By the Seed SistAs
As medically trained herbalists, we wear many hats. We’re passionate about plant medicine, and understand the intricacies of human physiology, pharmacology (the effects of drugs), and the interplay between them. Many of our clients come to us with a history of chronic conditions or acute health issues, and are often already taking prescription medications. This means herb-drug interactions come into play so we’re not just thinking about which herbs might support their health—we’re also considering how these herbs might interact with the medications they’re taking.
Herb-drug interactions aren’t just a theoretical concern; they’re a real part of our practice. Whether it’s herbs altering drug metabolism (potentially speeding up the rate a medication is excreted from the system, thus reducing effects), enhancing the side effects, or interfering with a drug’s intended action, it is important to understand the potential interactions. To do our jobs well, we need to have a solid grasp of how herbal constituents and pharmaceutical agents can collide or cooperate.
Understanding Herb-Drug Interactions
Key Actions and Constituents to Consider
Herb-drug interactions occur when the constituents present in herbal remedies affect the pharmacokinetics (how a drug moves through the body) or pharmacodynamics (how a drug acts in the body) of medications. These interactions can result in altered drug efficacy or increased risk of adverse effects. Understanding these interactions is crucial for herbal practitioners to ensure safe and effective care.
Mechanisms of Herb-Drug Interactions
Enzyme Modulation
Many interactions involve the cytochrome P450 (CYP) enzyme system, a group of liver enzymes responsible for metabolising most drugs. They can increase the enzyme and therefore the rate a drug is metabolised and excreted from the body or slow down metabolism, essentially, increasing the length of time a dose is present in the body, the resultant effect is an increase in dose.
Enzyme Induction
Certain herbal constituents can increase the activity of these enzymes, leading to faster drug metabolism. This reduces drug levels in the bloodstream, potentially making the pharmaceutical medications less effective, or altering the drug dose in such a way that it could be harmful. Many drugs are very dose dependent, and interfering with the length of time a drug is present in the body could lead to issues. Think antipsychotic medications, heart drugs, the contraceptive pill.
Enzyme Inhibition
Other constituents may inhibit these enzymes, slowing drug metabolism and causing elevated drug levels, which can increase the risk of toxicity.
Herbal Effects on Liver Enzyme Modulation
Here are three herbal examples illustrating how enzyme modulation can affect drug metabolism:
1. Increasing drug metabolism
St. John’s Wort (Hypericum perforatum)
St. John’s Wort is a well-documented inducer of the cytochrome P450 (CYP3A4) enzyme, one of the major enzymes responsible for drug metabolism. By increasing CYP3A4 activity, it accelerates the breakdown of many medications.
This induction can significantly reduce the effectiveness of oral contraceptives, leading to an increased risk of unintended pregnancy. Similarly, it can lower the plasma concentrations of immunosuppressants, like cyclosporine, risking transplant rejection.
Ginseng (Panax ginseng)
Ginseng contains ginsenosides, which have been shown to induce CYP enzymes, including CYP3A4. This can lead to faster drug clearance.
Ginseng’s enzyme induction may reduce the effectiveness of anticoagulants, like warfarin, potentially increasing the risk of clot formation.
Garlic (Allium sativum)
Garlic, particularly when consumed as a concentrated supplement, can induce CYP3A4. This speeds up the metabolism of certain drugs, reducing their therapeutic effects.
Studies have shown that garlic can also lower blood concentrations of HIV protease inhibitors such as saquinavir, potentially compromising antiviral therapy.
(nccih.nih.gov).
2. Decreasing drug metabolism
And here are three examples of herbs that can inhibit enzymes, potentially leading to elevated drug levels and increased risk of toxicity
Grapefruit (Citrus paradisi)
While not an herb in the traditional sense, grapefruit is often referenced in herbal pharmacology because its furanocoumarins inhibit CYP3A4. This enzyme inhibition slows the metabolism of drugs, leading to higher plasma concentrations.
Grapefruit can significantly elevate levels of statins (used to lower cholesterol), increasing the risk of side effects like muscle damage and liver toxicity.
Kava (Piper methysticum)
Kava’s active compounds, kavalactones, have been shown to inhibit CYP enzymes. This inhibition slows drug metabolism, potentially causing drug accumulation in the bloodstream.
