Can Dietary Supplements Interact with Other Medications? - A Comprehensive Guide

Combining dietary supplements and medications can have dangerous and even fatal effects. According to Walls, dietary supplements are products manufactured to provide the body with the nutrients it lacks. He also states that these supplements can interfere with the prescription medications you're taking, leading to chemical interactions that can be minor or dangerous. This can weaken your medications and make them less effective, or make your prescriptions more powerful.

It is estimated that nearly 25% of U. S. adults report taking a prescription medication with a dietary supplement. St.

John's Wort and golden seal are known to cause clinically important drug interactions and should be avoided by most patients receiving any drug treatment. However, many other supplements are expected to cause interactions based solely on in vitro studies that have not been confirmed or refuted in human clinical trials. Some supplements may cause interactions with some medications, but are likely to be safe with other medications (e.g., some supplements have a low chance of drug interactions and, with certain caveats, can be safely taken with most medications).Physicians should consult reliable resources on dietary supplements, or from clinical or pharmaceutical pharmacists, to help evaluate the safety of specific combinations of herbal supplements and drugs. Since most patients do not disclose the use of supplements to doctors, the most important strategy for detecting herbal and drug interactions is to develop a relationship of trust that encourages patients to discuss the use of dietary supplements. Estimates show that between 40 and 60% of U.

adults with chronic diseases consume dietary supplements and, among patients taking prescription medications, it is estimated that between 20 and 25% use a dietary supplement concurrently. This review focuses on drug interactions with herbal dietary supplements, which are defined as supplements that contain whole plant extracts or that are consumed in the form of powder, capsules, tablets, or liquid formulations.

Types of Interactions

Clinically important interactions between an herbal supplement and a drug usually manifest as pharmacokinetic interactions, affecting the concentration of a drug in the blood and the pharmacological action. In many cases, pharmacokinetic interaction can be safely counteracted by adjusting the dose of the drug. The risk of pharmacokinetic interaction occurs when an herbal supplement shares the same absorption, distribution, metabolism, or excretion mechanism (ADME) as a concomitantly administered drug.

The competition between an herbal supplement and a drug by a shared ADME mechanism can cause a change in the concentration of the drug at the site of action. Less commonly, herbal and drug interactions can manifest as pharmacodynamic interactions, which involve direct pharmacological actions of an herbal supplement that are not related to changes in blood concentrations. The risk of pharmacodynamic interaction occurs when an herbal supplement has a direct effect on the mechanism of action of a co-administered drug. The direct pharmacological effects of an herbal supplement can antagonize or exacerbate the clinical effects of the drug without changing the concentration of the drug. In most cases, a change in the dosage of the drug will not counteract the pharmacodynamic interaction between herbs and drugs.

Evaluating Interactions

Drug interactions are initially evaluated by in vitro systems.

Although in vitro evaluations are highly sensitive and can be used to rule out possible interactions between herbs and drugs, it is important to follow up positive results in vitro with a human clinical trial to estimate the possible impact of an interaction on clinical outcomes. Many positive in vitro interactions have not been confirmed in human trials, which highlights the importance of confirming potential interactions.


In several clinical trials in humans, it has been demonstrated that racemose cimicifuga (Actaea racemosa) has no clinically significant effects on multiple CYP and P-GP enzymes. However, there is potential concern about interactions with OATP2B1, which could reduce the effectiveness of drugs such as amiodarone, fexofenadine (Allegra), glyburide and many statin drugs.

Echinacea (Echinacea purpurea) has shown no inhibitory or inductive effects on CYP2D6, CYP2C9 or P-gP in human studies. However, there are conflicting results on CYP1A2 and CYP3A4 even with potentially short-term use; for this reason care must be taken when combining echinacea with medications that are metabolized by any of these CYP enzymes including antipsychotic and antidepressant medications. Goldenseal (Hydrastis canadensis) has been shown to inhibit two major metabolic enzymes: CYP2D6 and CYP3A4 which are responsible for metabolizing more than half of pharmaceutical agents currently in use. Although some goldenseal drug combinations may be safe until data from other human clinical trials is available doctors should recommend not using goldenseal in combination with most other medications.

Several human studies have demonstrated that kava kava (Piper methysticum) has no effect on CYP1A2, CYP2D6, CYP3A4 or P-gp; however one study showed inhibition of CYP2E1 which participates in metabolism of several anesthetic agents as well as acetaminophen; two in vitro studies suggest potential inhibition of CYP2C9 and CYP2C19 metabolism which are involved in metabolism of several anaesthetic agents many non-steroidal anti-inflammatory drugs blockers of angiotensin glipizide (Glucotrol) glyburide rosiglitazone (Avandia) valproic acid (Depakene) warfarin proton pump inhibitors phenytoin (Dilantin) clopidogrel (Plavix). Patients taking medications that are metabolized by CYP2C9 or CYP2C19 should be closely monitored for clinical adverse effects and laboratory abnormalities (e.g., caution should be used in patients who use central nervous system depressants such as benzodiazepines or alcohol due to increased risk of somnolence and depression of motor reflex). Several human studies have shown that St John's Wort (Hypericum perforatum) is a potent inducer of CYP3A4 and P-gp; clinical studies have demonstrated reductions in cyclosporine (Sandimmune) tacrolimus etc.


It is important for physicians to consult reliable resources on dietary supplements when evaluating safety for specific combinations of herbal supplements and drugs.

Patients should also develop a relationship with their doctor based on trust so they can discuss their use of dietary supplements openly. In vitro evaluations are highly sensitive but should be followed up with human clinical trials to estimate possible impacts on clinical outcomes.

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