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

Mol Nutr Food Res. 2014 Oct;58(10):1962-9. doi: 10.1002/mnfr.201400245. Epub 2014 Sep 16.


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 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-prenylnaringenin, IX, and XN, sex hormones, and prothrombin time 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.

Keywords: 8-Prenylnaringenin; Hops; Isoxanthohumol; Pharmacokinetics; Xanthohumol.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Beer
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Dietary Supplements* / adverse effects
  • Dietary Supplements* / analysis
  • Dietary Supplements* / economics
  • Enterohepatic Circulation
  • Female
  • Food-Processing Industry / economics
  • Glucuronides / blood
  • Glucuronides / metabolism
  • Half-Life
  • Humans
  • Humulus / chemistry*
  • Industrial Waste / analysis
  • Industrial Waste / economics
  • Inflorescence / chemistry*
  • Intestinal Absorption
  • Kinetics
  • Methylation
  • Middle Aged
  • Phenols / administration & dosage
  • Phenols / adverse effects
  • Phenols / economics
  • Phenols / metabolism*
  • Phytoestrogens / administration & dosage
  • Phytoestrogens / adverse effects
  • Phytoestrogens / economics
  • Phytoestrogens / metabolism*
  • Plant Extracts / administration & dosage
  • Plant Extracts / adverse effects
  • Plant Extracts / chemistry
  • Plant Extracts / metabolism*
  • Postmenopause
  • Prenylation


  • Biomarkers
  • Glucuronides
  • Industrial Waste
  • Phenols
  • Phytoestrogens
  • Plant Extracts