High absorption but very low bioavailability of oral resveratrol in humans.
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.
Walle
Thomas
T
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA. wallet@musc.edu
Hsieh
Faye
F
DeLegge
Mark H
MH
Oatis
John E
JE
Walle
U Kristina
UK
D000284:Administration, Oral; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D013058:Mass Spectrometry; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013431:Sulfates / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D013431:Sulfates; D000077185:Resveratrol