Homocysteine, folate, and cardiovascular disease

Cardiovascular disease (CVD) continues to be one of the main causes of mort ality in the western world, however approximately only two-thirds of all ep isodes can be attributed to traditional environmental and genetic risk fact ors. Over the past decade it has emerged that a moderate elevation in plasm a concentrations of the amino acid homocysteine (tHcy) constitutes a risk f actor for atherosclerotic vascular disease in the coronary, cerebral and pe ripheral vessels. Furthermore, this association is a graded one with no app arent threshold and is independent of, but may enhance the effect of conven tional 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 met abolism 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 t hese vitamins. Of the three, folate appears to be the most important determ inant 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 northe rn and southern European countries. A common dietary element in regions wit h lower CVD incidence i.e. southern European countries appears to be the hi gher consumption of fruit and vegetables. In the past this protective effec t of fruit and vegetables has been primarily attributed to antioxidants. Fr uit and vegetables are however also one of the main sources of folate in th e diet, contributing to more than 30% of total dietary foliate intake (even in countries where consumption of fruit and vegetables is low). Thus, in l ight of the evidence that folate may play a role in primary prevention of C VD via homocysteine-lowering the protective effect of fruit and vegetables may be partly explained by folate.