CR diet with moderate weight loss has favorable effects on NAFLD, and resveratrol supplementation induced weight loss but failed to mimic other aspects of CR diet. Future studies are warranted to evaluate the long-term and dose-dependent effects of resveratrol on metabolic diseases.

Purpose: Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), antioxidant approaches have not been sufficiently investigated in human NAFLD management. Resveratrol has been reported to possess a wide range of biological functions, including antioxidant activities. This study aimed to evaluate the effects of resveratrol supplementation on oxidative/anti-oxidative status in patients with NAFLD.Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 60 patients with NAFLD (males and females) aged 20 to 60 years, and body mass index (BMI) of 25-35 kg/m2. Subjects were randomly assigned to receive a daily dose of 600 mg resveratrol (2×300 mg pure trans-resveratrol capsules; n=30) or placebo capsules (n=30) for 12 wk. Fasting blood samples, anthropometric measurements, and dietary intakes were collected for all patients at baseline and at the end of the trial. Oxidative stress was evaluated by measurement of serum malondialdehyde (MDA), oxidized low-density lipoprotein (ox-LDL), total antioxidant capacity (TAC), and erythrocyte superoxide dismutase (SOD) as well as glutathione peroxidase (GSH-Px) activities. Changes in the outcomes were analyzed using analysis of covariance (ANCOVA).Results: Resveratrol supplementation did not significantly affect neither serum MDA, ox-LDL, and TAC levels, nor erythrocyte SOD and GSH-Px activities, compared to placebo group (All P>0.05). Moreover, changes in serum levels of liver enzymes (ALT, AST, GGT, and ALP) were not significant in neither of the study groups (All P>0.05).Conclusion: Resveratrol supplementation did not modify oxidative/anti-oxidative status in patients with NAFLD.

Abstract. Introduction: Cardiovascular disease (CVD) accounts as a major cause of mortality among patients with nonalcoholic fatty liver disease (NAFLD). Resveratrol, a natural polyphenol compound, is known for its antioxidant and antiatherogenic properties and is purported to be beneficial in decreasing CVD risk factors in NAFLD patients. Objectives: This study aimed to investigate the effects of resveratrol on atherogenic risk factors in patients with NAFLD. Methods: This randomized, double-blind, placebo-controlled clinical trial was performed on 50 patients with NAFLD aged 20-60 years. Subjects were randomly assigned to receive a daily dose of 600 mg resveratrol (n = 25) or placebo (n = 25) for 12 wk. Serum liver enzymes, lipid profile and atherogenic indices, blood pressure and anthropometric values were assessed pre and post-treatment. Results: Resveratrol supplementation reduced body weight (from 88.75 ± 11.41 to 87.54 ± 11.18 kg, P = 0.005) and BMI (from 31.00 ± 3.16 to 30.60 ± 3.26 kg/m², P = 0.01) significantly compared to the placebo group. A significant reduction in waist circumference was observed within resveratrol group (from 102.70 ± 7.68 to 101.39 ± 7.62 cm, P = 0.02). There were no significant changes in lipid profile (ox-LDL, ApoA1 and ApoB), serum atherogenic indices (LDL-C/HDL-C, ApoB/ApoA1, ox-LDL/ApoB, LDL-C/ox-LDL and AIP), liver enzymes (AST, ALT, ALP and GGT), hip circumference, waist-to-hip ratio and blood pressure in either group (P > 0.05 for all). Conclusion: These findings indicated that resveratrol supplementation in dose and duration used in this study did not affect most of the CVD risk factors in NAFLD patients. Further studies are warranted to explain more effects of resveratrol on CVD complications of NAFLD. Registration ID in IRCT: IRCT201511233664N16

Oxidative stress plays a fundamental role in the development and progression of nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of a calorie-restricted (CR) diet on oxidative/anti-oxidative status in patients with NAFLD and the potential mediating role of fibroblast growth factor 21 (FGF-21) in this regard. This randomized, controlled clinical trial was carried out on sixty patients with NAFLD aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m2. Participants were randomly assigned to either the CR diet group (received a prescribed low-calorie diet for twelve weeks, n = 30) or the control group (n = 30). Fasting blood samples, anthropometric measurements, dietary intake, and physical activity data were collected for all participants at baseline and at the end of the trial. Significant reductions in weight, BMI, waist circumference, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed in the CR diet group compared to the control group (all p< 0.05). Liver steatosis grade, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and FGF-21, as well as erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities did not show significant changes in the CR group when compared to the controls at the end of the study (p > 0.05). CR diet with moderate weight loss has some favorable effects on NAFLD but was not able to modify oxidative/anti-oxidative status in these patients. Future studies are warranted to target the effects of long-term interventions with a greater weight loss in this patient population.

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