Kava may increase the sedative effects of benzodiazepines or other central nervous system depressants, raising the risk of excessive sedation or respiratory depression.
Goldenseal (Hydrastis canadensis)
Goldenseal contains berberine, which inhibits CYP2D6 and CYP3A4. This can prolong the metabolism of drugs processed by these enzymes, leading to higher drug levels.
Goldenseal can interfere with the metabolism of drugs, like metoprolol (a beta-blocker) or antidepressants, increasing the risk of toxicity and side effects such as bradycardia or serotonin syndrome
Effects on Drug Transport
Herbal compounds can affect proteins which transport drugs across cellular membranes. Modulation of this transporter can change how drugs are absorbed, distributed, or eliminated from the body.
Additive or Synergistic Effects
Herbs with pharmacological actions, like medications, can amplify the effects of those drugs. For example:
o Sedative herbs combined with central nervous system depressants can increase drowsiness.
o Anticoagulant and antiplatelet herbs may enhance the blood-thinning effects of medications, increasing the risk of bleeding.
Alteration of Absorption
Certain herbs or rather their constituents, can bind with drugs in the gastrointestinal tract, reducing drug absorption. Conversely, some herbs may enhance absorption, leading to higher drug levels.
Here are examples of herbs that can alter drug absorption through their effects in the gastrointestinal (GI) tract – illustrating how herbs can physically or chemically interfere with drug absorption, either decreasing therapeutic effects or increasing drug levels in the bloodstream. Timing of administration and awareness of potential interactions are key to mitigating these risks.
Psyllium (Plantago ovata)
Psyllium is a soluble fibre that forms a gel-like substance in the gut, potentially binding to drugs and reducing their absorption. This effect is most pronounced when psyllium is taken simultaneously with medications. Psyllium can decrease the absorption of certain oral medications, such as lithium or carbamazepine, reducing their therapeutic efficacy.
Slippery Elm (Ulmus rubra)
Slippery elm contains mucilage, which coats the stomach lining and can interfere with the absorption of medications by creating a physical barrier. The mucilage in slippery elm may reduce the absorption of drugs like tetracycline antibiotics or digoxin when taken concurrently.
Aloe Vera (Aloe barbadensis)
Aloe vera, particularly when consumed as juice, can enhance intestinal permeability and alter the absorption of certain drugs. Aloe vera may increase the absorption of hydrocortisone or other corticosteroids, potentially leading to higher-than-expected drug levels and side effects.
Liquorice (Glycyrrhiza glabra)
Liquorice can impact drug absorption indirectly by altering gastric pH and mucosal integrity, potentially enhancing or inhibiting the uptake of some medications. Changes in absorption caused by liquorice have been reported with proton pump inhibitors, altering their effectiveness in reducing stomach acid. Liquorice also has blood thinning properties so caution is taken where there are already blood thinning pharmaceuticals in place.
Categories of Concern
Medications with a Narrow Therapeutic Index (A narrow therapeutic index means there is a small margin between the effective dose of a drug and the dose that can cause toxicity, making precise dosing crucial for safety and efficacy)
Examples include:
- Anticoagulants
- Immunosuppressants
- Anti-seizure medications
- Chemotherapy agents
Herb-induced changes in the metabolism or elimination of these drugs can have significant clinical consequences.
Drugs Metabolised by Cytochrome P450 Enzymes
Many commonly prescribed drugs, such as antidepressants, antihypertensives, and statins, rely on CYP enzymes for metabolism. Herbal modulation of these enzymes can lead to therapeutic failure or toxicity.
Drugs Affected by the Protein P-glycoprotein
Drugs such as digoxin, certain antivirals, and chemotherapy agents depend on P-glycoprotein for proper distribution and elimination. Changes in this transporter’s activity can significantly alter drug levels.
Medications with Similar Pharmacological Actions to Herbs
Caution is necessary when combining herbs and drugs with overlapping effects, as this can result in exaggerated therapeutic or side effects. For example, garlic or liquorice with the anticoagulant/blood thinning medications.
