Folic acid may be effective in the primary prevention of ischemic heart disease when aspirin is not taken routinely, a new UK study suggests.
The study compared the results of two meta-analyses assessing the relationship between the folic acid-related decrease of serum homocysteine concentrations and the incidence of ischemic heart disease (1): The first meta-analysis included 75 case control studies on the prevalence of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (a common genetic variant that leads to moderate increases in serum homocysteine levels) among people with and without ischemic heart disease (IHD). The second meta-analysis included 14 randomized controlled trials of B vitamins, which lower serum homocysteine, in the prevention of IHD. The first meta-analysis showed a statistically significant higher risk of IHD in individuals with increased homocysteine levels due to a certain mutation in the MTHFR gene. The second meta-analysis, however, showed no significant IHD risk reduction in participants with folic acid supplementation, despite a significant reduction in homocysteine serum concentrations. The results of both meta-analyses are thus contradictory.
The researchers identified a possible explanation for this discrepancy: the finding that there was a statistically significant difference in risk reduction between the 5 trials with the lowest prevalence of anti-platelet therapy, usually with aspirin, and the 5 trials with the highest prevalence. Folic acid showed only an IHD preventing effect via lowering homocysteine levels when aspirin was not taken routinely. A possible reason is that the lowering of homocysteine by folic acid may not add to the anti-thrombotic effect of aspirin, and potentially other anti-platelet drugs, in preventing ischemic heart disease.
Homocysteine has been shown to increase platelet activation and aggregation, effects which may explain the pathological effects of homocysteine in both arterial and venous disease. Aspirin inhibits platelet activation and platelet aggregation preventing thrombosis. Given that homocysteine exerts a thrombotic effect through its action on platelet function, concomitant treatment with aspirin (or possibly other anti-platelet drugs) could reduce or negate the anti-platelet effect of folic acid-induced lowering of homocysteine in the trials. The researchers concluded that the fact that most of the trials included patients with pre-existing cardiovascular disease would leave open the possibility that folic acid has a useful role in the primary prevention of ischemic heart disease where aspirin is generally not used, but not in secondary prevention, where it is routine.