Effect of methionine supplementation on endothelial function, plasma homocysteine, and lipid peroxidation

Background: Acetaminophen (paracetamol) poisoning is a major source of morb idity and mortality. It has been proposed that methionine be incorporated i nto acetaminophen tablets routinely as a protective mechanism. Methionine h as been shown to be effective in the treatment of acetaminophen toxicity an d a combination preparation of acetaminophen and methionine may prevent tox icity. However, there has been some concern that chronic methionine supplem entation may be associated with vascular disease. The aim of the study was to investigate if methionine supplementation causes changes in endothelial function, plasma homocysteine, or lipid peroxidation which may be associate d with atherosclerosis. Methods: Sixteen healthy volunteers were studied. F orearm blood flow in response to local intra-arterial infusion of acetylcho line to assess endothelium-dependent vasodilatation and sodium nitroprussid e to assess endothelium-independent vasodilatation was measured by venous o cclusion plethysmography. Plasma homocysteine and lipid peroxidation, measu red as thiobarbituric acid reactive substances, were measured using high-pe rformance liquid chromatography. Forearm vascular responses, plasma homocys teine concentrations, and thiobarbituric acid reactive substances were meas ured at baseline and following methionine supplementation. Results: There w as no significant difference in endothelial-dependent vascular responses af ter acute (methionine 250 mg orally, p > 0.05), 1 month of low-dose (methio nine 250 mg daily, p > 0.05), or 1 week of high-dose (methionine 100 mg/kg daily, p > 0.05) methionine administration. There was no significant differ ence in plasma homocysteine concentrations after acute (p > 0.05) or 1 mont h of low-dose (p > 0.05) methionine administration. However, 1 week of high -dose methionine (100 mg/kg) administration daily significantly increased h omocysteine concentrations (p < 0.0015), Thiobarbituric acid reactive subst ances were unchanged during the period of study (p > 0.05), Conclusions: Me thionine supplementation does not impair endothelial-dependent vascular res ponses in healthy volunteers. Although high-dose methionine administration causes elevation of plasma homocysteine concentrations, doses similar to th ose used in combination preparations with acetaminophen do not affect plasm a homocysteine concentrations.