Veronique S Chachay1, Graeme A Macdonald2, Jennifer H Martin3, Jonathan P Whitehead4, Trisha M O'Moore-Sullivan5, Paul Lee5, Michael Franklin6, Kerenaftali Klein7, Paul J Taylor6, Maree Ferguson8, Jeff S Coombes9, Gethin P Thomas10, Gary J Cowin11, Carl M J Kirkpatrick12, Johannes B Prins13, Ingrid J Hickman14. 1. University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia; Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Australia. Electronic address: v.chachay@uq.edu.au. 2. School of Medicine Metro-South, University of Queensland, Brisbane, Australia; Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia. 3. School of Medicine Metro-South, University of Queensland, Brisbane, Australia. 4. Mater Medical Research Institute, Brisbane, Australia. 5. School of Medicine Metro-South, University of Queensland, Brisbane, Australia; Department of Endocrinology, Princess Alexandra Hospital, Brisbane, Australia. 6. Department of Clinical Pharmacology, Princess Alexandra Hospital, Brisbane, Australia. 7. Queensland Clinical Trials and Biostatistics Centre, University of Queensland, Brisbane, Australia. 8. Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Australia; School of Human Movement Studies, University of Queensland, Brisbane, Australia. 9. School of Human Movement Studies, University of Queensland, Brisbane, Australia. 10. University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia. 11. Centre for Advanced Imaging, University of Queensland, Brisbane, Australia. 12. Centre for Medicine Use and Safety, Monash University, Melbourne, Australia. 13. University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia; Mater Medical Research Institute, Brisbane, Australia. 14. University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, Australia; Department of Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane, Australia; Mater Medical Research Institute, Brisbane, Australia.
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.
RCT Entities:
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 obesemen 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.
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