What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol Ole Vang1*, Nihal Ahmad 2 , Clifton A. Baile3, Joseph A. Baur4, Karen Brown 5 , Anna Csiszar6, Dipak K. Das7, Dominique Delmas8, Carmem Gottfried 9 , Hung-Yun Lin10, Qing-Yong Ma11, Partha Mukhopadhyay12, Namasivayam Nalini13, John M. Pezzuto14, Tristan Richard15, Yogeshwer Shukla16, Young-Joon Surh17, Thomas Szekeres18, Tomasz Szkudelski19, Thomas Walle20, Joseph M. Wu21 1 Department of Science, System and Models, Roskilde University, Roskilde, Denmark, 2 Department of Dermatology, University of Wisconsin, Madison, Wisconsin, United States of America, 3 Department of Animal and Dairy Science, University of Georgia, Athens, Georgia, United States of America, 4 Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 5 Department of Cancer Studies and Molecular Medicine, The Biocentre, University of Leicester, Leicester, Great Britain, United Kingdom, 6 Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America, 7 Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, Connecticut, United States of America, 8 INSERM U866, University of Burgundy, Dijon, France, 9 Department of Biochemistry, Postgraduate Programme of Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil, 10 Signal Transduction Laboratory, Ordway Research Institute, Albany, New York, United States of America, 11 Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, China, 12 Laboratory of Physiological Studies, Section on Oxidative Stress Tissue Injury, National Institutes of Health, Rockville, Maryland, United States of America, 13 Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu, India, 14 College of Pharmacy, University of Hawaii at Hilo, Hilo, Hawaii, United States of America, 15 UFR Pharmacie, University of Bordeaux, Villenave d’Ornon, France, 16 Proteomics Laboratory, Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India, 17 College of Pharmacy, Seoul National University, Seoul, South Korea, 18 Clinical Institute of Medical and Chemical Laboratory Diagnostics, General Hospital of Vienna, Medical University of Vienna, Vienna, Austria, 19 Department of Animal Physiology and Biochemistry, August Cieszkowski University of Agriculture, Poznan, Poland, 20 Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina, United States of America, 21 Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, United States of America Abstract Background: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingør, Denmark. Methodology: Literature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: 1Can resveratrol be recommended in the prevention or treatment of human diseases?; 2Are there observed ‘‘side effects’’ caused by the intake of resveratrol in humans?; 3What is the relevant dose of resveratrol?; 4What valid data are available regarding an effect in various species of experimental animals?; 5Which relevant (overall) mechanisms of action of resveratrol have been documented? Conclusions/Significance: The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects. Citation: Vang O, Ahmad N, Baile CA, Baur JA, Brown K, et al. (2011) What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol. PLoS ONE 6(6): e19881. doi:10.1371/journal.pone.0019881 Editor: Jose Vina, University of Valencia, Spain Received January 21, 2011; Accepted April 6, 2011; Published June 16, 2011 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: This study was made as a part of the Resveratrol 2010 conference (www.resveratrol2010.com) and did not receive any specific funding from third parties. The conference was organized by Roskilde University, Danish Society for Biochemistry and Molecular Biology, The Danish Society of Engineers, Øresund Food with support from The European Union. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: OV is a scientific consultant for Fluxome Science A/S. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials. * E-mail: ov@ruc.dk Introduction Resveratrol (Resv) is a simple molecule that has taken the spotlight since the first scientific paper described a possible preventive effect on cancer in mice [1]. Resveratrol occurs naturally in low amounts in various edible plants, but the fact that Resv is found in red wine increases its relevance as being easily accessible to the general population. The applications of Resv PLoS ONE | www.plosone.org 1 June 2011 | Volume 6 | Issue 6 | e19881