Homocysteine lowering with folic acid and B vitamins in vascular disease.

The New England journal of medicine
Q1
Apr 2006
Citations:1131
Influential Citations:14
Interventional (Human) Studies
98
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Enhanced Details

Methods
Randomized, double-blind, placebo-controlled trial; 5522 participants aged 55 years or older with vascular disease or diabetes and additional risk factors; 145 centers across 13 countries.
Intervention
Oral, daily, combined pill containing 2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12; duration averaged five years.
Results
Lowering homocysteine with folic acid and vitamins B6 and B12 lowered homocysteine but did not reduce major vascular events. Primary outcome occurred in 18.8% of active vs 19.8% of placebo (relative risk 0.95; 95% CI 0.84–1.07; P=0.41). Stroke decreased in the active group (4.0% vs 5.3%; RR 0.75; 95% CI 0.59–0.97; P=0.03), but hospitalization for unstable angina was higher (9.7% vs 7.9%; RR 1.24; 95% CI 1.04–1.49; P=0.02). No significant differences in death from cardiovascular causes or myocardial infarction; overall, no reduction in major vascular events; not recommended for prevention.
Limitations
Limitations include a relatively small number of stroke events with wide confidence intervals; outcomes not adjusted for multiplicity; regional folate fortification status may limit generalizability; results may not apply to populations without folate fortification; five-year follow-up may not capture longer-term effects.

Abstract

BACKGROUND In observational studies, lower homocysteine levels are associated with lower rates of coronary heart disease and stroke. Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of...