Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial

Study Questions:

Does long-term multivitamin supplementation affect cognitive health in later life?


The Physicians Health Study II was a randomized, double-blind, placebo controlled, 2 x 2 x 2 x 2 factorial trial testing beta-carotene (50 mg), vitamin E (400 IU), ascorbic acid (500 mg) or its placebo given every other day, and a multivitamin or placebo daily for their role in preventing chronic diseases among male physicians ages 50 years or older. Cognitive function was a prespecified secondary outcome in the study, conducted from 1997 to June 2011. The cognitive function substudy began in 1998, and was conducted in willing participants who were 65 years or older. Up to four repeated cognitive assessments by telephone interview were completed over 12 years.


Mean age was 71.6 years and the groups were well matched for cardiovascular risk factors and cardiovascular 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 four assessments. Specifically, for the global composite score, the mean difference in cognitive change over follow-up was -0.01 SU (95% confidence interval [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, or verbal memory (mean difference in cognitive change over follow-up, -0.005 SU [CI, -0.04 to 0.03 SU]).


The authors concluded that in male physicians ages 65 years or older, long-term use of a daily multivitamin did not provide cognitive benefits.


The strengths of the study include the large number of participants, long-term follow-up, and frequency of assessment of cognitive function. Among the many potential limitations of this study include that the physicians probably had better than average nutrition, the vitamin supplements need to begin earlier in life, and the most appropriate dose of micronutrients to enhance cognitive function is not known.

Clinical Topics: Prevention, Nonstatins, Diet

Keywords: Cognition, Vitamin E, Dietary Supplements

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