Genistein reduces plasma homocysteine concentrations in a folate deficient rat model

Abstract

Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine (Hcy) is an intermediate in methyl group metabolism, as S‐adenosylmethionine (SAM), the methyl group donor for most biological methylations, results in the formation of S‐adenosylhomocysteine and ultimately Hcy. Genistein, a 17β‐estradiol‐like isoflavone, has been shown to maintain normal methyl group metabolism in the agouti mouse model fed a methyl‐deficient diet. Although dietary genistein does not provide a methyl group, it may modulate the one‐carbon pool and influence DNA methylation in estrogen‐responsive tissues. To date, it is not known to what extent genistein directly influences Hcy and methyl group metabolism. In the present study, the effects of genistein supplementation on elevated Hcy during moderate folate deficiency were examined. Male Sprague Dawley rats (n=24) were fed ad‐lib control and folate deficient (FD) diets for 14 d, followed by supplementation of each diet with 300mg/kg diet genistein for an additional 24 d. Hcy concentrations in the genistein supplemented FD animals (18.2 + 0.9μM) were reduced (24%; P = 0.01) relative to concentration in unsupplemented, FD rats (24.0 + 2.2μM). Analysis of other hepatic enzymes (i.e. GNMT, PEMT) indicate that the Hcy‐lowering effect of genistein does not reside in reduced production, but rather in increased metabolism.