HIGH ABSORPTION BUT VERY LOW BIOAVAILABILITY OF ORAL RESVERATROL IN HUMANS

TLDR

The dietary polyphenol resveratrol has shown chemopreventive activity against cardiovascular disease and various cancers in model systems, but it is unclear whether it reaches its proposed sites of action in vivo after oral ingestion, especially in humans. The study examined the absorption, bioavailability, and metabolism of 14C‑resveratrol after oral and intravenous doses in six human volunteers. The authors administered 14C‑resveratrol orally and intravenously, measuring plasma concentrations, urinary excretion, and metabolite profiles by liquid chromatography/mass spectrometry. The oral 25‑mg dose was absorbed at ≥70 % with peak plasma levels of ~2 µM and a 9.2‑h half‑life, yet unchanged resveratrol was <5 ng/ml, most of the dose was excreted in urine, and LC‑MS revealed sulfate, glucuronide, and microflora‑mediated hydrogenation pathways, with rapid intestinal sulfate conjugation limiting systemic bioavailability, though epithelial accumulation and active metabolites may still confer chemopreventive effects.

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 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 μM) and a plasma half-life of 9.2 ± 0.6 h. However, only trace amounts of unchanged resveratrol (&lt;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 resveratrol9s 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.