The Pharmacokinetics of Individual Conjugated Xanthohumol Metabolites Show Efficient Glucuronidation and Higher Bioavailability of Micellar than Native Xanthohumol in a Randomized, Double-Blind, Crossover Trial in Healthy Humans

ScopePrenylated chalcones and flavonoids are found in many plants and are believed to have beneficial effects on health when consumed. Xanthohumol is present in beer and likely the most consumed prenylated chalcone, but poorly absorbed and rapidly metabolized and excreted, thus limiting its bioavailability. Micellar formulations of phytochemicals have been shown to improve bioavailability.Methods and resultsIn a randomized, double-blind, crossover trial with five healthy (three males and two females) volunteers, a single dose of 43 mg was orally administered as a native or micellar formulation. The major human xanthohumol metabolites are quantified in plasma. Unmetabolized free xanthohumol makes 1% or less of total plasma xanthohumol. The area under the plasma concentration-time curve of xanthohumol-7-O-glucuronide following the ingestion of the micellular formulation is 5-fold higher and its maximum plasma concentration is more than 20-fold higher compared to native xanthohumol.ConclusionMetabolism of orally ingested xanthohumol is complex and efficiently converts the parent compound to predominantly glucuronic acid and to a lesser extent sulfate conjugates. The oral bioavailability of micellar xanthohumol is superior to native xanthohumol, making it a useful delivery form for future human trials. The bioavailability of xanthohumol, a beneficial compound found in plants and beer is rather low. In a human-trial with five participants, micellar formulation shows significant advantages over the native form, resulting in higher plasma concentrations (20-fold) and improved absorption (5-fold). These findings highlight micellar delivery's potential for enhancing xanthohumol's effectiveness in human trials.image

Automated summary

In a human trial, it was found that micellar formulation of xanthohumol significantly improved its oral bioavailability compared to the native form, leading to higher plasma concentrations (20-fold) and improved absorption (5-fold).