Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease

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.

KEYWORDS:

• Anti-inflammatory agents
• antioxidants
• non-alcoholic fatty liver disease
• non-alcoholic steatohepatitis
• resveratrol

Acknowledgements

We are thankful for the skilled technical assistance and multiple services provided by R. Andersen, B. Nielsen, I. Schjødt, P. Hornbæk, L. Pedersen, K. Petersen, and H. Steen.

Declaration of interest

The authors declare no conflict of interest.

Funding information

This study was supported by Aarhus University (2010-218/2-82); the Danish Council for Independent Research, Medical Sciences (no. 11-107912); and the Danish Strategic Research Council, (no. 10-093499 and 10-092797). This study was also supported by grants to H Grønbæk from The NOVO Nordisk Foundation and from “Savværksejer Jeppe Juhl og hustru Ovita Juhls mindelegat”. Resveratrol was provided by Evolva SA (Basel, Switzerland), free of charge. The funders had no role in study design, data collection and analysis, or preparation of the manuscript.