validation cohort of 1,422 people undergoing modified fasting | During about 10 days of water-only fasting, inflammation markers and blood clotting activity rose. | Small, uncontrolled; COI | low | C-SYS-04 |
| I-SYS-108 | Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Ettehad D et al. | 2016 | PMID 26724178 DOI 10.1016/S0140-6736(15)01225-8 | Meta-analysis | Participants of 123 RCTs | Each 10 mm Hg lower systolic pressure cut major heart and stroke events by 20% and deaths by 13%. | Absolute effects depend on baseline risk | high | C-SYS-06 C-SYS-07 C-SYS-01 |
| I-SYS-109 | Evaluating the impact of medication review and deprescribing on prescribing appropriateness and clinical outcomes in older people residing in long-term care facilities: a systematic review and meta-analysis. Carollo M et al. | 2026 | PMID 41967033 DOI 10.1093/ageing/afag084 | Meta-analysis | Older residents of long-term care facilities | Supervised medicine reviews reduced the number of drugs without increasing falls, hospital stays or deaths. | Heterogeneous; Risk of bias | moderate | C-SYS-06 |
| I-SYS-110 | Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Voight BF et al. | 2012 | PMID 22607825 DOI 10.1016/S0140-6736(12)60312-2 | Other | Up to 20,913 MI cases and 95,407 controls | Genes that raise HDL did not lower heart attack risk, whereas genes that raise LDL did raise it. | Pleiotropy possible; Instrument strength | high | C-SYS-07 |
| I-SYS-111 | Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. Sacks FM et al. | 2001 | PMID 11136953 DOI 10.1056/NEJM200101043440101 | Randomised controlled trial | Adults with and without hypertension | Less salt and the DASH diet lowered systolic pressure by up to 11.5 mm Hg in people with high blood pressure. | 30-day periods; long-term adherence not tested | high | C-SYS-07 |
| I-UPF-01 | Ultraprocessed or minimally processed diets following healthy dietary guidelines on weight and cardiometabolic health: a randomized, crossover trial. Dicken SJ et al. | 2025 | PMID 40760353 DOI 10.1038/s41591-025-03842-0 | Randomised controlled trial | Adults in England with BMI >=25 to <40 kg/m2 and habitual UPF intake >=50% of energy (mean 67.4%); mean age 43.2 years; 90.9% women; mostly NHS staff (e.g. 43.6% nurses); mean BMI 32.7 | Both diets led to weight loss, but about twice as much on minimally processed food. | Modest sample (50 ITT, 43 PP), 91% women, mostly health-care staff; Observed difference (1.01%) much smaller than the 2.7% the trial was powered for; P=0.024 with CI close to zero | high | C-UPF-02 |
| I-UPF-02 | Ultra-processed foods: how functional is the NOVA system? Braesco V et al. | 2022 | PMID 35314769 DOI 10.1038/s41430-022-01099-1 | Other | French food and nutrition specialists | Experts often disagreed when sorting foods into NOVA groups, though typical UPF were mostly classified alike. | French experts only; Authors with industry links | moderate | C-UPF-01 |
| I-UPF-03 | Ultra-processed foods in human health: a critical appraisal. Gibney MJ et al. | 2017 | PMID 28793996 DOI 10.3945/ajcn.117.160440 | Narrative review | Not applicable | Critics argue the UPF category is too broad and adds little beyond nutrients. | Opinion piece; predates RCTs (Hall 2019, Dicken 2025) | low | C-UPF-01 C-UPF-03 |
| I-UPF-04 | Food additive emulsifiers and risk of cardiovascular disease in the NutriNet-Santé cohort: prospective cohort study. Sellem L et al. | 2023 | PMID 37673430 DOI 10.1136/bmj-2023-076058 | Cohort study | French adults without prevalent CVD; mean age 43.1 (SD 14.5); 79.0% women; more educated and health-conscious than the general population | Higher intake of some emulsifiers, including CMC, was linked with slightly more heart disease. | Single volunteer cohort (79% women, health-conscious); limited generalisability (authors); Very small per-SD HRs (1.03-1.11); absolute risks not reported | moderate | C-UPF-06 C-UPF-11 |
| I-UPF-05 | Food additive emulsifiers and the risk of type 2 diabetes: analysis of data from the NutriNet-Santé prospective cohort study. Salame C et al. | 2024 | PMID 38663950 DOI 10.1016/S2213-8587(24)00086-X | Cohort study | Adults, 79% women | Several emulsifiers were linked with slightly higher diabetes risk. | Single cohort; Multiple testing | moderate | C-UPF-06 C-UPF-11 |
| I-UPF-06 | European Commission: Re-evaluation of food additives (incl. Q&A on titanium dioxide, Regulation (EU) 2022/63) and EU rules on food additives (Regulation (EC) No 1333/2008) European Commission (DG SANTE) | 2026 (accessed) | Guideline / position statement | Not applicable | EU additives need authorisation, are re-evaluated, and E171 was banned in 2022. | Regulatory status may change | high | C-UPF-09 C-UPF-11 | |
| I-UPF-101 | Ultra-processed foods cause weight gain and increased energy intake associated with reduced chewing frequency: A randomized, open-label, crossover study. Hamano S et al. | 2024 | PMID 39267249 DOI 10.1111/dom.15922 | Randomised controlled trial | Overweight/obese Japanese men without regular medical conditions | In 9 men, one week of ultra-processed food led to eating about 800 kcal more per day and gaining 1.1 kg more weight. | Only 9 participants; 1-week periods, open-label | low | C-UPF-02 |
| I-UPF-102 | Eating rate has sustained effects on energy intake from ultraprocessed diets: a 2-week ad libitum dietary randomized controlled crossover trial. Forde CG et al. | 2026 | PMID 41314613 DOI 10.1016/j.ajcnut.2025.11.012 | Randomised controlled trial | Healthy young adults (mean BMI 23.4) | When ultra-processed meals were chosen to be eaten slowly, people ate about 370 kcal less per day than with fast-to-eat ultra-processed meals. | Healthy-weight young adults only; First author reports multiple food-industry relationships (see COI) | high | C-UPF-02 |
| I-UPF-103 | Reliability and validity of assigning ultraprocessed food categories to 24-h dietary recall data. Sneed NM et al. | 2023 | PMID 36789937 DOI 10.1016/j.ajcnut.2022.10.016 | Other | Children aged 3-5 years in an RCT | With training and detailed food records, two coders agreed on the Nova category for 88% of foods. | Single dataset and protocol; US children; Reliability depends on detailed food descriptions and training | moderate | C-UPF-01 |
| I-UPF-104 | Does the concept of "ultra-processed foods" help inform dietary guidelines, beyond conventional classification systems? Debate consensus. Astrup A et al. | 2022 | PMID 36253965 DOI 10.1093/ajcn/nqac230 | Narrative review | Not applicable | Two leading nutrition scientists agreed that processing matters but disagreed on whether the UPF definition is clear enough. | Opinion; no new data | low | C-UPF-01 |
| I-UPF-105 | Association of ultra-processed food consumption with all cause and cause specific mortality: population based cohort study. Fang Z et al. | 2024 | PMID 38719536 DOI 10.1136/bmj-2023-078476 | Cohort study | US female nurses and male health professionals free of cancer, CVD and diabetes | Over about 30 years, people eating the most ultra-processed food had a 4% higher death rate; processed meat and sweet drinks drove most of it, while cancer and heart deaths were not linked. | FFQ not designed for Nova; Health professionals, mostly white | high | C-UPF-03 |
| I-UPF-106 | Ultra-processed foods and cardiovascular disease: analysis of three large US prospective cohorts and a systematic review and meta-analysis of prospective cohort studies. Mendoza K et al. | 2024 | PMID 39286398 DOI 10.1016/j.lana.2024.100859 | Cohort study | US adults (cohorts); multinational (meta-analysis) | People eating the most ultra-processed food had 11% more cardiovascular disease; sweet drinks and processed meats drove the link, while some UPF like cereals and yoghurt did not. | Observational; Overlap between cohorts and meta-analysis | high | C-UPF-03 |
| I-UPF-107 | Associations between degree of food processing and all-cause and cause-specific mortality: a multicentre prospective cohort analysis in 9 European countries. González-Gil EM et al. | 2025 | PMID 39867840 DOI 10.1016/j.lanepe.2024.101208 | Cohort study | European adults | In 429,000 Europeans, more UPF was linked to more deaths from heart and circulation diseases, but not from cancer. | Single baseline dietary assessment; Nova applied retrospectively to questionnaires | high | C-UPF-03 |
| I-UPF-108 | Food consumption by degree of food processing and risk of type 2 diabetes mellitus: a prospective cohort analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC). Dicken SJ et al. | 2024 | PMID 39529810 DOI 10.1016/j.lanepe.2024.101043 | Cohort study | European adults | Each 10% more of the diet from UPF was linked to 17% more type 2 diabetes, but some UPF groups such as breads and cereals were linked to less. | Observational; Single dietary assessment | high | C-UPF-03 |
| I-UPF-109 | Consumption of Ultraprocessed Food and Risk of Depression. Samuthpongtorn C et al. | 2023 | PMID 37728928 DOI 10.1001/jamanetworkopen.2023.34770 | Cohort study | Middle-aged US women free of depression at baseline (95% non-Hispanic white) | Women eating the most ultra-processed food had about 50% more new depression; the link was mainly with artificial sweeteners. | Self-reported diagnosis; misclassification possible; Mostly white women | moderate | C-UPF-04 |
| I-UPF-110 | Food Processing and Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Narula N et al. | 2023 | PMID 36731590 DOI 10.1016/j.cgh.2023.01.012 | Meta-analysis | Adults in cohort studies | Across five cohorts, high UPF intake was linked to 71% more Crohn's disease but not to ulcerative colitis. | Only 5 cohorts; Includes PURE (A-UPF-12) - overlap | moderate | C-UPF-05 |
| I-UPF-111 | Ultra-processed Foods and Risk of Crohn's Disease and Ulcerative Colitis: A Prospective Cohort Study. Lo CH et al. | 2022 | PMID 34461300 DOI 10.1016/j.cgh.2021.08.031 | Cohort study | US health professionals | In 245,000 adults, the highest UPF eaters had 70% more Crohn's disease, but no more ulcerative colitis. | Observational; Health professionals | high | C-UPF-05 |
| I-UPF-112 | Dietary Patterns, Ultra-processed Food, and the Risk of Inflammatory Bowel Diseases in the NutriNet-Santé Cohort. Vasseur P et al. | 2021 | PMID 32055825 DOI 10.1093/ibd/izaa018 | Cohort study | French adults | In a French cohort followed for about two years, ultra-processed food was not linked to IBD, but only 75 people developed the disease. | Only 75 cases; short follow-up; low power (minimum detectable HR about 1.9) | low | C-UPF-05 |
| I-UPF-113 | The effect of dietary emulsifiers and thickeners on intestinal barrier function and its response to acute stress in healthy adult humans: A randomised controlled feeding study. Fitzpatrick JA et al. | 2024 | PMID 39072856 DOI 10.1111/apt.18172 | Randomised controlled trial | Healthy adults | A diet high in common food emulsifiers did not cause gut inflammation; the gut barrier was tighter at rest but leakier under stress. | 22 participants; Surrogate outcomes | moderate | C-UPF-06 |
| I-UPF-114 | Clinical Trial: The Effects of Emulsifiers in the Food Supply on Disease Activity in Crohn's Disease: An Exploratory Double-Blinded Randomised Feeding Trial. Fitzpatrick JA et al. | 2025 | PMID 39967287 DOI 10.1111/apt.70041 | Randomised controlled trial | Adults with symptomatic, sonographically active ileal CD on stable therapy | In a small blinded trial, a diet high in food emulsifiers did not worsen Crohn's disease over four weeks compared with a low-emulsifier diet. | Exploratory, 24 patients; 4 weeks only | moderate | C-UPF-06 |
| I-UPF-115 | Can Artificial Sweeteners Increase the Risk of Cancer Incidence and Mortality: Evidence from Prospective Studies. Yan S et al. | 2022 | PMID 36145117 DOI 10.3390/nu14183742 | Meta-analysis | Adults in cohort studies | Across 25 studies, sweeteners were not linked to cancer overall; a small link appeared only in European studies. | Subgroup findings; high heterogeneity for mortality; Observational | moderate | C-UPF-07 |
| I-UPF-116 | Intake of Sugar-Sweetened and Low-Calorie Sweetened Beverages and Risk of Cardiovascular Disease: A Meta-Analysis and Systematic Review. Yin J et al. | 2021 | PMID 32696948 DOI 10.1093/advances/nmaa084 | Meta-analysis | Adults in cohorts | Each daily diet drink was linked to 7% more cardiovascular disease across cohort studies; the authors warn this may reflect who drinks them. | Reverse causation (people at risk switch to diet drinks); Beverages, not total sweetener intake | moderate | C-UPF-07 |
