title: Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects.
abstract: We hypothesized that physiological increments in plasma homocysteine after low-dose oral methionine or dietary animal protein induce vascular endothelial dysfunction and that there is a graded, inverse relationship between homocysteine concentration and endothelial function. We studied 18 healthy volunteers aged 18 to 59 years. Brachial artery flow-mediated and glyceryltrinitrate-induced dilatation were measured after 1) oral L-methionine (10, 25, and 100 mg/kg), 2) dietary animal protein (lean chicken 551+/-30 g, comprising 3.2+/-0.2 g methionine), and 3) methionine-free amino acid mix (100 mg/kg). Methionine (10, 25, and 100 mg/kg) induced a dose-related increase in homocysteine (9.4+/-1.3 to 12.2+/-2.1, 17. 6+/-2.6, and 26.1+/-4.2 micromol/L, respectively; P<0.001) and a reduction in flow-mediated dilatation (4.1+/-0.8 to 2.1+/-0.8, 0. 3+/-0.8, and -0.7+/-0.8%, respectively; P<0.001) at 4 hours. Compared with usual meal, animal protein increased plasma homocysteine (9.6+/-0.8 to 11.2+/-0.9 micromol/L, P=0.005) and reduced flow-mediated dilatation (4.5+/-0.7% to 0.9+/-0.6%, P=0.003). Methionine-free amino acid mix did not induce any changes. Glyceryltrinitrate-induced dilatation was unchanged throughout. In this study, small physiological increments in plasma homocysteine after low-dose methionine and dietary animal protein induced vascular endothelial dysfunction. We propose that protein intake-induced increments in plasma homocysteine may have deleterious effects on vascular function and contribute to the development and progression of atherosclerosis.
authors.affiliation: National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
authors.forename: J C
authors.initials: JC
authors.lastname: Chambers
authors.forename: O A
authors.initials: OA
authors.lastname: Obeid
authors.forename: J S
authors.initials: JS
authors.lastname: Kooner
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000008:administration & dosage; D001628:Beverages; D001916:Brachial Artery / Q000502:physiology; D004044:Dietary Proteins / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005638:Fruit; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008715:Methionine / Q000008:administration & dosage; D008875:Middle Aged; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D000596:Amino Acids; D004044:Dietary Proteins; D006710:Homocysteine; D008715:Methionine