Omega-3 polyunsaturated fatty acids in treating non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial

Clin Nutr. 2016 Jun;35(3):578-86. doi: 10.1016/j.clnu.2015.05.001. Epub 2015 May 21.


Background: & aims: Few clinical trials have addressed the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) on non-alcoholic steatohepatitis (NASH). We evaluated the effects of supplementation with omega-3 PUFAs from flaxseed and fish oils in patients with biopsy-proven NASH.

Methods: Patients received three capsules daily, each containing 0.315 g of omega-3 PUFAs (64% alpha-linolenic [ALA], 16% eicosapentaenoic [EPA], and 21% docosahexaenoic [DHA] acids; n-3 group, n = 27) or mineral oil (placebo group, n = 23). Liver biopsies were evaluated histopathologically by the NASH activity score (NAS). Plasma levels of omega-3 PUFAs were assessed as a marker of intake at baseline and after 6 months of treatment. Secondary endpoints included changes in plasma biochemical markers of lipid metabolism, inflammation, and liver function at baseline and after 3 and 6 months of treatment.

Results: At baseline, NAS was comparable between the groups (p = 0.98). After intervention with omega-3 PUFAs, plasma ALA and EPA levels increased (p ≤ 0.05). However in the placebo group, we also observed increased EPA and DHA (p ≤ 0.05), suggesting an off-protocol intake of PUFAs. NAS improvement/stabilization was correlated with increased ALA in the n-3 group (p = 0.02) and with increased EPA (p = 0.04) and DHA (p = 0.05) in the placebo group. Triglycerides were reduced after 3 months in the n-3 group compared to baseline (p = 0.01).

Conclusions: In NASH patients, the supplementation of omega-3 PUFA from flaxseed and fish oils significantly impacts on plasma lipid profile of patients with NASH. Plasma increase of these PUFAs was associated with better liver histology. (ID 01992809).

Keywords: Alpha-linolenic acid; Docosahexaenoic acid; Eicosapentaenoic acid; Fish oil; Flaxseed oil; Nonalcoholic steatohepatitis.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Biopsy
  • Brazil
  • Dietary Supplements* / adverse effects
  • Double-Blind Method
  • Fatty Acids, Omega-3 / adverse effects
  • Fatty Acids, Omega-3 / blood
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Fish Oils / adverse effects
  • Fish Oils / therapeutic use*
  • Hospitals, Teaching
  • Humans
  • Hypertriglyceridemia / etiology
  • Hypertriglyceridemia / prevention & control
  • Linseed Oil / adverse effects
  • Linseed Oil / therapeutic use*
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology*
  • Liver / physiopathology
  • Lost to Follow-Up
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / diet therapy*
  • Non-alcoholic Fatty Liver Disease / immunology
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Patient Compliance
  • Patient Dropouts
  • Reproducibility of Results
  • Severity of Illness Index


  • Biomarkers
  • Fatty Acids, Omega-3
  • Fish Oils
  • Linseed Oil