| I-UPF-117 | Intake of food additive preservatives and incidence of cancer: results from the NutriNet-Santé prospective cohort. Hasenböhler A et al. | 2026 | PMID 41500678 DOI 10.1136/bmj-2025-084917 | Cohort study | French adults >=15 years without prevalent cancer (78.7% women) | Higher intake of several common preservatives was linked to slightly more cancer (about 1-2 more cases per 100 people by age 60); most preservatives studied showed no link. | Observational; residual confounding; Many comparisons | high | C-UPF-11 |
| I-UPF-118 | Associations between preservative food additives and type 2 diabetes incidence in the NutriNet-Santé prospective cohort. Hasenböhler A et al. | 2026 | PMID 41501013 DOI 10.1038/s41467-025-67360-w | Cohort study | French adults (79.2% women; mean age 42.5) | In the same French cohort, 12 widely used preservatives were linked to more type 2 diabetes. | Observational; effect sizes not in abstract; Associations include antioxidants such as ascorbate and tocopherol, suggesting possible confounding by food matrix | moderate | C-UPF-11 |
| I-UPF-119 | Preservative food additives, hypertension, and cardiovascular diseases: the NutriNet-Santé study. Hasenböhler A et al. | 2026 | PMID 42161430 DOI 10.1093/eurheartj/ehag308 | Cohort study | French adults (78.7% women; mean age 42.8) | People with higher preservative intake had more high blood pressure and somewhat more cardiovascular disease in a French cohort. | Observational; same cohort; Antioxidant preservatives (e.g. vitamin C/E) also associated - possible confounding | moderate | C-UPF-11 |
| I-UPF-120 | Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. McCann D et al. | 2007 | PMID 17825405 DOI 10.1016/S0140-6736(07)61306-3 | Randomised controlled trial | 3-year-old and 8/9-year-old children | In a blinded trial, drinks with artificial colours plus the preservative sodium benzoate slightly increased hyperactive behaviour in children. | Cannot separate benzoate from colours; Small effect sizes; per-protocol analysis | moderate | C-UPF-11 |
| I-UPF-121 | Re-evaluation of celluloses E 460(i), E 460(ii), E 461, E 462, E 463, E 464, E 465, E 466, E 468 and E 469 as food additives. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) et al. | 2018 | PMID 32625652 DOI 10.2903/j.efsa.2018.5047 | Risk assessment | General population (exposure assessment) | EFSA found no safety concern for cellulose additives such as carboxymethylcellulose at the levels used in food. | Did not weigh microbiome/mucus findings from Chassaing 2015 as adverse endpoints (not stated in abstract); Animal toxicology endpoints | high | C-UPF-06 |
| I-UPF-122 | Safety of titanium dioxide (E171) as a food additive for humans. Warheit DB | 2024 | PMID 39100893 DOI 10.3389/ftox.2024.1333746 | Narrative review | Not applicable | A former employee of a titanium dioxide maker argues that EFSA was wrong and says other countries' agencies disagreed. | Single author with industry ties (former DuPont/Chemours employee); Opinion piece; agency positions not verified here from primary sources | very low | C-UPF-09 |
| I-UPF-123 | Is the experimental evidence on ultra-processed food and obesity reliable? Ludwig DS | 2026 | PMID 42063358 DOI 10.1080/10408398.2026.2664043 | Narrative review | Not applicable | A 2026 review argues that short feeding studies cannot prove that ultra-processed foods cause obesity. | Single-author opinion; no systematic methods stated; No COI statement in the PubMed record | low | C-UPF-02 |
| I-UPF-124 | Effect of ultra-processed-rich versus ultra-processed-free preload meals at high and low energy density on ad libitum energy intake: a randomized crossover trial. Barros LM et al. | 2026 | PMID 42633852 DOI 10.1016/j.appet.2026.108761 | Randomised controlled trial | Healthy young adults | When people ate fixed portions, ultra-processed meals did not make them eat more at the next meal. | 19 participants; single-day conditions; Fixed preloads (not ad libitum all day) | moderate | C-UPF-02 |
| I-VEG-01 | Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Reynolds A et al. | 2019 | PMID 30638909 DOI 10.1016/S0140-6736(18)31809-9 | Meta-analysis | Adults without chronic disease | High fibre intake is linked to 15-30% lower death and disease rates; trials show better weight, blood pressure and cholesterol. | Observational for hard endpoints | high | C-LEG-09 C-VEG-01 C-VEG-02 C-VEG-16 |
| I-VEG-02 | Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies. Aune D et al. | 2017 | PMID 28338764 DOI 10.1093/ije/dyw319 | Meta-analysis | Adult general-population prospective cohorts: 44 from Europe, 26 USA, 20 Asia, 5 Australia; no cohorts from Africa, West Asia or Latin America | Each extra 200 g of fruit and vegetables a day was linked to 10% lower death risk; green leafy vegetables and salads were also protective. | Observational: residual confounding by healthy lifestyle and healthcare access possible (acknowledged); High heterogeneity for all-cause mortality and stroke | high | C-VEG-01 C-VEG-08 C-VEG-10 C-VEG-13 C-VEG-15 C-VEG-16 |
| I-VEG-03 | From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Koh A et al. | 2016 | PMID 27259147 DOI 10.1016/j.cell.2016.05.041 | Narrative review | Not applicable | Gut bacteria turn fibre into short-chain fatty acids that act as fuel and signals for the body. | Mechanistic; much animal data | moderate | C-LEG-09 C-VEG-01 C-VEG-02 |
| I-VEG-04 | Attribution of foodborne illnesses, hospitalizations, and deaths to food commodities by using outbreak data, United States, 1998-2008. Painter JA et al. | 2013 | PMID 23622497 DOI 10.3201/eid1903.111866 | Other | US outbreak data | Leafy vegetables caused the most outbreak illnesses (22%), poultry the most deaths. | Outbreak data may not represent sporadic illness | moderate | C-VEG-03 |
| I-VEG-05 | Oxalate intake and the risk for nephrolithiasis. Taylor EN, Curhan GC | 2007 | PMID 17538185 DOI 10.1681/ASN.2007020219 | Cohort study | US health professionals | Highest oxalate intake raised stone risk only modestly (about 20%) in some groups; authors: not a major risk factor. | FFQ oxalate estimates imprecise; Self-reported stones | high | C-VEG-05 |
| I-VEG-06 | DASH-style diet associates with reduced risk for kidney stones. Taylor EN et al. | 2009 | PMID 19679672 DOI 10.1681/ASN.2009030276 | Cohort study | US health professionals | People with a diet rich in vegetables, fruit and legumes had about 40-45% fewer kidney stones. | Observational | high | C-LEG-13 C-VEG-05 C-VEG-16 |
| I-VEG-07 | Contribution of Dietary Oxalate and Oxalate Precursors to Urinary Oxalate Excretion. Crivelli JJ et al. | 2020 | PMID 33379176 DOI 10.3390/nu13010062 | Narrative review | Not applicable | Dietary oxalate contributes to urinary oxalate, modified by gut bacteria and calcium. | Narrative; Industry consulting | moderate | C-VEG-05 |
| I-VEG-08 | Infant methemoglobinemia: the role of dietary nitrate in food and water. Greer FR, Shannon M | 2005 | PMID 16140723 DOI 10.1542/peds.2005-1497 | Guideline / position statement | Infants | Babies can be poisoned by nitrate mainly from well water or home-made vegetable foods; breastfed babies are not at risk. | Not systematic | moderate | C-VEG-07 |
| I-VEG-09 | Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis. Siervo M et al. | 2013 | PMID 23596162 DOI 10.3945/jn.112.170233 | Meta-analysis | Adults | Nitrate from beetroot juice lowered systolic blood pressure by about 4 mm Hg in short trials. | Small, short (2 h - 15 d) | moderate | C-VEG-08 |
| I-VEG-10 | Poisoning by non-edible squash: retrospective series of 353 patients from French Poison Control Centers. Le Roux G et al. | 2018 | PMID 29323540 DOI 10.1080/15563650.2018.1424891 | Case series / case report | Exposures reported to French PCCs | 353 cases, usually mild, no deaths; discard bitter squash. | Passive reporting | moderate | C-VEG-09 |
| I-VEG-101 | Role of dietary vitamin K intake in chronic oral anticoagulation: prospective evidence from observational and randomized protocols. Franco V et al. | 2004 | PMID 15121490 DOI 10.1016/j.amjmed.2003.12.036 | Randomised controlled trial | Outpatients on chronic oral anticoagulation (coumarin) at an anticoagulation clinic | In 12 patients, a diet low in vitamin K raised INR from 2.6 to 3.3 within a week, and a vitamin K-rich diet lowered it from 3.1 to 2.8. | Very small (n = 12 in the trial); Short exposure (4 days) | moderate | C-VEG-12 |
| I-VEG-102 | Dietary vitamin K variability affects International Normalized Ratio (INR) coagulation indices. Couris R et al. | 2006 | PMID 16941417 DOI 10.1024/0300-9831.76.2.65 | Cohort study | Outpatients who began warfarin within 14 days, Massachusetts General Hospital | A weekly change of about 714 micrograms of vitamin K changed INR by about one unit in 43 new warfarin users. | Small; 28% drop-out; Short follow-up | moderate | C-VEG-12 |
| I-VEG-103 | Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects. Schurgers LJ et al. | 2004 | PMID 15231565 DOI 10.1182/blood-2004-04-1525 | Other | Healthy volunteers anticoagulated for 13 weeks on individualized doses | In anticoagulated volunteers, INR fell significantly only from 150 micrograms of daily vitamin K1 upwards; spinach and broccoli meals had short-lived effects. | Healthy volunteers, not patients; Sample size not given in abstract | moderate | C-VEG-12 |
| I-VEG-104 | Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Sconce E et al. | 2007 | PMID 17110451 DOI 10.1182/blood-2006-09-049262 | Randomised controlled trial | Warfarin-treated patients with unexplained unstable anticoagulation control | A daily 150 microgram vitamin K supplement more than doubled the share of unstable patients who reached stable control (19 of 35 vs 7 of 33). | Small (n = 70); Selected unstable patients | moderate | C-VEG-12 |
| I-VEG-105 | Effect of Vitamin K Intake on the Stability of Treatment with Vitamin K Antagonists: A Systematic Review of the Literature. Dentali F et al. | 2016 | PMID 27232386 DOI 10.1055/s-0036-1581105 | Systematic review | Patients on vitamin K antagonists | A review of 15 studies (1,838 patients) found unstable control more often in people with LOW vitamin K intake. | Narrative synthesis; Small, heterogeneous primary studies | low | C-VEG-12 |
| I-VEG-106 | Fruit and Vegetable Intake and Mortality: Results From 2 Prospective Cohort Studies of US Men and Women and a Meta-Analysis of 26 Cohort Studies. Wang DD et al. | 2021 | PMID 33641343 DOI 10.1161/CIRCULATIONAHA.120.048996 | Meta-analysis | 66,719 women (NHS 1984-2014) and 42,016 men (HPFS 1986-2014) free of CVD, cancer and diabetes; meta-analysis 1,892,885 participants | Compared with 2 servings a day, 5 servings were linked to 13% lower mortality in 2 US cohorts and in a meta-analysis of 26 cohorts with nearly 1.9 million people. | Observational: residual confounding by health consciousness possible; FFQ measurement error | high | C-VEG-16 C-VEG-01 |
| I-VEG-107 | Raw and Cooked Vegetable Consumption and Risk of Cardiovascular Disease: A Study of 400,000 Adults in UK Biobank. Feng Q et al. | 2022 | PMID 35265657 DOI 10.3389/fnut.2022.831470 | Cohort study | UK Biobank adults without prior CVD, mean age 56, 55% women | In 400,000 UK adults, raw vegetables were linked to 11% lower CVD risk, but adjustment for lifestyle and social factors explained over 80% of the association. | Crude intake measure (tablespoons, single baseline); Healthy-volunteer cohort | moderate | C-VEG-16 |
| I-VEG-108 | Genetically Predicted Vegetable Intake and Cardiovascular Diseases and Risk Factors: An Investigation with Mendelian Randomization. Feng Q et al. | 2023 | PMID 37686714 DOI 10.3390/nu15173682 | Other | UK Biobank and GWAS consortia | Gene-based estimates of vegetable intake were not linked to heart disease, with a weak signal for less stroke. | Weak and pleiotropic instruments for a behaviour; Instruments capture small intake differences | moderate | C-VEG-16 |
| I-VEG-109 | Behavioral Characteristics and Self-Reported Health Status among 2029 Adults Consuming a "Carnivore Diet". Lennerz BS et al. | 2021 | PMID 34934897 DOI 10.1093/cdn/nzab133 | Cross-sectional study | Adults reporting a carnivore diet for >=6 months (recruited via social media) | Over 2,000 self-selected carnivore dieters reported few side effects and feeling better, but their reported LDL cholesterol was markedly high. | Self-selected, self-reported, no control group; Survivorship and enthusiasm bias | very low | C-VEG-16 |
