Folate metabolism and cardiovascular disease.

Folate is a water-soluble vitamin that occurs in different chemical forms distinguished by their oxidation state and the specific type of one-carbon substitution. Folates occur in natural food sources as reduced methylated or formylated tetrahydrofolate. Folic acid is a synthetic analogue with no metabolic activity of its own. Pharmacological doses of folic acid cause it to appear in plasma, where it has unknown, but potentially adverse, effects. This review discusses folate absorption, body distribution, and intracellular folate metabolism. The main physiological functions of folate can be classified as methylation and DNA synthesis. Several mechanisms act in concert to regulate the folate metabolic pathways to ensure that both functions of folate are fulfilled properly. B-vitamin deficiencies and genetic polymorphisms (particularly the C677T mutation in the methylenetetrahydrofolatereductase gene) have multiple effects on folate metabolism. Impairment of the methylation cycle, for example, leads to hyperhomocysteinemia, a proposed atherothrombotic factor. However, methylation disturbances also result in hypomethylation of DNA and other molecules, which may also contribute to the pathogenesis of cardiovascular disease. As cardiovascular researchers, we should try to develop a more integrative view on folate metabolism, rather than focusing merely on hyperhomocysteinemia.