OBJECTIVE: To investigate whether dietary supplementation with B vitamins or 
omega 3 fatty acids, or both, could prevent major cardiovascular events in 
patients with a history of ischaemic heart disease or stroke.
DESIGN: Double blind, randomised, placebo controlled trial; factorial design.
SETTING: Recruitment throughout France via a network of 417 cardiologists, 
neurologists, and other physicians.
PARTICIPANTS: 2501 patients with a history of myocardial infarction, unstable 
angina, or ischaemic stroke.
INTERVENTION: Daily dietary supplement containing 5-methyltetrahydrofolate (560 
μg), vitamin B-6 (3 mg), and vitamin B-12 (20 μg) or placebo; and containing 
omega 3 fatty acids (600 mg of eicosapentanoic acid and docosahexaenoic acid at 
a ratio of 2:1) or placebo. Median duration of supplementation was 4.7 years.
MAIN OUTCOME MEASURES: Major cardiovascular events, defined as a composite of 
non-fatal myocardial infarction, stroke, or death from cardiovascular disease.
RESULTS: Allocation to B vitamins lowered plasma homocysteine concentrations by 
19% compared with placebo, but had no significant effects on major vascular 
events (75 v 82 patients, hazard ratio, 0.90 (95% confidence interval 0.66 to 
1.23, P=0.50)). Allocation to omega 3 fatty acids increased plasma 
concentrations of omega 3 fatty acids by 37% compared with placebo, but also had 
no significant effect on major vascular events (81 v 76 patients, hazard ratio 
1.08 (0.79 to 1.47, P=0.64)).
CONCLUSION: This study does not support the routine use of dietary supplements 
containing B vitamins or omega 3 fatty acids for prevention of cardiovascular 
disease in people with a history of ischaemic heart disease or ischaemic stroke, 
at least when supplementation is introduced after the acute phase of the initial 
event.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN41926726.