| I-VEG-11 | Pesticide Residues in Vegetables and Fruits from Farmer Markets and Associated Dietary Risks. El-Sheikh EA et al. | 2022 | PMID 36432173 DOI 10.3390/molecules27228072 | Measurement / residue study | Composite vegetable and fruit samples (3 kg each from 3 sellers) from three farmers' markets | About 4 in 10 detected residues exceeded legal limits; some may pose risks. | Small sample (120 composites) from one governorate; not nationally representative; Exceedance expressed per residue finding, not per sample | moderate | C-VEG-14 C-FRU-04 |
| I-VEG-110 | Carnivore Diet: A Scoping Review of the Current Evidence, Potential Benefits and Risks. Lietz A et al. | 2026 | PMID 41599961 DOI 10.3390/nu18020348 | Systematic review | Human studies of carnivore diets | A 2026 review of 9 small studies found possible short-term benefits but risks of vitamin C, fibre and mineral deficiency and high LDL cholesterol. | Scoping review, no risk-of-bias pooling; Only 9 low-quality studies | low | C-VEG-16 |
| I-VEG-111 | Complementary Feeding: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition. Fewtrell M et al. | 2017 | PMID 28027215 DOI 10.1097/MPG.0000000000001454 | Guideline / position statement | Healthy term infants in Europe | ESPGHAN advises starting solids between 4 and 6 months and offering varied foods including bitter green vegetables. | Consensus, not a formal GRADE guideline; Healthy term infants in Europe | moderate | C-VEG-16 C-VEG-07 |
| I-VEG-112 | Healthy diet (WHO fact sheet) World Health Organization | 2026 | Guideline / position statement | General population incl. children | WHO recommends at least 400 g of fruit and vegetables daily for everyone over 10 and 250-350 g for young children, plus minimum fibre intakes. | Fact sheet summarizing underlying guidelines | moderate | C-VEG-16 | |
| I-VEG-113 | Methemoglobinemia induced by vegetable intake in infants in northern Spain. Martinez A et al. | 2013 | PMID 23287806 DOI 10.1097/MPG.0b013e3182849d2b | Case-control study | Infants with diet-induced methaemoglobinaemia, Pamplona; 78 age- and sex-matched controls | In 78 Spanish infants, purees made more than a day in advance and nitrate-rich leaves such as borage and chard were linked to methaemoglobinaemia. | Bivariate analysis only; Wide CIs | low | C-VEG-07 |
| I-VEG-114 | Acquired methemoglobinemia in children presenting to Italian pediatric emergency departments: a multicenter report. Raucci U et al. | 2022 | PMID 35416740 DOI 10.1080/15563650.2022.2061986 | Case series / case report | Children with acquired methaemoglobinaemia | 19 children (median age 8 months) developed methaemoglobinaemia, mostly after home-made vegetable broth that had been badly preserved; all survived with treatment. | Small retrospective series; No denominator | low | C-VEG-07 |
| I-VEG-115 | Statement on possible public health risks for infants and young children from the presence of nitrates in leafy vegetables EFSA Panel on Contaminants in the Food Chain (CONTAM) | 2010 | DOI 10.2903/j.efsa.2010.1935 | Risk assessment | Infants and young children (EU) | EFSA judged spinach nitrate unlikely to be a concern for most infants, but could not exclude risk for some, and warned that badly stored cooked vegetables form nitrite. | 2010; exposure modelling rather than outcome data | moderate | C-VEG-07 |
| I-VEG-116 | Dietary oxalate and kidney stone formation. Mitchell T et al. | 2019 | PMID 30566003 DOI 10.1152/ajprenal.00373.2018 | Narrative review | Humans; stone formers | About half of urinary oxalate comes from food; a cited controlled-diet estimate is 2.7 mg more urinary oxalate per 100 mg eaten. | Narrative review; Full text not accessed; 2.7 mg figure taken from a secondary citation | low | C-VEG-05 |
| I-VEG-117 | Determinants of 24-hour urinary oxalate excretion. Taylor EN et al. | 2008 | PMID 18650406 DOI 10.2215/CJN.01410308 | Cross-sectional study | Stone formers and non-stone formers from US health-professional cohorts | People eating the most oxalate excreted only 1.7 mg/day more oxalate than those eating the least. | Cross-sectional; FFQ oxalate estimates imprecise | moderate | C-VEG-05 |
| I-VEG-118 | Contribution of dietary oxalate to urinary oxalate excretion. Holmes RP et al. | 2001 | PMID 11135080 DOI 10.1046/j.1523-1755.2001.00488.x | Other | Healthy adults | In controlled diets, food supplied 24-42% of urinary oxalate, and more (53%) when calcium intake was low. | Small (size not in abstract); Healthy volunteers, not stone outcomes | moderate | C-VEG-05 |
| I-VEG-119 | Effect of different cooking methods on vegetable oxalate content. Chai W et al. | 2005 | PMID 15826055 DOI 10.1021/jf048128d | Measurement / residue study | Nine vegetable types | Boiling cut soluble oxalate by 30-87% in nine vegetables; steaming removed less. | Food chemistry only; no human outcomes | moderate | C-VEG-05 C-VEG-06 |
| I-VEG-12 | Monitoring of pesticide residues in Egyptian fruits and vegetables during 1997. Dogheim SM et al. | 2002 | PMID 12456272 DOI 10.1080/02652030210157655 | Measurement / residue study | 2,318 domestic samples from 8 markets | Most samples had no detectable residues; 1.9% exceeded limits. | Old (1997) | moderate | C-VEG-14 |
| I-VEG-120 | Secondary Oxalate Nephropathy: A Systematic Review. Lumlertgul N et al. | 2018 | PMID 30450463 DOI 10.1016/j.ekir.2018.07.020 | Systematic review | Biopsy-proven oxalate nephropathy (native or transplant kidneys) | Among 108 published cases of secondary oxalate nephropathy, excessive dietary oxalate was a cause in about 1 in 5; over half needed dialysis. | Case reports: publication bias toward severe cases; no denominator | low | C-VEG-06 |
| I-VEG-121 | Clinical Outcomes and Histological Patterns in Oxalate Nephropathy due to Enteric and Nonenteric Risk Factors. Reddy S et al. | 2021 | PMID 34844241 DOI 10.1159/000520286 | Case series / case report | Native-kidney biopsies with oxalate nephropathy, Mayo Clinic sites | Of 64 biopsy cases, 7 were attributed to dietary oxalate; outcomes were often poor. | Retrospective; referral population; no denominator of exposure | low | C-VEG-06 |
| I-VEG-122 | "Green Smoothie Cleanse" Causing Acute Oxalate Nephropathy. Makkapati S et al. | 2018 | PMID 29203127 DOI 10.1053/j.ajkd.2017.08.002 | Case series / case report | 65-year-old woman with remote gastric bypass and recent antibiotics | A 65-year-old woman with earlier gastric bypass developed permanent kidney failure after a green juice cleanse. | Single case; multiple predisposing factors | very low | C-VEG-06 |
| I-VEG-123 | Vegetable nitrate intake, blood pressure and incident cardiovascular disease: Danish Diet, Cancer, and Health Study. Bondonno CP et al. | 2021 | PMID 33884541 DOI 10.1007/s10654-021-00747-3 | Cohort study | Danish adults without baseline CVD | Danes eating about a cup of leafy greens' worth of nitrate daily had 15% less cardiovascular disease than those eating the least. | Observational; Single FFQ at baseline | moderate | C-VEG-08 |
| I-VEG-124 | Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study. Bondonno NP et al. | 2024 | PMID 38802612 DOI 10.1007/s10654-024-01133-5 | Cohort study | Danish adults | Nitrate from plants was linked to 17% lower mortality, whereas nitrate from processed meat and tap water was linked to higher mortality. | Observational; plant nitrate tracks vegetable intake; Single baseline diet | moderate | C-VEG-08 |
| I-VEG-125 | Source-specific nitrate and nitrite intake and association with colorectal cancer in the Danish Diet, Cancer and Health Cohort. Erichsen DW et al. | 2025 | PMID 40628182 DOI 10.1016/j.envint.2025.109658 | Cohort study | Danish adults | In 54,610 Danes, nitrate from vegetables was not linked to colorectal cancer; high nitrate in tap water was linked to distal colon cancer. | Observational; Multiple subgroup analyses | moderate | C-VEG-08 |
| I-VEG-126 | Nitrate intake and the risk of thyroid cancer and thyroid disease. Ward MH et al. | 2010 | PMID 20335813 DOI 10.1097/EDE.0b013e3181d6201d | Cohort study | Older women in Iowa using the same water supply >10 years | In Iowa women, the highest dietary nitrate intake was linked to more thyroid cancer, but the estimate was very imprecise. | Few cases; imprecise; Self-reported thyroid disease | low | C-VEG-08 |
| I-VEG-127 | Do Brassica Vegetables Affect Thyroid Function?-A Comprehensive Systematic Review. Galanty A et al. | 2024 | PMID 38612798 DOI 10.3390/ijms25073988 | Systematic review | In vitro, animal and human studies | A review of 123 studies concluded that daily brassica vegetables, especially with enough iodine, do not harm thyroid function. | Mixed evidence levels; few human trials; Narrative synthesis | low | C-VEG-10 |
| I-VEG-128 | Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in brassica vegetables, and associated potential risk for hypothyroidism. Felker P et al. | 2016 | PMID 26946249 DOI 10.1093/nutrit/nuv110 | Narrative review | Not applicable | Only a few varieties (collards, Brussels sprouts, some kale) contain enough goitrin to possibly reduce iodine uptake; broccoli and most kale contain little. | Narrative; Industry-affiliated authors | low | C-VEG-10 |
| I-VEG-129 | Neutral detergent fiber, hemicellulose and cellulose digestibility in human subjects. Slavin JL et al. | 1981 | PMID 6257867 DOI 10.1093/jn/111.2.287 | Other | Seven women | In 7 women on controlled diets, about 70% of cellulose from fruits and vegetables was broken down in the gut, but only 8-16% of purified cellulose. | n = 7; 1981 methods (apparent digestibility) | moderate | C-VEG-01 C-VEG-02 |
| I-VEG-13 | Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. Aburto NJ et al. | 2013 | PMID 23558164 DOI 10.1136/bmj.f1378 | Meta-analysis | Apparently healthy adults and children without impaired renal potassium handling; acutely ill, hospitalised and HIV-positive people excluded | More potassium lowered blood pressure in people with hypertension and was linked to 24% lower stroke risk. | Most RCTs tested supplements, so food-based evidence for vegetables is indirect; High heterogeneity in overall BP analysis (reduced by excluding outliers) | high | C-VEG-16 |
| I-VEG-130 | Effect of fiber from fruits and vegetables on metabolic responses of human subjects: fiber intakes, fecal excretions, and apparent digestibilities. Kelsay JL et al. | 1981 | PMID 6269418 DOI 10.1093/ajcn/34.9.1849 | Other | 12 men | In 12 men eating fruits and vegetables, 42% of cellulose and 88% of hemicellulose were broken down in the gut. | n = 12; Old methods | moderate | C-VEG-01 C-VEG-02 |
| I-VEG-131 | The cellulose-degrading microbial community of the human gut varies according to the presence or absence of methanogens. Chassard C et al. | 2010 | PMID 20662929 DOI 10.1111/j.1574-6941.2010.00941.x | Other | Methane-excreting and non-methane-excreting human volunteers | French researchers found bacteria able to degrade spinach cell walls in all volunteers, of different types depending on methane production. | Small; sample size not in abstract; In vitro culture | moderate | C-VEG-02 C-VEG-01 |
| I-VEG-132 | Outbreaks attributed to fresh leafy vegetables, United States, 1973-2012. Herman KM et al. | 2015 | PMID 25697407 DOI 10.1017/S0950268815000047 | Other | US outbreaks reported to CDC | Over 40 years, US leafy-vegetable outbreaks caused 20,003 illnesses and 19 deaths; many involved infected food workers. | Outbreak data miss sporadic cases; Reporting changes over time | moderate | C-VEG-03 |
| I-VEG-133 | Produce-associated foodborne disease outbreaks, USA, 1998-2013. Bennett SD et al. | 2018 | PMID 29923474 DOI 10.1017/S0950268818001620 | Other | US foodborne outbreaks | Raw produce caused 972 outbreaks in 1998-2013, rising from 8% to 16% of outbreaks with a known food; leafy row crops led. | Outbreak-only data | moderate | C-VEG-03 |
| I-VEG-134 | Scientific Opinion on the risk posed by pathogens in food of non-animal origin. Part 1 (outbreak data analysis and risk ranking of food/pathogen combinations). EFSA Panel on Biological Hazards (BIOHAZ) | 2013 | PMID 42124987 DOI 10.2903/j.efsa.2013.3025 | Risk assessment | EU outbreak data (EU Zoonoses Monitoring) | EFSA ranked Salmonella in raw leafy greens as the highest-risk plant food combination; outside the 2011 sprout outbreak, plant foods caused 5% of outbreak deaths. | Outbreak-based; dominated by one 2011 event | moderate | C-VEG-03 |
| I-VEG-135 | Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. Frank C et al. | 2011 | PMID 21696328 DOI 10.1056/NEJMoa1106483 | Outbreak report | Reported cases in Germany | The outbreak caused 3,816 cases and 54 deaths; sprouts were identified as the most likely vehicle. | Descriptive | high | C-VEG-04 |
