High-dose B vitamin supplementation and progression of subclinical atherosclerosis: A randomized controlled trial

Abstract

Background and Purpose - Although plasma total homocysteine (tHcy) levels are associated with cardiovascular disease, it remains unclear whether homocysteine is a cause or a marker of atherosclerotic vascular disease. We determined whether reduction of tHcy levels with B vitamin supplementation reduces subclinical atherosclerosis progression. Methods - In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy >8.5 μmol/L without diabetes and cardiovascular disease were randomized to high-dose B vitamin supplementation (5 mg folic acid+0.4 mg vitamin B 12+50 mg vitamin B6) or matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3 vascular beds was assessed using high-resolution B-mode ultrasonography to measure carotid artery intima media thickness (primary outcome) and multidetector spiral CT to measure aortic and coronary artery calcium (secondary outcome). Results - Although the overall carotid artery intima media thickness progression rate was lower with B vitamin supplementation than with placebo, statistically significant between-group differences were not found (P=0.31). However, among subjects with baseline tHcy ≥9.1 μmol/L, those randomized to B vitamin supplementation had a statistically significant lower average rate of carotid artery intima media thickness progression compared with placebo (P=0.02); among subjects with a baseline tHcy <9.1 μmol/L, there was no significant treatment effect (probability value for treatment interaction=0.02). B vitamin supplementation had no effect on progression of aortic or coronary artery calcification overall or within subgroups. Conclusion - High-dose B vitamin supplementation significantly reduces progression of early-stage subclinical atherosclerosis (carotid artery intima media thickness) in well-nourished healthy B vitamin "replete" individuals at low risk for cardiovascular disease with a fasting tHcy ≥9.1 μmol/L. © 2009 American Heart Association, Inc.