A meta-analysis of randomized, controlled trials (RCTs) was performed to evaluate the effects of folic acid supplementation on risk of cardiovascular diseases and all-cause mortality among persons with pre-existing cardiovascular or renal disease. The researchers performed a Medline search of articles from 1966 to 2006 without language restrictions, as well as a manual search of references cited in specific articles, and contacted experts who might know of trials near completion. Of 165 identified reports, 12 RCTs comparing folate with placebo or usual care for a minimum of six months, and with clinical cardiovascular disease events reported as endpoint, were analyzed. The data set included information on close to 17,000 people, with the majority of articles (eight) coming out of European countries. Trials were primarily parallel in design, with seven using placebo, and five employing usual care as a control. The dosage of folate used ranged from 0.5 mg/d to 15 mg/d, and duration of intervention ranged from six months to five years. Data were independently reviewed by two of the investigators, and in the case of a discrepancy a third reviewer was called in to offer an opinion.Abstract:
All trials showed a decrease in serum homocysteine levels, but no statistically significant relationship was identified between net change in homocysteine level and relative risk (RR) for examined clinical outcomes. The overall RR for people with pre-existing cardiovascular or renal disease using folate supplementation compared with placebo was 0.95 for cardiovascular disease, 1.04 for coronary heart disease, 0.86 for stroke, and 0.96 for all-cause mortality. The data suggest that folic acid supplementation is not effective for secondary prevention of cardiovascular disease or all-cause mortality in people with pre-existing cardiovascular or renal disease.