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Clinical Assessment of Effects of Botanical Supplementation on Cytochrome P450 Phenotypes in the Elderly

St John’s Wort, Garlic Oil, Panax ginseng and Ginkgo biloba

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Abstract

Objectives

Elderly patients are more likely to ingest prescription medications concurrently with botanical supplements, and may therefore be vulnerable to herb-drug interactions. Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Some evidence suggests that CYP activity may decrease in the elderly. If so, herb-mediated changes in CYP activity may take on greater clinical relevance in this population. In this study, single timepoint, phenotypic metabolic ratios were used to determine whether long-term supplementation of St John’s wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1 or CYP3A4 activity in elderly subjects.

Methods

Twelve healthy volunteers between the ages of 60 and 76 years (mean age 67 years) were randomly assigned to receive each botanical supplement for 28 days followed by a 30-day washout period. Probe drug cocktails of midazolam, caffeine, chlorzoxazone and debrisoquine were administered before and at the end of supplementation. Pre- and post-supplementation phenotypic ratios were determined for CYP3A4, CYP1A2, CYP2E1 and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour), paraxanthine/caffeine serum ratios (6-hour), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour) and debrisoquine urinary recovery ratios (8-hour), respectively. The content of purported ‘active’ phytochemicals was determined for each supplement.

Results

Comparisons of pre- and post-St John’s wort phenotypic ratios revealed significant induction of CYP3A4 (≈140%) and CYP2E1 activity (≈28%). Garlic oil inhibited CYP2E1 activity by approximately 22%. P. ginseng inhibition of CYP2D6 was statistically significant, but the magnitude of the effect (≈7%) did not appear to be clinically relevant. None of the supplements tested in this study appeared to affect CYP1A2 activity.

Conclusions

Elderly subjects, like their younger counterparts, are susceptible to herb-mediated changes in CYP activity, especially those involving St John’s wort. Pharmacokinetic herb-drug interactions stemming from alterations in CYP activity may adversely affect drug efficacy and/or toxicity. When compared with earlier studies that employed young subjects, the data suggest that some age-related changes in CYP responsivity to botanical supplementation may exist. Concomitant ingestion of botanical supplements with prescription medications, therefore, should be strongly discouraged in the elderly.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

Supported through grants from the NIH/NIA (RO3AG17733-01) and NIH/NCRR to the General Clinical Research Center of the University of Arkansas for Medical Sciences (M01RR14288).

The authors would like to acknowledge Dr Ikhlas Khan (University of Mississippi, National Center for Natural Products Research), and Dr Mark Roman and Brian Schaneberg (Chromadex, Inc., Clearwater, Florida) for analysis of supplements containing Panax ginseng, Ginkgo biloba and garlic oil.

The authors have no financial or other interests to disclose.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, 4301 W. Markham St, Slot 522, Little Rock, Arkansas, 72205, USA

    Bill J. Gurley & Martha A. Hubbard

  2. Department of Pharmacy Practice, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    Stephanie F. Gardner

  3. Department of Biometry, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    D. Keith Williams

  4. Department of Anesthesiology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    W. Brooks Gentry

  5. Division of Chemistry, National Center for Toxicological Research, Jefferson, Arkansas, USA

    Yanyan Cui & Catharina Y. W. Ang

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  1. Bill J. Gurley
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Correspondence to Bill J. Gurley.

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Gurley, B.J., Gardner, S.F., Hubbard, M.A. et al. Clinical Assessment of Effects of Botanical Supplementation on Cytochrome P450 Phenotypes in the Elderly. Drugs Aging 22, 525–539 (2005). https://doi.org/10.2165/00002512-200522060-00006

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