Folic acid supplementation does not appear to reduce risk of cardiovascular diseases

December 12, 2006

An analysis of previous studies suggests that for people with a history of vascular disease, folic acid supplementation does not decrease the risk of coronary heart disease or stroke, as has been suggested in some research, according to a review article in the December 13 issue of JAMA.

Cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide, accounting for 30.9 percent of deaths world-wide and 10.3 percent of the global burden of disease. Of all deaths in the United States, 37.3 percent (910,120 or 1 in every 2.7) are due to CVD. It is estimated that approximately 71.3 million persons in the U.S. have 1 or more forms of CVD, according to background information in the article.

Observational epidemiologic studies have indicated that increased folate intake is related to a lower risk of CVD, and randomized controlled trials have documented that dietary supplementation with folic acid reduces blood levels of homocysteine, which has been associated with an increased risk of CVD. Most trials generally have had insufficient statistical power on their own and have provided inconsistent findings, the authors write.

Lydia A. Bazzano, M.D., Ph.D., of Tulane University School of Public Health and Tropical Medicine, New Orleans, and colleagues performed a meta-analysis of randomized clinical trials to determine the relationship between folic acid supplementation and risk of CVD and all-cause death among persons with pre-existing vascular disease. The study included 12 randomized controlled trials (with 16,958 participants) that compared folic acid supplementation with either placebo or usual care for a minimum duration of 6 months and with clinical cardiovascular disease events reported as an end point.

The researchers found that in comparing the folic acid supplementation groups with the controls groups, the total proportion of events were:"The findings of this analysis suggest that folic acid supplementation is ineffective in the secondary prevention of CVD among persons with a history of vascular diseases. Therefore, it is important to focus on strategies of proven benefit in the secondary prevention of CVD, including smoking cessation, lipid reduction, treatment of hypertension and diabetes, maintenance of a healthy weight, and physical activity," the authors conclude.
(JAMA. 2006;296:2720-2726. Available pre-embargo to the media at

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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