Sara Heebøll1,2, Martin Kreuzfeldt1, Stephen Hamilton-Dutoit3, Marianne Kjær Poulsen4, Hans Stødkilde-Jørgensen5, Holger Jon Møller2, Niels Jessen6,7, Kasper Thorsen7, Ylva Kristina Hellberg8, Steen Bønløkke Pedersen5, Henning Grønbæk1. 1. a Department of Hepatology and Gastroenterology , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ; 2. b Department of Clinical Biochemistry , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ; 3. c Department of Pathology , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ; 4. d Department of Endocrinology and Internal Medicine , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ; 5. e MR Research Centre , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ; 6. f Research Laboratory for Biochemical Pathology , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ; 7. g Department of Molecular Medicine , Aarhus University Hospital and Department of Clinical Medicine, Aarhus University , Aarhus , Denmark ; 8. h Department of Pathology , Hvidovre Hospital , Hvidovre , Denmark.
Abstract
OBJECTIVE: "The obesity epidemic" has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease (NAFLD), for which effective treatments are in demand. The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction. We aimed to test the hypothesis that resveratrol alleviates NAFLD in a randomised, clinical trial. MATERIALS AND METHODS: A total of 28 overweight patients with transaminasemia and histological NAFLD were randomised 1:1 to placebo or resveratrol 1.5 g daily for 6 months. Twenty-six participants completed the trial and underwent repeated clinical investigation, blood work, MR spectroscopy; and 19 participants agreed to a repeat liver biopsy. RESULTS: Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury (primary outcome: alanine transaminase, p = 0.51). Resveratrol-treated patients showed a 3.8% decrease in liver lipid content (p = 0.03), with no difference between the two treatment arms (p = 0.38) and no improvement of histological features. Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome, except for a transient decrease in systolic BP. Microarray analysis and qRT-PCR revealed no major changes in expression profile. Also, we report a serious adverse event in a patient who developed fever and bicytopenia. CONCLUSIONS: In this placebo-controlled, high-dose and long-term study, resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD, though there may be a small ameliorating effect on liver function tests and liver fat accumulation.
RCT Entities:
OBJECTIVE: "The obesity epidemic" has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease (NAFLD), for which effective treatments are in demand. The polyphenolresveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction. We aimed to test the hypothesis that resveratrol alleviates NAFLD in a randomised, clinical trial. MATERIALS AND METHODS: A total of 28 overweight patients with transaminasemia and histological NAFLD were randomised 1:1 to placebo or resveratrol 1.5 g daily for 6 months. Twenty-six participants completed the trial and underwent repeated clinical investigation, blood work, MR spectroscopy; and 19 participants agreed to a repeat liver biopsy. RESULTS:Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury (primary outcome: alanine transaminase, p = 0.51). Resveratrol-treated patients showed a 3.8% decrease in liver lipid content (p = 0.03), with no difference between the two treatment arms (p = 0.38) and no improvement of histological features. Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome, except for a transient decrease in systolic BP. Microarray analysis and qRT-PCR revealed no major changes in expression profile. Also, we report a serious adverse event in a patient who developed fever and bicytopenia. CONCLUSIONS: In this placebo-controlled, high-dose and long-term study, resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD, though there may be a small ameliorating effect on liver function tests and liver fat accumulation.
Authors: Elias Immanuel Ordell Sundelin; Lars Christian Gormsen; Sara Heebøll; Mikkel Holm Vendelbo; Steen Jakobsen; Ole Lajord Munk; Søren Feddersen; Kim Brøsen; Stephen Jacques Hamilton-Dutoit; Steen Bønløkke Pedersen; Henning Grønbaek; Niels Jessen Journal: Br J Clin Pharmacol Date: 2019-06-18 Impact factor: 4.335
Authors: William M Schultz; Elliot N Mahlof; Devinder S Dhindsa; Tina Varghese; Robert E Heinl; Hannah C Cai; Pratik B Sandesara; Danny J Eapen; Laurence S Sperling Journal: Cardiovasc Endocrinol Date: 2017-11-15
Authors: Luis E Simental-Mendía; Claudia I Gamboa-Gómez; Fernando Guerrero-Romero; Mario Simental-Mendía; Adriana Sánchez-García; Mariana Rodríguez-Ramírez Journal: Adv Exp Med Biol Date: 2021 Impact factor: 2.622
Authors: S Heebøll; M K Poulsen; M J Ornstrup; T N Kjær; S B Pedersen; S Nielsen; H Grønbæk; A Handberg Journal: Int J Obes (Lond) Date: 2016-12-05 Impact factor: 5.095