Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by abnormal
hepatic accumulation of triacylglycerides in the absence of alcohol consumption, in association with
Oxidative Stress (OS), a pro-inflammatory state and Insulin Resistance (IR), which are attenuated by
n-3 long-chain polyunsaturated Fatty Acids (FAs) C20-C22 (LCPUFAs) supplementation. Main
causes of NAFLD comprise high caloric intake and a sedentary lifestyle, with high intakes of saturated
Methods: The review includes several searches considering the effects of n-3 LCPUFAs in NAFLD
in vivo and in vitro models, using the PubMed database from the National Library of Medicine-
National Institutes of Health.
Result: The LCPUFAs eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n-
3, DHA) have a positive effect in diminishing liver steatosis, OS, and the levels of aspartate
aminotransferase, alanine aminotransferase and pro-inflammatory cytokines, with improvement of
insulin sensitivity and adiponectin levels. The molecular pathways described for n-3 LCPUFAs in
cellular and animal models and humans include peroxisome proliferator–activated receptor-α activation
favouring FA oxidation, diminution of lipogenesis due to sterol responsive element binding
protein-1c downregulation and inflammation resolution. Besides, nuclear factor erythroid-2-related
factor-2 activation is elicited by n-3 LCPUFA-derived oxidation products producing direct and indirect
antioxidant responses, with concomitant anti-fibrogenic action.
Conclusion: The discussed effects of n-3 LCPUFA supplementation support its use in NAFLD,
although having a limited value in NASH, a contention that may involve n-3 LCPUFA oxygenated
derivatives. Clinical trials establishing optimal dosages, intervention times, type of patients and
possible synergies with other natural products are needed in future studies.