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Original Article
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Volume 354:2764-2772 June 29, 2006 Number 26
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A Controlled Trial of Homocysteine Lowering and Cognitive Performance
Jennifer A. McMahon, Ph.D., Timothy J. Green, Ph.D., C. Murray Skeaff, Ph.D., Robert G. Knight, Ph.D., Jim I. Mann, Ph.D., and Sheila M. Williams, D.Sc.

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ABSTRACT

Background The 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.

Methods We 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 µmol per liter. Homocysteine-lowering treatment was a daily supplement containing folate (1000 µg) and vitamins B12 (500 µg) 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.

Results On average, during the course of the study, the plasma homocysteine concentration was 4.36 µmol per liter (95 percent confidence interval, 3.81 to 4.91 µmol 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.

Conclusions The 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.)


Source Information

From the Departments of Human Nutrition (J.A.M., T.J.G., C.M.S., J.I.M.), Psychology (R.G.K.), and Preventive and Social Medicine (S.M.W.), University of Otago, Dunedin, New Zealand.

Address reprint requests to Dr. Skeaff at the Department of Human Nutrition, University of Otago, P.O. Box 56, Dunedin, New Zealand, or at murray.skeaff{at}stonebow.otago.ac.nz.

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Related Letters:

Homocysteine Lowering and Cognitive Performance
Lucca U., Tettamanti M., Quadri P., Dettling M., Opgen-Rhein C., Anghelescu I.-G., Narayan R. L., Skeaff C. M., Green T. J., McMahon J. A.
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N Engl J Med 2006; 355:1390-1391, Sep 28, 2006. Correspondence

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