Clinical assessment of CYP2D6‐mediated herb–drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea

Abstract

Cytochrome P450 2D6 (CYP2D6), an important CYP isoform with regard to drug-drug interactions, accounts for the metabolism of ∼30% of all medications. To date, few studies have assessed the effects of botanical supplementation on human CYP2D6 activity in vivo. Six botanical extracts were evaluated in three separate studies (2 extracts per study), each incorporating 18 healthy volunteers (9 females). Subjects were randomized to receive a standardized botanical extract for 14 days on separate occasions. A 30-day washout period was interposed between each supplementation phase. In study 1, subjects received milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa). In study 2, kava kava (Piper methysticum), and goldenseal (Hydrastis canadensis) extracts were administered, and in study 3 subjects received St. John's wort (Hypericum perforatum) and Echinacea (Echinacea purpurea). The CYP2D6 substrate, debrisoquine (5 mg), was administered before and at the end of supplementation. Pre-and post-supplementation phenotypic trait measurements were determined for CYP2D6 using 8-hour debrisoquine urinary recovery ratios (DURR). Comparisons of pre-and post-supplementation DURR revealed significant inhibition (∼50%) of CYP2D6 activity for goldenseal, but not for the other extracts. Accordingly, adverse herb-drug interactions may result with concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 substrates.

Essentials of Herb-Drug Interactions in the Elderly With Cardiovascular Disease

“…Thus, the effect of echinacea in the elderly using medications metabolized by CYP3A4 should be closely monitored or used with caution. 120 Echinacea does not change the pharmacokinetics of digoxin, a P-glycoprotein substrate, 121 nor does it alter the pharmacokinetics of chlorzoxazone (CYP2E1 probe), 122 debrisoquine (CYP2D6 probe) 122 or tolbutamide (CYP2C9 probe). 119 In 12 healthy subjects, after a single dose of warfarin before and after taking echinacea for 14 days, the pharmacokinetics and pharmacodynamics of warfarin were not significantly altered.…”

Herbs for the Treatment of Insomnia

“…Not well understood -affects the enzyme CYP2D6, vulnerable to liver damage from use of kava (banned in many countries) (Gurley et al, 2008 Common tea Action similar to the benzodiazepine drugs (Shinomiya et al, 2005) St. John's wort…”

Bioactive Foods and Nutraceutical Supplementation Criteria in Cardiovascular Protection

“…The cardiovascular disease has been reported associated with vascular endothelial growth factor [64].…”

“…Combination of garlic, ginko biloba, herbs with reverastrol inhibited a full 92 percent of age-related gene changes in the heart [2,64].…”