"B" Wary: Folate and Cardiovascular Disease
March 1, 2007
"B" Wary: Folate and Cardiovascular Disease
By Russell H. Greenfield, MD, Dr. Greenfield is Clinical Assistant Professor, School of Medicine, University of North Carolina, Chapel Hill, NC, and Visiting Assistant Professor, University of Arizona, College of Medicine, Tucson, AZ; he reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
Source: Bazzano LA, et al. Effect of folic acid supplementation on risk of cardiovascular diseases: A meta-analysis of randomized controlled trials. JAMA 2006;296:2720-2726.
Abstract: 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.
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.
Comments: Meta-analyses are frequently rife with limitations. Although interpretation of the results of this article likewise has its limitations, the authors are quick to point out those limitations themselves. Perhaps the biggest limitation has to do with duration of follow-up (the longest follow-up was only five years). It should also be noted that the study focused on secondary, not primary, prevention. All this aside, as meta-analyses go this one is quite strong. There was almost no heterogeneity identified. RCTs were examined, thereby lessening the potential for bias and confounders often problematic in observational trials (examples of which might include sudden adoption of healthy lifestyles, additional folate supplementation, and dietary changes). Since the homocysteine hypothesis of arteriosclerosis first came to prominence with McCully's early work on people with inherited cystathione synthase deficiency, the promise of folic acid and vitamin B12 supplementation for lessening the incidence of cardiovascular disease has garnered worldwide interest. Most observational trials suggest a cardiovascular benefit with lowering of serum homocysteine levels with folic acid, but clinical data have been mixed at best. Perhaps it has been naïve to believe that a single nutrient could significantly alter the incidence of what remains the leading cause of death in the world; primary prevention of cardiovascular disease may still be enhanced using appropriate folate supplementation, but support for its use for secondary prevention has faded to a considerable extent.
Greenfield RH. "B" wary: Folate and cardiovascular disease. Altern Ther Women's Health 2007;9(3):22.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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