Background: It has been known for many years that there is a relationship between elevated plasma and serum homocysteine and the risk of cardiovascular disease (CVD). Because folate intake is associated with reduced CVD risk and reduced homocysteine levels, several randomized studies have examined the effect of folic acid and vitamin B supplementation on CVD risk. Bazzano and colleagues sought to clarify whether these trials supported the use of folic acid supplementation in patients with preexisting CVD.

The Study: This meta-analysis identified 12 randomized trials that studied the impact of folic acid supplementation in patients with CVD using coronary heart disease, stroke, and all-cause mortality as end points. The studies were conducted in multiple countries and included men and women taking folic acid dosages ranging from 0.5 mg to 15 mg per day. They were compared with persons taking placebo or those receiving usual care.

Results: Reduction in homocysteine levels in the intervention group was demonstrated in all trials; however, there was no difference in outcomes regardless of the level of reduction. There was no statistically significant effect of lowered homocysteine levels on any outcome.

Conclusion: Using data from the 12 trials, which showed little or no heterogeneity, the authors conclude that there is neither benefit nor harm from folic acid supplementation on cardiovascular outcomes in patients with preexisting CVD. These results may be confounded because some countries mandate or recommend folic acid supplementation in cereals, reducing the statistical power of intervention trials. However, the studies had other strengths that were sufficient in discouraging the use of folic acid as a secondary prevention of CVD. Folic acid may still have a role in primary prevention.