title: The effect of N-acetylcysteine on plasma total homocysteine levels in hemodialysis: a randomized, controlled study.
abstract: BACKGROUND
  The chronic hemodialysis population has an accelerated rate of cardiovascular morbidity and death. Furthermore, elevated levels of the putative atherothrombotic risk factor homocysteine are almost ubiquitous in this population. Attempts to normalize elevated plasma total homocysteine (tHcy) levels in dialysis patients using pharmacological-dose vitamin therapy or other strategies generally have been unsuccessful. Preliminary uncontrolled evidence suggests that N-acetylcysteine (NAC) may be an effective tHcy-lowering agent. We designed a randomized placebo-controlled study to determine the effect of prolonged oral NAC therapy on lowering tHcy levels in vitamin-replete chronic hemodialysis patients.
  
  
  METHODS
  Thirty-eight subjects were treated before intervention with a standard dialysis vitamin supplement to ensure a uniform vitamin-replete state. They were then block randomized to treatment with NAC, 1.2 g twice a day, for 4 weeks or matched placebo.
  
  
  RESULTS
  There were no significant baseline differences between the two groups, although differences in pyridoxal 5'-phosphate (active form of vitamin B(6)) levels approached significance (P = 0.06). In a paired analysis, there was no statistically significant difference between the NAC and placebo groups. NAC was very well tolerated in hemodialysis patients.
  
  
  CONCLUSIONS
  This randomized placebo-controlled trial found that chronic oral NAC therapy did not significantly reduce tHcy levels in hemodialysis patients. Although a larger sample size theoretically could have increased the statistical significance between groups, implications of the potentially very modest reduction in tHcy levels are not yet known. Finally, based on this limited study, NAC appears to be a safe and well-tolerated therapy in the hemodialysis population.
authors.affiliation: Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA. allfried@iupui.edu
authors.forename: Allon N
authors.initials: AN
authors.lastname: Friedman
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Bostom
authors.forename: Priscilla
authors.initials: P
authors.lastname: Laliberty
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Douglas
authors.initials: D
authors.lastname: Shemin
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000368:Aged; D019587:Dietary Supplements; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000379:methods*; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D014815:Vitamins; D006710:Homocysteine; D000111:Acetylcysteine