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Systematic review and meta-analysis
No effect of folic acid supplementation on cardiovascular events, cancer or mortality after 5 years in people at increased cardiovascular risk, although homocysteine levels are reduced
  1. Lydia A Bazzano
  1. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA
  1. Correspondence to: Lydia A Bazzano
    1440 Canal Street, SL-18, New Orleans, LA 70112-2715, USA; lbazzano{at}

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Several large randomised controlled trials designed to examine the effect of homocysteine lowering with folic acid and B-vitamin supplementation on cardiovascular disease, cancer and overall mortality were conducted in the past decade and have reported results. However, many of those were designed to detect large reductions in risk and may have been underpowered to detect smaller but still important effects. Therefore, a collaboration between trial investigators was established to pool individual-level results.


This is a meta-analysis of individual-level data from trials of folic acid and B-vitamin supplements for the prevention of vascular disease. Trials were considered eligible if they were randomised, double-blinded and placebo controlled; if treatment arms differed only by the homocysteine-lowering intervention and if ≥1000 participants were treated for ≥1 year. Data on 37 485 individuals from eight trials completed by the end of 2009 were included. The primary outcomes were major cardiovascular events (including coronary events, …

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  • Competing interests None.