Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis

Abstract

Background: Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant properties, and calorie restriction-like effects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efficacy of resveratrol in the management of NAFLD.Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted.Results: Four RCTs (n=158 patients) were included in the final analysis. The overall effect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous.Conclusion: Current evidence is insufficient to support the efficacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fibrosis or show a significant decrease in any of its parameters.Abbreviations: ALT: Alanine aminotransferase; AMPK: AMP-activated protein kinase; AST: Aspartate aminotransferase; BMI: Body mass index; CK-18: Cytokeratin-18; CRP: C-reactive protein; HC: Head circumference; HDL: High density lipoprotein; IL-6: Interleukin-6; LDL: Low density lipoprotein; MD: Mean difference; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; RCT: Randomized Controlled Trial; RR: Relative risk; SIRT1: Silent information regulation 2 homologue 1; TNF-α: Tumor necrosis factor α; WC: Waist circumference; WHR: Waist hip ratio.

Nutraceutical Approach to Non-Alcoholic Fatty Liver Disease (NAFLD): The Available Clinical Evidence

“…Resveratrol (3,5,4′-trihydroxy-trans-stilbene, C14H12O3, molar mass: 228.25 g/mol) is a non-flavonoid phenol ( Figure 9 ) particularly concentrated in the grape skin peel, but also in the extracts of Polygonum cuspidatum , poorly orally bioavailable (if not chemically modified), characterized by an important antioxidant, vasoprotective (both cerebral and peripheral) and insulin-sensitizing activity [ 73 , 74 ]. Preliminary clinical data appear to contradict preclinical literature, suggesting a potential efficacy of resveratrol in improving NAFLD-related parameters [ 75 ]. However, these studies are usually short (too short to have an impact on the liver structure) and are conducted with resveratrol doses incompatible with the insulin-sensitizing action that could improve NAFLD.…”

Developmental Programming of the Metabolic Syndrome: Can We Reprogram with Resveratrol?

“…A meta-analysis of 283 subjects with type 2 diabetes reported that high-dose resveratrol (≥100 mg/day) supplementation improved the fasting plasma glucose level [ 38 ]. Nevertheless, other reports of meta-analysis fail to show the beneficial effects of resveratrol on lipid profile ( n = 763 subjects) [ 39 ] and NAFLD ( n = 158 subjects) [ 40 ].…”

Resveratrol: Is It Really Good for Liver Health?

“…In contrast to these encouraging studies, another very recent, randomized, clinical trial from Denmark including 28 patients with overweight found no indication that RES treatment (1.5 g RES/day for 6 months) had any consistent therapeutic effects (63). In line, a recent systematic review and meta-analysis study published during the revision of the current review concluded that the current evidence was insufficient to support the efficacy of resveratrol in the management of NAFLD (64). A detailed search in the Clinicaltrials.gov registry for clinical RES trials led to the identification of 13 clinical trials when using the search terms "resveratrol" and "liver".…”