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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. n‐3 polyunsaturated fatty acids (n‐3‐PUFAs) have been reported to ameliorate the progression of NAFLD in experimental studies; however, clinical trials have yielded contradictory results. The aim of our study was to assess the effects of n‐3‐PUFA administration on lipid metabolism and the progression of NAFLD in patients with metabolic syndrome. Sixty patients with metabolic syndrome and NAFLD were randomized in a double‐blind placebo‐controlled trial (3.6 g/day n‐3‐PUFA vs. placebo). During the 1‐year follow‐up, the patients underwent periodic clinical and laboratory examinations, liver stiffness measurements, magnetic resonance spectroscopy of the liver, and plasma lipidomic analyses. After 12 months of n‐3‐PUFA administration, a significant decrease in serum GGT activity was recorded compared with the placebo group (2.03 ± 2.8 vs. 1.43 ± 1.6;  P  < 0.05). Although no significant changes in anthropometric parameters were recorded, a significant correlation between the reduction of liver fat after 12 months of treatment—and weight reduction—was observed; furthermore, this effect was clearly potentiated by n‐3‐PUFA treatment ( P  < 0.005). In addition, n‐3‐PUFA treatment resulted in substantial changes in the plasma lipidome, with n‐3‐PUFA‐enriched triacylglycerols and phospholipids being the most expressed lipid signatures.  Conclusion:  Twelve months of n‐3‐PUFA treatment of patients with NAFLD patients was associated with a significant decrease in GGT activity, the liver fat reduction in those who reduced their weight, and beneficial changes in the plasma lipid profile.

Effect of Omega‐3 Polyunsaturated Fatty Acids on Lipid Metabolism in Patients With Metabolic Syndrome and NAFLD