| I-VEG-136 | Outbreak of Shiga toxin-producing Escherichia coli O104:H4 associated with organic fenugreek sprouts, France, June 2011. King LA et al. | 2012 | PMID 22460976 DOI 10.1093/cid/cis255 | Outbreak report | Adults attending a community event | In a 2011 French cluster with the same strain, eating fenugreek sprouts raised illness risk five-fold. | Small | moderate | C-VEG-04 |
| I-VEG-137 | Clinical characteristics of melon (Cucumis melo) allergy. Figueredo E et al. | 2003 | PMID 14533664 DOI 10.1016/s1081-1206(10)63534-x | Case-control study | Melon-allergic patients (oral challenge-confirmed) and pollen-allergic controls | All 66 melon-allergic patients also had pollen allergy; symptoms were mostly in the mouth and none had anaphylaxis. | Single allergy centre; selected patients | moderate | C-VEG-11 |
| I-VEG-138 | Profilin, a Change in the Paradigm. Rodríguez Del Río P et al. | 2018 | PMID 28760720 DOI 10.18176/jiaci.0193 | Narrative review | Pollen-, latex- and plant-food-allergic patients | Profilin, present in all plant foods, is particularly associated with allergy to grass pollen and melon-family fruits. | Narrative | low | C-VEG-11 |
| I-VEG-14 | Commission Regulation (EU) 2023/915 on maximum levels for certain contaminants in food (Annex I, section 6.1 Nitrates) European Commission | 2023 | Guideline / position statement | Not applicable | The EU caps nitrate in spinach, lettuce and rocket and sets a much lower limit for baby food. | Not peer-reviewed study | moderate | C-VEG-07 C-VEG-08 | |
| I-VEG-140 | Association Between Pesticide Residue Intake From Consumption of Fruits and Vegetables and Pregnancy Outcomes Among Women Undergoing Infertility Treatment With Assisted Reproductive Technology. Chiu YH et al. | 2018 | PMID 29084307 DOI 10.1001/jamainternmed.2017.5038 | Cohort study | Women at a US fertility centre | Women eating the most high-residue fruit and vegetables had 26% lower chance of live birth after fertility treatment. | Small, selected infertility population; Single centre | moderate | C-VEG-13 |
| I-VEG-141 | The effects of organic food on human health: a systematic review and meta-analysis of population-based studies. Jiang B et al. | 2024 | PMID 37930102 DOI 10.1093/nutrit/nuad124 | Meta-analysis | Human population-based studies | A review of 50 studies found that organic food lowers pesticide markers, but evidence on specific diseases was insufficient. | Heterogeneous, mostly observational; confounding by lifestyle of organic consumers | low | C-VEG-13 |
| I-VEG-142 | Consumption of organic compared with conventional fruits and vegetables in relation to cancer risk: findings from the NutriNet-Santé cohort study. Berlivet J et al. | 2026 | PMID 41862000 DOI 10.1016/j.ajcnut.2026.101284 | Cohort study | French adults (75% women) | Replacing 100 g/day conventional with organic fruit and vegetables was linked to 10% lower postmenopausal breast cancer risk, not to lower overall cancer. | Volunteer cohort; organic consumers differ; Multiple outcomes | moderate | C-VEG-13 |
| I-VEG-143 | Nationwide Surveillance and Cumulative Risk Assessment of Pesticide Residues in Egyptian Vegetables: Results from 2018 to 2021 Malhat F et al. | 2024 | DOI 10.3390/separations11110318 | Measurement / residue study | Vegetable samples (cucumber, squash, eggplant, okra, peas, onion, green onion, parsley, lettuce, cantaloupe) | Of 4,200 vegetable samples from 20 Egyptian markets (2018-2021), 13% exceeded residue limits, but estimated chronic intakes stayed below safety thresholds. | Abstract only; Acute risk and banned-compound details not in abstract | moderate | C-VEG-14 |
| I-VEG-145 | Nightshade Vegetables: A Dietary Trigger for Worsening Inflammatory Bowel Disease and Irritable Bowel Syndrome? Kuang R et al. | 2023 | PMID 37202602 DOI 10.1007/s10620-023-07955-9 | Narrative review | Not applicable | A 2023 review proposes that nightshade vegetables such as eggplant might worsen symptoms in IBD or IBS, but human evidence is limited. | Narrative; mostly animal/in vitro mechanisms; no controlled human trials | very low | C-VEG-15 |
| I-VEG-15 | Pesticide residues in food: what's the situation in the EU? (EFSA news on the 2023 EU report) EFSA | 2025 | Risk assessment | Not applicable | Only about 2% of random EU samples exceeded legal limits; EFSA judged consumer risk low. | Not peer-reviewed study | moderate | C-VEG-13 | |
| I-VEG-16 | EFSA Task Force report on tracing seeds in relation to the STEC O104:H4 2011 outbreaks (press release 5 July 2011) EFSA | 2011 | Risk assessment | Not applicable | EFSA traced the outbreak to fenugreek seeds from Egypt used for sprouts. | Not peer-reviewed study | moderate | C-VEG-04 | |
| I-VEG-17 | Vorsicht beim Verzehr von bitteren Zucchini (Mitteilung Nr. 027/2015) BfR (German Federal Institute for Risk Assessment) | 2015 | Guideline / position statement | Not applicable | Bitter zucchini should be discarded; cultivated zucchini is bred to lack the toxin; poisonings are rare and usually mild. | Not peer-reviewed study | moderate | C-VEG-09 | |
| I-WHT-01 | Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Reynolds A et al. | 2019 | PMID 30638909 DOI 10.1016/S0140-6736(18)31809-9 | Meta-analysis | Adults without chronic disease | High fibre/whole grain intake linked to 15-30% lower risk of several diseases; GI/GL evidence weaker. | Observational core | high | C-WHT-04 C-WHT-05 C-WHT-03 C-GRN-08 C-CAN-08 |
| I-WHT-02 | Refined grain intake and cardiovascular disease: Meta-analyses of prospective cohort studies. Gaesser GA | 2024 | PMID 36075506 DOI 10.1016/j.tcm.2022.08.002 | Meta-analysis | Cohort participants | Pooled cohorts showed no clear link between refined grains and heart disease. | Single author; Likely industry links | low | C-WHT-03 C-WHT-04 C-GRN-05 |
| I-WHT-03 | Dietary intake and the risk of gastro-oesophageal reflux disease: a cross sectional study in volunteers. El-Serag HB et al. | 2005 | PMID 15591498 DOI 10.1136/gut.2004.040337 | Cross-sectional study | Employees of Houston VAMC | More fibre linked to fewer reflux symptoms; more fat to more symptoms. | Small, cross-sectional; Volunteers | low | C-WHT-01 C-WHT-08 C-GUT-01 |
| I-WHT-04 | Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis. Singh P et al. | 2018 | PMID 29551598 DOI 10.1016/j.cgh.2017.06.037 | Meta-analysis | General populations | About 1 in 70 have coeliac antibodies and about 1 in 140 biopsy-confirmed disease worldwide. | Heterogeneous sources | moderate | C-WHT-02 C-GRN-01 C-GRN-03 |
| I-WHT-05 | Food groups and the likelihood of non-alcoholic fatty liver disease: a systematic review and meta-analysis. He K et al. | 2020 | PMID 32138796 DOI 10.1017/S0007114520000914 | Meta-analysis | Observational study participants | Refined grains were not linked to fatty liver; soft drinks and red meat were. | No prospective studies | low | C-WHT-07 |
| I-WHT-06 | Associations between types and sources of dietary carbohydrates and liver fat: a UK Biobank study. Orliacq J et al. | 2023 | PMID 37968623 DOI 10.1186/s12916-023-03135-8 | Cohort study | UK Biobank adults without diabetes/liver/CVD | Refined-grain starch linked to liver fat in one analysis but not on MRI; free sugars linked on MRI. | Diet measured by 24-h recall; Inconsistent between analyses | moderate | C-WHT-07 |
| I-WHT-07 | Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. Lebwohl B et al. | 2017 | PMID 28465308 DOI 10.1136/bmj.j1892 | Cohort study | 64,714 female nurses (NHS) and 45,303 male health professionals (HPFS) without CHD, stroke, CABG, cancer or self-reported coeliac disease, with plausible energy intake on the 1986 FFQ | Eating more gluten was not linked to more heart disease over 26 years. | Gluten estimated indirectly from FFQ with a fixed 75% protein conversion; not validated directly; Could not identify people following gluten-free diets or eating gluten-free substitutes; undiagnosed coeliac disease not excluded | high | C-WHT-09 C-GRN-01 |
| I-WHT-101 | Matched whole grain wheat and refined wheat milled products do not differ in glycemic response or gastric emptying in a randomized, crossover trial. Pletsch EA et al. | 2022 | PMID 34999739 DOI 10.1093/ajcn/nqab434 | Randomised controlled trial | Healthy adults | In a randomised trial with matched porridges, refined and whole-wheat flour did not differ in gastric emptying or blood sugar. | Small (n=16); Healthy volunteers | moderate | C-WHT-01 C-GRN-04 |
| I-WHT-102 | Gastric emptying of wholemeal and white bread. Grimes DS et al. | 1977 | PMID 604193 DOI 10.1136/gut.18.9.725 | Other | Volunteers | Isotope measurements showed the same emptying of solids for white and wholemeal bread. | Old, small; Sample size not in abstract | low | C-WHT-01 |
| I-WHT-103 | Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans. Coletta M et al. | 2016 | PMID 26522233 DOI 10.1017/S0007114515004183 | Randomised controlled trial | Healthy adults | MRI showed more heterogeneous stomach contents with high-gluten bread, but emptying time and symptoms did not differ. | n=12; Open-label | low | C-WHT-01 |
| I-WHT-104 | Effects of gluten on dyspeptic symptoms: a systematic review and meta-analysis of clinical trials. Hosseinian SZ et al. | 2023 | PMID 37115663 DOI 10.1093/nutrit/nuad034 | Meta-analysis | Patients in trials of gluten-free diet, low-gluten diet or gluten challenge with dyspeptic symptoms | In five pooled trials, gluten challenge modestly increased bloating, early fullness and upper abdominal pain. | Only 5 RCTs pooled; High heterogeneity | moderate | C-WHT-01 |
| I-WHT-105 | Prevalence of Celiac Disease in Patients With Iron Deficiency Anemia-A Systematic Review With Meta-analysis. Mahadev S et al. | 2018 | PMID 29689265 DOI 10.1053/j.gastro.2018.04.016 | Meta-analysis | Patients with IDA | Across 18 studies, 3.2% of patients with iron-deficiency anaemia had biopsy-confirmed coeliac disease (5.5% in better studies). | Fixed-effects despite heterogeneity; Referral populations | moderate | C-WHT-02 |
| I-WHT-106 | Screening for coeliac disease among Egyptian children. Abd El Dayem SM et al. | 2010 | PMID 22371752 DOI 10.5114/aoms.2010.13900 | Cross-sectional study | Egyptian children at clinical risk | Biopsies confirmed coeliac disease in 11 of 25 Egyptian children with refractory iron-deficiency anaemia. | Small, selected referral groups; Wide CIs (11/25: 26.7-62.9%) | low | C-WHT-02 |
| I-WHT-107 | British Society of Gastroenterology guidelines for the management of iron deficiency anaemia in adults. Snook J et al. | 2021 | PMID 34497146 DOI 10.1136/gutjnl-2021-325210 | Guideline / position statement | Adults with IDA | About a third of men and post-menopausal women with iron-deficiency anaemia have an underlying disease, often in the gut, including cancer; coeliac disease is found in 3-5%. | UK health-system context | high | C-WHT-02 |
| I-WHT-108 | Consumption of whole grains and refined grains and associated risk of cardiovascular disease events and all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies. Hu H et al. | 2023 | PMID 36789934 DOI 10.1016/j.ajcnut.2022.10.010 | Meta-analysis | Adults in prospective cohorts | In 1.6 million people, each 30 g/day of whole grains was linked to 6-8% lower CVD and death risk; refined grains showed no clear link with heart disease. | Observational; Overlap with Aune 2016 cohorts | moderate | C-WHT-03 C-WHT-04 |
| I-WHT-109 | Umbrella Review of Systematic Reviews and Meta-analyses on Consumption of Different Food Groups and Risk of All-cause Mortality. Onni AT et al. | 2025 | PMID 39956388 DOI 10.1016/j.advnut.2025.100393 | Systematic review | Adults | An umbrella review of 41 meta-analyses found lower mortality with whole grains but no clear association for refined grains. | Overlapping meta-analyses; Observational base | high | C-WHT-03 C-WHT-04 |
| I-WHT-110 | Whole grain cereals for the primary or secondary prevention of cardiovascular disease. Kelly SA et al. | 2017 | PMID 28836672 DOI 10.1002/14651858.CD005051.pub3 | Meta-analysis | Healthy adults or at increased CVD risk | A Cochrane review found 9 short trials and none measured heart attacks or deaths; cholesterol did not change. | Few small short trials | high | C-WHT-04 |
| I-WHT-111 | The Effect of Replacing Refined Grains with Whole Grains on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Clinical Recommendation. Marshall S et al. | 2020 | PMID 32933853 DOI 10.1016/j.jand.2020.06.021 | Meta-analysis | Adults with or without chronic disease | In 22 pooled trials, whole grains (especially oats) modestly lowered LDL cholesterol, HbA1c and CRP. | Short trials; Effect driven partly by oats | moderate | C-WHT-04 |
