Wang X et al. (2007) Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 369: 1876–1882

Folic acid is an important regulator of homocysteine metabolism, and evidence suggests that folate supplementation might reduce the risk of stroke; however, studies examining the effects of folate supplementation on other cardiovascular end points have produced conflicting results. A recent meta-analysis by Wang and co-workers has assessed whether folic acid supplementation can prevent stroke.

The authors identified eight randomized clinical trials that compared folic acid supplementation with one of three alternative regimens: placebo, usual care, or supplementation with a lower dose of folic acid. Three trials were conducted in the USA or Canada, where folic acid fortification of grain products was fully implemented by 1998. Four trials were conducted in regions with unfortified grain, and one was conducted in a partially fortified population. Overall, folic acid supplementation was associated with a significant reduction in the risk of stroke (relative risk [RR] 0.82, 95% CI 0.68–1.00; P = 0.045). The relationship seemed to be causal, because longer duration of supplementation was associated with greater reduction in the risk of stroke (RR 1.00 for interventions of ≤36 months vs 0.71 for interventions >36 months). Folic acid supplementation had a smaller beneficial effect on the risk of stroke in regions with folic acid fortification of grain than in regions with no or partial fortification. Supplementation did not reduce risk of stroke in patients with previous history of stroke, but was effective for primary prevention (RR 0.75, 95% CI 0.62–0.94; P = 0.002).