Systematic review and meta-analysis of controlled intervention studies on the effectiveness of long-chain omega-3 fatty acids in patients with nonalcoholic fatty liver disease

Nutr Rev. 2018 Aug 1;76(8):581-602. doi: 10.1093/nutrit/nuy022.


Context: Treatment options for nonalcoholic fatty liver disease (NAFLD) are needed.

Objective: The aim of this review was to systematically assess the effects of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), particularly eicosapentaenoic acid and docosahexaenoic acid, on liver-related and metabolic outcomes in adult and pediatric patients with NAFLD.

Data sources: The online information service ProQuest Dialog was used to search 8 literature databases.

Study selection: Controlled intervention studies in which the independent effects of n-3 LC-PUFAs could be isolated were eligible for inclusion.

Data extraction: The 18 unique studies that met the criteria for inclusion were divided into 2 sets, and data transcriptions and study quality assessments were conducted in duplicate. Each effect size was expressed as the weighted mean difference and 95%CI, using a random-effects model and the inverse of the variance as a weighting factor.

Results: Based on the meta-analyses, supplementation with n-3 LC-PUFAs resulted in statistically significant improvements in 6 of 13 metabolic risk factors, in levels of 2 of 3 liver enzymes, in liver fat content (assessed via magnetic resonance imaging/spectroscopy), and in steatosis score (assessed via ultrasonography). Histological measures of disease [which were assessed only in patients with nonalcoholic steatohepatitis (NASH)] were unaffected by n-3 LC-PUFA supplementation.

Conclusions: Omega-3 LC-PUFAs are useful in the dietary management of patients with NAFLD. Additional trials are needed to better understand the effects of n-3 LC-PUFAs on histological outcomes in patients with NASH.

Systematic review registration: PROSPERO CRD42017055951.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Clinical Trials as Topic
  • Dietary Fats / administration & dosage*
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage
  • Eicosapentaenoic Acid / administration & dosage
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Humans
  • Liver / metabolism
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / therapy*
  • Treatment Outcome


  • Dietary Fats
  • Fatty Acids, Omega-3
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid