--- topic: "Herb-Drug Interactions" title: "Which Herbs Interact with Medications?" order: 1 description: "Which herbs and foods change how common medicines work, from St John's wort and grapefruit to licorice, kava and ginkgo, and how strong the evidence is." question: "Which herbs and supplements interact with common medications?" answer: "St John's wort and grapefruit probably change blood levels of many drugs; licorice and kava have narrower risks, and ginkgo's bleeding risk is unproven." actions: - "Show your pharmacist everything you take before starting a herb: in clinical trials St John's wort alone lowered the levels of more than two dozen drugs [1]." - "If a medicine's label warns about grapefruit, avoid the fruit and its juice; in one study the juice raised simvastatin exposure 16-fold [2]." - "Use our [Interaction Checker](/tools/interactions) as a first screen only; it covers a limited list, so no warning there is not clearance." cautions: - "On birth control, HIV, transplant, blood-thinner or antidepressant medicines, avoid St John's wort unless your prescriber agrees: it lowered contraceptive exposure, cut indinavir over 50% and blunted warfarin's effect [3][4][5]." - "On diuretics, digoxin or blood-pressure medicines? Avoid black licorice and licorice supplements, which can cause low potassium, high blood pressure and heart-rhythm problems [6]." - "Liver disease, heavy alcohol use or liver-toxic medicines? Avoid kava; rare but serious liver injury has been reported, mostly with overdose, long use and other medicines [7]." confidence: 4 confidenceNote: "St John's wort and grapefruit are backed by many controlled studies in volunteers; licorice and kava rest on case reports, and ginkgo's bleeding risk is unproven." evidenceSummary: rctCount: 5 observationalCount: 2 metaAnalysisCount: 2 totalParticipants: "2,000+" replicated: true newestStudyYear: 2023 references: - id: "1" pmid: "19719333" title: "Interactions between herbal medicines and prescribed drugs: an updated systematic review" authors: "Izzo AA, Ernst E" year: 2009 journal: "Drugs" - id: "2" pmid: "9834039" title: "Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors" authors: "Lilja JJ, Kivistö KT, Neuvonen PJ" year: 1998 journal: "Clin Pharmacol Ther" - id: "3" pmid: "15914127" title: "Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding" authors: "Murphy PA, Kern SE, Stanczyk FZ, et al." year: 2005 journal: "Contraception" - id: "4" pmid: "10683007" title: "Indinavir concentrations and St John's wort" authors: "Piscitelli SC, Burstein AH, Chaitt D, et al." year: 2000 journal: "Lancet" - id: "5" pmid: "15089812" title: "Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects" authors: "Jiang X, Williams KM, Liauw WS, et al." year: 2004 journal: "Br J Clin Pharmacol" - id: "6" pmid: "37764649" title: "Liquorice Toxicity: A Comprehensive Narrative Review" authors: "Ceccuzzi G, Rapino A, Perna B, et al." year: 2023 journal: "Nutrients" - id: "7" pmid: "20720265" title: "Kava hepatotoxicity--a clinical review" authors: "Teschke R" year: 2010 journal: "Ann Hepatol" - id: "8" pmid: "21923430" title: "Is there a risk of bleeding associated with standardized Ginkgo biloba extract therapy? A systematic review and meta-analysis" authors: "Kellermann AJ, Kloft C" year: 2011 journal: "Pharmacotherapy" - id: "9" pmid: "21142260" title: "Grapefruit-drug interactions" authors: "Seden K, Dickinson L, Khoo S, et al." year: 2010 journal: "Drugs" - id: "10" pmid: "10675182" title: "Herb-drug interactions" authors: "Fugh-Berman A" year: 2000 journal: "Lancet" - id: "11" pmid: "15801937" title: "Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects" authors: "Jiang X, Williams KM, Liauw WS, et al." year: 2005 journal: "Br J Clin Pharmacol" - id: "12" pmid: "24790635" title: "Updates on the clinical evidenced herb-warfarin interactions" authors: "Ge B, Zhang Z, Zuo Z" year: 2014 journal: "Evid Based Complement Alternat Med" --- Yes, some herbs change how medicines work. St John's wort is the clearest case: in trials it lowered blood levels of more than two dozen drugs, including birth-control pills, HIV drugs and warfarin [1][3][4][5]. Grapefruit does the opposite for others, raising levels of drugs such as simvastatin [2]. Licorice and kava carry narrower risks. Evidence that ginkgo causes bleeding is weak [8]. Tell your pharmacist everything you take. ## How it works Most herb-drug problems come from the same few routes. Some herbs switch on gut and liver enzymes and transporters that clear drugs, so drug levels fall. St John's wort does this through CYP enzyme and P-glycoprotein induction [1]. Others block those enzymes. Grapefruit furanocoumarins inhibit CYP3A4 in the intestine, so more of a drug gets into the blood [9]. A third group adds to a drug's own effect or side effects, such as licorice with corticosteroids [10]. **Herb by herb** - **St John's wort (strongest evidence).** It reduced exposure to contraceptive hormones by 13 to 15 percent, with more breakthrough bleeding and signs of ovulation [3]. It cut the HIV drug indinavir's exposure by 57 percent [4] and warfarin's anticoagulant effect [5]. It also lowered cyclosporine, tacrolimus, digoxin and statin levels, and with SSRIs it has been linked to mild serotonin syndrome [1][10]. See [St John's wort](/st-johns-wort/depression-and-mood). - **Grapefruit.** It affects calcium-channel blockers, immunosuppressants, antihistamines and statins, but the size of the effect depends on the product, the amount, and the person [9][2]. See [grapefruit](/grapefruit/naringenin-and-metabolic-health). - **Licorice.