Homocysteine and vascular disease: review of published results of the homocysteine-lowering trials.
Moderately elevated homocysteine levels have been associated with a higher risk of cardiovascular disease in observational studies, but whether these associations are causal is uncertain. Randomized trials of dietary supplementation with B vitamins were set up to assess whether lowering homocysteine levels could reduce the risk of vascular disease. This review is based on a meta-analysis of published results of eight homocysteine-lowering trials for preventing vascular disease. The eight trials comprised a total of 37,485 individuals and provided comparisons of the effects of B vitamins on 5,074 coronary heart disease (CHD) events, 1,483 stroke events, 2,692 incident cancer events, and 5,128 deaths. Our meta-analysis assessed the effects of lowering homocysteine levels by about 25% for about 5 years. Allocation to B vitamins had no beneficial effects on any cardiovascular events, with hazard ratios (95% confidence intervals) of 1.01 (0.96-1.07) for CHD and 0.96 (0.87-1.07) for stroke. Moreover, allocation to B vitamins had no significant adverse effects on cancer [1.08 (0.99-1.17)], or for death from any cause [1.02 (0.97-1.07)]. Thus, supplementation with B vitamins had no statistically significant effects on the risks of cardiovascular events, total mortality rates, or cancer. A meta-analysis based on individual participant data from all available trials will assess the effects of lowering homocysteine levels on a broader range of outcomes, overall and in all relevant subgroups. However, available evidence does not support the routine use of B vitamins to prevent cardiovascular disease.
Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Oxford, UK. robert.clarke@ctsu.ox.ac.uk
Robert
R
Clarke
Jim
J
Halsey
Derrick
D
Bennett
Sarah
S
Lewington
D002423:Cause of Death; D002986:Clinical Trials as Topic / Q000379:methods*; D019587:Dietary Supplements; D015536:Down-Regulation; D005492:Folic Acid / Q000378:metabolism / Q000502:physiology; D006710:Homocysteine / Q000009:adverse effects / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D014652:Vascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000401:mortality; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000378:metabolism / Q000502:physiology
D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid