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

Abstract

Conclusion: Dietary supplementation with high-dose B vitamins reduces progression of carotid intima media thickness in individuals with a fasting total homocysteine ≥ 9.1 μmol/L and who are at low risk for cardiovascular disease. Summary: Both meta-analysis and observational studies have indicated that elevated total plasma homocysteine (tHcy) is an independent risk factor for cardiovascular disease with risk increasing 40-60% for each 3-5 μmol/L increase in tHcy. However, clinical trials have failed to show reduction of cardiovascular events with homocysteine lowering therapy. The B-vitamin atherosclerosis intervention trial (BVAIT) assessed the impact on subclinical atherosclerosis, in a population presumably free of cardiovascular disease, of reducing total plasma homocysteine with B-vitamin supplementation. This was a randomized double-blind placebo controlled trial conducted from November 2000 to June 2006. Subjects were men and post-menopausal women more than 40-years of age with fasting total homocysteine levels ≥ 8.5 μmol/L. All subjects had no clinical signs or symptoms of cardiovascular disease. Patients with diabetes, systolic blood pressures > 160 mmHg, diastolic blood pressure > 100 mmHg and creatinine clearance < 70 mL/min were excluded. There were 506 participants randomized to high-dose of 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 was assessed using carotid artery intima media thickness values obtained with duplex scanning, the primary outcome measure. Measurements of aortic and coronary artery calcification with multidetector spiral CT scanning were secondary outcome measures. At follow-up there was no statistical significant difference in the primary or secondary outcomes comparing the patients with B-vitamin supplementation to those treated with the placebo. A post-hoc analysis showed that subjects with baseline tHcy's ≥ 9.1 μmol/L and randomized to B-vitamin supplementation had statistically significant lower average rates of carotid intima media thickness progression compared to the placebo group, p = 0.02. Subjects with baseline total homocysteines < 9.1 μmol/L had no treatment effect. Comment: The authors contend that despite this being a post-hoc analysis, their findings that vitamin-B supplementation can decrease carotid intemia media thickness in individuals with fasting total homocysteine > 9.1 μmol/L is “highly relevant”. Perhaps this is true for the basic biology of atherosclerosis but it is unlikely to have any clinical effect. Patients who had decreases in carotid intima media thickness were an average age of 61-years and had no signs of cardiovascular disease, no decrease in cardiovascular events, and “benefitted” only by reduction in a subclinical marker of atherosclerosis. The public health impact of these findings is likely to be nothing.