What is the role of omega 3 (Omega-3) fatty acids, specifically EPA (Eicosapentaenoic acid) and DHA (Docosahexaenoic acid), in the management of fatty liver disease?

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Last updated: July 3, 2025View editorial policy

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From the Guidelines

Omega-3 fatty acids, particularly EPA and DHA, are likely to be beneficial in managing fatty liver disease, with a recommended daily dose of 1-4 grams, as they reduce liver fat accumulation, decrease inflammation, and improve insulin sensitivity. The most recent and highest quality study, 1, suggests that omega-3 fatty acids can improve hepatic fat content, but the optimal dose has not been determined.

Key Findings

  • A systematic review and meta-analysis concluded that omega-3 fatty acids reduce liver fat in NAFLD patients, but better controlled trials are needed to confirm this 1.
  • A recent systematic review found that marine n-3 PUFAs are likely to be an important tool for NAFLD treatment, but further studies are required to confirm this 1.
  • Twelve out of seventeen published human studies showed a decrease in liver fat and/or other markers of NAFLD with n-3 PUFA supplementation, while five studies, including the largest study, were negative 1.

Recommendations

  • For patients with non-alcoholic fatty liver disease (NAFLD), supplementation with fish oil capsules containing at least 1 gram of combined EPA and DHA daily may help reduce liver fat content and improve liver enzyme levels.
  • Omega-3s can be obtained from fatty fish like salmon and mackerel (2-3 servings weekly), but supplements may be necessary to achieve therapeutic doses.
  • These supplements should be taken with meals to improve absorption and reduce potential side effects like fishy aftertaste.

Mechanism of Action

  • Omega-3s work by activating PPAR-α receptors that increase fatty acid oxidation, reducing inflammatory cytokines, and improving insulin signaling pathways.

Safety and Precautions

  • Though generally safe, patients should consult healthcare providers before starting supplementation, especially those on blood thinners or with fish allergies, as noted in earlier guidelines 1.

From the Research

Role of Omega-3 Fatty Acids in Fatty Liver Disease

  • Omega-3 fatty acids, specifically EPA and DHA, have been shown to have beneficial effects on liver lipid metabolism and inflammation in the context of nonalcoholic fatty liver disease (NAFLD) 2, 3, 4, 5, 6.
  • The biological mechanisms by which omega-3 fatty acids act to ameliorate liver disease in NAFLD include:
    • Beneficial effects on bioactive metabolites involved in inflammatory pathways
    • Alteration of nuclear transcription factor activities, such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c), and carbohydrate-responsive element-binding protein (ChREBP)
    • Regulation of hepatic lipid metabolism, including decreased hepatic triacylglycerol accumulation and increased beta-oxidation

Effects of Omega-3 Fatty Acids on Liver Fat and Inflammation

  • Omega-3 fatty acid treatment has been shown to decrease liver fat in patients with NAFLD, with docosahexaenoic acid (DHA) possibly being more effective than eicosapentaenoic acid (EPA) 2, 4, 5.
  • However, the effects of omega-3 fatty acids on other features of steatohepatitis, such as inflammation and fibrosis, are less clear and require further study 2, 3, 5.
  • Recent meta-analyses and clinical trials have evaluated the efficacy of omega-3 fatty acid supplementation in adults and children with NAFLD, with mixed results regarding the attenuation of more severe NAFLD markers, such as hepatic injury, inflammation, and fibrosis 3, 5.

Potential Therapeutic Applications

  • Dietary supplementation with omega-3 fatty acids, particularly DHA and EPA, may be a viable and effective option to lower liver fat in obese adults and children with NAFLD 4, 5.
  • Further research is needed to establish the optimal dose and duration of omega-3 fatty acid treatment, as well as to determine its effects on the different component features of NAFLD (hepatic fat, inflammation, and fibrosis) 2, 3, 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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