Effect of Folic Acid and B Vitamins on Risk of Cardiovascular Events and Total Mortality Among Women at High Risk for Cardiovascular Disease

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Abstract
Homocysteine levels have been directly associated with cardiovascular risk in observational studies1; and daily supplementation with folic acid, vitamin B6, vitamin B12, or a combination have been shown to reduce homocysteine levels to varying degrees in intervention studies.2 Based on these data, several randomized trials were designed to test the hypothesis that supplementation with folic acid or B vitamins or both would prevent cardiovascular disease (CVD). However, published trials on patients with preexisting vascular disease have not demonstrated a benefit of folic acid or B vitamins on CVD risk.3 Participants in observational studies were followed up for longer durations then participants in randomized trials1; therefore, it is plausible that homocysteine lowering may have had a greater effect if participants were treated and observed for longer periods of time. Meta-analyses of randomized trials suggest that benefits may be greater with longer treatment durations,4 but the majority of published trials have 2 years or less of follow-up,3 with only 1 trial having 5 years of follow-up.5