| I-WHT-112 | Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100 000 participants. Jenkins DJA et al. | 2024 | PMID 38272606 DOI 10.1016/S2213-8587(23)00344-3 | Meta-analysis | Participants of 10 large cohorts | In ten very large cohorts, people with the highest dietary glycaemic index had 27% higher diabetes risk. | Fixed-effect model; Observational | moderate | C-WHT-05 |
| I-WHT-113 | Intake of whole grain foods and risk of type 2 diabetes: results from three prospective cohort studies. Hu Y et al. | 2020 | PMID 32641435 DOI 10.1136/bmj.m2206 | Cohort study | US women and men free of T2D, CVD, cancer | In 195,000 US adults, the highest whole grain intake was linked to 29% lower diabetes risk; dark bread and oatmeal about 20% lower. | Observational; Health-professional cohorts | high | C-WHT-05 |
| I-WHT-114 | Whole- and Refined-Grain Consumption and Longitudinal Changes in Cardiometabolic Risk Factors in the Framingham Offspring Cohort. Sawicki CM et al. | 2021 | PMID 34255848 DOI 10.1093/jn/nxab177 | Cohort study | Middle-aged to older US adults | Over 18 years, people eating the most refined grains gained about 0.9 cm more waist per 4 years than those eating the least. | Observational; Single cohort, mostly white | moderate | C-WHT-06 |
| I-WHT-115 | Whole-Grain Consumption Does Not Affect Obesity Measures: An Updated Systematic Review and Meta-analysis of Randomized Clinical Trials. Sadeghi O et al. | 2020 | PMID 31390462 DOI 10.1093/advances/nmz076 | Meta-analysis | Adults >=18 years in RCTs | In 21 randomised trials, eating whole instead of refined grains did not change weight, BMI, waist or fat mass. | Short trials; Mostly isocaloric designs | moderate | C-WHT-06 |
| I-WHT-116 | A 12-wk whole-grain wheat intervention protects against hepatic fat: the Graandioos study, a randomized trial in overweight subjects. Schutte S et al. | 2018 | PMID 30541093 DOI 10.1093/ajcn/nqy204 | Randomised controlled trial | Overweight men and postmenopausal women aged 45-70 | In 50 overweight adults, 12 weeks of refined wheat products increased liver fat by 49% relative to whole-grain wheat. | Small (n=50); 12 weeks | moderate | C-WHT-07 |
| I-WHT-117 | Whole-grain consumption and its effects on hepatic steatosis and liver enzymes in patients with non-alcoholic fatty liver disease: a randomised controlled clinical trial. Dorosti M et al. | 2020 | PMID 31685037 DOI 10.1017/S0007114519002769 | Randomised controlled trial | Adults with NAFLD (mean BMI 32.2) | In 112 NAFLD patients, advice to eat half of cereals as whole grains for 12 weeks lowered fatty-liver grade and liver enzymes. | Open-label; Ultrasound grading (subjective) | low | C-WHT-07 |
| I-WHT-118 | The Effects of Modifying Amount and Type of Dietary Carbohydrate on Esophageal Acid Exposure Time and Esophageal Reflux Symptoms: A Randomized Controlled Trial. Gu C et al. | 2022 | PMID 35973185 DOI 10.14309/ajg.0000000000001889 | Randomised controlled trial | US veterans with symptomatic GERD and overweight/obesity on PPI therapy | In 98 veterans with reflux, a diet much lower in simple sugars reduced oesophageal acid exposure over 9 weeks compared with a high-sugar diet. | Mostly men (veterans); Short (9 weeks) | moderate | C-WHT-08 C-GUT-01 C-GUT-02 |
| I-WHT-119 | Higher Carbohydrate Amount and Lower Glycemic Index Increase Hunger, Diet Satisfaction, and Heartburn in Overweight and Obese Adults in the OmniCarb Randomized Clinical Trial. Wu Y et al. | 2021 | PMID 34049396 DOI 10.1093/jn/nxab128 | Randomised controlled trial | Overweight or obese adults | In a feeding trial, high-GI diets did not increase heartburn, while higher-carbohydrate diets increased it by about half. | Secondary outcomes; Not GERD patients | moderate | C-WHT-08 |
| I-WHT-120 | The Effect of Rice vs. Wheat Ingestion on Postprandial Gastroesophageal Reflux (GER) Symptoms in Patients with Overlapping GERD-Irritable Bowel Syndrome (IBS). Patcharatrakul T et al. | 2021 | PMID 35010152 DOI 10.3390/foods11010026 | Randomised controlled trial | Patients with overlapping GERD and IBS | In 21 patients with both reflux and IBS, wheat noodles caused more heartburn and regurgitation than rice noodles. | Very small; Specific subgroup | low | C-WHT-08 |
| I-WHT-121 | Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Hollon J et al. | 2015 | PMID 25734566 DOI 10.3390/nu7031565 | Laboratory / cell study | Duodenal biopsies: active coeliac (6), coeliac in remission (6), gluten-sensitive (6), non-coeliac controls (5) | Biopsy samples from coeliac patients, gluten-sensitive people and controls all became more permeable when exposed to gliadin for two hours. | Ex vivo, 120 minutes; Very small groups | low | C-WHT-09 |
| I-WHT-122 | Impact of Acute and Sub-Acute Gluten Exposure on Gastrointestinal Symptoms and Psychological Responses in Non-Coeliac Gluten Sensitivity: A Randomised Crossover Study. Iven J et al. | 2025 | PMID 40138597 DOI 10.1002/ueg2.70014 | Randomised controlled trial | Healthy controls and people with NCGS | In 36 adults, eating 16 g of gluten daily for 5 days did not change gut permeability or inflammation markers compared with gluten-free food. | Single-blind; Small | moderate | C-WHT-09 C-GRN-01 |
| I-WHT-123 | Serum zonulin as a marker of intestinal mucosal barrier function: May not be what it seems. Ajamian M et al. | 2019 | PMID 30640940 DOI 10.1371/journal.pone.0210728 | Other | Patients with GI dysfunction and healthy individuals (sera) | Analysis showed two widely used commercial zonulin tests detect other proteins (haptoglobin, complement C3). | Two kits only | moderate | C-WHT-09 |
| I-WHT-124 | Association of whole and refined grains food consumption with coronary artery disease in a multi-center, case-control study of Iranian adults: Iran Premature Coronary Artery Disease (IPAD). Tabesh F et al. | 2025 | PMID 39986935 DOI 10.1016/j.numecd.2025.103866 | Case-control study | Iranian adults (Fars, Azari, Kurd, Arab, Lor, Gilak, Qashqaei, Bakhtiari) undergoing angiography | In an Iranian case-control study, whole grains were linked to 46% lower odds of coronary disease; the refined-grain result (OR 1.43) is reported with a confidence interval that includes no effect. | Case-control: recall bias, reverse causation; Controls are patients referred for angiography | low | C-WHT-03 |
| I-WHT-125 | The Efficacy of Dietary Interventions in Patients with Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis of Intervention Studies. Lakananurak N et al. | 2024 | PMID 38337748 DOI 10.3390/nu16030464 | Meta-analysis | Patients with GERD in intervention studies | Across three studies, low-carbohydrate diets reduced the time the oesophagus was exposed to acid by about 3 percentage points. | Only 3 low-carbohydrate studies; Short interventions | moderate | C-WHT-08 C-GUT-01 |
Sources of the case study EU/Germany – Egypt
- Regulation (EC) No 178/2002 laying down the general principles and requirements of food law, establishing EFSA (General Food Law); consolidated version 01.01.2026 (CELEX 02002R0178-20260101) – European Parliament and Council, 2002. https://eur-lex.europa.eu/eli/reg/2002/178/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force (Cellar flag in_force=true). Art. 14(1): 'Food shall not be placed on the market if it is unsafe.' Establishes EFSA and the rapid alert system (RASFF). - Regulation (EU) 2017/625 on official controls (Official Controls Regulation); consolidated version 05.01.2025 – European Parliament and Council, 2017. https://eur-lex.europa.eu/eli/reg/2017/625/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Governs official controls on food and feed in Member States and on entry of goods from third countries; legal basis for third-country lists (Art. 127) and increased import controls. - Regulation (EC) No 396/2005 on maximum residue levels of pesticides in or on food and feed – European Parliament and Council, 2005. https://eur-lex.europa.eu/eli/reg/2005/396/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 18(1)(b): default MRL of 0,01 mg/kg for products for which no specific MRL is set; recital: MRLs set at the lower level of analytical determination where uses are not authorised. - Commission Regulation (EU) No 37/2010 on pharmacologically active substances and their classification regarding maximum residue limits in foodstuffs of animal origin; consolidated 16.08.2026 – European Commission, 2010. https://eur-lex.europa.eu/eli/reg/2010/37/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Lists allowed substances with MRLs and prohibited substances (Table 2) for food-producing animals. - Regulation (EU) 2019/6 on veterinary medicinal products; consolidated 28.01.2022 – European Parliament and Council, 2019. https://eur-lex.europa.eu/eli/reg/2019/6/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 107(1): antimicrobials 'shall not be applied routinely nor used to compensate for poor hygiene, inadequate animal husbandry'; Art. 107(2): not to be used 'for the purpose of promoting growth nor to increase yield'; Art. 107(3): prophylaxis only in exceptional cases, antibiotic prophylaxis limited to an individual animal; Art. 107(4): metaphylaxis only when risk of spread is high and no appropriate alternatives exist. Art. 105: a veterinary prescription for antimicrobials 'shall be valid for five days from the date of its issue'. Art. 118(1): growth-promotion and reserved-antimicrobial prohibitions extended to imports. - Council Directive 96/22/EC concerning the prohibition on the use in stockfarming of certain substances having a hormonal or thyrostatic action and of beta-agonists; consolidated 18.12.2008 – Council of the EU, 1996. https://eur-lex.europa.eu/eli/dir/1996/22/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 3: Member States prohibit administering listed substances to farm or aquaculture animals. Art. 4/5 allow narrowly defined therapeutic/zootechnical veterinary use by a veterinarian; Art. 4 text: 'young fish may be treated for the first three months for the purpose of sex inversion with veterinary medicinal products that have an androgenous action' (authorised products only). - Commission Regulation (EU) 2023/915 on maximum levels for certain contaminants in food (repealing Reg. 1881/2006); consolidated 19.08.2026 – European Commission, 2023. https://eur-lex.europa.eu/eli/reg/2023/915/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force (1881/2006 not in force since 2023-05-24). Values as read in Annex I: aflatoxin M1 in raw/heat-treated milk 0,050 µg/kg; groundnuts for direct consumption B1 2,0 / sum 4,0 µg/kg (8,0/15,0 before sorting); eggs (except goose) sum dioxins 2,5 pg WHO-TEQ/g fat, dioxins+dl-PCBs 5,0 pg/g fat, ndl-PCBs 40 ng/g fat; PFAS in eggs PFOS 1,0, PFOA 0,30, PFNA 0,70, PFHxS 0,30, sum of 4 PFAS 1,7 µg/kg; lead in fish muscle 0,30 mg/kg; cadmium in fish muscle (most species) 0,050 mg/kg; mercury in fish muscle (most species) 0,50 mg/kg; nitrate in fresh spinach 3 500 mg/kg, fresh lettuce 2 000–5 000 mg/kg depending on type/season/cover, rucola up to 7 000 mg/kg. - Commission Regulation (EC) No 2073/2005 on microbiological criteria for foodstuffs; consolidated 01.07.2026 – European Commission, 2005. https://eur-lex.europa.eu/eli/reg/2005/2073/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Food safety criterion 1.28: fresh poultry meat – Salmonella Typhimurium and S. Enteritidis 'Not detected in 25 g' (n=5, c=0). Process hygiene criteria for Salmonella/Campylobacter on poultry carcases (neck skin). Criteria for egg products and RTE foods containing raw egg. - Regulation (EC) No 2160/2003 on the control of salmonella and other specified food-borne zoonotic agents; consolidated 21.04.2021 – European Parliament and Council, 2003. https://eur-lex.europa.eu/eli/reg/2003/2160/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Obliges Member States to run national Salmonella control programmes in poultry populations with Union reduction targets. - Commission Regulation (EU) No 517/2011 – Union target for reduction of Salmonella serotypes in laying hens; and Commission Regulation (EU) No 200/2012 – Union target for S. Enteritidis and S. Typhimurium in broiler flocks – European Commission, 2011/2012. https://eur-lex.europa.eu/eli/reg/2011/517/oj ; https://eur-lex.europa.eu/eli/reg/2012/200/oj (Type: regulation; verified: yes; accessed 2026-10-25)
