Pharmacokinetics of prenylated hop phenols in women following oral administration of a standardized extract of hops

Abstract

SCOPE Women seeking alternatives to hormone replacement therapy for menopausal symptoms often try botanical dietary supplements containing extracts of hops (Humulus lupulus L.). Hops contain 8-prenylnaringenin (8-PN), a potent phytoestrogen, the related flavanones 6-prenylnaringenin (6-PN) and isoxanthohumol (IX), and the prenylated chalcone xanthohumol (XN). METHODS AND RESULTS After chemically and biologically standardizing an extract of spent hops to these marker compounds, an escalating dose study was carried out in menopausal women to evaluate safety and pharmacokinetics. 8-PN, 6-PN, IX, and XN, sex hormones, and prothrombin time (PT/INR) were determined in blood samples and/or 24-h urine samples. There was no effect on sex hormones or blood clotting. The maximum serum concentrations of the prenylated phenols were dose-dependent and were reached from 2 to 7 h, indicating slow absorption. The marker compounds formed glucuronides that were found in serum and urine. Secondary peaks at 5 h in the serum concentration-time curves indicated enterohepatic recirculation. The serum concentration-time curves indicated demethylation of IX to form 8-PN and cyclization of XN to IX. Slow absorption and enterohepatic recirculation contributed to half-lives exceeding 20 h. CONCLUSION This human study indicated long half-lives of the estrogenic and proestrogenic prenylated phenols in hops but no acute toxicity.

Prenylated Flavonoids as Valuable Biologically Active Compounds from Hops

“…The results of the toxicity tests were very promising as no acute toxicity, no negative effects on the production of sexual hormones and no blood clotting was discovered (van Breemen et al, 2014). Milligan et al (2002) observed in vitro, a negative impact of 8-prenylnaringinin at a concentration of 15.9 mg/kg body weight on the uterus function and its affection of development the mitosis of vaginal cells in rats.…”

“…V nedávné době byly provedeny klinické studie u žen po menopauze s cílem vyhodnotit bezpečnost chmelového extraktu obohaceného o xanthohumol a 8-prenylnaringenin (van Breemen et al, 2014). Výsledky testů toxicity byly velmi slibné, jelikož nebyla zjištěna žádná akutní toxicita a ani žádné negativní účinky na tvorbu pohlavních hormonů nebo na srážlivost krve (van Breemen et al, 2014). Milligan a kol.…”

“…(2002) uvádějí negativní dopady 8-prenylnaringenininu in vivo na funkci dělohy a ovlivnění vývoje vaginální mitózy u myší při dávce 15,9 mg/kg, která ovšem výrazně překračuje běž-né dávky při aplikaci potravinových doplňků, kde se dávka pohybuje okolo 100 μg/g jedné pilulky podané jednou denně (Milligan et al, 2002). Bez ohledu na počet studií in vitro (Effenberger a Westendorf, 2009;Tokalov et al, 2004), in vivo a již provedených klinických studií (van Breemen et al, 2014), jsou tedy zapotřebí další epidemiologické a klinické studie 8-prenylnaringeninu pro zjištění všech zdravotních účinků a zejména toxicity, která prozatím není plně objasněna.…”

“…Recently, several clinical studies in women were carried out in order to evaluate the safety of hop extracts enriched with xanthohumol and 8-prenylnaringinin (van Breemen et al, 2014).…”

Drink your prevention: beverages with cancer preventive phytochemicals

“…67 Moreover, a toxicity study showed that mice receiving an XN-supplemented diet showed no signs of toxicity on a histopathological examination and biochemical serum analysis as compared with mice on a standard diet. 77 Taken together, XN may be considered as a promising phytochemical in the field of chemoprevention.…”