Folate deficiencies and cardiovascular pathologies.
Although folates are widely distributed in foods, folate deficiencies may be more frequent than expected because their true availability may be impaired due to their lability under various food cooking and processing conditions. Folate deficiency is frequently observed in elderly people, smokers, alcoholics and oral contraceptive users. It is also associated with the mutation leading to the thermolabile variant of N5,10-methylenetetrahydrofolate reductase which is observed in about 10% of the population. In addition to the essential role of the intracellular pool of polyglutamates in de novo biosynthesis of deoxyribonucleotides which allow cell growth and division, the reduced and methylated form of folate, N5-methyltetrahydrofolate, is required for the remethylation of homocysteine to methionine. By inhibiting this remethylation pathway, folate deficiency induces homocysteine efflux into the circulation. Many studies have shown a negative correlation between plasma folate, particularly N5-methyltetrahydrofolate, and circulating homocysteine levels. In addition, folate deficiency is a major cause of hyperhomocysteinemia which is fully recognised as an independent risk factor for atherothrombosis. Epidemiological and recent experimental studies have demonstrated that folate deficiency might increase the risk of cardiovascular disease by increasing circulating homocysteine levels. Thus, the clinical efficiency of folate supplementation, especially N5-methyltetrahydrofolate, in reducing homocysteine-dependent cardiovascular risk should be evaluated.
Durand
P
P
INSERM U 498, Biochimie des Lipoprotéines et Interactions Vasculaires, Faculté de Médecine, Université de Bourgogne, Dijon, France.
Prost
M
M
Blache
D
D
D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology*; D005492:Folic Acid / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure
D006710:Homocysteine; D005492:Folic Acid