• Jennifer A McMahon, Timothy J Green, C Murray Skeaff, Robert G Knight, Jim I Mann, and Sheila M Williams.
• Departments of Human Nutrition, University of Otago, Dunedin, New Zealand.
• N. Engl. J. Med. 2006 Jun 29; 354 (26): 276427722764-72.

BackgroundThe results of observational studies suggest that plasma homocysteine concentrations are inversely related to cognitive function in older people. Our objective was to test the hypothesis that lowering the plasma homocysteine concentration improves cognitive function in healthy older people.MethodsWe conducted a two-year, double-blind, placebo-controlled, randomized clinical trial involving 276 healthy participants, 65 years of age or older, with plasma homocysteine concentrations of at least 13 micromol per liter. Homocysteine-lowering treatment was a daily supplement containing folate (1000 microg) and vitamins B12 (500 microg) and B6 (10 mg). Tests of cognition were conducted at baseline and after one and two years of treatment. Treatment effects were adjusted for baseline values, sex, and education.ResultsOn average, during the course of the study, the plasma homocysteine concentration was 4.36 micromol per liter (95 percent confidence interval, 3.81 to 4.91 micromol per liter) lower in the vitamin group than in the placebo group (P<0.001). Overall, there were no significant differences between the vitamin and placebo groups in the scores on tests of cognition.ConclusionsThe results of this trial do not support the hypothesis that homocysteine lowering with B vitamins improves cognitive performance. (Australian Clinical Trials registry number, ACTR NO 12605000030673.).Copyright 2006 Massachusetts Medical Society.

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