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In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes

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GURLEY, B, GARDNER, S, HUBBARD, M, WILLIAMS, D, GENTRY, W, KHAN, I, SHAH, A·2005·Clinical Pharmacology & Therapeutics
DOI 10.1016/j.clpt.2005.01.009PMC PMC1894911
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Abstract

OBJECTIVES: Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal ( Hydrastis canadensis ), black cohosh ( Cimicifuga racemosa ), kava kava ( Piper methysticum ), or valerian ( Valeriana officinalis ) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity. METHODS: Twelve healthy volunteers (6 women) were randomly assigned to receive goldenseal, black cohosh, kava kava, or valerian for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4/5, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported "active" phytochemicals was determined for each supplement. RESULTS: Comparisons of presupplementation and postsupplementation phenotypic ratio means revealed significant inhibition (approximately 40%) of CYP2D6 (difference, -0.228; 95% confidence interval [CI], -0.268 to -0.188) and CYP3A4/5 (difference, -1.501; 95% CI, -1.840 to -1.163) activity for goldenseal. Kava produced significant reductions (approximately 40%) in CYP2E1 only (difference, -0.192; 95% CI, -0.325 to -0.060). Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference, -0.046; 95% CI, -0.085 to -0.007), but the magnitude of the effect (approximately 7%) did not appear to be clinically relevant. No significant changes in phenotypic ratios were observed for valerian. CONCLUSIONS: Botanical supplements containing goldenseal strongly inhibited CYP2D6 and CYP3A4/5 activity in vivo, whereas kava inhibited CYP2E1 and black cohosh weakly inhibited CYP2D6. Accordingly, serious adverse interactions may result from the concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 and CYP3A4/5 substrates. Kava kava and black cohosh may interact with CYP2E1 and CYP2D6 substrates, respectively. Valerian appears to be less likely to produce CYP-mediated herb-drug interactions.

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Research works printed but not linked: 6

  1. [4]Gurley BJ, Hagan DW. Herbal and dietary supplement interactions with drugs. In: McCabe BJ, Frankel EH, Wolfe JJ, editors. Handbook of Food-Drug Interactions. Boca Raton: CRC Press; 2003. pp. 259–293. [Google Scholar]
  2. [46]Ganzera M, Bedir E, Khan IA. Separation of Cimicifuga racemosa triterpene glycosides by evaporative light scattering detection. Chromatographia. 2000;52:301–304. [Google Scholar]
  3. [48]The Pharmacopeia of the United States Twenty-seventh Revision, and the National Formulary. 22. Rockville: United States Pharmacopeial Convention, Inc.; 2004. Disintegration and dissolution of dietary supplements; pp. 2645–2646. [Google Scholar]
  4. [49]Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2. Lawrence Erlbaum Associates Publishers; 1988. pp. 19–42. [Google Scholar]
  5. [50]Chatterjee P, Franklin MR. Human cytochrome P450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos. 2003;31:1391–1397. doi: 10.1124/dmd.31.11.1391. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  6. [61]Food and Drug Administration. Letter to health-care professionals: FDA issues consumer advisory that kava products may be associated with severe liver injury. Vol. 36. US Department of Health and Human Services; Rockville, MD: May/June, 2002. p. 4. Available at http://www.cfsan.fda.gov/~dms/addskava.html. [Google Scholar]

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Metadata

Authors
GURLEY, B., GARDNER, S., HUBBARD, M., WILLIAMS, D., GENTRY, W., KHAN, I., & SHAH, A.
Affiliations
University of Mississippi (US)
Corresponding author
GURLEY, B
ORCID
Venue
Clinical Pharmacology & Therapeutics
Publisher
Wiley
Published
2005-05
Volume
77
Issue
5
Pages
415-426
ISSN
0009-9236 (ISSN-L)
DOI
10.1016/j.clpt.2005.01.009
PMC
PMC1894911
OpenAlex
W1966006812
Cited by
271
References
58
Citations by year
2026: 7 · 2025: 9 · 2024: 8 · 2023: 5 · 2022: 12 · 2021: 12 · 2020: 16 · 2019: 10 · 2018: 12 · 2017: 4 · 2016: 7 · 2015: 15 · 2014: 15 · 2013: 15 · 2012: 20
FWCI
15.25
Type
journal article
Language
en
Open access
Locations
  • Clinical Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R01GM071322, GM71322-01A2)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Complementary and alternative medicine › Complementary and Alternative Medicine Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
goldenseal, Hydrastis canadensis, kava, black cohosh, Cimicifuga racemosa, Valeriana officinalis, cytochrome P450, herb-drug interactions, CYP2D6 inhibition, CYP2E1, CYP1A2, phytochemicals, herbal supplements, midazolam hydroxylation
MeSH terms
Adult, Aryl Hydrocarbon Hydroxylases, Caffeine, Capsules, Drug Administration Schedule, Female, Humans, Male, Midazolam, Phenotype, Time Factors, Valerian, Patient Selection, Dietary Supplements, Kava, Cimicifuga, Hydrastis, Herb-Drug Interactions

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