Cardiovascular diseases are the primary cause of mortality in France. Many epidemiological studies have shown that the total homocysteine concentration is a risk indicator for cardiovascular disease. Furthermore, it has been shown that the homocysteine concentration can be effectively lowered by supplementation with folic acid, vitamin B6 and B12. However, it is not yet known whether a reduction of the homocysteine concentration by such a supplementation indeed leads to a decreased risk of cardiovascular disease. Another possible dietary factor that may lower the risk of cardiovascular disease is fish-oil, which is rich in omega-3 fatty acids. These fatty acids lower platelet aggregation and triglyceride rich lipoproteins and may have antiarrhythmic effects. Some trials have investigated the effect of fish or fish-oil on cardiovascular mortality, and the results, although not conclusive, suggest a protective effect of a higher intake. In the SU.FOL.OM3 study we will evaluate the effect of supplementation at nutritional doses of folate (in the natural 5-methyl-tetrahydrofolate form) in combination with vitamin B6 and B12 and/or omega-3 fatty acids and/or placebo on recurrent ischemic diseases in a factorial design. The supplements will be randomly allocated to the participants in a double-blind fashion. In total 3,000 patients aged between 45 and 80 years who had a past history of myocardial infarction or unstable angina pectoris or an ischemic stroke will be included. The participants will be supplemented and followed up for a period of five years.