Background: Additional folic acid treatment appears to have a neutral effect on reducing vascular risk in countries that mandate fortification of food with folic acid (e.g. US and Canada). However, it is uncertain whether folic acid therapy reduces stroke risk in countries without folic acid food fortification.
Objective: To comprehensively evaluate the efficacy of folic acid therapy on stroke prevention in countries without folic acid food fortification.
Methods: Pubmed, EMBASE, and Clinicaltrials.gov from January 1966 to August 2015 were searched to identify relevant studies. Relative risk (RR) with 95% CI was used as a measure of the association between folic acid supplementation and risk of stroke, after pooling data across trials in a random-effects model.
Results: The search identified 14 randomized controlled trials involving treatment with folic acid that had enrolled 71,334 participants, all of which stroke was reported as an outcome measure. Across all trials, folic acid therapy vs. control was associated with a lower risk of stroke (RR=0.84; 95% CI, 0.76-0.93; P=0.0007) and there was no heterogeneity among include trials (P for heterogeneity =0.27, I2=17%) (Figure). The RR of stroke in primary prevention trials was 0.81 (12 trials, 95% CI, 0.72-0.91; P=0.0006). Among 3 trials, which distinguished ischemic from hemorrhagic stroke as endpoints, folic acid therapy reduced risk of ischemic stroke (RR=0.77; 95% CI 0.67-0.90, P=0.0006), but had a neutral effect on hemorrhagic stroke (RR=0.92, 95% CI 0.66-1.28, P=0.61).
Conclusion: Among people living in countries without mandatory folic acid food fortification, folic acid therapy reduces the occurrence of a stroke.