title: Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults.
abstract: BACKGROUND
  Elevated plasma homocysteine is a risk factor for arteriosclerosis, but a cause-and-effect relationship remains to be fully established. Endothelial dysfunction, an early event in the atherogenic process, has been shown to be associated with hyperhomocysteinemia in experimental and human studies. To further establish a direct relationship between changes in plasma homocysteine and endothelial dysfunction, we investigated whether moderate hyperhomocysteinemia induced by an oral methionine load would acutely impair flow-mediated endothelium-dependent vasodilatation in healthy adults.
  
  
  RESULTS
  Twenty-four healthy volunteers completed a randomized crossover study in which an oral methionine load (0.1 g/kg) was administered on 1 of 2 study days, 7 days apart. At each visit, plasma homocysteine and brachial artery endothelium-dependent and -independent dilatation were measured at baseline and at 4 hours. To further elucidate the temporal relationship between methionine, homocysteine, and endothelial function, an oral methionine load was administered in 10 subjects on a separate visit, and the time courses of plasma methionine, homocysteine, and flow-mediated brachial artery dilatation were measured at baseline and after 1, 2, 3, 4, and 8 hours. After oral methionine, plasma homocysteine increased from 7. 9+/-2.0 micromol/L at baseline to 23.1+/-5.4 micromol/L at 4 hours (P<0.0001, n=24) and was associated with a decrease in flow-mediated brachial artery dilatation from 0.12+/-0.09 to 0.06+/-0.09 mm (P<0. 05). The time course of the impairment of flow-mediated vasodilatation mirrored the time course of the increase in homocysteine concentration.
  
  
  CONCLUSIONS
  Oral methionine loading raises plasma homocysteine and impairs flow-mediated endothelium-dependent vasodilatation. This supports the view that homocysteine may promote vascular disease by inducing endothelial dysfunction.
authors.affiliation: Cardiovascular Sciences Research Group and Department of Medical Computing and Statistics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
authors.forename: M F
authors.initials: MF
authors.lastname: Bellamy
authors.forename: I F
authors.initials: IF
authors.lastname: McDowell
authors.forename: M W
authors.initials: MW
authors.lastname: Ramsey
authors.forename: M
authors.initials: M
authors.lastname: Brownlee
authors.forename: C
authors.initials: C
authors.lastname: Bones
authors.forename: R G
authors.initials: RG
authors.lastname: Newcombe
authors.forename: M J
authors.initials: MJ
authors.lastname: Lewis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001916:Brachial Artery / Q000503:physiopathology; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006801:Humans; D020138:Hyperhomocysteinemia / Q000503:physiopathology*; D008297:Male; D008715:Methionine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow / Q000502:physiology; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology
chemical_list: D008715:Methionine