Both in force. Laying hens: reduction to '2 % or less of positive flocks of adult laying hens' (target serovars S. Enteritidis/Typhimurium). Broilers: maximum percentage of flocks positive for S. Enteritidis/Typhimurium 'equal to 1% or less'. - Regulation (EU) No 1169/2011 on the provision of food information to consumers; consolidated 01.04.2025 – European Parliament and Council, 2011. https://eur-lex.europa.eu/eli/reg/2011/1169/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Mandatory food information (ingredients, allergens, nutrition declaration, origin rules). EFSA's 2024 pesticide report cites it as part of the obligation to report country of origin. - Directive (EU) 2020/2184 on the quality of water intended for human consumption (recast) – European Parliament and Council, 2020. https://eur-lex.europa.eu/eli/dir/2020/2184/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. EU drinking water quality parameters, risk-based approach; transposed in Germany by TrinkwV 2023. - Trinkwasserverordnung (TrinkwV) vom 20. Juni 2023 (BGBl. 2023 I Nr. 159) – Bundesministerium für Gesundheit (Germany), 2023. https://www.gesetze-im-internet.de/trinkwv_2023/BJNR09F0B0023.html (Type: regulation; verified: yes; accessed 2026-10-25)
Transposes Directive (EU) 2020/2184. Values read: nitrate 50 mg/l (with nitrate/50 + nitrite/3 ≤ 1); pesticides 0,00010 mg/l per substance; 'Summe PFAS-20' 0,00010 mg/l applicable from 12 January 2026; 'Summe PFAS-4' 0,000020 mg/l applicable from 12 January 2028. - Commission Implementing Regulation (EU) 2019/1793 on the temporary increase of official controls and emergency measures governing the entry of certain goods from certain third countries; consolidated text 30.06.2026 – European Commission, 2019. https://eur-lex.europa.eu/eli/reg_impl/2019/1793/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Annex I (increased identity/physical checks) entries for Egypt (EG), hazard 'pesticide residues': sweet and other Capsicum peppers 30 %; oranges 10 %; sugar apple 30 %; vine leaves 50 %; mango 20 %; strawberries (fresh, chilled or frozen) 20 %. Annex II (special conditions incl. official certificate): Egypt groundnuts (peanuts), peanut butter and preparations, groundnut oilcake/flours – aflatoxins, 30 %. - Regulation (EC) No 1831/2003 on additives for use in animal nutrition; consolidated 27.03.2021 – European Parliament and Council, 2003. https://eur-lex.europa.eu/eli/reg/2003/1831/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. 'Antibiotics, other than coccidiostats or histomonostats, shall not be authorised as feed additives'; transitional Art. 11(2): such antibiotics 'may be marketed and used as feed additives only until 31 December 2005; as from 1 January 2006, those substances shall be deleted from the Register'. - Commission Delegated Regulation (EU) 2023/905 on the application of the prohibition of use of certain antimicrobial medicinal products in animals or products of animal origin exported from third countries into the Union – European Commission, 2023. https://eur-lex.europa.eu/eli/reg_del/2023/905/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 3: animals/products exported to the EU shall not have been administered antimicrobials for growth promotion/yield increase, nor antimicrobials reserved for humans (Implementing Reg. 2022/1255). Conditions apply 24 months after the implementing list act; per Implementing Reg. 2026/1189 this is 3 September 2026. - Commission Implementing Regulation (EU) 2026/1189 amending Implementing Regulation (EU) 2021/405 as regards the restrictions on the use of certain antimicrobial medicinal products (repealing Implementing Reg. 2024/2598) – European Commission, 2026. https://eur-lex.europa.eu/eli/reg_impl/2026/1189/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force; Art. 1 applies from 3 September 2026. New Annex XVIa of 2021/405 lists third countries with guarantees of compliance with Art. 3 of 2023/905. Egypt's row has an 'X' only in the column 'Casings' (no entry for bovine, poultry, aquaculture, milk, eggs, honey). Recital 17: Brazil's entries for poultry, aquaculture etc. deleted for lack of guarantees. - Commission Implementing Regulation (EU) 2021/405 laying down the lists of third countries authorised for entry into the Union of certain animals and goods intended for human consumption; consolidated 03.09.2026 – European Commission, 2021. https://eur-lex.europa.eu/eli/reg_impl/2021/405/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Annex -I (approved residue control plans): Egypt marked 'X' only for 'Casings' (no approved plan for bovine, poultry, aquaculture, milk, eggs, honey). Annex IX (fishery products): Egypt 'Only wild catch'. Annex XI: Egypt 'Only frogs' legs'. - Council Directive 1999/74/EC laying down minimum standards for the protection of laying hens; and Commission Delegated Regulation (EU) 2023/2465 on marketing standards for eggs – Council of the EU / European Commission, 1999/2023. https://eur-lex.europa.eu/eli/dir/1999/74/oj ; https://eur-lex.europa.eu/eli/reg_del/2023/2465/oj (Type: regulation; verified: yes; accessed 2026-10-25)
Both in force. 1999/74: rearing in unenriched cages 'prohibited with effect from 1 January 2012'. 2023/2465: eggs marked with a producer code identifying farming method and production site; meaning of the producer code must be explained on or inside the pack. - The 2024 European Union report on pesticide residues in food – EFSA, 2026. https://pubmed.ncbi.nlm.nih.gov/42095190/ (Type: monitoring_data; verified: yes; accessed 2026-10-25)
Abstract: EU-coordinated programme 9842 samples, 1.2 % non-compliant; national programmes 86,449 samples, 1.8 % non-compliant; increased import control programme 39,433 samples, 3.6 % non-compliant; 'the estimated dietary risk was found to be low for most of the EU subpopulation groups'. Full text (Europe PMC): EU MACP 97.6 % within legal limits; 46.6 % domestic, 29.3 % other reporting countries, 20.1 % third countries; a pesticide quantified in 14.1 % of 759 samples 'Most of the quantifications were in oranges ... coming from Egypt' (0.01–0.13 mg/kg, none non-compliant); imidacloprid findings in 'pomegranate from Peru and Egypt, potato from Egypt'. For authorised uses non-compliance shares were similar for EU and third-country origin ('very similar independently of the country of origin'). - The European Union One Health 2024 Zoonoses Report – EFSA and ECDC, 2025. https://pubmed.ncbi.nlm.nih.gov/41377167/ (Type: monitoring_data; verified: yes; accessed 2026-10-25)
Full text (Europe PMC PMC12686834): adult laying-hen flocks 2024 EU Salmonella flock prevalence 4.0 % (3.9 % 2023), target serovars 1.6 %; broiler flocks Salmonella 4.3 %, target serovars 0.29 %; 'Fourteen MSs and the United Kingdom (Northern Ireland) met all targets'; Salmonella in 'eggs and egg products' the agent/food pair of most concern; official FSC verification samples: 4.9 % positive at manufacturing vs 2.3 % at distribution. Travel-associated salmonellosis acquired outside the EU (n=5473): Türkiye 25.5 %, Egypt 11.5 % (628/5473). - EFSA news 'Veterinary drug residues in food: what's the latest in the EU?' (report on 2024 monitoring data; technical report doi 10.2903/sp.efsa.2026.EN-9913) – EFSA, 2026. https://www.efsa.europa.eu/en/news/veterinary-drug-residues-food-whats-latest-eu (Type: monitoring_data; verified: yes; accessed 2026-10-25)
News of 10 February 2026: 2024 data from EU MS plus Iceland and Norway; '0.13% (629 of 493,664 samples)' non-compliant (0.11 % previous year); risk-based production plan 0.16 %, randomised surveillance plan 0.22 %, risk-based third-country import plan 0.2 %. - European Sales and Use of Antimicrobials for Veterinary Medicine (ESUAvet) – Annual surveillance report for 2024 (EMA/CVMP/ESUAVET/376993/2025) – European Medicines Agency, 2025. https://www.ema.europa.eu/en/documents/report/european-sales-use-antimicrobials-veterinary-medicine-annual-surveillance-report-2024_en.pdf (Type: monitoring_data; verified: yes; accessed 2026-10-25)
2018 baseline 118.3 mg/PCU, 2030 target 59.2 mg/PCU (50 % reduction, Farm to Fork). 'In 2024, aggregated sales in the EU were 89.6 mg/PCU, a reduction of 24.3% compared to 2018.' - BVL Pressemitteilung 'Antibiotikaabgabe in der Tiermedizin weiter auf niedrigem Niveau' (data year 2025) – Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (BVL), 2026. https://www.bvl.bund.de/SharedDocs/Pressemitteilungen/05_tierarzneimittel/2026/PM_Antibiotika-Abgabemengen.html (Type: monitoring_data; verified: yes; accessed 2026-10-25)
Dated 06.10.2026: 562 t antibiotics dispensed in veterinary medicine in Germany in 2025 (−0.3 t vs 2024); 67 % lower than 2011 (1,706 t); colistin 31 t (2024) → 26 t (2025); fluoroquinolones +~18 % to 6.3 t. - BfR Stellungnahme 031/2024: Ergebnisse des Nationalen Rückstandskontrollplans und des Einfuhrüberwachungsplans 2022 – Bundesinstitut für Risikobewertung (BfR), 2024. https://bfr.bund.de/cm/343/ergebnisse-des-nationalen-rueckstandskontrollplans-und-des-einfuhrueberwachungsplans-2022.pdf (Type: official_report; verified: yes; accessed 2026-10-25)
NRKP 2022: 53.267 Planproben, 191 (0,36 %) non-compliant (2021: 0,32 %); EÜP 2022: 1.055 import samples, 2 (0,19 %) non-compliant. Group A (anabolic/unauthorised substances): 38.585 samples, 1 non-compliant. Dioxins/PCBs: 'nur eine von etwa 180 Eierproben' exceeded maximum levels. BfR: health impairment 'nicht zu erwarten' for most samples; some antibacterial residues could select less-susceptible bacteria. - Nationale Berichterstattung 'Pflanzenschutzmittelrückstände in Lebensmitteln' – Zusammenfassung der Ergebnisse des Jahres 2024 – BVL, 2026. https://www.bvl.bund.de/SharedDocs/Downloads/01_Lebensmittel/nbpsm/00_Berichte/NBPSMR_2024.pdf?__blob=publicationFile&v=2 (Type: monitoring_data; verified: yes; accessed 2026-10-25)
Dated 15 January 2026: 16.423 samples. Origin: 6.668 Germany, 4.368 other EU, 2.694 third countries, 2.629 unknown. MRL exceedances (surveillance sampling): Germany 1,0 %, other EU 1,5 %, third countries 6,7 % (2023: 8,5 %); Beanstandungen 0,4 % / 0,4 % / 4,3 %. No quantifiable residues: Germany 57,8 %, other EU 38,3 %, third countries 40,1 %. Egypt-specific: sweet potatoes from Egypt Beanstandungsquote 10,9 % (5 of 46 samples, mainly mepiquat); one mango sample from Egypt objected for four substances; vine leaves from Egypt listed as frequently conspicuous (hence in Reg. 2019/1793). - Bericht des BMG und des UBA an die Verbraucherinnen und Verbraucher über die Qualität von Wasser für den menschlichen Gebrauch (Trinkwasser) in Deutschland (2020–2022), Reihe Umwelt & Gesundheit 03/2025 – Bundesministerium für Gesundheit / Umweltbundesamt, 2025. https://www.umweltbundesamt.de/publikationen/bericht-des-bundesministeriums-fuer-gesundheit-des-5 (Type: official_report; verified: yes; accessed 2026-10-25)
Period 1.1.2020–31.12.2022; 2 507 large supply areas serving 74.1 million people (88.6 %) in 2022; 'Bei den meisten mikrobiologischen und chemischen Qualitätsparametern erfüllten über 99 % der untersuchten Proben' the TrinkwV requirements. - Risk to human health related to the presence of perfluoroalkyl substances in food – EFSA CONTAM Panel, 2020. https://pubmed.ncbi.nlm.nih.gov/32994824/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
TWI 4.4 ng/kg bw per week for sum of PFOA, PFNA, PFHxS, PFOS; 'Fish meat', 'Fruit and fruit products' and 'Eggs and egg products' contributed most to exposure; 'parts of the European population exceed this TWI, which is of concern.' - Risk for animal and human health related to the presence of dioxins and dioxin-like PCBs in feed and food – EFSA CONTAM Panel, 2018. https://pubmed.ncbi.nlm.nih.gov/32625737/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
TWI 2 pg TEQ/kg bw/week; mean and P95 intake of adolescents/adults/elderly 2.1–10.5 and 5.3–30.4 pg TEQ/kg bw/week, 'implying a considerable exceedance of the TWI'; PCDD/Fs and DL-PCBs transfer to milk and eggs. - National Food Safety Authority (NFSA) of Egypt – official website (Law No. 1 of 2017) – National Food Safety Authority, Egypt, 2017. https://www.nfsa.gov.eg/ (Type: official_report; verified: yes; accessed 2026-10-25)
Law No. 1 of 2017 establishing NFSA published in the Official Gazette on 10 January 2017; NFSA created as a single body because more than 17 bodies under several ministries previously shared food-safety duties. - NFSA legislation index (القوانين والتشريعات والقرارات الغذائية) – National Food Safety Authority, Egypt, 2017-2023. https://nfsa.gov.eg/ar-eg/SitePages/Index/%D8%A7%D9%84%D9%82%D9%88%D8%A7%D9%86%D9%8A%D9%86%20%D9%88%D8%A7%D9%84%D8%AA%D8%B4%D8%B1%D9%8A%D8%B9%D8%A7%D8%AA%20%D9%88%D8%A7%D9%84%D9%82%D8%B1%D8%A7%D8%B1%D8%A7%D8%AA%20%D8%A7%D9%84%D8%BA%D8%B0%D8%A7%D8%A6%D9%8A%D8%A92 (Type: regulation; verified: yes; accessed 2026-10-25)
