The effects of oral methionine and homocysteine on endothelial function

Background-Raised homocysteine is a risk factor for vascular disease. Homoc ysteine is formed from methionine, and dietary manipulation of homocysteine in primates and humans with oral methionine is associated with endothelial dysfunction. A cause-effect relation has not been clearly established. Aim-To study the effect of oral methionine and then oral homocysteine on en dothelial function. Methods-22 healthy adults were recruited for two randomised crossover studi es, each containing 11 subjects. Endothelial function was determined by mea suring forearm blood flow in response to intra-arterial infusion of acetylc holine (endothelium dependent) and sodium nitroprusside (endothelium indepe ndent). Subjects received methionine or placebo (study I), or homocysteine or placebo (study 2). Methionine and homocysteine were determined at baseli ne and t = 4 hours. Endothelial function was determined at four hours. The responses to the vasoactive substances are expressed as the area under the curve of change in forearm blood flow from baseline. Results-Study 1: plasma methionine and homocysteine concentrations increase d significantly versus placebo. The increases were associated with a reduct ion of endothelium dependent responses (mean (95% confidence interval), arb itrary units), from 48.8 (95% CI 36.4 to 61.2) to 29.9 (95% CI 18.0 to 41.1 ), P < 0.04; endothelium independent responses were unchanged. Study 2: hom ocysteine concentration increased significantly while methionine remained u nchanged. Endothelium dependent responses were reduced from 34.6 (95% CI 20 .6 to 48.6) to 22.8 (95% CI 12.0 to 33.6), p < 0.03. Conclusions-Homocysteine and not methionine is responsible for the changes in endothelial function. This supports the hypothesis that homocysteine pro motes atherosclerosis by inducing endothelial dysfunction.