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Herb-drug interactions: the ones with numbers behind them

St John's wort changes how fast your body clears other drugs. This is measured, not theoretical.

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The interaction between a plant and a prescription is not a vague caution about "combining medicines". It is a measurable change in the enzyme that clears the drug, or in the transporter that moves it, and the change is large.

The best-characterised example is St John's wort, which induces CYP3A4 and P-glycoprotein. In a systematic review and meta-analysis, St John's wort significantly decreased the area under the curve of midazolam — a standard probe for CYP3A4 — in the studies pooled. The clinical consequence is that drugs cleared by that route (some oral contraceptives, ciclosporin, some HIV antivirals, some anticoagulants) are cleared faster and can fail. The same review found measurable effects from echinacea and a large fall in nadolol plasma concentration with green tea.

The direction is not one-way. Some herbs inhibit the same enzymes and raise drug levels: piperine from black pepper, berberine and others inhibit CYP3A4 and P-glycoprotein, which is why a turmeric supplement with piperine has a different pharmacokinetic profile from turmeric alone.

The rule for a household: tell both the prescriber and the pharmacist about every herbal product, in names, and treat any new drug start as a reason to re-check. A narrow-therapeutic-index drug — warfarin, digoxin, ciclosporin, levothyroxine, lithium — is where a small pharmacokinetic change becomes a clinical event.

What the studies found

Cautions and interactions

• St John's wort and hormonal contraception: reduced efficacy is documented. Do not rely on a combined oral contraceptive while taking it.
• Immunosuppressants and St John's wort: ciclosporin levels fall, and organ rejection has occurred. Never combine them.
• Grapefruit juice inhibits intestinal CYP3A4 and raises levels of a long list of drugs. It is a pharmacokinetic intervention, not a folk belief.
• This list is not exhaustive and cannot be made exhaustive. The pharmacy's interaction check is the authoritative screen.

When this is not a self-care problem — get help

• A transplant, an anticoagulant, an antiepileptic, or a narrow-index drug plus any new herbal product — check with the prescriber before starting, every time.

Known interactions

• St John's wort: CYP3A4 and P-gp induction; reduces midazolam exposure and reduces levels of many co-administered drugs.
• Green tea: reduced nadolol plasma concentration.
• Piperine: inhibits CYP3A4 and P-gp; raises curcumin and other substrate levels.
• Grapefruit: intestinal CYP3A4 inhibition; raises substrate levels.

Related

• Herbal liver injury, and the plant that ends the matter
• What is actually in the bag
• Liquorice, glycyrrhizin, and the potassium it costs you

Sources

1. Medicine for chronic atrophic gastritis: a systematic review, meta- and network pharmacology analysis. Annals of medicine 2023; doi:10.1016/j.lfs.2022.120752 PubMed 38170849
2. Interaction of herbal products with prescribed medications: A systematic review and meta-analysis. Pharmacological research 2019; doi:10.1016/j.phrs.2019.01.028 PubMed 30660822
3. Review on the pharmacological effects and pharmacokinetics of scutellarein. Archiv der Pharmazie 2024; doi:10.1002/ardp.202400053 PubMed 38849327
4. Herb-drug interactions: a mechanistic approach. Drug and chemical toxicology 2022; doi:10.1080/01480545.2020.1738454 PubMed 32160796
5. Warfarin and food, herbal or dietary supplement interactions: A systematic review. British journal of clinical pharmacology 2021; doi:10.1111/bcp.14404 PubMed 32478963
6. Benefit-risk profile of black cohosh (isopropanolic Cimicifuga racemosa extract) with and without St John's wort in breast cancer patients. Climacteric : the journal of the International Menopause Society 2019; doi:10.1080/13697137.2018.1551346 PubMed 30626212