Homocysteine and stroke prevention: have the trials settled the issue?

Recent publicity surrounding disappointing results of clinical trials of homocysteine lowering has led to the claim that 'homocysteine is dead'. However, there is strong evidence that elevated plasma total homocysteine is an important independent risk factor, and the highly plausible biological rationale is the following: total homocysteine increases coagulation, impairs endothelial function, increases oxidative stress and low density lipoprotein oxidation, and treatment with vitamins reverses these effects and halts progression of carotid plaque. Some studies have shown clinical benefit of vitamin therapy in coronary angioplasty and peripheral vascular disease. It has recently become apparent that vitamin B12 absorption is impaired in the elderly, and that metabolic B12 deficiency is much commoner than would be appreciated by statistical definitions of 'normal' serum B12; higher doses of B12 and perhaps other therapies such as betaine and thiols may be needed to achieve adequate reductions of total homocysteine. It remains likely that effective lowering of total homocysteine will reduce stroke and other vascular events.