Lists e.g.: Executive regulations (Cabinet Decision 412/2019); Decision 13/2020 binding technical rules on maximum limits of veterinary drug residues in food; Decision 6/2021 on permitted pesticide residues; Decision 6/2022 on maximum limits of chemical contaminants; Decision 1/2021 microbiological criteria; Decision 4/2020 food additives; Decision 11/2020 food-safety requirements in food establishments; Decision 16/2022 traceability (amended 3/2023); Decision 1/2022 technical requirements for fish exports to the EU; Decision 7/2020 risk-based import control. - DG SANTE audit CT-2025-0205, Egypt, October 2025: Pesticides (controls of pesticide residues in food of plant origin intended for export to the EU); published 26-02-2026 – European Commission, DG SANTE, 2026. https://ec.europa.eu/food/audits-analysis/audit-report/details/4976 (Type: audit_report; verified: yes; accessed 2026-10-25)
Read in full (PDF download 17197). Scope: oranges, sugar apples, peppers, vine leaves, strawberries. 2023 EFSA data: Egypt-origin food non-compliance 4.61 %, MRL exceedance 8.14 %, vs 3.4 % and 6.2 % average for non-EU exporters. Orange non-compliance at EU import fell from 15 % (2nd half 2022) to 1.41 % (1st half 2025); peppers ~8 % (4.59–13.16 %); all sampled vine-leaf consignments rejected. 3 408 PPP formulations on 296 active substances registered in Egypt; 118 substances in Egyptian-registered PPPs not approved in the EU; chlorpyrifos banned in Egypt June 2022; Egyptian MRL list referenced primarily to Codex, some higher than EU. National monitoring 'shows relatively low non-compliance rates ... But since the benchmarks for compliance are different, the results are not fully comparable.' Export controls (registration, traceability, pre-export sampling) are additional programmes for the export chain; frozen/processed products can come from non-registered growers; 'From January 2026 the mandate will include the domestic market' (NFSA). 'the potential trade of illegal PPPs is still a matter of concern'. - DG SANTE audit 2024-8055, Egypt, November 2024: Food of non-animal origin intended for export to the EU (microbiological risks); published 22-04-2025 – European Commission, DG SANTE, 2025. https://ec.europa.eu/food/audits-analysis/audit-report/details/4863 (Type: audit_report; verified: yes; accessed 2026-10-25)
Executive summary: official control system for export FNAO covers farms, processors, exporters; GAP inspection/certification for nine main commodities incl. strawberries; for herbs and spices farm controls generally limited to random inspections; post-harvest system 'well-established, comprehensive and efficient'; 'The report contains no recommendations to Egypt.' - DG SANTE audit 2024-8106, Egypt, May–June 2024: Fishery products intended for export to the EU; published 23-09-2024 – European Commission, DG SANTE, 2024. https://ec.europa.eu/food/audits-analysis/audit-report/details/4800 (Type: audit_report; verified: yes; accessed 2026-10-25)
After the 2021 audit Egypt withdrew all establishments from the EU list and suspended certification; 'no exports of fishery products have taken place' since 2021; no RASFF notifications on Egyptian fishery products since then. 2023 sampling plan: heavy metals 22 samples (all compliant), dioxins/PCBs 14 samples; PFAS 'not subject to control' at the time (not in line with Reg. 2019/627); histamine reference method not used. Deficiencies weaken guarantees. - DG SANTE audit 2022-7391, Egypt, September 2022: Contaminants (aflatoxin in peanuts for export to the EU); published 17-02-2023 – European Commission, DG SANTE, 2023. https://ec.europa.eu/food/audits-analysis/audit-report/details/4574 (Type: audit_report; verified: yes; accessed 2026-10-25)
Egypt has the necessary legal/organisational framework; accredited laboratories perform well; but official controls at primary producers do not verify GAP for aflatoxin prevention; packing houses allowed to export even if not complying with all certificate conditions ('raises concerns about the reliability of the certification system'); increase in RASFF notifications possibly related to strongly increased export volume; a small number of operators account for most rejections. - DG SANTE audit 2021-7328, Egypt, May–June 2021 (remote): Fishery products; published 04-01-2022 – European Commission, DG SANTE, 2022. https://ec.europa.eu/food/audits-analysis/audit-report/details/4439 (Type: audit_report; verified: yes; accessed 2026-10-25)
Remote audit; 'important shortcomings in virtually all of the areas relevant to this audit' (legislation, written procedures, training, controls of primary production, landing sites, additives). - DG SANTE audit 2019-6697, Egypt, Jan–Feb 2019: Microbiological contamination in food of non-animal origin; published 03-07-2019 – European Commission, DG SANTE, 2019. https://ec.europa.eu/food/audits-analysis/audit-report/details/4148 (Type: audit_report; verified: yes; accessed 2026-10-25)
Control system for microbiological risks in export FNAO 'in a phase of transition and reforms'; hygiene practices at visited farms/exporters in line with EU requirements; background cites the 2011 STEC O104:H4 outbreak in Germany (about 4,000 ill, more than 56 deaths). - DG SANTE audit 2011-6265, Egypt, August 2011: trace back the source of infection of the recent E. coli O104:H4 strain outbreaks in the EU (detail page) – European Commission, DG SANTE, 2011. https://ec.europa.eu/food/audits-analysis/audit-report/details/2769 (Type: audit_report; verified: yes; accessed 2026-10-25)
Detail page confirms an EU audit in Egypt in August 2011 to trace back the source of the O104:H4 outbreaks (published 26-10-2011). - RASFF Window – public notification search (consolidated), queried for notifications with 'Egypt' in the subject and origin country EG, validation years 2023–2025 – European Commission (RASFF), 2026. https://webgate.ec.europa.eu/rasff-window/screen/search (Type: database; verified: yes; accessed 2026-10-25)
Own query of the public backend (POST .../rasff-window/backend/public/notification/search/consolidated/) on 2026-10-25: 2023: 113 notifications; 2024: 153; 2025: 119. Keyword-based classification of subjects (approximate): pesticide residues 73 / 70 / 82; aflatoxins 15 / 47 / 14; microbiological 11 / 13 / 4; other (additives, pyrrolizidine alkaloids, foreign bodies, certificates etc.) 14 / 23 / 19. Product categories 2023–2025: fruits and vegetables 217, nuts/nut products/seeds 86, herbs and spices 41; only one animal-product notification (lead in salted beef casings, 2023); none for poultry, eggs, milk or fish. - Pesticide Residues in Egyptian Strawberries Inspected at the EU Border (2021-2024) – Sikorska-Zimny KM et al., 2025. https://pubmed.ncbi.nlm.nih.gov/41471804/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Egyptian strawberries inspected at the Polish border: detection rates rose from 63 % (2022) to over 90 % (2023–2024); some samples with no residues each year; eleven MRL exceedances; up to eleven pesticides in a single sample. - Pesticide Residues in Vegetables and Fruits from Farmer Markets and Associated Dietary Risks – El-Sheikh EA et al., 2022. https://pubmed.ncbi.nlm.nih.gov/36432173/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Farmers' markets, Sharkia Governorate, Egypt; LC-MS/MS and GC-MS/MS; 40 pesticides detected; 35 (40.7 %) of 86 residues detected in vegetables and 35 (38.9 %) of 90 residues in fruits exceeded MRLs; acute/chronic risk flagged for lambda-cyhalothrin (spinach), fipronil (zucchini), dimethoate (kaki), omethoate (strawberry). - Assessment of antibiotic residues in chicken meat – Kamouh HM et al., 2024. https://pubmed.ncbi.nlm.nih.gov/38633178/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
100 chicken meat samples (breast, thigh, gizzard, liver; 25 each) retailed in Egypt; microbial inhibition assay + HPLC; 23 % positive for oxytetracycline, 21 % gentamicin, 17 % ciprofloxacin; boiling 30 min reduced residues by 88.2 %, 95.2 %, 31.3 %. - Health risk assessment of enrofloxacin, oxytetracycline, and sulfadimidine residues in broiler chicken carcasses marketed in Mit Ghamr, Egypt – Noah SM et al., 2026. https://pubmed.ncbi.nlm.nih.gov/42527435/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
180 tissue samples (60 breast, 60 thigh, 60 liver) from poultry shops; HPLC; detected enrofloxacin 51.67 %, oxytetracycline 71.67 %, sulfadimidine 16.67 %; of positives 54.84 %, 55.81 %, 70 % exceeded MRLs; hazard quotients 0.0002–0.050 – 'no significant health risk for either adults or children'. - Antibiotic residues correlate with antibiotic resistance of Salmonella typhimurium isolated from edible chicken meat – Ali HR et al., 2025. https://pubmed.ncbi.nlm.nih.gov/40307359/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Chilled chicken meat, Fayoum province: 22.2 % of meat/liver contaminated with S. Typhimurium, all isolates drug-resistant; residues of tylosin, chloramphenicol, oxytetracycline (and 4-epi-OTC) detected; isolates from samples above MRL resistant to the same antibiotic. - Antimicrobial use in animal farms in Egypt: rates, patterns, and determinants – ElSayed N et al., 2025. https://pubmed.ncbi.nlm.nih.gov/39828782/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Survey, 111 of 150 farms (74 %) in 15 governorates: all used antimicrobials; 65 % reported non-therapeutic use; penicillins 81 %, macrolides 78 %, tetracyclines 72 %; half used colistin, 55 % of those non-therapeutically; non-therapeutic use had no impact on feed conversion ratio; authors: 'Egyptian guidelines for AMU in livestock are urgently needed'. - Hormonal residues in chicken and cattle meat: A risk threat the present and future consumer health – Kamaly HF et al., 2023. https://pubmed.ncbi.nlm.nih.gov/37956705/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
92 chicken and 56 cattle meat samples, Assiut City 2022; ELISA for estradiol, progesterone, testosterone; authors report estimated intake of estradiol exceeding ADI in nearly all samples and HI >1; 'in Egypt ... no safe limits have been set till now'. - Antimicrobial Resistance of Salmonella enteritidis and Salmonella typhimurium Isolated from Laying Hens, Table Eggs, and Humans ... – Abou Elez RMM et al., 2021. https://pubmed.ncbi.nlm.nih.gov/34944331/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Sharkia Governorate: Salmonella in 19.3 % of tested samples; laying hens 33.1 %; S. Enteritidis 5.8 %, S. Typhimurium 2.8 %; MDR 83.8 % of isolates. - Prevalence of Non-typhoidal Salmonellae in the Retail Chicken Meat in Alexandria, Egypt – Barac D et al., 2024. https://pubmed.ncbi.nlm.nih.gov/39678989/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
60 raw chicken carcass samples from six markets: 33.3 % Salmonella; liver and gizzard 60 %; one supermarket showed no Salmonella; authors attribute contamination largely to market handling. - Ecological prevalence, genetic diversity, and multidrug resistance of Salmonella enteritidis recovered from broiler and layer chicken farms – Elsayed MM et al., 2024. https://pubmed.ncbi.nlm.nih.gov/38215504/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Salmonella in 20 (17 %) of 117 samples from small-scale broiler flocks; isolates MDR. - A Public Health Insight into Salmonella in Poultry in Africa: A Review of the Past Decade: 2010-2020 – Ramtahal MA et al., 2022. https://pubmed.ncbi.nlm.nih.gov/35696336/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
PRISMA-guided narrative review; MDR Salmonella prevalence ranged from 12.1 % (Zimbabwe) to 100 % in Egypt, Ethiopia, Nigeria, Senegal, South Africa; AMU described in only 11.5 % of studies. - Dietary intake of dioxins and dioxin-like PCBs, due to the consumption of dairy products, fish/seafood and meat from Ismailia city, Egypt – Loutfy N et al., 2006. https://pubmed.ncbi.nlm.nih.gov/16806402/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
HRGC/HRMS; intake 6.04–6.68 pg WHO-TEQ/kg bw/day incl. DL-PCBs from dairy, fish/seafood, meat; dairy (mainly cheese) contributed 89 % of PCDD/F intake; 'higher than the maximum WHO TDI of 4 pg TEQ/kg bw/day'. Eggs were not measured (EU data used for estimation). - Aflatoxin M1 in Africa: Exposure Assessment, Regulations, and Prevention Strategies - A Review – Zinedine A et al., 2021. https://pubmed.ncbi.nlm.nih.gov/34611756/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Egypt, Kenya and Nigeria have the most AFM1 investigations in Africa; some reports showed 100 % of samples exceeding the EU limit (50 ng/kg), e.g. in Egypt; AFM1 up to 8,000 ng/kg reported in milk from Egypt. - The prevalence of aflatoxin M1 in milk of Middle East region: A systematic review, meta-analysis and probabilistic health risk assessment – Rahmani J et al., 2018. https://pubmed.ncbi.nlm.nih.gov/29902498/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
