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Long-term multivitamin supplementation and cognitive function in men: a randomized trial
Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, Manson JE, Glynn RJ et al.. Annals of internal medicine, 2013-12-01
Topic: Risk, prevention and care in population studies
Background Despite widespread use of multivitamin supplements, their effect on cognitive health-a critical issue with aging-remains inconclusive. To date, no long-term clinical trials have studied multivitamin use and cognitive decline in older persons. Objective To evaluate whether long-term multivitamin supplementation affects cognitive health in later life. Design Randomized, double-blind, placebo-controlled trial of a multivitamin from 1997 to 1 June 2011. The cognitive function substudy began in 1998. Up to 4 repeated cognitive assessments by telephone interview were completed over 12 years. (ClinicalTrials.gov: NCT00270647) SETTING: The Physicians' Health Study II. Patients 5947 male physicians aged 65 years or older. Intervention Daily multivitamin or placebo. Measurements A global composite score averaging 5 tests of global cognition, verbal memory, and category fluency. The secondary end point was a verbal memory score combining 4 tests of verbal memory, which is a strong predictor of Alzheimer disease. Results No difference was found in mean cognitive change over time between the multivitamin and placebo groups or in the mean level of cognition at any of the 4 assessments. Specifically, for the global composite score, the mean difference in cognitive change over follow-up was -0.01 SU (95% CI, -0.04 to 0.02 SU) when treatment was compared with placebo. Similarly, cognitive performance did not differ between the multivitamin and placebo groups on the secondary outcome, verbal memory (mean difference in cognitive change over follow-up, -0.005 SU [CI, -0.04 to 0.03 SU]). Limitation Doses of vitamins may be too low or the population may be too well-nourished to benefit from a multivitamin. Conclusion In male physicians aged 65 years or older, long-term use of a daily multivitamin did not provide cognitive benefits. Primary funding source National Institutes of Health, BASF, Pfizer, and DSM Nutritional Products.
Key findings
- Results No difference was found in mean cognitive change over time between the multivitamin and placebo groups or in the mean level of cognition at any of the 4 assessments.
- Specifically, for the global composite score, the mean difference in cognitive change over follow-up was -0.01 SU (95% CI, -0.04 to 0.02 SU) when treatment was compared with placebo.
Why it matters
In this randomized trial of 5,947 male physicians aged 65 or older followed for up to 12 years, long-term multivitamin supplementation showed no difference from placebo in mean cognitive change over time or in mean cognition at any of the four assessments. The result was null for both the global composite score and the verbal memory score.
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Study details
- Evidence strengthHigh
How this study scored 69/100
Published in a leading specialty journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of internal medicine) |
| Journal's citation record | 4 / 4 | Annals of Internal Medicine: journal h-index 648 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 109 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.3 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 4 / 6 | Cited 10.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Howard D. Sesso: h-index 103 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24490265) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 100 | — |
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Read the original
- DOI: 10.7326/0003-4819-159-12-201312170-00006
- PubMed: 24490265
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Grodstein, F., O'Brien, J., Kang, J. H., Dushkes, R., Cook, N. R., Okereke, O., et al. (2013). Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Annals of internal medicine. https://doi.org/10.7326/0003-4819-159-12-201312170-00006
Vancouver
Grodstein F, O'Brien J, Kang JH, Dushkes R, Cook NR, Okereke O, et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Annals of internal medicine. 2013. doi:10.7326/0003-4819-159-12-201312170-00006. PMID: 24490265.
BibTeX
@article{grodstein2013-24490265,
author = {Grodstein, F. and O'Brien, J. and Kang, J. H. and Dushkes, R. and Cook, N. R. and Okereke, O. and Manson, J. E. and Glynn, R. J. and others},
title = {{Long-term multivitamin supplementation and cognitive function in men: a randomized trial}},
journal = {Annals of internal medicine},
year = {2013},
doi = {10.7326/0003-4819-159-12-201312170-00006},
pmid = {24490265},
url = {https://doi.org/10.7326/0003-4819-159-12-201312170-00006}
}
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