Does Folic Acid Therapy Reduce Risk for First Stroke?

Although stroke is the second leading cause of death globally, in China, it is the most frequent cause of death. Some trials and meta-analyses have found that folic acid supplementation has no effect on cardiovascular events in general, but it may reduce stroke risk.

To test the efficacy of folic acid supplementation as a treatment, researchers in China conducted a randomized, double blind clinical trial (the China Stroke Primary Prevention Trial, CSPPT). They published their results online in JAMA on March 15, 2015.

The researchers hypothesized that enalapril-folic acid therapy would decrease the risk of first stroke better than enalapril alone. The study took place from May 2008 until August 2013 in 32 Chinese communities. The researchers enrolled 20,702 adults aged 40 to 75 years old with no history of either myocardial infarction (MI) or stroke.

To qualify, participants had to have blood pressure >140 mm Hg / 90 mm Hg or be taking antihypertensive medication. The gene stratified patients for methylenetetrahydrofolate reductase (MTHFR) — the central enzyme regulating folate metabolism. They were then randomly assigned to receive either 10 mg enalapril with 0.8 mg folic acid or enalapril alone in a single tablet. The investigators followed up with patients every three months.

The CSPPT’s primary outcome was first stroke, and they monitored multiple secondary outcomes, including first hemorrhagic stroke, first ischemic stroke, MI, composite cardiovascular events (cardiovascular death, stroke, and MI), and all-cause death.

The researchers reported that among the enalapril-folic group, relative risk of first stroke in the enalapril-folic acid group was 20% lower than in the enalapril-only group. They noted similar reductions in risk for the enalapril-folic group in terms of risk reduction for first ischemic stroke (2.2% who received folic acid experienced an ischemic stroke vs. 2.8% who did not), and composite cardiovascular events (3.1% who received folic acid experienced a composite cardiovascular event vs. 3.9% who did not).

The authors noted that they found no significant reduction in risks between the treatment groups for hemorrhagic stroke and all-cause deaths.

The authors concluded that using both enalapril and folic acid significantly reduced the risk of a first stroke among adults with no history of MI or stroke. The authors cautioned their results could only be applied to primary stroke prevention.