** Regularly eating large amounts of licorice can cause high blood pressure and low potassium, sometimes with arrhythmias [6]. See [licorice root](/licorice-root/gut-immunity-and-safety). - **Kava.** Rare liver injury has been reported, linked to overdose, long courses and co-medication [7]. See [kava](/kava/anxiety-and-sleep). - **Ginkgo and ginger.** In a controlled study, neither changed warfarin's effect [11], and a meta-analysis found no clotting changes with ginkgo [8]. Case reports of bleeding exist but are hard to interpret [1]. See [ginkgo](/ginkgo-biloba/cognitive-support-and-circulation). - **Ginseng.** It did not change warfarin levels or effect in a volunteer trial, though case reports suggest possible interactions [5][1]. **How to protect yourself.** Keep one up-to-date list of every prescription, over-the-counter drug and supplement, and show it to your pharmacist at each refill. Never stop a prescription yourself. Our [Interaction Checker](/tools/interactions) can flag obvious conflicts, but it is not a clinical screen. ## The evidence in detail ### The overall picture Izzo and Ernst reviewed seven popular herbs (ginkgo, St John's wort, ginseng, garlic, echinacea, saw palmetto and kava) and found 128 case reports or series and 80 clinical trials. Trials showed that St John's wort reduced plasma levels of 27 drugs or drug classes, including warfarin, digoxin, simvastatin, ciclosporin, tacrolimus, oral contraceptives, indinavir and methadone. Ginkgo lowered omeprazole, ritonavir and tolbutamide levels, and no interactions were reported for saw palmetto. The authors concluded that the significance of many interactions is uncertain, but several, particularly with St John's wort, may have serious consequences [1]. A review of herb-warfarin evidence rated nine of 38 herbs as major-severity interactions yet judged only four of the 38 as highly probable and 21 as doubtful, a reminder of how thin much of the evidence is [12]. An earlier review warned that many reports are sketchy and lack analysis of the suspect product [10]. ### St John's wort Murphy and colleagues gave 16 healthy women a low-dose pill and placebo for two cycles, then added St John's wort 300 mg three times daily for two cycles. Contraceptive exposure fell 13 to 15 percent, breakthrough bleeding increased, and there was evidence of follicle growth and probable ovulation. The study was small and single-blind and did not measure pregnancy [3]. Piscitelli's letter reported that St John's wort cut indinavir's area under the curve by a mean of 57% and the trough level by 81% in healthy volunteers, a drop large enough to risk treatment failure and drug resistance [4]. Jiang and colleagues gave 12 healthy men a single warfarin dose alone or after 14 days of St John's wort in a randomized crossover. The herb raised S-warfarin clearance (ratio 1.29, 90% CI 1.16 to 1.46) and lowered the INR area under the curve (ratio 0.79, 0.70 to 0.95) [5]. ### Grapefruit In a randomized crossover, 10 volunteers took double-strength grapefruit juice or water for two days, then 60 mg of simvastatin. The juice raised simvastatin's peak concentration about 9-fold and its area under the curve 16-fold, probably by blocking first-pass CYP3A4 metabolism in the small intestine. The authors advised avoiding large amounts or reducing the dose [2]. A review lists calcium-channel blockers, immunosuppressants and antihistamines among the affected drug classes and stresses the variability between products and people [9]. Note that this study used repeated glasses of double-strength juice, more than a typical breakfast glass. ### Licorice and kava A review of 104 case reports of licorice toxicity found pseudo-hyperaldosteronism with hypertension and low potassium as the typical picture, occasionally with arrhythmias, paralysis or rhabdomyolysis; toxicity often required hospital care but mortality was low [6]. Licorice has also been reported to potentiate corticosteroids [10]. Because low potassium is a recognized risk for digoxin toxicity and for some heart-rhythm problems, a hazard with digoxin or potassium-wasting diuretics is plausible, but we found no trial testing licorice with those drugs. For kava, a structured causality review of 14 patients with liver disease rated the link highly probable in one, probable in four and possible in nine. Risk factors included overdose, prolonged use and co-medication, and poor raw-material quality may contribute [7]. ### Bleeding herbs: where the evidence is weak Jiang and colleagues found that ginkgo and ginger, at recommended doses for a week before warfarin, did not change S-warfarin clearance (ginkgo ratio 1.05, 90% CI 0.98 to 1.21) or the INR area under the curve (ginkgo 0.93, 0.81 to 1.05; ginger 1.01, 0.93 to 1.15) in 12 healthy men [11]. A meta-analysis of 18 randomized trials (1,985 adults) found no effect of standardized ginkgo extract on platelet aggregation or prothrombin time, so it indicated no higher bleeding risk [8]. These are surrogate measures in mostly short trials, not bleeding events in anticoagulated patients, and case reports persist [1]. Reasonable caution is not the same as proof. ### Limits of this evidence Most data come from small volunteer studies with single drug doses, from case reports, and from products of unknown quality. Few studies follow patients on real regimens, and almost none compare brands. **Bottom line (confidence 4 of 5).** St John's wort and grapefruit reliably alter drug levels and can matter clinically. Licorice and kava carry real but narrower risks. Ginkgo's bleeding risk is unproven. Always tell your pharmacist about everything you take.