Herb, Supplement and Drug Interactions: A Safety Framework for Integrated Practice
Level 2, Intermediate
In brief
Herb, supplement and drug interactions occur through pharmacokinetic mechanisms, such as enzyme induction or inhibition and reduced absorption, and pharmacodynamic mechanisms, such as additive bleeding, sedation, glucose lowering or serotonergic effects. Risk is highest with narrow therapeutic index drugs and in older adults, people taking many medicines, transplant and cancer patients, pregnancy and around surgery. A systematic framework of asking, recording, checking and coordinating prevents most harm.
A large proportion of adults in many countries take at least one supplement or herbal product, and many take them alongside prescribed medicines. Most combinations are harmless. Some are not. Interactions between herbs, supplements and drugs can reduce the effectiveness of essential medicines, cause bleeding, hypoglycaemia or serotonin toxicity, or lead to organ injury. Because patients often do not disclose these products and practitioners often do not ask, many interactions go unrecognised. A clear framework allows integrated practitioners to identify and prevent them.
How interactions happen
Pharmacokinetic interactions
These change the concentration of a drug in the body.
- Enzyme induction: some products increase the activity of drug metabolising enzymes or transporters, lowering drug levels. St John’s wort is the best known example, reducing levels of many medicines metabolised by CYP3A4 or transported by P glycoprotein.
- Enzyme inhibition: some products reduce enzyme activity, raising drug levels. Grapefruit juice inhibits intestinal CYP3A4; goldenseal inhibits several enzymes.
- Reduced absorption: minerals such as calcium, iron, magnesium and zinc bind to some drugs in the gut, reducing absorption of levothyroxine, some antibiotics and bisphosphonates. Fibre supplements can also reduce absorption.
Pharmacodynamic interactions
These occur when a product and a drug have additive or opposing effects.
- Bleeding: ginkgo, garlic, high dose fish oil, vitamin E, turmeric and others have antiplatelet or anticoagulant properties in laboratory studies, and case reports describe bleeding with anticoagulants.
- Glucose lowering: berberine, bitter melon, fenugreek, cinnamon and some traditional preparations may add to the effects of diabetes medicines, increasing hypoglycaemia risk.
- Serotonergic effects: St John’s wort, 5 HTP and tryptophan combined with antidepressants or some other drugs can cause serotonin syndrome.
- Sedation: kava, valerian and others can add to sedative medicines and alcohol.
- Blood pressure and electrolytes: liquorice causes sodium retention, low potassium and raised blood pressure; potassium supplements with ACE inhibitors, angiotensin receptor blockers or potassium sparing diuretics can cause dangerous hyperkalaemia.
- Vitamin K and warfarin: large changes in vitamin K intake from supplements or diet alter warfarin effect; consistency matters more than avoidance.
- Thyroid: kelp and iodine supplements can destabilise thyroid function; biotin distorts thyroid tests.
Direct toxicity
Some products cause harm independently of interactions. Liver injury has been associated with green tea extract, kava, some bodybuilding supplements, turmeric supplements and various herbal products. Comfrey and some other plants contain pyrrolizidine alkaloids toxic to the liver. Some traditional products contain heavy metals. Some supplements are adulterated with undeclared pharmaceuticals, particularly those marketed for weight loss, sexual enhancement and muscle building.
A risk matrix
Interaction risk depends on both the drug and the patient. Attention should be greatest where both are high risk.
| High risk drugs | High risk patients and situations |
|---|---|
| Warfarin and other anticoagulants | Older adults and people taking many medicines |
| Immunosuppressants such as ciclosporin and tacrolimus | Transplant recipients |
| Antiretrovirals | People with HIV |
| Chemotherapy and targeted cancer drugs | People with cancer |
| Antiepileptics | People with epilepsy |
| Lithium, digoxin and other narrow therapeutic index drugs | People with kidney or liver impairment |
| Antidepressants and other serotonergic drugs | Pregnancy and breastfeeding |
| Insulin and sulphonylureas | Before and after surgery |
| Hormonal contraceptives | Children |
A 5 step safety framework
- Ask. Ask every patient, specifically and without judgement, about supplements, herbs, traditional remedies, teas, sports products and anything bought online or sent from abroad. Patients often do not consider these relevant.
