Homocysteine lowering not helpful in women at high risk for CVD

Clinical Question

Can folic acid and B-vitamin supplementation lower the risk of CVD in high-risk women?

Bottom Line

Supplementation with folic acid and B vitamins significantly lowered homocysteine levels in women at high risk for cardiovascular disease (CVD), but did not reduce the risk of subsequent CVD events or reduce all-cause mortality. (LOE = 1b)


Albert CM, Cook NR, Gaziano JM, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease. A randomized trial. JAMA 2008;299:2027-2036.  [PMID:18460663]

Study Design

Randomized controlled trial (double-blinded)






Outpatient (any)


Current evidence from randomized trials does not support a benefit of folic acid or B-vitamin supplementation for preventing CVD in adults. Because women have been underrepresented in previous studies, these investigators identified 5442 women aged 42 years or older with either a history of CVD or 3 or more coronary risk factors. Eligible women randomly received (concealed allocation assignment) a once-daily combination pill of folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg), or matched placebo. This study was part of the Women's Antioxidant Cardiovascular Study, which also evaluated the effect of vitamin C, vitamin E, and beta carotene on CVD. Individuals assessing and verifying treatment outcomes remained masked to treatment group assignment. Complete follow-up occurred for 93% of participants for 7.3 years. Using intention-to-treat analysis, there was no significant difference in the incidence of CVD events (myocardial infarction, stroke, coronary revascularization procedures, and cardiovascular death) between the treatment group and control group (14.9% vs 14.3%, respectively). A secondary analysis also found no difference in those women reporting high compliance with following the treatment protocol. The risk of all-cause mortality was also similar between the 2 groups. Homocysteine levels were significantly reduced by 18.5% in the treatment group compared with the placebo group. The study was 82% powered to detect a 20% reduction in the primary end point.