Sex-related differences in methionine metabolism and plasma homocysteine concentrations

Background: Elevated fasting homocysteine concentrations are considered a r isk factor for vascular disease. Homocysteine, which is produced by the tra nsmethylation of methionine, can be either remethylated back to methionine or metabolized via transsulfuration to cystathionine. It has been speculate d that the lower risk of vascular disease among premenopausal women may be related to lower homocysteine concentrations in women than in men. Objective: This study was designed to determine whether sex-related differe nces exist in methionine cycle kinetics, which may account for the reported ly lower fasting homocysteine concentrations in premenopausal women. Design: Eleven healthy young men and 11 premenopausal women without cardiac risk factors were studied by using stable-isotope-labeled L-[methyl-H-2(3) ,1-C-13]methionine and L-[methyl-H-2(3)]leucine. After 3 h of tracer infusi on, 100 mg unlabeled L-methionine/kg body wt was ingested. Blood and breath samples were obtained at timed intervals. Fat-free mass was estimated by d ual-energy X-ray absorptiometry and muscle mass by urinary creatinine excre tion. Results: No significant sex-related differences were found in fasting homoc ysteine concentrations, responses to the oral methionine load, or rates of methionine flux based on carboxyl or methyl labels. However, women had sign ificantly higher remethylation rates than did men (P < 0.005) and a tendenc y toward higher transmethylation (P < 0.10). Whereas adjustment of remethyl ation rates for fat-free mass tended to attenuate the sex-related effect (P = 0.08), adjustment for muscle mass did not (P < 0.04). In contrast, signi ficant sex-related differences in leucine flux (P < 0.02) were eliminated a fter adjustment for either fat-free mass or muscle mass. Conclusion: Reported differences between men and women in homocysteine conc entrations may be partially explained by differences in rates of homocystei ne remethylation.