Effect of Methionine Supplementation on Endothelial Function, Plasma Homocysteine, and Lipid Peroxidation

• Published in: Journal of toxicology. Clinical toxicology Vol. 37; no. 4; pp. 435 - 440
• Main Authors: McAuley, Daniel F., McAuley, Daniel, Hanratty, Colm G., McGurk, Colm, Nugent, Ailish G., Johnston, G. Dennis
• Format: Journal Article
• Language: English
• Published: Monticello, NY Informa UK Ltd 01.01.1999; Taylor & Francis; Dekker
• Subjects: Acetylcholine - pharmacology; Adult; Biological and medical sciences; Chromatography, High Pressure Liquid; Dietary Supplements - adverse effects; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Endothelium, Vascular - drug effects; Female; Forearm - blood supply; homocysteine; Homocysteine - blood; Humans; Lipid Peroxidation - drug effects; Male; Medical sciences; Methionine - administration & dosage; Methionine - pharmacology; Miscellaneous (drug allergy, mutagens, teratogens...); Nitric Oxide - metabolism; Nitroprusside - pharmacology; Pharmacology. Drug treatments; Plethysmography; Thiobarbituric Acid Reactive Substances - analysis; Human; Drug combination; Healthy subject; Toxicity; Methionine; Lipids; Endothelium; Prevention; Paracetamol; Analgesic; Dosage form; Tablet; Supplementation; Peroxidation
• ISSN: 0731-3810; 1097-9875
• DOI: 10.1081/CLT-100102433

Background: Acetaminophen (paracetamol) poisoning is a major source of morbidity and mortality. It has been proposed that methionine be incorporated into acetaminophen tablets routinely as a protective mechanism. Methionine has been shown to be effective in the treatment of acetaminophen toxicity and a combination preparation of acetaminophen and methionine may prevent toxicity. However, there has been some concern that chronic methionine supplementation 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 associated with atherosclerosis. Methods: Sixteen healthy volunteers were studied. Forearm blood flow in response to local intra-arterial infusion of acetylcholine to assess endothelium-dependent vasodilatation and sodium nitroprusside to assess endothelium-independent vasodilatation was measured by venous occlusion plethysmography. Plasma homocysteine and lipid peroxidation, measured as thiobarbituric acid reactive substances, were measured using high-performance liquid chromatography. Forearm vascular responses, plasma homocysteine concentrations, and thiobarbituric acid reactive substances were measured at baseline and following methionine supplementation. Results: There was no significant difference in endothelial-dependent vascular responses after acute (methionine 250 mg orally, p > 0.05), 1 month of low-dose (methionine 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 difference in plasma homocysteine concentrations after acute (p > 0.05) or 1 month of low-dose (p > 0.05) methionine administration. However, 1 week of high-dose methionine (100 mg kg) administration daily significantly increased homocysteine concentrations (p < 0.0015). Thiobarbituric acid reactive substances were unchanged during the period of study (p > 0.05). Conclusions: Methionine supplementation does not impair endothelial-dependent vascular responses in healthy volunteers. Although high-dose methionine administration causes elevation of plasma homocysteine concentrations, doses similar to those used in combination preparations with acetaminophen do not affect plasma homocysteine concentrations.