title: Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine.
abstract: BACKGROUND
  Hyperhomocysteinemia is an independent risk factor for coronary heart disease (CHD). Dietary supplementation with B vitamins lowers plasma homocysteine by up to 30%. However, little is known about the potential beneficial effects of homocysteine lowering on vascular function in patients with CHD.
  
  
  RESULTS
  We investigated 89 men with CHD (aged 56 [range 39 to 67] years). Brachial artery flow-mediated dilatation (endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measured before and 8 weeks after treatment with either (1) folic acid (5 mg) and vitamin B(12) (1 mg) daily (n=59) or (2) placebo (n=30). Total, protein-bound, and free plasma homocysteine, serum folate, and vitamin B(12) were measured at baseline and at 8 weeks. Flow-mediated dilatation improved after treatment with B vitamins (2.5+/-3.2% to 4.0+/-3.7%, P:=0.002) but not placebo (2.3+/-2.6% to 1.9+/-2.6%, P:=0.5). Vitamin therapy lowered plasma concentrations of total homocysteine (from 13.0+/-3.4 to 9.3+/-1.9 micromol/L, P:<0.001), protein-bound homocysteine (from 8.7+/-2.8 to 6.2+/-1.4 micromol/L, P:<0.001), and free homocysteine (from 4.3+/-1.2 to 3.0+/-0.6 micromol/L, P:<0.001) and raised concentrations of serum folate (from 10.3+/-4.3 to 31.2+/-10.8 ng/mL, P:<0.001) and vitamin B(12) (from 314+/-102 to 661+/-297 pg/mL, P:<0.001). In regression analysis, improved flow-mediated dilatation correlated closely with the reduction in free plasma homocysteine (r=-0.26, P:=0.001), independent of changes in protein-bound homocysteine, folate, and vitamin B(12). Nitroglycerin-induced dilatation was unchanged after both B vitamins and placebo.
  
  
  CONCLUSIONS
  Folic acid and vitamin B(12) supplementation improves vascular endothelial function in patients with CHD, and this effect is likely to be mediated through reduced concentrations of free plasma homocysteine concentrations. Our data support the view that lowering homocysteine, through B vitamin supplementation, may reduce cardiovascular risk.
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: P M
authors.initials: PM
authors.lastname: Ueland
authors.forename: O A
authors.initials: OA
authors.lastname: Obeid
authors.forename: J
authors.initials: J
authors.lastname: Wrigley
authors.forename: H
authors.initials: H
authors.lastname: Refsum
authors.forename: J S
authors.initials: JS
authors.lastname: Kooner
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D019587:Dietary Supplements; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D005996:Nitroglycerin / Q000494:pharmacology; D012044:Regression Analysis; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D014665:Vasodilator Agents / Q000494:pharmacology; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000097:blood
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D014280:Triglycerides; D014665:Vasodilator Agents; D006710:Homocysteine; D005492:Folic Acid; D002784:Cholesterol; D005996:Nitroglycerin; D014805:Vitamin B 12