Submitted to: Stroke
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/29/2008
Publication Date: 3/1/2009
Citation: Hodis, H.N., Mack, W.J., Dustin, L., Mahrer, P.R., Azen, S.P., Detrano, R., Selhub, J., Alaupovic, P., Liu, C., Liu, C., Hwang, J., Wilcox, A.G., Selzer, R.H. 2009. High-Dose B-Vitamin Supplementation and Progression of Subclinical Atherosclerosis: A Randomized Controlled Trial. Stroke. 40:730-736.
Interpretive Summary: In this study we determined the effect of B vitamins supplementation on the progression of carotid intima-media thickness or CIMT. Intima-media is part of the arterial wall which is increased in thickness with aging and, when too thick it results in the reduction of the flow of the blood through the artery which could lead to stroke. In this study we found that supplementation of B vitamins could reduce the progression of the thickening of the arterial wall among those whose plasma homocysteine level is moderately high. Homocysteine is an amino acid with important functions in the body. These functions are closely associated with the activities of these B vitamins. High levels of homocysteine in the blood are an indication of inadequate vitamin intake.
Technical Abstract: Although plasma homocysteine levels (tHcy) are clearly associated with cardiovascular disease (CVD), it remains unclear whether tHcy is a cause or a marker of atherosclerotic vascular disease. To determine whether reduction of tHcy with B-vitamin supplementation reduces the progression of subclinical atherosclerosis, there was a single-center, randomized, double-blind, placebo-controlled, serial arterial imaging trial. The patients were a healthy population of 506 participants 40-89 years of age with an initial tHcy >8.5 micromol/L. The intervention was a high-dose B-vitamin supplementation (folic acid 5 mg + vitamin B12 0.4 mg + vitamin B6 50 mg) or matching placebo for 3.1 years. Measurements were of subclinical atherosclerosis progression across 3 vascular beds using high-resolution B-mode ultrasonography to measure carotid artery intima-media thickness (CIMT) and multidetector spiral computed tomography to measure aortic and coronary artery calcium. Although the overall CIMT 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 fasting tHcy >/-9.1 mcgmol/L, those randomized to B-vitamin supplementation had a statistically significant lower average rate of CIMT progression compared with placebo (p=0.02); among subjects with a baseline fasting tHcy <9.1 umol/L there was no significant treatment effect (p-value for treatment interaction=0.02). High-dose B-vitamin supplementation had no effect on the progression of aortic or coronary artery calcification overall or within subgroups. Results are limited to individuals without pre-existing CVD and the study had insufficient power to statistically compare CVD outcomes.