What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Most cited references 147

Record: found
Abstract: found
Article: not found

High absorption but very low bioavailability of oral resveratrol in humans.

Thomas Walle, Faye Hsieh, Mark Delegge … (2004)

The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v. doses in six human volunteers. The absorption of a dietary relevant 25-mg oral dose was at least 70%, with peak plasma levels of resveratrol and metabolites of 491 +/- 90 ng/ml (about 2 microM) and a plasma half-life of 9.2 +/- 0.6 h. However, only trace amounts of unchanged resveratrol (<5 ng/ml) could be detected in plasma. Most of the oral dose was recovered in urine, and liquid chromatography/mass spectrometry analysis identified three metabolic pathways, i.e., sulfate and glucuronic acid conjugation of the phenolic groups and, interestingly, hydrogenation of the aliphatic double bond, the latter likely produced by the intestinal microflora. Extremely rapid sulfate conjugation by the intestine/liver appears to be the rate-limiting step in resveratrol's bioavailability. Although the systemic bioavailability of resveratrol is very low, accumulation of resveratrol in epithelial cells along the aerodigestive tract and potentially active resveratrol metabolites may still produce cancer-preventive and other effects.

0 comments Cited 479 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes.

Jill Milne, Philip Lambert, Simon Schenk … (2007)

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.

0 comments Cited 437 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.

Dohoon Kim, Minh Dang Nguyen, Matthew M Dobbin … (2007)

A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.

0 comments Cited 306 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2011

Publication date (Electronic): 16 June 2011

Volume: 6

Issue: 6

Electronic Location Identifier: e19881

Affiliations

[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

University of Valencia, Spain

Author notes

* E-mail: ov@ 123456ruc.dk

Conceived and designed the experiments: OV. Analyzed the data: OV NA CAB JAB KB AC DKD DD CG H-YL Q-YM PM NN JMP TR YS Y-JS T. Szekeres T. Szkudelski TW JMW. Wrote the paper: OV. Evaluation of the cancer preventive effect: NA KB H-YL NN JMP YS T. Szekeres. Evaluation of the CHD preventive effect: DKD PM JMW. Evaluation of the obesity/diabetes effect: CAB T. Szkudelski. Evaluation of the anti-aging/anti-inflammatory effect: JAB AC Q-YM. Evaluation of the neuroprotective effect: CG TR. Metabolism and pharmacokinetic of resveratrol: DD TW.

Article

Publisher ID: PONE-D-11-01755

DOI: 10.1371/journal.pone.0019881

PMC ID: 3116821

PubMed ID: 21698226

SO-VID: 6b5ee9c1-8856-4be1-ae64-043508eb305b

Copyright © 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.

History

Date received : 21 January 2011

Date accepted : 6 April 2011

Page count

Pages: 11

Comments

Comment on this article

scite_

Cited by 114

See all cited by

- Version 1
- Version 1

What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol

Read this article at

Abstract

Background

Methodology

Conclusions/Significance

Related collections

PLOS Climate

Most cited references 147

High absorption but very low bioavailability of oral resveratrol in humans.

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes.

SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 343

Cited by 114