Does folic acid supplementation prevent stroke?

If these authors identified all the relevant clinical trials, folic acid supplementation for at least 36 months prevents stroke, especially in patients with no prior history of stroke. (LOE = 1a-)

Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 2007;369:1876-1882.  [PMID:17544768]

Meta-analysis (randomized controlled trials)

Self-funded or unfunded

Outpatient (any)

These authors searched MEDLINE and supplemented this strategy by searching bibliographies and by asking experts in the field to identify randomized controlled trials of folic acid supplementation for the prevention of stroke. Since they did not search other databases, however, they may have missed eligible studies. Two investigators independently evaluated study eligibility; a third investigator adjudicated discrepancies. The authors included 8 trials with 16,841 patients with pre-existing conditions like prior stroke, coronary heart disease, and end-stage renal disease. The studies lasted 24 months to 72 months. The folate doses ranged from 0.5 mg to 15 mg daily. Two of the studies were open-label trials. Among patients receiving folate, 4.2% had a stroke compared with 5.1% of control patients (number needed to treat = 104; 95% CI, 63-306). Patients generally had no benefit compared with placebo if they were treated for less than 36 months or if they had a prior stroke. Interestingly, in countries that fortify foods with folic acid (primarily the United States and Canada), the results were not statistically significant. Finally, the authors did not explicitly look for unpublished studies. Since there is a strong bias toward publishing studies with positive findings, these data may be skewed.