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Pharmacokinetic Interactions of a Hop Dietary Supplement with Drug Metabolism in Perimenopausal and Postmenopausal Women

  • Richard B. van Breemen*
    Richard B. van Breemen
    Linus Pauling Institute, College of Pharmacy, Oregon State University, 2900 SW Campus Way, Corvallis, Oregon 97331, United States
    UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States
    *Email: [email protected]. Phone: 541-737-5078. Fax: 541-737-5077.
  • Luying Chen
    Luying Chen
    Linus Pauling Institute, College of Pharmacy, Oregon State University, 2900 SW Campus Way, Corvallis, Oregon 97331, United States
    UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States
    More by Luying Chen
  • Alyssa Tonsing-Carter
    Alyssa Tonsing-Carter
    Clinical and Healthcare Research Policy Division, National Institutes of Health, 6705 Rockledge Dr., Suite 750, Bethesda, Maryland 20817, United States
    UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States
  • Suzanne Banuvar
    Suzanne Banuvar
    UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States
  • Elena Barengolts
    Elena Barengolts
    UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States
  • Marlos Viana
    Marlos Viana
    UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States
    More by Marlos Viana
  • Shao-Nong Chen
    Shao-Nong Chen
    UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States
  • Guido F. Pauli
    Guido F. Pauli
    UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States
  • , and 
  • Judy L. Bolton
    Judy L. Bolton
    UIC/NIH Center for Botanical Dietary Supplements Research, University of Illinois College of Pharmacy, 833 S. Wood Street, Chicago, Illinois 60612, United States
Cite this: J. Agric. Food Chem. 2020, 68, 18, 5212–5220
Publication Date (Web):April 14, 2020
https://doi.org/10.1021/acs.jafc.0c01077
Copyright © 2020 American Chemical Society
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Abstract

Abstract Image

Botanical dietary supplements produced from hops (Humulus lupulus) containing the chemopreventive compound xanthohumol and phytoestrogen 8-prenylnaringenin are used by women to manage menopausal symptoms. Because of the long half-lives of prenylated hop phenols and reports that they inhibit certain cytochrome P450 enzymes, a botanically authenticated and chemically standardized hop extract was tested for Phase I pharmacokinetic drug interactions. Sixteen peri- and postmenopausal women consumed the hop extract twice daily for 2 weeks, and the pharmacokinetics of tolbutamide, caffeine, dextromethorphan, and alprazolam were evaluated before and after supplementation as probe substrates for the enzymes CYP2C9, CYP1A2, CYP2D6, and CYP3A4/5, respectively. The observed area under the time–concentration curves were unaffected, except for alprazolam which decreased 7.6% (564.6 ± 46.1 h·μg/L pre-hop and 521.9 ± 36.1 h·μg/L post-hop; p-value 0.047), suggesting minor induction of CYP3A4/5. No enzyme inhibition was detected. According to FDA guidelines, this hop dietary supplement caused no clinically relevant pharmacokinetic interactions with respect to CYP2C9, CYP1A2, CYP2D6, or CYP3A4/5. The serum obtained after consumption of the hop extract was analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry to confirm compliance. Abundant Phase II conjugates of the hop prenylated phenols were observed including monoglucuronides and monosulfates as well as previously unreported diglucuronides and sulfate-glucuronic acid diconjugates.

Cited By


This article is cited by 4 publications.

  1. Luying Chen, Jaewoo Choi, Scott W. Leonard, Suzanne Banuvar, Elena Barengolts, Marlos Viana, Shao-Nong Chen, Guido F. Pauli, Judy L. Bolton, Richard B. van Breemen. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. Journal of Agricultural and Food Chemistry 2020, 68 (47) , 13929-13939. https://doi.org/10.1021/acs.jafc.0c05856
  2. Lance Buckett, Sabrina Schönberger, Veronika Spindler, Nadine Sus, Christian Schoergenhofer, Jan Frank, Oliver Frank, Michael Rychlik. Synthesis of Human Phase I and Phase II Metabolites of Hop (Humulus lupulus) Prenylated Flavonoids. Metabolites 2022, 12 (4) , 345. https://doi.org/10.3390/metabo12040345
  3. Mary Beth Babos, Michelle Heinan, Linda Redmond, Fareeha Moiz, Joao Victor Souza-Peres, Valerie Samuels, Tarun Masimukku, David Hamilton, Myra Khalid, Paul Herscu. Herb–Drug Interactions: Worlds Intersect with the Patient at the Center. Medicines 2021, 8 (8) , 44. https://doi.org/10.3390/medicines8080044
  4. Kurt Lucas, Janine Fröhlich-Nowoisky, Nicole Oppitz, Maximilian Ackermann. Cinnamon and Hop Extracts as Potential Immunomodulators for Severe COVID-19 Cases. Frontiers in Plant Science 2021, 12 https://doi.org/10.3389/fpls.2021.589783

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