title: Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  "The obesity epidemic" has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease (NAFLD), for which effective treatments are in demand. The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction. We aimed to test the hypothesis that resveratrol alleviates NAFLD in a randomised, clinical trial.
  
  
  METHODS
  A total of 28 overweight patients with transaminasemia and histological NAFLD were randomised 1:1 to placebo or resveratrol 1.5 g daily for 6 months. Twenty-six participants completed the trial and underwent repeated clinical investigation, blood work, MR spectroscopy; and 19 participants agreed to a repeat liver biopsy.
  
  
  RESULTS
  Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury (primary outcome: alanine transaminase, p = 0.51). Resveratrol-treated patients showed a 3.8% decrease in liver lipid content (p = 0.03), with no difference between the two treatment arms (p = 0.38) and no improvement of histological features. Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome, except for a transient decrease in systolic BP. Microarray analysis and qRT-PCR revealed no major changes in expression profile. Also, we report a serious adverse event in a patient who developed fever and bicytopenia.
  
  
  CONCLUSIONS
  In this placebo-controlled, high-dose and long-term study, resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD, though there may be a small ameliorating effect on liver function tests and liver fat accumulation.
authors.affiliation: a Department of Hepatology and Gastroenterology , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;|b Department of Clinical Biochemistry , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Sara
authors.initials: S
authors.lastname: Heebøll
authors.affiliation: a Department of Hepatology and Gastroenterology , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Martin
authors.initials: M
authors.lastname: Kreuzfeldt
authors.affiliation: c Department of Pathology , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Stephen
authors.initials: S
authors.lastname: Hamilton-Dutoit
authors.affiliation: d Department of Endocrinology and Internal Medicine , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Marianne
authors.initials: M
authors.lastname: Kjær Poulsen
authors.affiliation: e MR Research Centre , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Hans
authors.initials: H
authors.lastname: Stødkilde-Jørgensen
authors.affiliation: b Department of Clinical Biochemistry , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Holger Jon
authors.initials: HJ
authors.lastname: Møller
authors.affiliation: f Research Laboratory for Biochemical Pathology , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;|g Department of Molecular Medicine , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.affiliation: g Department of Molecular Medicine , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Kasper
authors.initials: K
authors.lastname: Thorsen
authors.affiliation: h Department of Pathology , Hvidovre Hospital , Hvidovre , Denmark.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Kristina Hellberg
authors.affiliation: e MR Research Centre , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Steen
authors.initials: S
authors.lastname: Bønløkke Pedersen
authors.affiliation: a Department of Hepatology and Gastroenterology , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ;
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbæk
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D011446:Prospective Studies; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D000077185:Resveratrol
keywords: Anti-inflammatory agents; antioxidants; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; resveratrol