High Absorption but Very Low Bioavailability of Oral Resveratrol in Humans

Abstract

ABSTRACT: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 14 C-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 M) 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 cancerpreventive and other effects.

Effects of resveratrol analogs on cell cycle progression, cell cycle associated proteins and 5fluoro‐uracil sensitivity in human derived colon cancer cells

“…13 Moreover, several reports showed that resveratrol could prevent or delay the onset of cancer. [49][50][51][52] These effects are observed despite extremely low bioavailability and rapid clearance from the circulation, 53 which explains why many laboratories develop resveratrol-derivatives with better in vivo efficacy.…”

Preparação e caracterização de suspensões coloidais de nanocarreadores lipídicos contendo resveratrol destinados à administração cutânea

“…A rápida conjugação com sulfato no intestino e fígado foi responsável pela baixa biodisponibilidade oral do resveratrol. 20,21 Outros fatores que limitam o aproveitamento terapêutico do resveratrol incluem a sua baixa estabilidade frente à oxidação e baixa solubilidade aquosa. 22 Inúmeros estudos relatam os benefícios do resveratrol sobre a pele, fazendo com que a liberação tópica deste composto constitua uma interessante alternativa à administração oral para o tratamento de várias desordens cutâneas.…”

“…Entretanto, a maioria deles tem sido focada em determinações simultâneas de vários compostos do vinho 2,35,36 e identificação de metabólitos do resveratrol em plasma humano e animal. 20,37,38 Assim, este trabalho também descreve o desenvolvimento e validação de um método de cromatografia líquida de alta eficiência para a determinação do resveratrol nas suspensões coloidais e nos hidrogeis obtidos após a incorporação da hidroxietilcelulose.…”

Is the use of resveratrol in the treatment and prevention of obesity premature?

“…Resveratrol forms extensive conjugated metabolites including glucuronides, sulfates and methylated products (25 -27) . Pharmacokinetic studies on acute resveratrol doses indicate significant distribution thereof to the kidneys (27,28) , with rapid excretion in urine (25,27,29) . These metabolites are capable of crossing glomerular membranes and accumulating in the kidney tubules where they may act as pro-oxidants or activate oxidative stress, as seen for various polyphenolic conjugates (27,30) .…”