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Am J Clin Nutr. 2008 Dec;88(6):1602-10. doi: 10.3945/ajcn.2008.26404.

A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease.

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  • 1Channing Laboratory, Boston, MA 02115, USA.



High homocysteine concentrations may be neurotoxic and contribute to cognitive decline in older persons.


The objective was to examine the effect of supplementation with folic acid, vitamin B-12, and vitamin B-6 on cognitive change in women with cardiovascular disease (CVD) or CVD risk factors.


The Women's Antioxidant and Folic Acid Cardiovascular Study is a randomized placebo-controlled trial designed to test the effect of a combination of B vitamins (2.5 mg folic acid/d, 50 mg vitamin B-6/d, and 1 mg vitamin B-12/d) on secondary prevention of CVD. Female health professionals aged >or=40 y (n = 5442) with CVD or >or=3 coronary risk factors in 1998 (after folic acid fortification began in the United States) were randomly assigned to treatment. Shortly after randomization (mean: 1.2 y), a substudy of cognitive function was initiated among 2009 participants aged >or=65 y. Telephone cognitive function testing was administered up to 4 times over 5.4 y with 5 tests of general cognition, verbal memory, and category fluency. Repeated-measures analyses were conducted, and the primary outcome was a global composite score averaging all test results.


Mean cognitive change from baseline did not differ between the B vitamin and placebo groups (difference in change in global score: 0.03; 95% CI: -0.03, 0.08; P = 0.30). However, supplementation appeared to preserve cognition among women with a low baseline dietary intake of B vitamins.


Combined B vitamin supplementation did not delay cognitive decline among women with CVD or CVD risk factors. The possible cognitive benefits of supplementation among women with a low dietary intake of B vitamins warrant further study.

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