Homocysteine, Folate, and Cardiovascular Disease

Abstract

Cardiovascular disease (CVD) continues to be one of the main causes of mortality in the western world, however approximately only two-thirds of all episodes can be attributed to traditional environmental and genetic risk factors. Over the past decade it has emerged that a moderate elevation in plasma concentrations of the amino acid homocysteine (tHcy) constitutes a risk factor for atherosclerotic vascular disease in the coronary, cerebral and peripheral vessels. Furthermore, this association is a graded one with no apparent threshold and is independent of, but may enhance the effect of conventional risk factors. Plasma homocysteine is determined by both genetic and nutritional factors. The B-vitamins folate, B-12 and B-6 all play a key role in homocysteine metabolism and in fact it has been proposed that about two-thirds of all cases of hyperhomocysteinemia are due to an inadequate status of one or all of these vitamins. Of the three, folate appears to be the most important determinant and has been shown to significantly lower homocysteine concentration when administered at doses ranging from 0.2 to 10 mg/d in both healthy and hyperhomocysteinemic subjects. There is considerable variation in the rate of CVD mortality between northern and southern European countries. A common dietary element in regions with lower CVD incidence i.e. southern European countries appears to be the higher consumption of fruit and vegetables. In the past this protective effect of fruit and vegetables has been primarily attributed to antioxidants. Fruit and vegetables are however also one of the main sources of folate in the diet, contributing to more than 30% of total dietary folate intake (even in countries where consumption of fruit and vegetables is low). Thus, in light of the evidence that folate may play a role in primary prevention of CVD via homocysteine-lowering the protective effect of fruit and vegetables may be partly explained by folate.