Key Herbal Constituents Involved in Herb-Drug Interactions
Flavonoids
Flavonoids are polyphenolic compounds found in many plants. They are known to inhibit certain cytochrome P450 (CYP) enzymes, particularly CYP3A4 and CYP2C9, which can affect drug metabolism. Flavonoids may also interact with drug transporters like P-glycoprotein, altering drug absorption and distribution.
Example:
Quercetin, a flavonoid found in onions and apples, has been shown to inhibit CYP3A4 and P-glycoprotein, potentially increasing the bioavailability of drugs like cyclosporine.
Alkaloids
Alkaloids are nitrogen-containing compounds that often have potent pharmacological effects. Some alkaloids can inhibit or induce CYP enzymes, while others mimic the pharmacological actions of drugs, leading to additive effects.
Example:
Berberine, an alkaloid found in goldenseal, inhibits CYP2D6 and CYP3A4, potentially leading to higher levels of drugs metabolised by these enzymes, such as metoprolol or statins.
Saponins
Saponins are glycosides that can influence membrane permeability and drug absorption in the gastrointestinal tract. They may also form complexes with certain drugs, altering their bioavailability.
Example:
Saponins from ginseng have been shown to enhance the absorption of poorly water-soluble drugs, potentially increasing their plasma levels..
Tannins
Tannins are polyphenolic compounds with astringent properties that can bind to proteins, alkaloids and other macromolecules, including drugs, in the gut. This binding can reduce drug solubility and absorption.
Example:
Tannins in green or black tea may bind with iron supplements, reducing their absorption and potentially leading to decreased therapeutic efficacy.
Each of these constituents contributes to herb-drug interactions through distinct mechanisms. Understanding these mechanisms is essential for anticipating potential risks and ensuring the safe and effective use of herbal and pharmaceutical therapies. This level of knowledge also emphasises the importance of proper timing and dosing of herbal remedies when used alongside medications.
By understanding the mechanisms behind herb-drug interactions and taking a thoughtful, evidence-based approach, herbal practitioners can help minimise risks while maximising the therapeutic benefits of herbal and pharmaceutical treatments.
Essential Reads on Herb-Drug Interactions
Understanding herb-drug interactions is vital for providing safe and effective care as a medical herbalist. The following resources are indispensable for gaining deeper insights into this complex field.
- Herb-Drug Interactions in the Clinical Practice by Barrie R. Cassileth
This book offers a concise, evidence-based overview of common herb-drug interactions, particularly useful for practitioners working in integrative medicine.
- Herbal Contraindications and Drug Interactions by Francis Brinker
A comprehensive reference detailing potential contraindications and interactions between herbs and pharmaceuticals, including practical guidance for clinical use.
- Natural Products Interactions by Mitchell Bebel Stargrove, Jonathan Treasure, and Dwight L. McKee
This text explores the pharmacokinetics and pharmacodynamics of natural products in relation to conventional medications, supported by clinical research and case studies.
- The Essential Guide to Herbal Safety by Simon Mills and Kerry Bone
This authoritative resource provides detailed safety profiles of herbs, including potential interactions with drugs and guidelines for safe practice.
Additional Recommended Texts
- Rational Phytotherapy: A Reference Guide for Physicians and Pharmacists by Volker Schulz, Rudolf Hänsel, and Mark Blumenthal
This guide bridges the gap between herbal medicine and pharmacology, offering detailed descriptions of interactions with a focus on clinical applicability. - Botanical Safety Handbook by Michael McGuffin and others
Published by the American Herbal Products Association (AHPA), this handbook provides an in-depth look at herbal safety, including detailed information on herb-drug interactions. - Clinical Pharmacology of Herbal Medicine by Iqbal Ramzan
This book offers a scientific overview of how herbal medicines interact with conventional drugs, with a focus on pharmacological mechanisms and clinical outcomes. - Principles and Practice of Phytotherapy by Simon Mills and Kerry Bone. In addition to discussing clinical applications of herbal medicine, this book includes a robust section on interactions and safety considerations.
These blog articles are herbal education resources, produced by the Seed Sistas. Gain insights and join us in the evolution of healthcare, please do leave a comment or question. Wellbeing empowerment for all…
Thank you! Important work. Am currently taking tamoxifen so trying to keep informed. Grateful for all that you do. X