Nonalcoholic Fatty Liver Disease and Omega-3 Fatty Acids: Mechanisms and Clinical Use

Annu Rev Nutr. 2023 Aug 21:43:199-223. doi: 10.1146/annurev-nutr-061021-030223. Epub 2023 May 19.


Nonalcoholic fatty liver disease (NAFLD) is the most common chronic fatty liver disease worldwide, particularly in obese and type 2 diabetic individuals. Currently, there are no therapies for NAFLD that have been approved by the US Food and Drug Administration. Herein, we examine the rationale for using ω3 polyunsaturated fatty acids (PUFAs) in NAFLD therapy. This focus is based on the finding that NAFLD severity is associated with a reduction of hepatic C20-22 ω3 PUFAs. Because C20-22 ω3 PUFAs are pleiotropic regulators of cell function, loss of C20-22 ω3 PUFAs has the potential to significantly impact hepatic function. We describe NAFLD prevalence and pathophysiology as well as current NAFLD therapies. We also present evidence from clinical and preclinical studies that evaluated the capacity of C20-22 ω3 PUFAs to treat NAFLD. Given the clinical and preclinical evidence, dietary C20-22 ω3 PUFA supplementation has the potential to decrease human NAFLD severity by reducing hepatosteatosis and liver injury.

Keywords: docosahexaenoic acid; fibrosis; inflammation; nonalcoholic steatohepatitis; steatosis.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Fatty Acids, Omega-3* / therapeutic use
  • Humans
  • Non-alcoholic Fatty Liver Disease* / drug therapy


  • Fatty Acids, Omega-3