addition, some experiences performed in this field demonstrated that these nutrients could favor some negative effects, as the growth of an unknown neoplastic mass, especially the cells of prostate cancer. Therefore, the supplementation with folates and other vitamins of B group can be performed cautiously in patients with increased Hcy serum concentration.
INTRODUCTIONApart from traditional risk factors for cardiovascular disease, a powerful cause for raised cardiovascular morbility and mortality can be the inherited or acquired hyper-homocysteinemia (H-Hcy). In this field, several reports referred that H-Hcy can be responsible for early and massive atherosclerosis, inducing some vascular diseases life threatening, such as myocardial infarction (MI), ischemic acute stroke (IS), and peripheral vascular disease (PVD) [1][2][3][4][5] . Concerning this, several studies and trials demonstrated that elevated plasma total Hcy may promote atherothrombosis with several mechanisms [6][7][8] . Among these, increased Hcy and S-adenosyl-homocysteine (SAH) serum values, inhibiting the methyltransferases, result in abnormal smooth muscle cell proliferation and reduction of endothelial cells' growth. A critical role in the atherosclerotic process is played by DNA hypomethylation [9,10] . But, H-Hcy also causes down regulation of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), resulting in depletion of H2S, an angiogenic agent with antioxidant and vasorelaxing properties. Therefore, its depletion results in
ABSTRACTFolic acid and/or Vitamins B6-12 deficiency induces high-homocysteine (H-Hcy) serum levels for reduced activity of methylene-tetra hydro folate reductase (MTHFR). This metabolic derangement can be responsible for early and massive atherosclerosis, that could favour ischemic acute events. It can be assumed that vitamins' supplementation, reducing the elevated Hcy serum concentration, could reduce atherosclerotic risk. In this review,we evaluated if, the reduction of the high Hcy values by the B-vitamins' supplementation, is able to reduce the incidence of atherosclerotic events.Retrospective trials performed in patients already suffered of acute ischemic episodes, demonstrated that vitamins B6-9-12 supplementation was unable to reduce the incidence of new ischemic events, even if it lowers the high Hcy levels. On the contrary, perspective studies carried out in patients not previously suffered of cardiovascular acute events, evidenced that the vitamins' supplementation significantly reduced both Hcy serum concentration and atherosclerotic risk. These conflicting results demonstrate that folic acid and vitamins B6/12 supplementation is effective in to reduce high Hcy serum concentration in patients with signs of previous atherosclerosis, but is unable to reduce the atherosclerotic risk. On the contrary, the supplementation is useful in to lower both high Hcy serum levels and atherosclerotic risk in patients without atherosclerotic marks. In