- Record. Document each product by name, ingredients, dose, frequency, source, start date and reason. Ask patients to bring the products or photograph the labels.
- Check. Look for interactions with prescribed medicines and conditions using reliable resources, such as specialist interaction databases and the NIH LiverTox database for hepatotoxicity. Prioritise high risk drugs and patients.
- Act proportionately. Not every theoretical interaction requires stopping a product. Consider the strength of evidence, the severity of the potential harm, the patient’s situation and alternatives. Options include continuing with monitoring, separating doses in time, reducing the dose, switching products or stopping.
- Coordinate. Communicate significant concerns to the prescriber, including specific product details. Never advise stopping prescribed medicines without the prescriber’s involvement.
Surgery
Some products increase bleeding risk or interact with anaesthesia. Many anaesthetic and surgical guidelines suggest stopping herbal and non essential supplements before elective surgery, often 1 to 2 weeks beforehand, and patients should always tell their surgical team about everything they take.
Communicating with patients
Patients may be attached to products they believe help them, or reluctant to admit using them. A respectful, curious approach encourages disclosure. Explaining the specific concern, such as “this herb can make your transplant medicine less effective”, is more persuasive than a general warning. Where possible, offer alternatives that meet the patient’s goals safely.
An illustrative case
A 72 year old woman taking warfarin for atrial fibrillation, levothyroxine and an antidepressant is admitted with a large bruise and an INR well above her target. Her history reveals that she recently started high dose turmeric and fish oil for joint pain, takes a calcium supplement with her levothyroxine, and began St John’s wort a month ago on a friend’s advice because she felt low.
Her care team identifies several issues: possible additive bleeding effects of turmeric and fish oil with warfarin; reduced levothyroxine absorption from the calcium taken at the same time; and a potentially dangerous combination of St John’s wort with her antidepressant, which also affects warfarin metabolism in ways that make her INR unstable when started or stopped. The St John’s wort, turmeric and high dose fish oil are stopped under medical supervision, with close INR monitoring, the calcium is separated from her levothyroxine, and her mood and joint pain are addressed with safer options. A simple, structured history would have prevented the admission.
Safety as the foundation of integration
Integrated care means understanding everything a patient uses, and that includes understanding how those things interact. A systematic approach of asking, recording, checking, acting and coordinating allows practitioners to respect patients’ choices while protecting them from preventable harm.
Interaction questions
Which supplements interact most with medicines?
Which patients are at highest risk?
Should supplements be stopped before surgery?
References and resources
- Izzo AA, Ernst E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs. 2009;69(13).
- Henderson L, Yue QY, Bergquist C, et al. St John’s wort (Hypericum perforatum): drug interactions and clinical outcomes. British Journal of Clinical Pharmacology. 2002;54(4).
- Bailey DG, Dresser G, Arnold JMO. Grapefruit medication interactions: forbidden fruit or avoidable consequences? CMAJ. 2013;185(4).
- Navarro VJ, Khan I, Björnsson E, et al. Liver injury from herbal and dietary supplements. Hepatology. 2017;65(1).
- National Institutes of Health. LiverTox: clinical and research information on drug induced liver injury. Bethesda: National Institute of Diabetes and Digestive and Kidney Diseases.
- Kennedy J, Wang CC, Wu CH. Patient disclosure about herb and supplement use among adults in the US. Evidence Based Complementary and Alternative Medicine. 2008;5(4).
Continue your learning
Keeping integrated care safe
Safety across all forms of care is a core principle of Integrated Functional Medicine and is emphasised throughout IIFM’s 6 month Functional Medicine and Clinical Nutrition program, including how to communicate concerns to prescribers.
This article is for the education of healthcare professionals. It is not a substitute for individual medical advice, diagnosis or treatment, and does not change any practitioner’s scope of practice. Regulation and guidelines differ between countries.