Comparison of resveratrol supplementation and calorie restricted diet on nutritional status, metabolic and oxidative parameters, serum sirtuin-1 and fibroblast growth factor-21 levels in patients with nonalcoholic fatty liver disease

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. It represents a spectrum of liver disease from simple hepatic steatosis to nonalcoholic steatohepatitis, and fibrosis, which may progress to cirrhosis and even hepatocellular carcinoma. To date, there is no specific pharmacologic therapy for NAFLD treatment. Lifestyle modification through diet and exercise has been considered to be the most effective strategies for NAFLD management. It has been claimed that the beneficial cellular effects of CR are largely mediated by induction of sirtuin enzymes. Sirtuin-1 (SIRT1) has been shown to regulate various metabolic pathways. There is an evidence that expression of the SIRT1 protein and its plasma levels decrease in NAFLD patients. Fibroblast growth factor 21 (FGF21) is also involved in the pathophysiology of NAFLD. Serum FGF21 is found to be elevated in NAFLD patients. It has been shown that weight loss could ameliorate FGF21-resistance and reduce its serum levels. Resveratrol, a natural nonflavonoid polyphenol was discovered as the most potent activator of SIRT1. Recently, resveratrol has been suggested to act as a calorie restriction mimetic. Thus, the aim of this study was to evaluate the effects of resveratrol supplementation in comparison to calorie-restricted (CR) diet on nutritional status, metabolic and oxidative parameters, serum sirtuin-1 and fibroblast growth factor-21 levels in patients with nonalcoholic fatty liver disease. Methods and materials: In this clinical trial, ninty subjects with NAFLD were randomized to recive prescribed low-calorie diet, resveratrol supplement capsules (2×300 mg) and placebo capsules (2×300 mg) daily for 12 weeks. Anthropometric and blood pressure measurements were collected at baseline and after the intervention. Dietary intakes and physical activity levels of participants were assessed at baseline, 6th week and the end of the study. Fasting blood samples were collected for all subjects at baseline and at the end of the trial. Biochemical measurements including serum liver enzymes, lipid profile, glycemic parameters, oxidative stress markers, sirtuin1 and FGF-21 were measured. Liver ultrasonography was performed for all participants in order to assess hepatic steatosis grade. Data were analyzed by one way analysis of variance (ANOVA), paired sample t-test, analysis of covariance (ANCOVA) and sidak post hoc test. Results: The mean age and BMI of all study subjects were 39.71 y and 31.04 kg/m2 repectively. There were no significant differences in baseline characteristics among the three study groups (p>0.05). CR diet significantly reduced weight (by 4.08 kg), BMI, waist circumference and waist to hip ratio (WHR) of subjcts compared to resveratrol and placebo groups (All p<0.05). Significant reductions in weight and BMI were found in resveratrol group compared to the placebo (P<0.05). Liver ultrasonography results did not show significant changes in any of the study groups at the end of the intervention. Following 12 weeks intervention, serum ALT and AST levels significantly reduced in CR group compared to that of resveratrol or placebo groups (p=0.03, p=0.02, respectively). Significant differences were also observed in TC, LDL-C and TG levels in CR group compared to resveratrol or placebo (All p<0.05). ALT, AST and lipid profile did not change significantly in resveratrol group compared to placebo (All P>0.05). Furthermore, no significant within and between group changes were seen in serum glycemic parameters, oxidative stress markers, HDL-C, sirtuin-1 and FGF-21 levels in any group (All P>0.05). Moreover, no significant changes were shown in systolic and diastolic blood pressure as well as physical activity level between three groups. There were significant differences in energy and macronutrient intakes in CR diet group compared to resveratrol and placebo groups at the middle and end of the study (All p<0.01). Whereas, changes in dietary intakes were not significant in resveratrol and placebo groups during the study (p>0.05). Conclusion: CR diet intervention with moderate weight loss improved metabolic parameters in patients with NAFLD. Further studies are warranted to evaluate the long-term effects and optimal dose of resveratrol that could mimic CR aspects in metabolic diseases.