Resveratrol does not benefit patients with nonalcoholic fatty liver disease

Chachay, Veronique S. and Macdonald, Graeme A. and Martin, Jennifer H. and Whitehead, Jonathan P. and O'Moore-Sullivan, Trisha M. and Lee, Paul and Franklin, Michael and Klein, Kerenaftali and Taylor, Paul J. and Ferguson, Maree and Coombes, Jeff S. and Thomas, Gethin P. and Cowin, Gary J. and Kirkpatrick, Carl M. J. and Prins, Johannes B. and Hickman, Ingrid J. (2014) Resveratrol does not benefit patients with nonalcoholic fatty liver disease. Clinical Gastroenterology and Hepatology, 12 (12). pp. 2092-2103. ISSN 1542-3565

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Item Type:Article
Item Status:Live Archive

Abstract

Background & Aims: Nonalcoholic 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 up-regulating pathways that regulate energy metabolism. We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD. Methods: 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). Plasma markers of inflammation, as well as metabolic, hepatic, and antioxidant function, were measured; transcription of target genes was measured in peripheral blood mononuclear cells. Resveratrol pharmacokinetics and safety were assessed. Results: Eight-week administration of resveratrol did not reduce insulin resistance, steatosis, or abdominal fat distribution when 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 when compared with the placebo group. Resveratrol did not significantly alter transcription of NQO1, PTP1B, IL6, or HO1 in peripheral blood mononuclear cells. Resveratrol was well-tolerated. Conclusions: Eight weeks administration of resveratrol did not significantly improve any features of NAFLD, compared with placebo, but it increased hepatic stress, based on observed increases in 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. © 2014 AGA Institute.

Keywords:alanine, aspartate aminotransferase, ho1 protein, interleukin 6, lipid, membrane protein, nqo1 protein, placebo, protein tyrosine phosphatase 1B, resveratrol, unclassified drug, gastrointestinal agent, stilbene derivative, abdominal fat, adult, antioxidant activity, Article, Australia, caloric restriction, clinical article, controlled study, double blind procedure, drug bioavailability, drug metabolism, drug safety, fatty liver, genetic transcription, human, image analysis, insulin resistance, lipid blood level, male, metabolic capacity, middle aged, nonalcoholic fatty liver, nuclear magnetic resonance imaging, nuclear magnetic resonance spectroscopy, obesity, outpatient department, patient compliance, peripheral blood mononuclear cell, randomized controlled trial, resting energy expenditure, treatment outcome, unspecified side effect, aged, liver, Non-alcoholic Fatty Liver Disease, pathology, Abdominal Fat, Gastrointestinal Agents, Humans, Placebos, Stilbenes
Subjects:B Subjects allied to Medicine > B100 Anatomy, Physiology and Pathology
Divisions:College of Science > School of Life Sciences
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ID Code:26213
Deposited On:14 Mar 2018 16:47

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