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

Drugs Aging. 2005;22(6):525-39. doi: 10.2165/00002512-200522060-00006.


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 (approximately 140%) and CYP2E1 activity (approximately 28%). Garlic oil inhibited CYP2E1 activity by approximately 22%. P. ginseng inhibition of CYP2D6 was statistically significant, but the magnitude of the effect (approximately 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Aged
  • Allyl Compounds / chemistry
  • Caffeine / administration & dosage
  • Caffeine / blood
  • Caffeine / pharmacology
  • Chlorzoxazone / administration & dosage
  • Chlorzoxazone / blood
  • Chlorzoxazone / pharmacology
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Dietary Supplements*
  • Drug Administration Schedule
  • Female
  • Ginkgo biloba / chemistry
  • Herb-Drug Interactions
  • Humans
  • Hypericum / chemistry
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Male
  • Midazolam / administration & dosage
  • Midazolam / blood
  • Midazolam / pharmacology
  • Panax / chemistry
  • Phenotype
  • Plant Preparations / administration & dosage
  • Plant Preparations / chemistry
  • Plant Preparations / pharmacology*
  • Sulfides / chemistry


  • Allyl Compounds
  • Cytochrome P-450 Enzyme Inhibitors
  • Isoenzymes
  • Plant Preparations
  • Sulfides
  • Caffeine
  • allyl sulfide
  • Cytochrome P-450 Enzyme System
  • Chlorzoxazone
  • Midazolam