Clinical trials of resveratrol
Ketan R. Patel,Edwina N. Scott,Victoria A. Brown,Andreas J. Gescher,William P. Steward,Karen Brown +5 more
TL;DR: The occurrence of mild to moderate side effects is likely to limit the doses employed in future trials to significantly less than this amount, and what additional information is needed is suggested to increase the chances of success in future clinical trials.
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Abstract: An expanding body of preclinical evidence suggests resveratrol has the potential to impact a variety of human diseases. To translate encouraging experimental findings into human benefits, information is first needed on the safety, pharmacokinetics, pharmacodynamics, and, ultimately, clinical efficacy of resveratrol. Published clinical trials have largely focused on characterizing the pharmacokinetics and metabolism of resveratrol. Recent studies have also evaluated safety and potential mechanisms of activity following multiple dosing, and have found resveratrol to be safe and reasonably well-tolerated at doses of up to 5 g/day. However, the occurrence of mild to moderate side effects is likely to limit the doses employed in future trials to significantly less than this amount. This review describes the available clinical data, outlines how it supports the continuing development of resveratrol, and suggests what additional information is needed to increase the chances of success in future clinical trials.
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Citations
Resveratrol: A Double-Edged Sword in Health Benefits
Bahare Salehi,Abhay Prakash Mishra,Manisha Nigam,Bilge Sener,Mehtap Kilic,Mehdi Sharifi-Rad,Patrick Valere Tsouh Fokou,Natália Martins,Javad Sharifi-Rad,Javad Sharifi-Rad +9 more
TL;DR: This review summarized current data on resveratrol pharmacological effects and confirmed its anticancer properties, as well as other bioactive effects, namely as anti-inflammatory, anticarcinogenic, cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective.
The Role of Resveratrol in Cancer Therapy
Jeong-Hyeon Ko,Gautam Sethi,Jae-Young Um,Muthu K. Shanmugam,Frank Arfuso,Alan Prem Kumar,Anupam Bishayee,Kwang Seok Ahn +7 more
TL;DR: The current focus of this review is resveratrol’s in vivo and in vitro effects in a variety of cancers, and intracellular molecular targets modulated by this polyphenol.
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Resveratrol and health – A comprehensive review of human clinical trials
TL;DR: The current state of knowledge on the effects of resveratrol on humans is examined to utilize this information to develop further guidelines for the implementation of human clinical trials.
572
Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence.
Joao Tomé-Carneiro,Mar Larrosa,Antonio González-Sarrías,Francisco A. Tomás-Barberán,María Teresa García-Conesa,Juan Carlos Espín +5 more
TL;DR: This review will focus on the currently available evidence regarding resveratrol’s effects on humans obtained from randomized clinical trials and provide a critical outlook for further research on this molecule that is evolving from a minor dietary compound to a possible multi-target therapeutic drug.
Resveratrol: French paradox revisited.
TL;DR: The main focus of this review will be the pathways affected by resveratrol, which may be beneficial in many disorders, particularly in diseases where oxidative stress plays an important role.
References
High absorption but very low bioavailability of oral resveratrol in humans
TL;DR: 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.
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Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis
Andrew G Renehan,Marcel Zwahlen,Christoph E. Minder,Sarah T O'Dwyer,Stephen M Shalet,Matthias Egger,Matthias Egger +6 more
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Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent
David J. Boocock,Guy Faust,Ketan R. Patel,Anna M. Schinas,Victoria Brown,Murray P. Ducharme,Tristan D. Booth,James A. Crowell,Marjorie Perloff,Andreas J. Gescher,William P. Steward,Dean E. Brenner +11 more
TL;DR: The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with cancer chemopreventive efficacy, however, the high systemic levels of resver atrol conjugate metabolites suggest that their cancer chemosynthetic properties warrant investigation.
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Repeat Dose Study of the Cancer Chemopreventive Agent Resveratrol in Healthy Volunteers: Safety, Pharmacokinetics and Effect on the Insulin-like Growth Factor Axis
Victoria A. Brown,Ketan R. Patel,Maria Viskaduraki,James A. Crowell,Marjorie Perloff,Tristan D. Booth,Grygoriy Vasilinin,Ananda Sen,Anna M. Schinas,Gianfranca Piccirilli,Karen Brown,William P. Steward,Andreas J. Gescher,Dean E. Brenner +13 more
TL;DR: It is suggested that repeated administration of high doses of resveratrol generates micromolar concentrations of parent and much higher levels of glucuronide and sulfate conjugates in the plasma, which might contribute to cancer chemopreventive activity.
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Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients
Ketan R. Patel,Victoria A. Brown,Donald J. L. Jones,Robert G. Britton,David Hemingway,Andrew S. Miller,Kevin West,Tristan D. Booth,Marjorie Perloff,James A. Crowell,Dean E. Brenner,William P. Steward,Andreas J. Gescher,Karen Brown +13 more
TL;DR: Resveratrol merits further clinical evaluation as a potential colorectal cancer chemopreventive agent after it was found to be well tolerated and to produce levels in the human gastrointestinal tract of an order of magnitude sufficient to elicit anticarcinogenic effects.
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