Francine Grodstein, ScD *; Jacqueline O’Brien, ScD *; Jae Hee Kang, ScD; Rimma Dushkes, PhD; Nancy R. Cook, ScD; Olivia Okereke, MD; JoAnn E. Manson, MD, DrPH; Robert J. Glynn, PhD; Julie E. Buring, ScD; J. Michael Gaziano, MD, MPH; Howard D. Sesso, ScD, MPH
Acknowledgment: The authors thank the 14 641 physician participants for their long-standing dedication and conscientious collaboration; the long-term contributions of Charles Hennekens, MD, DrPH, Florida Atlantic University, to the Physicians’ Health Study; and the exemplary contributions of the staff of the Physicians’ Health Study at Brigham and Women's Hospital.
Grant Support: By grants CA 097193, CA 34944, CA 40360, HL 26490, HL 34595, AG 15933, and T32-AG000158 from the National Institutes of Health, and an investigator-initiated grant from BASF. Study agents and packaging were provided by BASF and Pfizer, and study packaging was provided by DSM Nutritional Products.
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-1340.
Reproducible Research Statement: Study protocol: Available from Drs. Sesso (firstname.lastname@example.org) and Gaziano (email@example.com). Statistical code: Not available. Data set: Not available.
Requests for Single Reprints: Francine Grodstein, ScD, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Grodstein, O’Brien, Kang, Dushkes, Cook, Orereke, Manson, Glynn, Buring, Gaziano, and Sesso: Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115.
Author Contributions: Conception and design: F. Grodstein, J.E. Manson, R.J. Glynn, J.E. Buring, J.M. Gaziano.
Analysis and interpretation of the data: F. Grodstein, J. O’Brien, J.H. Kang, R. Dushkes, N.R. Cook, O. Okereke, J.E. Manson, R.J. Glynn, J.M. Gaziano, H.D. Sesso.
Drafting of the article: J. O’Brien, J.E. Buring.
Critical revision of the article for important intellectual content: F. Grodstein, J. O’Brien, J.H. Kang, R. Dushkes, N.R. Cook, O. Okereke, J.E. Manson, R.J. Glynn, J.E. Buring, J.M. Gaziano, H.D. Sesso.
Final approval of the article: F. Grodstein, J. O’Brien, J.H. Kang, R. Dushkes, N.R. Cook, O. Okereke, J.E. Manson, R.J. Glynn, J.E. Buring, J.M. Gaziano, H.D. Sesso.
Provision of study materials or patients: J.M. Gaziano, H.D. Sesso.
Statistical expertise: F. Grodstein, J.H. Kang, N.R. Cook, R.J. Glynn.
Obtaining of funding: F. Grodstein, J.M. Gaziano, H.D. Sesso.
Administrative, technical, or logistic support: F. Grodstein, J.M. Gaziano, H.D. Sesso.
Collection and assembly of data: F. Grodstein, J.E. Buring, J.M. Gaziano.
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.
To evaluate whether long-term multivitamin supplementation affects cognitive health in later life.
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)
The Physicians’ Health Study II.
5947 male physicians aged 65 years or older.
Daily multivitamin or placebo.
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.
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]).
Doses of vitamins may be too low or the population may be too well-nourished to benefit from a multivitamin.
In male physicians aged 65 years or older, long-term use of a daily multivitamin did not provide cognitive benefits.
National Institutes of Health, BASF, Pfizer, and DSM Nutritional Products.
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. Ann Intern Med. ;159:806–814. doi: 10.7326/0003-4819-159-12-201312170-00006
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Published: Ann Intern Med. 2013;159(12):806-814.
Dementia, Geriatric Medicine, Neurology, Prevention/Screening.
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