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Metab Syndr Relat Disord. 2016 Nov;14(9):417-430. Epub 2016 Oct 6.

Treatment of Nonalcoholic Fatty Liver Disease with Long-Chain n-3 Polyunsaturated Fatty Acids in Humans.

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Department of Internal Medicine, Santa Clara Valley Medical Center , San Jose, California.



Nonalcoholic fatty liver disease (NAFLD) is a major risk factor for type 2 diabetes, cardiovascular disease, and liver failure. Treatment with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) produced variable success in improving NAFLD. The purpose of this review is to determine if n-3 LCPUFA will decrease markers of NAFLD, compare the efficacies of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and identify factors that contribute to discrepancies in results.


This study reviewed published clinical studies with n-3 LCPUFA and NAFLD/nonalcoholic steatohepatitis (NASH) by using PubMed and Web of Science.


Seventeen human studies ranging in DHA 250 mg/day to a mixture of EPA+DHA 50 mL/day for 8 weeks to 2 years were identified. Results obtained varied because of different dosages of n-3 LCPUFA, EPA and DHA ratios, duration, subject characteristics, diet, exercise, compliance, methods, and other factors. Despite inconsistencies in the results reported, 13 of 17 published studies reported that n-3 LCPUFA supplementation decreased liver fat, liver enzymes, or markers of inflammation; four reported decrease in ballooning and two in fibrosis. Results also indicated that DHA was more effective than EPA in the treatment of NAFLD. Caloric restriction and supplementation with n-3 LCPUFA were additive in decreasing hepatic steatosis.


n-3 PUFA decreased several markers of NAFLD; however, there was a lower observed efficacy in NASH treatment. Further long-term placebo-controlled studies with adequate power and supplementation duration and standardized and sensitive detection methods are needed to determine the efficacy of EPA and DHA individually and in a mixture to treat NAFLD and NASH.


DHA; EPA; NASH; diabetes; fish oil; insulin resistance

[Indexed for MEDLINE]

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