49 articles, 7484 data (1995–2017); raw-milk AFM1 prevalence Egypt 38 %; country ranking for raw-milk concentration Syria > Turkey > Iran > Egypt > Lebanon > Palestine; hazard index for Egyptian raw milk 0.18 (adults), 0.84 (children). - A Comprehensive Systematic Review and Meta-Analysis on the Prevalence of Aflatoxin M1 in Dairy Products in Selected Middle East Countries – Arghavan B et al., 2025. https://pubmed.ncbi.nlm.nih.gov/39840829/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
193 studies, 297,530 samples (to Aug 2023); AFM1 in 87 % of dairy products overall; ranking by prevalence Iran > Jordan > Turkey > Kuwait > Lebanon > Syria > Egypt > Cyprus > UAE. - Assessment of some chemical residues in Egyptian raw milk and traditional cheese – Ibrahim AA et al., 2024. https://pubmed.ncbi.nlm.nih.gov/38549581/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Raw milk: elevated lead in 46 % and cadmium in 4 % of samples; p,p'-DDE in 45 % of raw milk and 29 % of Ras cheese; AFM1 exceeded acceptable limits in only 7 % of milk and 2.9 % of Ras cheese samples (ELISA). - Heavy Metal Residues in Some Fishes from Manzala Lake, Egypt, and Their Health-Risk Assessment – Sallam KI et al., 2019. https://pubmed.ncbi.nlm.nih.gov/31242536/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
600 fish (200 each Nile tilapia, flathead grey mullet, African catfish); mean Pb 0.704, 0.635, 0.64 µg/g; Hg 0.045, 0.0145, 0.017 µg/g; Cd 0.024, 0.006, 0.020 µg/g wet weight; health-risk indices suggest potential hazard. - Carcinogenic and non-carcinogenic health risks associated with the consumption of fishes contaminated with heavy metals from Manzala Lake, Egypt – Abd-Elghany SM et al., 2024. https://pubmed.ncbi.nlm.nih.gov/38657491/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Mean Pb 1.01, 0.87, 0.95 mg/kg; Cd 0.05, 0.12, 0.06 mg/kg; Hg 0.01, 0.15, 0.29 mg/kg; As 3.16–4.74 mg/kg (tilapia, mullet, catfish); 'levels ... exceeded their maximum permissible limits in most samples'; THQ >1 for Hg and Cd. - Exposure assessment of pesticide residues, heavy metals, and veterinary drugs through consumption of Egyptian fish samples – Ghuniem MM et al., 2024. https://pubmed.ncbi.nlm.nih.gov/39309634/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
48 fish samples, Kafr El-Sheikh governorate; LC-MS/MS, ICP-MS, GC-MS; mean Cd 0.02, Hg 0.051, Pb 0.031 mg/kg; 'All levels of cadmium, mercury, and lead ... significantly lower than the maximum permissible limits set by Egyptian and European standards'; antibiotics and pesticide residues not detected in any sample. - One health risk assessment of heavy-metal contamination in Nile tilapia (Oreochromis niloticus) from contrasting aquaculture systems in Egypt – Farahat Abdelmawla M et al., 2026. https://pubmed.ncbi.nlm.nih.gov/42662802/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Aquaculture relying on agricultural drainage water; Kitchener Drain water Pb, Cd, Cr, Hg exceeded WHO limits 5–54-fold; liver Pb up to 4.90 mg/kg; 'Muscle remained within FAO/WHO limits'; all THQ <1; narrow Pb margin (0.28 vs 0.3 mg/kg). - Systems-thinking approach to identify and assess feasibility of potential interventions to reduce antibiotic use in tilapia farming in Egypt – Desbois AP et al., 2021. https://pubmed.ncbi.nlm.nih.gov/34276104/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Full text (Europe PMC PMC8164158): 'Egypt produces more fish from aquaculture than the rest of Africa combined ... 1.56 million tonnes in 2018 (FAO, 2020)'; grow-out ponds supplied mainly by agricultural drainage water (ca. 70 % of farms), Nile ca. 20 %, groundwater ca. 10 %; antibiotics enter via medicated feed/pond water and via drainage water; ponds stocked with mono-sex fry. - World Bank World Development Indicators API – SH.H2O.SMDW.ZS, SH.H2O.BASW.ZS, SH.STA.SMSS.ZS (source: WHO/UNICEF JMP) – World Bank / WHO-UNICEF Joint Monitoring Programme, 2026. https://api.worldbank.org/v2/country/EGY;DEU/indicator/SH.H2O.SMDW.ZS?format=json (Type: database; verified: yes; accessed 2026-10-25)
Safely managed drinking water 2024: Egypt 78.94 %, Germany 99.92 %; at least basic drinking water 2024: Egypt 97.30 %, Germany 100 %; safely managed sanitation 2024: Egypt 57.34 %. - Prevalence of glucose-6-phosphate dehydrogenase deficiency in neonates in Egypt – Elella SA et al., 2017. https://pubmed.ncbi.nlm.nih.gov/28988250/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Full text (Europe PMC PMC6074198): infants born 2015 at a university hospital screened by quantitative fluorometric assay; G6PD deficiency in 119 (4.3 %) newborns; 6.2 % (91/1453) of males and 2.1 % (28/1329) of females. - Prevalence of and mothers' knowledge, attitude and practice towards glucose-6-phosphate dehydrogenase deficiency among neonates with jaundice: a cross-sectional study – Kasemy ZA et al., 2020. https://pubmed.ncbi.nlm.nih.gov/32102818/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
487 Egyptian neonates with indirect hyperbilirubinaemia (2018–2019): G6PD deficiency 10.10 %; risk factors male sex, family history, consanguinity. - The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis – Nkhoma ET et al., 2009. https://pubmed.ncbi.nlm.nih.gov/19233695/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
~400 million affected worldwide; 280 prevalence estimates from 88 countries; highest prevalence in sub-Saharan Africa; high heterogeneity largely due to differing assessment methods. - [Increase in genetically determined anemia as a result of migration in Germany] – Zur B et al., 2016. https://pubmed.ncbi.nlm.nih.gov/26899228/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Haemoglobinopathies and G6PD deficiency 'are no longer rare diseases in Germany' because of migration from endemic regions where prevalence of 40 % and higher has been found. - Favism: Clinical Features at Different Ages – Beretta A et al., 2023. https://pubmed.ncbi.nlm.nih.gov/36678214/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Favism = haemolysis after fava-bean ingestion in G6PD-deficient individuals; wide inter-/intra-individual variability; most severe in youngest children and pregnant women; deaths reported in infants. - Analysis of Reported Aflatoxin Levels in EU's Rapid Alert System for Food and Feed (RASFF) Notifications – Kow R et al., 2025. https://pubmed.ncbi.nlm.nih.gov/41008222/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
RASFF aflatoxin notifications 2010–2023: peanuts 34.4 %, pistachios 17.3 %, figs 12.5 % of notifications; country-specific patterns. - German outbreak of Escherichia coli O104:H4 associated with sprouts – Buchholz U et al., 2011. https://pubmed.ncbi.nlm.nih.gov/22029753/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
Sprouts identified as most likely vehicle (restaurant cohort RR 14.2; sprout consumption explained 100 % of cases); trace-back to producer A; outbreak strain not found on seeds of implicated lot. - Outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in Germany causes a paradigm shift ... – Beutin L et al., 2012. https://pubmed.ncbi.nlm.nih.gov/22289607/ (Type: peer_reviewed; verified: yes; accessed 2026-10-25)
3,842 cases; 'Epidemiological investigations revealed fenugreek seeds as the source of entry ... however, microbiological analysis of seeds for this pathogen produced negative results.' - Digitale-Dienste-Gesetz (DDG) vom 6. Mai 2024 (BGBl. 2024 I Nr. 149), § 5 Allgemeine Informationspflichten; § 7 Beschränkte Verantwortlichkeit – Bundesrepublik Deutschland, 2024. https://www.gesetze-im-internet.de/ddg/__5.html ; https://www.gesetze-im-internet.de/ddg/__7.html (Type: regulation; verified: yes; accessed 2026-10-25)
§ 5(1): providers of 'geschäftsmäßige, in der Regel gegen Entgelt angebotene digitale Dienste' must keep available name and address, rapid electronic contact incl. e-mail, register data, VAT ID etc., 'leicht erkennbar, unmittelbar erreichbar ... ständig verfügbar'. § 7(1): Articles 4–8 of Regulation (EU) 2022/2065 apply to all service providers. Fassung last amended by Art. 1 G v. 12.5.2026. - Leitfaden zur Impressumspflicht im Internet (2024) – Niedersächsische Landesmedienanstalt (NLM), 2024. https://www.nlm.de/fileadmin/dateien/pdf/leitfaden_impressumspflicht_2024.pdf (Type: official_report; verified: yes; accessed 2026-10-25)
Impressum duty arises from § 18 MStV and § 5 DDG; journalistic-editorial offers must additionally name a 'Verantwortlicher' (name, address; permanent residence in Germany, full legal capacity etc.) under § 18 Abs. 2 MStV; other telemedia not exclusively personal/family purposes need a simple Impressum under § 18 Abs. 1 MStV (name, ladungsfähige Anschrift); purely private use 'sehr eng ausgelegt', in doubt an Impressum is recommended; reachable within max. two clicks; fines up to 50.000 EUR (§ 115 MStV / § 33 DDG). - Regulation (EU) 2016/679 (General Data Protection Regulation) – European Parliament and Council, 2016. https://eur-lex.europa.eu/eli/reg/2016/679/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Art. 6(1)(f) (text read): processing lawful where 'necessary for the purposes of the legitimate interests pursued by the controller or by a third party, except where such interests are overridden by the interests or fundamental rights and freedoms of the data subject'; Art. 13: information to be provided where data are collected from the data subject. Relevant for server logs containing IP addresses. - Telekommunikation-Digitale-Dienste-Datenschutz-Gesetz (TDDDG, formerly TTDSG) § 25 Schutz der Privatsphäre bei Endeinrichtungen – Bundesrepublik Deutschland, 2021/2024. https://www.gesetze-im-internet.de/ttdsg/__25.html (Type: regulation; verified: yes; accessed 2026-10-25)
§ 25(1): storing/accessing information in the end user's terminal equipment only with consent; § 25(2) Nr. 2: no consent needed if 'unbedingt erforderlich' to provide a digital service explicitly requested by the user. - Urheberrechtsgesetz (UrhG) § 51 Zitate; § 62 Änderungsverbot; § 63 Quellenangabe – Bundesrepublik Deutschland, 1965 (current). https://www.gesetze-im-internet.de/urhg/__51.html ; https://www.gesetze-im-internet.de/urhg/__62.html ; https://www.gesetze-im-internet.de/urhg/__63.html (Type: regulation; verified: yes; accessed 2026-10-25)
§ 51: quotation of a published work permitted 'sofern die Nutzung in ihrem Umfang durch den besonderen Zweck gerechtfertigt ist', esp. passages in an independent work. § 62(1): no changes; § 62(2): translations and excerpts allowed where the purpose requires. § 63(1): 'ist stets die Quelle deutlich anzugeben'. - UrhG § 44b Text und Data Mining; Directive (EU) 2019/790 Art. 4 – Bundesrepublik Deutschland / European Union, 2019/2021. https://www.gesetze-im-internet.de/urhg/__44b.html ; https://eur-lex.europa.eu/eli/dir/2019/790/oj (Type: regulation; verified: yes; accessed 2026-10-25)
§ 44b(3): TDM uses only allowed if the rightholder has not reserved them; a reservation for online works is effective only if machine-readable. Dir. 2019/790 Art. 4(3) equivalent. - eltayebat.com robots.txt (Content-Signal declarations) – Operator of eltayebat.com (Cloudflare-managed content block), 2026. https://eltayebat.com/robots.txt (Type: database; verified: yes; accessed 2026-10-25)
'Content-Signal: search=yes,ai-train=no,use=reference'; states restrictions are 'EXPRESS RESERVATIONS OF RIGHTS UNDER ARTICLE 4 OF ... DIRECTIVE 2019/790'; disallows training crawlers incl. ClaudeBot, GPTBot, Google-Extended, CCBot. - eltayebat.com 'About the archive' page (حول الأرشيف) – Operator of eltayebat.com, 2026. https://eltayebat.com/about/ (Type: database; verified: yes; accessed 2026-10-25)
Arabic text: 'حقوق النشر الحقوق الأدبية للراحل ولورثته. الأرشيف غير ربحي ولا يحتوي إعلانات. أرشيف تعليمي يحفظ محتوى الراحل د. ضياء العوضي بإذن من الورثة. لا يتحمل الأرشيف مسؤولية المحتوى الطبي.' (moral/copyright rights belong to the deceased and his heirs; non-profit, no ads; with permission of the heirs; no responsibility for medical content). - Heilmittelwerbegesetz (HWG) § 1 Anwendungsbereich – Bundesrepublik Deutschland, 1965 (current). https://www.gesetze-im-internet.de/heilmwerbg/__1.html (Type: regulation; verified: yes; accessed 2026-10-25)
§ 1(1): applies to 'Werbung' for medicinal products, medical devices, and other means/procedures/treatments where the advertising statement relates to recognising, eliminating or alleviating diseases. - Regulation (EU) 2022/2065 (Digital Services Act) – European Parliament and Council, 2022. https://eur-lex.europa.eu/eli/reg/2022/2065/oj (Type: regulation; verified: yes; accessed 2026-10-25)
In force. Arts. 4–8: liability exemptions for intermediary services (mere conduit, caching, hosting); referenced by § 7 DDG.