Health Effects of Resveratrol: Results from Human Intervention Trials

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Abstract

The effect of resveratrol (RV) intake has been reviewed in several studies performed in humans with different health status. The purpose of this review is to summarize the results of clinical trials of the last decade, in which RV was determined in biological samples such as human plasma, urine, and feces. The topics covered include RV bioavailability, pharmacokinetics, effects on cardiovascular diseases, cognitive diseases, cancer, type 2 diabetes (T2D), oxidative stress, and inflammation states. The overview of the recent research reveals a clear tendency to identify RV in plasma, showing that its supplementation is safe. Furthermore, RV bioavailability depends on several factors such as dose, associated food matrix, or time of ingestion. Notably, enterohepatic recirculation of RV has been observed, and RV is largely excreted in the urine within the first four hours after consumption. Much of the research on RV in the last 10 years has focused on its effects on pathologies related to oxidative stress, inflammatory biomarkers, T2D, cardiovascular diseases, and neurological diseases.

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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.

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Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans

J. P. Gambini, M. Inglés, G. Olaso … (2015)

Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol.

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Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients.

Pál Brasnyó, Gergő A Molnár, Márton Mohás … (2011)

Although resveratrol has widely been studied for its potential health benefits, little is known about its metabolic effects in humans. Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action. After an initial general examination (including blood chemistry), nineteen patients enrolled in the 4-week-long double-blind study were randomly assigned into two groups: a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo. Before and after the second and fourth weeks of the trial, insulin resistance/sensitivity, creatinine-normalised ortho-tyrosine level in urine samples (as a measure of oxidative stress), incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B (Akt) ratio in platelets were assessed and statistically analysed. After the fourth week, resveratrol significantly decreased insulin resistance (homeostasis model of assessment for insulin resistance) and urinary ortho-tyrosine excretion, while it increased the pAkt:Akt ratio in platelets. On the other hand, it had no effect on parameters that relate to β-cell function (i.e. homeostasis model of assessment of β-cell function). The present study shows for the first time that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway.

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Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 03 December 2018

Publication date Collection: December 2018

Volume: 10

Issue: 12

Electronic Location Identifier: 1892

Affiliations

[1 ]Department of Nutrition, Food Science and Gastronomy, School of Pharmacy and Food Sciences XaRTA, Institute of Nutrition and Food Safety (INSA-UB), University of Barcelona, 08921 Santa Coloma de Gramenet, Spain; sonialrmz@ 123456gmail.com (S.L.R.-G.); elaversa21@ 123456alumnes.ub.edu (E.P.L.-S.); mmarhuendam@ 123456ub.edu (M.M.-M.); carolina.e.storniolo@ 123456gmail.com (C.E.S.); avallverdu@ 123456ub.edu (A.V.-Q.)

[2 ]CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, 28029 Madrid, Spain

[3 ]Human Nutrition Unit, University Hospital of Sant Joan de Reus, Department of Biochemistry and Biotechnology, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Center, University Rovira i Virgili, 43201 Reus, Tarragona, Spain; anna.tresserra@ 123456iispv.cat

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[* ]Correspondence: lamuela@ 123456ub.edu ; Tel.: +34-934-034-843; Fax: +34-934-035-931

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Emily P. Laveriano-Santos https://orcid.org/0000-0002-4852-6074

Anna Tresserra-Rimbau https://orcid.org/0000-0002-7022-9041

Anna Vallverdú-Queralt https://orcid.org/0000-0001-6287-799X

Rosa M. Lamuela-Raventós https://orcid.org/0000-0002-1287-4560

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Publisher ID: nutrients-10-01892

DOI: 10.3390/nu10121892

PMC ID: 6317057

PubMed ID: 30513922

SO-VID: f8800947-7003-4540-8095-dfbdeaecb82a

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Health Effects of Resveratrol: Results from Human Intervention Trials

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Most cited references 45

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

Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans

Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients.

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