title: Oral antioxidant supplementation for fatigue associated with primary biliary cirrhosis: results of a multicentre, randomized, placebo-controlled, cross-over trial.
abstract: BACKGROUND
  We have previously reported, in an uncontrolled trial, an improvement in fatigue scores in patients with primary biliary cirrhosis given oral antioxidant supplementation. We now present data from a controlled trial.
  
  
  METHODS
  Sixty-one patients with primary biliary cirrhosis-associated fatigue were randomized into a double-blind, placebo-controlled, cross-over trial. Participants received 12 weeks each of placebo and antioxidant supplementation (vitamins A, C and E, selenium, methionine and ubiquinone) in random order, separated by a 4-week washout period. The primary trial outcome (fatigue) was assessed using the Fisk scale. Other symptoms of primary biliary cirrhosis were measured using Likert and visual analogue scales.
  
  
  RESULTS
  Forty-four patients completed both arms of the trial. No significant changes in fatigue were recorded in the active phase of treatment (median improvement in Fisk score, 1; P = 0.61). Small improvements in Fisk scores were recorded during placebo therapy (median improvement, 4; P = 0.03). Neither medication was associated with improvement in any other symptoms related to primary biliary cirrhosis. Adverse effects were more common during active therapy and were mild and self-limiting. One patient died from unrelated causes during active treatment.
  
  
  CONCLUSIONS
  Although oral antioxidant supplementation appears to be safe, we could not find any evidence for a beneficial effect on fatigue or other liver-related symptoms.
authors.affiliation: Centre for Liver Research, Newcastle University Medical School, Framlington Place, Newcastle, Tyne & Wear, NE2 4LL, UK. martin.prince@ncl.ac.uk
authors.forename: M I
authors.initials: MI
authors.lastname: Prince
authors.forename: H C
authors.initials: HC
authors.lastname: Mitchison
authors.forename: D
authors.initials: D
authors.lastname: Ashley
authors.forename: D A
authors.initials: DA
authors.lastname: Burke
authors.forename: N
authors.initials: N
authors.lastname: Edwards
authors.forename: M G
authors.initials: MG
authors.lastname: Bramble
authors.forename: O F W
authors.initials: OF
authors.lastname: James
authors.forename: D E J
authors.initials: DE
authors.lastname: Jones
mesh_terms: D000284:Administration, Oral; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005221:Fatigue / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000150:complications*; D008715:Methionine / Q000008:administration & dosage; D012643:Selenium / Q000008:administration & dosage; D014451:Ubiquinone / Q000008:administration & dosage; D014801:Vitamin A / Q000008:administration & dosage; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D014801:Vitamin A; D014451:Ubiquinone; D014810:Vitamin E; D008715:Methionine; D012643:Selenium; D001205:Ascorbic Acid