Myocardial infarction (MI) is the leading cause of mortality in the United States, with an estimated incidence of 800,000 new and recurrent coronary attacks annually.1
In focusing on the role of homocysteine levels in MI risk, researchers found that patients with homocysteine levels in
the 95th percentile had a threefold increase in MI risk independent of other coronary risk factors.2 These results led researchers to identify moderately high plasma homocysteine levels as an independent risk factor for myocardial infarction. In response to these findings and other observational research, homocysteine-lowering treatments, including folic acid supplementation, have gained popularity for patients at risk for cardiovascular disease (CVD).
Folic acid is a water-soluble B complex vitamin that occurs naturally in leafy green vegetables, fruits, and beans. Folic acid aids in the production and maintenance of new cells (most importantly RBCs), assists with manufacturing DNA and RNA, and is essential for metabolizing homocysteine.3
POTENTIAL BENEFITS
Plasma concentrations of folic acid are inversely related to plasma concentrations of homocysteine. The cardiovascular benefit of folic acid is believed to be associated with its critical role in converting homocysteine to methionine, directly impacting endothelial function, which has a major role in the pathogenesis of atherosclerosis.4 Several earlier studies demonstrated that daily folic acid supplementation effectively lowers homocysteine levels by 25%, and by an additional 7% when vitamin B12 is added.5 Considering the low cost of folic acid, this information piqued the interests of researchers, medical providers, and patients.
After the effects on homocysteine levels were demonstrated, further studies were conducted to determine the actual reduction in MI risk. Current scientific evidence does not support a reduction in cardiovascular events as a direct result of folic acid supplementation; in fact, the evidence actually discourages its use. The Norwegian Vitamin Trial (NORVIT) randomized patients with acute MI into four treatment groups consisting of various combinations of folic acid, vitamin B12, and vitamin B6, or placebo.6 Study results revealed that while homocysteine levels were reduced, no advantage related to clinical end points, including MI, was seen. In actuality, the group that received all three therapies trended toward increased cardiovascular risk.6
One of the largest studies concerning the role of folic acid on cardiovascular risk studied MI survivors who received 2 mg of folic acid plus 1 mg of vitamin B12 versus placebo for 10 years.7 Researchers reported that study participants experienced improved endothelial function. However, a reduction in morbidity or mortality related to major coronary events was not demonstrated.7 The American College of Cardiology/American Heart Association (ACC/AHA) recommends a diet emphasizing increased consumption of fresh fruits and vegetables for the prevention of coronary artery disease. However, it makes no recommendations for folic acid supplementation.
THE BOTTOM LINE
Folic acid has been shown to consistently lower plasma homocysteine levels, a proven independent risk factor for MI. However, long-term reductions in homocysteine levels have not been correlated with improved clinical outcomes. This suggests that the homocysteine-lowering action of folic acid may not be the primary mechanism for reduction of CVD risk. Furthermore, emerging evidence suggests that combining high-dose folic acid supplementation, vitamin B6, and vitamin B12 increases the risk of cardiovascular events.
Although the current studies are not likely to be the final word on the role of folic acid in the reduction of coronary events, the most recent data prove that recommending folic acid supplementation in an effort to reduce MI risk is premature. JAAPA
Nicole L. Hatcher works in the Cardiac Assessment, Recovery, and Evaluation (CARE) unit at Sentara Norfolk General's Heart Hospital, Norfolk, Virginia, and is an adjunct instructor in the School of Health Science at Kaplan University. The author has indicated no relationships to disclose relating to the content of this article.
Mary L. Hewett, PA-C, MS, department editor
REFERENCES
1. Rosamond W, Flegal K, Friday G, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007;115(5):e69-e171.
2. Stampfer MJ, Malinow MR, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA. 1992;268(7):877-881.
3. National Institutes of Health (NIH) Office of Dietary Supplements. Dietary supplement fact sheet: Folate. NIH Web site. http://ods.od.nih.gov/factsheets/folate.asp. Accessed October 4, 2010.
4. Moat SJ, Lang D, McDowell IF, et al. Folate, homocysteine, endothelial function and cardiovascular disease. J Nutr Biochem. 2004;15(2):64-79.
5. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. BMJ. 1998;316(7135):894-898.
6. Bonaa KH, Njolstad I, Ueland PM, et al; NORVIT investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Eng J Med. 2006;354(15):
1578-1588.
7. Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Armitage JM, Bowman L, et al. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA. 2010;303(24):2486-2494.
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