High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial.
OBJECTIVE
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 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).


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 >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.


CONCLUSIONS
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.
Hodis
Howard N
HN
Atherosclerosis Research Unit, Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, Calif. 90033, USA. athero@usc.edu
Mack
Wendy J
WJ
Dustin
Laurie
L
Mahrer
Peter R
PR
Azen
Stanley P
SP
Detrano
Robert
R
Selhub
Jacob
J
Alaupovic
Petar
P
Liu
Chao-ran
CR
Liu
Ci-hua
CH
Hwang
Juliana
J
Wilcox
Alison G
AG
Selzer
Robert H
RH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology; D019587:Dietary Supplements; D018450:Disease Progression; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
D008055:Lipids; D006710:Homocysteine; D014803:Vitamin B Complex; D002118:Calcium