High-Dose B Vitamin Supplementation and Progression of Subclinical Atherosclerosis : A Randomized Controlled Trial

• Published in: Stroke (1970) Vol. 40; no. 3; pp. 730 - 736
• Main Authors: HODIS, Howard N, MACK, Wendy J, HWANG, Juliana, WILCOX, Alison G, SELZER, Robert H, DUSTIN, Laurie, MAHRER, Peter R, AZEN, Stanley P, DETRANO, Robert, SELHUB, Jacob, ALAUPOVIC, Petar, LIU, Chao-Ran, LIU, Ci-Hua
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.03.2009
• Subjects: Adult; Aged; Aged, 80 and over; Aorta, Abdominal - diagnostic imaging; Atherosclerosis (general aspects, experimental research); Atherosclerosis - diagnostic imaging; Atherosclerosis - drug therapy; Atherosclerosis - pathology; Biological and medical sciences; Blood and lymphatic vessels; Calcium - metabolism; Cardiology. Vascular system; Carotid Arteries - diagnostic imaging; Coronary Vessels - diagnostic imaging; Coronary Vessels - pathology; Dietary Supplements; Disease Progression; Double-Blind Method; Echocardiography; Female; Homocysteine - blood; Humans; Lipids - blood; Male; Medical sciences; Middle Aged; Neurology; Patient Compliance; Treatment Outcome; Vascular diseases and vascular malformations of the nervous system; Vitamin B Complex - adverse effects; Vitamin B Complex - blood; Vitamin B Complex - therapeutic use; computed tomography; homocysteine; Thiol; Stroke; Nervous system diseases; intima media thickness; vitamin B6; Cardiovascular disease; Asymptomatic; B-Vitamins; randomized controlled trials; Folic acid; Cyanocobalamin; Cerebral disorder; Sulfur containing aminoacid; Vascular disease; folate; Homocystein; Central nervous system disease; Atherosclerosis; Computerized axial tomography; vitamin B12; High dose; Cerebrovascular disease
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.108.526798

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. In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy >8.5 micromol/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 B(6)) 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). 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 >or=9.1 micromol/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 micromol/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. 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 >or=9.1 micromol/L.