Richard van Breemen (Presenter)
Linus Pauling Institute
Bio: Richard B. van Breemen is the Linus Pauling endowed chair and director of the Linus Pauling Institute at Oregon State University. Previously, he was the director of the UIC/NIH Center for Botanical Dietary Supplements Research at the University of Illinois at Chicago. He received his B.A. in chemistry from Oberlin College and Ph.D. in Pharmacology and Experimental Therapeutics from the Johns Hopkins University working with Catherine Fenselau. He carried out post-doctoral research in laser desorption mass spectrometry at Johns Hopkins with Robert Cotter. His research concerns the discovery and development of natural products as chemoprevention agents, the safety and efficacy of botanical dietary supplements, and the application of biomedical mass spectrometry to translational clinical research.
Authorship: Richard B. van Breemen and Alyssa Tonsing-Carter
University of Illinois College of Pharmacy and Oregon State University
| Short Abstract Among botanical supplement alternatives to hormone therapy, hops (Humulus lupulus L.) is an increasingly popular alternative and has a long history of use in the brewing industry. To ensure the safe use of hop dietary supplements, we investigated their potential for drug interactions. Standardized extracts of spent hops (pre-extracted to remove the bitter acid flavor components), which are rich in prenylated phenols and flavonoids with estrogenic and chemoprevention activities, were studied for possible inhibition or induction of cytochrome P450 enzymes involved in drug metabolism both in vitro and in a Phase I clinical trial. |
Long Abstract
Introduction
Concerns regarding increased risks of stroke and breast cancer have prompted many women to consider botanical dietary supplements instead of conventional hormone therapy for the management of menopausal symptoms such as hot flashes. Among botanical supplement alternatives to hormone therapy, hops (Humulus lupulus L.) is an increasingly popular alternative and has a long history of use in the brewing industry. To ensure the safe use of hop dietary supplements, we investigated their potential for drug interactions.
Methods
The potential for inhibition or induction of human cytochrome P450 was investigated first in vitro using human liver microsomes and human primary hepatocytes. Subsequently, a Phase I clinical trial was carried out using four probe substrates of specific cytochrome P450 enzymes to test for pharmacokinetic interactions. A total of 16 women completed the study, which involved an initial pharmacokinetic evaluation of the probe substrates, and two-week interaction using a standardize hop extract, and a repeat pharmacokinetic evaluation using the probe substrates.
Results
Hop extracts showed inhibition of the cytochrome P450 enzymes CYP1A2, CYP2C8, CYP2C9, and CYP2C19 in vitro at concentrations predicted to be physiologically relevant (based on human Phase I pharmacokinetic single dose studies). However, no induction of cytochromes P450 was observed using human hepatocytes in combination with function enzyme assays or mRNA measurements. Chronic dosing of the standardized hop extract in a clinical trial using 16 women receiving probe substrates for four different cytochrome P450 enzymes showed no clinically relevant drug interactions.
Conclusions & Discussion
Hop dietary supplements are not expected to cause clinically relevant drug interactions in women taking these products for the management of menopausal symptoms such as hot flashes.
References & Acknowledgements:
This research was supported by grant P50 AT000155 from the NIH Office of Dietary Supplements and the National Center for Complementary and Integrative Health. We also thank Hopsteiner and Shimadzu Scientific Instrument for providing research materials and instrumentation, respectively.
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