title: Acute methionine loading does not alter arterial stiffness in humans.
abstract: Hyperhomocystinemia is a risk factor for cardiovascular disease, and acute elevation of plasma homocysteine after methionine loading impairs endothelial function in healthy subjects. Interestingly, pretreatment with vitamin C can ameliorate this effect. We have already shown that acute oral vitamin C administration reduces arterial stiffness in healthy subjects, and the aim of the present study was to investigate the effect of methionine loading on arterial stiffness with and without concomitant vitamin C using the noninvasive technique of pulse wave analysis. Eight healthy male subjects (mean age, 29 years; range, 20-42 years) were studied on three occasions at weekly intervals. In a double-blind, double-dummy, randomized order they received orally either 100 mg/kg methionine, 100 mg/kg methionine plus 2 g of vitamin C, or matching placebos. Peripheral and central blood pressure, heart rate, cardiac index, arterial stiffness, and plasma homocysteine levels were assessed at baseline and 6 hours after dosing. Compared with placebo, there was no significant change in any of the hemodynamic parameters, including arterial stiffness, after oral methionine, although plasma homocysteine did increase from 11.5 +/- 1.6 to 28.7 +/- 4.4 microM (mean +/- SEM; p < 0.001). Combined methionine and vitamin C led to a similar increase in plasma homocysteine but significantly reduced augmentation index by 10.5 +/- 3.2% (p = 0.02). Acute hyperhomocystinemia does not significantly alter arterial stiffness, as assessed by pulse wave analysis, whereas a combination of methionine and vitamin C leads to a similar reduction in augmentation index to that previously described after vitamin C alone. These data reinforce evidence that vitamin C reduces arterial stiffness but do not indicate any important interaction with oral methionine.
authors.affiliation: Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, UK. ibw20@cam.ac.uk
authors.forename: I B
authors.initials: IB
authors.lastname: Wilkinson
authors.forename: I L
authors.initials: IL
authors.lastname: Megson
authors.forename: T
authors.initials: T
authors.lastname: MacCallum
authors.forename: D F
authors.initials: DF
authors.lastname: Rooijmans
authors.forename: S M
authors.initials: SM
authors.lastname: Johnson
authors.forename: J L
authors.initials: JL
authors.lastname: Boyd
authors.forename: J R
authors.initials: JR
authors.lastname: Cockcroft
authors.forename: D J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000975:Antioxidants / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000188:drug therapy; D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004338:Drug Combinations; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006710:Homocysteine / Q000097:blood / Q000187:drug effects*; D006801:Humans; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
chemical_list: D000975:Antioxidants; D004338:Drug Combinations; D006710:Homocysteine; D008715:Methionine; D001205:Ascorbic Acid