title: Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial.
abstract: OBJECTIVE
  This study's aim was to assess the histological and metabolic effects of n-3 polyunsaturated fatty acids (PUFAs) vs. placebo while adjusting for the impact of age and weight change in NASH patients. (ClinicalTrials.gov: NCT00681408).
  
  
  METHODS
  Forty-one subjects with non-cirrhotic NASH were enrolled, and 34 completed the study. 17 received n-3 fish oil 3000 mg/day and 17 received placebo daily for 1 year with typical counselling on caloric intake and physical activity for all subjects.
  
  
  RESULTS
  N-3- and placebo-treated groups showed no significant difference for the primary end point of NASH activity score (NAS) reduction ⩾ 2 points without fibrosis progression after adjustment for known covariates (n-3, 4/17 (23.5%); placebo, 3/17, (17.6%), p = 0.99). Among subjects with increased or stable weight, n-3 subjects showed a larger decrease in liver fat content by MRI than placebo-treated subjects (p = 0.014 for 2nd quartile, p = 0.003 for 3rd quartile of weight change). N-3 treatment showed significant fat reduction on the paired analysis of image-assisted fat morphometry regardless of weight loss or gain. Exercise capacity remained markedly reduced in all subjects. No independent effects on markers of hepatocyte injury or insulin sensitivity indices were observed.
  
  
  CONCLUSIONS
  N-3 PUFAs at 3000 mg/day for one year did not lead to an improvement in the primary outcome of histological activity in NASH patients (⩾ 2 point NAS reduction). N-3 led to reduced liver fat by multiple measures. Other metabolic effects were not seen, although no detrimental effects were apparent. Whether longer duration, higher dose, or different composition of n-3 therapy would lead to additional benefits is uncertain.
authors.affiliation: Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA. Electronic address: cka3d@virginia.edu.
authors.forename: Curtis K
authors.initials: CK
authors.lastname: Argo
authors.affiliation: Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Patrie
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Carolin
authors.initials: C
authors.lastname: Lackner
authors.affiliation: Department of Radiology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Henry
authors.affiliation: Department of Radiology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Eduard E
authors.initials: EE
authors.lastname: de Lange
authors.affiliation: Department of Exercise Physiology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Weltman
authors.affiliation: Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Neeral L
authors.initials: NL
authors.lastname: Shah
authors.affiliation: Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Al-Osaimi
authors.affiliation: Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Patcharin
authors.initials: P
authors.lastname: Pramoonjago
authors.affiliation: Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA; Division of Gastroenterology & Hepatology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Saumya
authors.initials: S
authors.lastname: Jayakumar
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors.forename: Lukas P
authors.initials: LP
authors.lastname: Binder
authors.affiliation: Surgical Therapeutic Advancement Center, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Winsor D
authors.initials: WD
authors.lastname: Simmons-Egolf
authors.affiliation: Surgical Therapeutic Advancement Center, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Burks
authors.affiliation: Biomolecular Research Facility, School of Medicine, University of Virginia, Charlottesville, VA, USA.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Center for the Study of Complementary and Alternative Therapies, University of Virginia, Charlottesville, VA, USA.
authors.forename: Ann Gill
authors.initials: AG
authors.lastname: Taylor
authors.affiliation: Clinical Research Unit, Metabolic Research Kitchen, University of Virginia, Charlottesville, VA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rodriguez
authors.affiliation: Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA. Electronic address: shc5c@virginia.edu.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Caldwell
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies
chemical_list: D015525:Fatty Acids, Omega-3
keywords: Cardiorespiratory fitness; Exercise; Fatty liver; N-3 fatty acid; Obesity; Steatohepatitis