Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals.
Clarke R1, Bennett D, Parish S, Lewington S, Skeaff M, Eussen SJ, Lewerin C, Stott DJ, Armitage J, Hankey GJ, Lonn E, Spence JD, Galan P, de Groot LC, Halsey J, Dangour AD, Collins R, Grodstein F (2014) The American Journal of Clinical Nutrition 100 (2) 657-666 American Society for Clinical Nutrition
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BACKGROUND: Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate ofcognitive aging is uncertain.
OBJECTIVE: The aim was to assess the effects of treatment with B vitamins compared with placebo, when administered for several years, on composite domains of cognitive function, global cognitive function, and cognitive aging.
DESIGN: A meta-analysis was conducted by using data combined from 11 large trials in 22,000 participants. Domain-based z scores (for memory, speed, and executive function and a domain-composite score for global cognitive function) were available before and after treatment (mean duration: 2.3 y) in the 4 cognitive-domain trials (1340individuals); Mini-Mental State Examination (MMSE)-type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognitiontrials (20,431 individuals).
RESULTS: The domain-composite and MMSE-type global cognitive function z scores both decreased with age (mean ± SE: -0.054 ± 0.004 and -0.036 ± 0.001/y, respectively). Allocation to B vitamins lowered homocysteine concentrations by 28% in the cognitive-domaintrials but had no significant effects on the z score differences from baseline for individual domains or for global cognitive function (z score difference: 0.00; 95% CI: -0.05, 0.06). Likewise, allocation to B vitamins lowered homocysteine by 26% in the global cognition trials but also had no significant effect on end-treatment MMSE-type global cognitive function (z score difference: -0.01; 95% CI: -0.03, 0.02). Overall, the effect of a 25% reduction inhomocysteine equated to 0.02 y (95% CI: -0.10, 0.13 y) of cognitive aging per year and excluded reductions of >1 mo per year of treatment.
CONCLUSION: Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging.
FAB RESEARCH COMMENT:
Extraordinarily, this meta-analysis does not even include the major clinical trial carried out at Oxford University (the VITACOG study
) - which was specifically designed to invesitgate the effects of B vitamin supplementation in preventing cognitive decline, and found significant benefits.
Instead, it includes other trials that were simply not even capable of addressing the question.
For a discussion of the serious flaws in this meta analysis, and the implications of the attention it has received, see: