Randomised controlled trialindependent cross-checkabstract checked★ key study I-SUP-106 in-depth review
Daily multivitamin in older adults (COSMOS trial)
Multivitamins in the prevention of cancer and cardiovascular disease: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial.
Overview
Sesso HD et al.. Am J Clin Nutr 2022 · PMID 35294969 · DOI 10.1093/ajcn/nqac056
Over 3.6 years a daily multivitamin neither reduced nor increased cancer, heart disease or deaths.
Does the study support the specific claim? Partly · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
To test whether a daily multivitamin prevents cancer and heart disease.
- How was the study done?
Randomised placebo-controlled trial.
- How many people, animals or samples were studied?
21,442 older US adults.
- What was actually found?
No effect on total cancer, CVD or deaths; possible fewer lung cancers (secondary).
- How large was the observed effect?
Cancer HR 0.97 (0.86-1.09); death HR 0.93 (0.81-1.08).
- What do the results mean in everyday life?
Multivitamins do not prevent major diseases in well-fed older people, and did not cause harm.
- What are the study's limitations?
Short follow-up.
- What does it say about Elawady's specific claim?
- Do the results apply to Germany and Europe?
Applicable.
- What can explicitly not be concluded from this study?
Cannot exclude small long-term effects.
Scientific in-depth review
1. Full reference
- Authors
- Sesso HD et al.
- Journal
- Am J Clin Nutr
- Year
- 2022
- Identifier
- PMID 35294969 DOI 10.1093/ajcn/nqac056 · PMC9170475
- Verification
- verified – PubMed efetch 2026-10-26; Crossref works API 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
No COI statement in PubMed record; funding listed: NEI NIH HHS, NHLBI NIH HHS, NIA NIH HHS, NIH HHS, WHI NIH HHS
2. Research question
Does a daily multivitamin-multimineral (MVM) supplement reduce invasive cancer and cardiovascular disease in older adults?
3. Study design and population
- Study design
- Randomised controlled trial – Randomised, double-blind, placebo-controlled 2x2 factorial trial (COSMOS, multivitamin arm)
- Population
Older US adults (women >=65, men >=60) without major CVD or recent cancer
- Country
USA
- Period
Intervention June 2015 - December 2020; median follow-up 3.6 years
- Sample size
21,442 (12,666 women, 8,776 men)
- Inclusion and exclusion criteria
Free of major CVD and recently diagnosed cancer
4. Methods and endpoints
- Exposure / intervention
Daily multivitamin-multimineral
- Comparator
Placebo
- Endpoints
Primary: total invasive cancer; secondary: site-specific cancers, CVD, all-cause mortality
- Statistical methods
Cox proportional hazards (intention to treat)
5. Actual results
- Results
Invasive cancer 518 (MVM) vs 535 (placebo), HR 0.97 (0.86-1.09), P=0.57; breast cancer HR 1.06 (0.79-1.42); colorectal HR 1.30 (0.80-2.12); lung cancer HR 0.62 (0.42-0.92) (secondary); composite CVD 429 vs 437, HR 0.98 (0.86-1.12); all-cause mortality HR 0.93 (0.81-1.08). No safety concerns.
- Absolute risks
Cancer about 4.8% vs 5.0% over 3.6 years (approximate, equal arms assumed; stats/C-SUP-06_cosmos.py)
- Authors' conclusion
A daily MVM did not significantly reduce total invasive cancer among older adults.
6. Strengths
- Large placebo-controlled RCT
- Hard outcomes
- Recent
7. Weaknesses
- Median follow-up only 3.6 years
- Older, mostly well-nourished US population
- Multiple secondary outcomes (lung cancer finding may be chance)
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Double-blind placebo-controlled; simplified judgement from abstract.
9. Assessment of the statistical interpretation
Upper confidence bound for mortality (1.08) argues against a large harm; lung-cancer HR 0.62 is a secondary finding among many.
10. Relevance to the specific claim
Adds a large modern RCT showing no benefit and no harm of a standard multivitamin for cancer, CVD and mortality.
11. Independent contrary findings
Secondary lung-cancer reduction; PHS II found a small cancer reduction.
12. Transferability to Germany and Europe
Applicable to well-nourished older adults in Europe.
13. Overall methodological judgement
Supports 'no benefit for prevention' (C-SUP-01) and contradicts 'multivitamins increase mortality' (C-SUP-06).
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | low |
| Precision of results | moderate |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Longer-term effects; effects in poorly nourished populations.
15. Linked fact checks
- When popular oral supplements (calcium, beta-carotene, vitamin E, omega-3, multivitamins, glucosamine, selenium, vitamin A) were tested in large long-term placebo-controlled trials, most failed to deliver the promised prevention of disease. – Studies supporting the claim
- Multivitamins, iron, folic acid, B6, magnesium, zinc and copper supplements increase mortality, and folic acid (with B12) increases cancer. – Studies contradicting or limiting the claim