Homocysteine has been noted to be consistently higher in patients with occlusive vascular disease than in controls, and this difference is also seen prior to the onset of disease.  Although previous large-scale randomised trials have failed to show any benefit from lowering homocysteine levels through the use of folic acid based supplements, the reasons for this have remained unclear, and subsequent subgroup analysis has suggested a protective effect on stroke.  The SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) trial examined the affects of lowering homocysteine levels using 2mg of folic acid and 1mg vitamin B12 daily.

The study followed 12064 survivors of myocardial infarction who were assigned to either B12/folate or placebo.  The main outcome measure was the first major vacular event, defined as a major coronary event (coronary death, myocardial infarction, or revascularisation), stroke, or noncoronary revascularisation.

Although allocation to the study vitamins reduced homocysteine levels by a mean of 3.8 umol/L (28%), over 6.7 years of follow-up no significant difference was noted in the incidence of major vascular events between the treatment and control groups (25.5% vs 24.8%; p=.28).  Furthermore there was no significant difference in the numbers of deaths attributed to vascular causes (9.6% vs 9.3%) or nonvascular causes (6.7% vs 6.5%).  No adverse effect on cancer incidence was noted.

Conclusion:
Despite significant reductions in blood homocysteine levels, B12/folic acid supplementation had no beneficial effects on vascular outcomes in patients who had previously sustained a myocardial infarction.
• SEARCH Collaborative Group.  Effects of Homocysteine-Lowering With Folic Acid Plus Vitamin B12 vs Placebo on Mortality and Major Morbidityin Myocardial Infarction Survivors.  JAMA 2010;303(24):2486-2494.