& Aims: Non-alcoholic fatty liver disease (NAFLD), characterized by accumulation of hepatic triglycerides (steatosis), is associated with abdominal obesity, insulin resistance, and inflammation. Although weight loss via calorie restriction reduces features of NAFLD, there is no pharmacologic therapy. Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by upregulating pathways that regulate energy metabolism. We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD.
Overweight or obese men diagnosed with NAFLD were recruited from hepatology outpatient clinics in Brisbane, Australia from 2011 through 2012. They were randomly assigned to groups given 3000 mg resveratrol (n=10) or placebo (n=10) daily for 8 weeks. Outcomes included insulin resistance (assessed by the euglycemic-hyperinsulinemic clamp), hepatic steatosis, and abdominal fat distribution (assessed by magnetic resonance spectroscopy and imaging). Metabolic, hepatic, inflammatory, and antioxidant activities were measured using plasma samples; transcription of resveratrol target genes was measured in peripheral blood mononuclear cells (PBMC). Resveratrol pharmacokinetics and safety were assessed.
Eight weeks administration of resveratrol did not reduce insulin resistance, steatosis, or abdominal fat distribution, compared with baseline. No change was observed in plasma lipids or antioxidant activity. Levels of alanine and aspartate aminotransferases increased significantly among patients in the resveratrol group until week 6, compared with the placebo group. Resveratrol did not significantly alter transcription of NQO1,PTP1B, IL6, or HO1 in PBMC. Resveratrol was well tolerated.
Eight weeks administration of resveratrol did not significantly improve any features of NAFLD, compared with placebo, but increased hepatic stress, based on increased levels of liver enzymes. Further studies are needed to determine whether agents that are purported to mimic calorie restriction, such as resveratrol, are safe and effective for complications of obesity. Clinical trials registration no: ACTRN12612001135808.
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