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(Stroke. 2009;40:730.)
© 2009 American Heart Association, Inc.

Original Contributions

High-Dose B Vitamin Supplementation and Progression of Subclinical Atherosclerosis

A Randomized Controlled Trial

Howard N. Hodis, MD; Wendy J. Mack, PhD; Laurie Dustin, MS; Peter R. Mahrer, MD; Stanley P. Azen, PhD; Robert Detrano, MD; Jacob Selhub, PhD; Petar Alaupovic, PhD; Chao-ran Liu, MD; Ci-hua Liu, MD; Juliana Hwang, PharmD; Alison G. Wilcox, MD; Robert H. Selzer, MS for the BVAIT Research Group

From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser Permanente Medical Center (P.R.M.), Los Angeles, Calif; Harbor–University of California at Los Angeles Medical Center (R.D.), Los Angeles, Calif; the USDA Human Nutrition Research Center on Aging and Department of Vitamin Metabolism and Aging (J.S.), Tufts University, Boston, Mass; Oklahoma Medical Research Foundation (P.A.), Oklahoma City, Okla; and the Jet Propulsion Laboratory (R.H.S.), California Institute of Technology, Pasadena, Calif.

Correspondence to Howard N. Hodis, MD, USC Keck School of Medicine, Atherosclerosis Research Unit, 2250 Alcazar Street, CSC132, Los Angeles, CA 90033. E-mail athero{at}usc.edu

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 B₁₂+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.

Key Words: atherosclerosis • computed tomography • folate • homocysteine • intima media thickness • randomized controlled trials • vitamin B₁₂ • vitamin B₆ • folic acid

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Stroke 2009 40: 670-671. [Extract] [Full Text] [PDF]