Patrício Soares da Silva on Trans-Resveratrol Pharmacokinetics

New Hot Paper Commentary, January 2011

Patrício Soares da Silva

Article: Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers


Authors: Almeida, L;Vaz-da-Silva, M;Falcao, A;Soares, E;Costa, R;Loureiro, AI;Fernandes-Lopes, C;Rocha, JF;Nunes, T;Wright, L;Soares-da-Silva, P
Journal: MOL NUTR FOOD RES
Volume: 53, Issue: , Page: :S7-S15, Year: Suppl. 1 MAY 2009
* Portela & Co SA, Dept Res & Dev, BIAL, A Av Siderurgia Nacl, P-4745457 S Mamede Do Coronado, Portugal.
(Addresses have been truncated)

Patrício Soares da Silva talks with ScienceWatch.com and answers a few questions about this month's New Hot Papers paper in the field of Agricultural Sciences.


SW: Why do you think your paper is highly cited?

Trans-resveratrol is a nonflavonoid polyphenolic compound found in several plant species, a number of which are part of the human diet such as mulberries, peanuts, grapes, and red wines. Evidence has accumulated that trans-resveratrol acts as a free-radical scavenger and a potent antioxidant, promotes nitric oxide production, increases HDL cholesterol, and inhibits platelet aggregation and the oxidation of low-density lipoproteins.

These biological effects may be cardioprotective and contribute to the phenomenon known as the "French paradox": a decreased incidence of cardiovascular diseases in moderate consumers of red wines despite an intake of a high-fat diet. This study addresses topics of particular relevance concerning the pharmacokinetics of trans-resveratrol and its tolerability in humans.

SW: Does it describe a new discovery, methodology, or synthesis of knowledge?

"Although the systemic bioavailability of trans-resveratrol is very low, accumulation of resveratrol in epithelial cells along the digestive tract and potentially active trans-resveratrol metabolites may still produce cancer preventive and other effects"

This was a double-blind, randomized, placebo-controlled study to investigate the pharmacokinetics and safety of trans-resveratrol. In four groups of 10 healthy adult subjects (five males and five females), two subjects were randomized to receive placebo and eight subjects to receive trans-resveratrol 25, 50, 100, or 150 mg, six times/day, for 13 doses. Trans-resveratrol was subjectively and objectively well tolerated by the subjects in this study. Trans-resveratrol minimum plasma levels were highest in the morning and tended to decrease along the day, being lowest in the night.

SW: Would you summarize the significance of your paper in layman's terms?

This study was the first evaluation of the pharmacokinetics of trans-resveratrol in a multiple-dose regimen in healthy volunteers. Repeated oral administration of high daily doses of trans-resveratrol was well-tolerated but produced relatively low plasma concentrations of trans-resveratrol, despite the relatively high doses and frequent dosing regimen used.

SW: How did you become involved in this research, and how would you describe the particular challenges, setbacks, and successes that you've encountered along the way?

Despite its actual use as dietary supplement and its potential therapeutic interest, few formal clinical trials have been performed and only limited data on the kinetics of trans-resveratrol have been published and were obtained mainly in single-dose studies. Therefore, further investigation into the pharmacokinetics, tolerability, and safety of trans-resveratrol in multiple-doses in man was warranted.

SW: Where do you see your research leading in the future?

Trans-resveratrol pharmacokinetics showed circadian variation. Circadian variations in absorption, distribution, metabolism, or elimination of drugs may be due to diurnal variations in gastric motility and emptying time, intestinal and hepatic blood flow, drug protein binding, enzyme activity, and renal function. The trans-resveratrol chronopharmacokinetics can be the result of several factors, which deserve further evaluation.

SW: Do you foresee any social or political implications for your research?

Although the systemic bioavailability of trans-resveratrol is very low, accumulation of resveratrol in epithelial cells along the digestive tract and potentially active trans-resveratrol metabolites may still produce cancer preventive and other effects.End

Patrício Soares da Silva
Director of Research & Development
BIAL – Portela & Cª S.A.
São Mamede do Coronado, Trofo, Portugal
and
Professor and Head
Institute of Pharmacology and Therapeutics
Faculty of Medicine
University of Porto
Porto, Portugal

KEYWORDS: BIOAVAILABILITY; HEALTHY SUBJECTS; PHARMACOKINETICS; SAFETY; TRANS-RESVERATROL; RED WINE; CHEMOPREVENTIVE AGENT; BIOAVAILABILITY; HUMANS; CANCER; METABOLITES; ABSORPTION; MECHANISMS; QUERCETIN.

 
 

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