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Am J Clin Nutr. 2014 Aug;100(2):657-66. doi: 10.3945/ajcn.113.076349. Epub 2014 Jun 25.

Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals.

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From the Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, United Kingdom (R Clarke, DB, SP, SL, JA, JH, and R Collins); the Department of Human Nutrition, University of Otago, Dunedin, New Zealand (MS); the Section for Pharmacology and Department of Public Health and Primary Care, University of Bergen, Bergen, Norway (SJPME); the Department of Epidemiology, School for Public Health and Primary Care, CAPHRI, Maastricht University Medical Centre, Maastricht, Netherlands (SJPME); the Section of Hematology and Coagulation, Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden (CL); the Division of Cardiovascular and Medical Science, University of Glasgow, Glasgow, United Kingdom (DJS); the School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia (GJH); the Population Health Research Institute and Department of Medicine, McMaster University, Hamilton, Canada (EL); the Department of Neurology, Western University, London, Canada (JDS); Unité de Recherche en Epidémiologie Nutritonnelle (UREN), Sorbonne-Paris-Cité, UMR Inserm U557, France (PG); Inra U1125, Paris, France (PG); Cnam, Paris, France (PG); Université Paris 13, CRNH IdF, Bobigny, France (PG); the Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, Netherlands (LCdG); the Department of Nutrition and Public Health Intervention Research, London School of Hygiene and Tropical Medicine, London, United Kingdom (ADD); and the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (FG).



Elevated plasma homocysteine is a risk factor for Alzheimer disease, but the relevance of homocysteine lowering to slow the rate of cognitive aging is uncertain.


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.


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 (1340 individuals); Mini-Mental State Examination (MMSE)-type tests were available at the end of treatment (mean duration: 5 y) in the 7 global cognition trials (20,431 individuals).


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-domain trials 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 in homocysteine 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.


Homocysteine lowering by using B vitamins had no significant effect on individual cognitive domains or global cognitive function or on cognitive aging.

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