Homocysteine and B vitamins.

Homocysteine (tHcy) is an intermediate sulfur-containing amino acid which acts as a methyl group donor for methionine metabolism. Increased serum concentrations (=hyperhomocysteinemia, >10 micromol/l) have been associated with an increased cardiovascular risk. Homocystinuria, an infrequent genetic disease usually due to lack of cystathione beta-synthase, has been found with severely elevated serum homocysteine values (>150 micromol/l). Functional gene polymorphisms of key enzymes (e.g., N5,N10-methylene-tetrahydrofolate reductase) and dietary B-vitamin deficiencies in the elderly are, however, frequent in the 'Western' population. Hyperhomocysteinemia has been associated with other vascular effects such as atherothrombosis and endothelial dysfunction due to its auto-oxidative potential, thereby increasing the production of reactive oxygen species. Other effects may involve neurodegenerative diseases such as Alzheimer or dementia praecox of the elderly. Therapeutic interventions lowering tHcy may therefore offer novel tools for the prevention and treatment of atherosclerosis. B-vitamin supplementation (folic acid=vitamin B9, vitamin B6 and vitamin B12) is an efficient and safe tHcy-lowering therapy, decreases tHcy by 30%-50% and has been shown to lower cardiovascular morbidity and mortality. Furthermore, folic acid supplementation has been shown to reduce or even almost eliminate neurotubular birth defects (spina bifida) and to markedly decrease the rate of megaloblastic anemia. Thus, fortification of flour with folic acid in the USA was advocated several years ago in order to prevent these entities.