title: Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?
abstract: BACKGROUND
  Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the effect on adverse vascular events is unknown. We hypothesized that in patients with chronic renal failure, a condition associated with both hyperhomocysteinemia and atherosclerosis, treatment with folic acid would improve endothelial function.
  
  
  RESULTS
  In a prospective, double-blind protocol, 100 patients (mean age 62 years, 67 men) with predialysis chronic renal failure were randomized to 5 mg folic acid or placebo daily for 12 weeks. Endothelial function was assessed by measuring (1) endothelium-dependent dilation of the brachial artery, (2) combined serum nitrite/nitrate concentrations, and (3) plasma von Willebrand factor concentration. Baseline characteristics of the 2 groups were similar. At the end of the study, both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [mean (95% CI) 39.0 (29.8 to 51.0) versus 7.7 (6.6 to 8.9) microg/L and 739 (613 to 891) versus 220 (184 to 262) microg/L, respectively; both P<0.001]. Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [15.1 (14.1 to 16.2) versus 20.1 (18.2 to 22.2) micromol/L; P<0.001], there were no significant differences in endothelium-dependent dilation, combined serum nitrite/nitrate concentrations, or plasma von Willebrand factor concentration between the 2 groups.
  
  
  CONCLUSIONS
  High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure. This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia.
authors.affiliation: Division of Medical Sciences (Cardiology), University of Birmingham Birmingham, UK. J.Thambyrajah@bham.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Thambyrajah
authors.forename: M J
authors.initials: MJ
authors.lastname: Landray
authors.forename: F J
authors.initials: FJ
authors.lastname: McGlynn
authors.forename: H J
authors.initials: HJ
authors.lastname: Jones
authors.forename: D C
authors.initials: DC
authors.lastname: Wheeler
authors.forename: J N
authors.initials: JN
authors.lastname: Townend
mesh_terms: D000368:Aged; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010919:Placebos; D011446:Prospective Studies; D006435:Renal Dialysis; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D006397:Hematinics; D009566:Nitrates; D009573:Nitrites; D010919:Placebos; D014841:von Willebrand Factor; D006710:Homocysteine; D005492:Folic Acid