Yarnell E, Abascal K. Interaction of herbal constituents with cytochrome P450 enzymes. Altern Complement Ther. Oct 2007:239-247.
Cytochrome P450 (CYP450) enzymes are involved in the metabolism of many drugs and herbal medicines. This has led to recent concern over herb-drug interactions.
Constituents of St. John's wort (SJW; Hypericum perforatum) induce CYP3A4, and constituents of grapefruit (Citrus decumana) inhibit it.
The major CYP3A4-inducing constituent of SJW is hyperforin. SJW extracts with little or no hyperforin have little to no effect on CYP3A4 in humans.
SJW has a broad effect on CYP450 enzymes and should not be administered with any drug that is metabolized by CYP3A4, such as estrogen analogue oral birth control pills, digoxin, warfarin, and cyclosporin.
SJW's effect on CYP3A4 reduces the absorption of these drugs.
The authors also write that the observed interactions do not always translate into changes in efficacy or toxicity, citing the example of SJW's interaction with quazepam, which does not affect the drug's pharmacodynamics.
Furanocoumarins, fouranocoumarin polymers, and flavonoids from grapefruit are known inhibiters of CYP3A4.
Grapefruit also inhibits the drug transporter p-glycoprotein.
Grapefruit increases the absorption of drugs including immunosuppressives such as cyclosporin, statin drugs such as atorvastatin, and antiseizure drugs including carbamazepine.
The authors write that grapefruit is not always contraindicated in patients taking CYP3A4-metabolized drugs if there is close supervision by an experienced clinician.
However, the use of grapefruit as a dose-sparing agent needs more research, and it is particularly risky with drugs with a narrow therapeutic index. Grapefruit and other bitter citrus fruits have also been shown to improve the absorption of substrates of CYP2A6 by blocking the effect of the enzyme.
An example is the effect on nicotine, which may make grapefruit a useful dose-sparing agent for nicotine substitution.
Several members of the Boraginaceae and Asteraceae families, such as comfrey (Symphytum officinale), contain unsaturated pyrrolizidine alkaloids (PAs) that are converted by CYP3A enzymes into toxic intermediates.
This may explain the variation in the toxicity of PAs because the activity of these enzymes varies between individuals.
CYP3A4 inhibitors like grapefruit may theoretically reduce the toxicity of PAs, but research is needed to confirm this.
Alkylbenzenes, such as safrole from Sassafras spp. and betel nut (Areca catechu), are also converted to toxic intermediates, including the carcinogenic 1′-hydroxysafrole, by CYP450 enzymes.
Research suggests that individuals with low levels of CYP2A6 may have resistance to the toxicity of betel nut. The authors write that more research on the role of CYP3A4 enzymes in plant toxicities is warranted.
Piperine, an alkaloid found in black pepper (Piper nigrum), is an inhibitor of CYP3A4 and may affect other CYP450 enzymes.
Piperine increases the absorption of phenytoin, propanolol, and theophylline, and it may have potential as a dose-sparing agent.
Piperine has been shown to significantly enhance the absorption of curcumin, an antioxidant constituent of turmeric (Curcuma longa) that also inhibits several CYP450 enzymes in vitro.
The authors write that more research is needed to determine if turmeric and/or curcumin could cause drug-herb interactions.
Cruciferous vegetables like broccoli (Brassica oleracea italica) and watercress (Nasturtium officinale) contain isothiocyanates, which inhibit CYP2E1 and stimulate CYP1A1 and CYP1A2.
Although the mechanism for the anticarcinogenic effects of cruciferous vegetables is very complex, it involves their ability to accelerate the breakdown of carcinogens by CYP1A1 and CYP1A2.
Eating broccoli together with charred meats containing carcinogenic heterocyclic amines may reduce the damage caused by these compounds; however, more research is needed to confirm this.
Isothiocyanates, particularly indole-3-carbinol, induce CYP1A2 and may reduce the risk of metabolizing estrogen into harmful metabolites with minimal adverse side effects.
Sweet Annie (Artemisia annua) is the source of the antimalarial compound artemisinin, which is metabolized by CYP2B6, CYP2A6, and CYP3A4.
As well as being metabolized by CYP2B6, artemisinin also induces this enzyme, which leads to decreased absorption of artemisinin doses over a period of several days, so artemisinin is prescribed for 5-7 days at a time and is combined with other antimalarials.
Resveratrol is an antioxidant constituent found in red wine. CYP450 enzymes are involved in the hydroxylation of resveratrol to the metabolite piceatannol, which may have more potent cardioprotective and antineoplastic effects and/or synergistic effects.
This is a probable example of the transformation of medicinal plant constituents into more active substances by CYP450 enzymes.
CYP2C19 is an enzyme that affects the disposition of a small number of drugs.
Ginkgo (Ginkgo biloba) and artemisinin may induce CYP2C19, decreasing serum levels of the drug omeprazole.
Most research has focused on the ways in which herbal medicines may interfere with drugs metabolized through the CYP450 pathway.
However, research is also needed concerning the ways in which drugs may interfere with the beneficial effects of herbal medicines.
Potential interactions between herbal constituents through CYP450 enzymes, as well as the mechanisms through which CYP450 enzymes may increase the beneficial effects of herbal constituents or change them into toxic metabolites also need exploration.
Genotypic and phenotypic differences among individuals that affect CYP450 enzymes may also affect the actions of herbal medicines.
The authors conclude that there is clearly a need for more research and understanding "of the relationships between botanical products and the CYP450 system."
-Marissa N. Oppel, MS
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
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Vermont_Lymie
Frequent Contributor (1K+ posts)
Member # 9780
posted
Thanks for posting this. I have been wondering why piperine is used to coat the magnesium supplement that I take. And will have to keep eating broccoli with the grilled stuff! Posts: 2557 | From home | Registered: Aug 2006
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AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
I thought the info about the broccoli/grilling was great too! Grilling is SO MUCH easier than messing with pots & pans.
I also really enjoy grilled veggies.
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
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AliG
Frequent Contributor (1K+ posts)
Member # 9734
posted
up for someone asking about CYP 450
-------------------- Note: I'm NOT a medical professional. The information I share is from my own personal research and experience. Please do not construe anything I share as medical advice, which should only be obtained from a licensed medical practitioner. Posts: 4881 | From Middlesex County, NJ | Registered: Jul 2006
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