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Homocysteine-Lowering and Cognitive Performance

No evidence supports routine B vitamin supplementation for the purpose of improving or maintaining cognitive performance.

Epidemiologic studies have suggested an association between high homocysteine levels and cognitive deficits; in addition, vitamin B₁₂ deficiency (which is a cause of high homocysteine levels) is associated with neuropsychiatric disorders. These observations prompted New Zealand researchers to examine whether homocysteine-lowering B-vitamin therapy improves cognition.

A total of 276 healthy nondemented people (age, 65 or older), with plasma homocysteine levels 13 µmol/L, were randomized to receive either daily supplements (containing folate [1 mg], vitamin B₁₂ [0.5 mg], and vitamin B₆ [10 mg]) or placebo. Subjects underwent extensive neuropsychological testing at baseline and after 1 and 2 years of treatment. Vitamin therapy significantly reduced homocysteine levels, by an average of 4.4 µmol/L. Nevertheless, cognition testing revealed no benefit in the B-vitamin group compared with the placebo group. In fact, a combined score for 8 tests of cognition was marginally lower in the B-vitamin group (P=0.05).

Comment: Once again, homocysteine-lowering therapy with B vitamins has not yielded clinical benefit in a randomized trial; in other recent trials, homocysteine-lowering therapy did not lower the incidence of myocardial infarction or stroke (Journal Watch 2006 Mar 28). The authors discuss several limitations of their trial (for example, relatively short duration), but for now, no evidence supports routine B-vitamin supplementation for the purpose of improving or maintaining cognitive performance. Obviously, these results do not apply to patients with documented B₁₂ deficiency, and they might not apply to people with considerably higher baseline homocysteine levels.

— Allan S. Brett, MD

Published in Journal Watch General Medicine June 30, 2006

Citation(s):

McMahon JA et al. A controlled trial of homocysteine lowering and cognitive performance. N Engl J Med 2006 Jun 29; 354:2764-72.

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