Dietary Supplements and their Interaction with Medications

Nearly 25% of US adults report concurrently taking a prescription medication with a dietary supplement. Some supplements, such as St. John’s wort and goldenseal, are known to cause clinically important drug interactions and should be avoided by most patients receiving any pharmacologic therapy.

Some other supplements are predicted to cause interactions based on in vitro studies but have not been confirmed or have been refuted in human clinical trials. Some others may cause interactions with a few medications but are likely to be safe with other medications. 

Estimates show that between 40% and 60% of U.S. adults with chronic disease use dietary supplements, and among patients taking prescription medications, an estimated 20%-25% concurrently use a dietary supplement.

Important interactions between an herbal supplement and drug typically manifest as pharmacokinetic interactions, which affect a drug’s concentration in the blood and the pharmacologic action. This can happen when a supplement shares the same mechanism of absorption, distribution, metabolism or excretion (ADME) as the co-administered drug.

Less commonly, herb-drug interactions may manifest as pharmacodynamic interactions. This occurs when an herbal supplement has a direct effect on the mechanism of action of the coadministred drug. Direct pharmacologic effects of an herbal supplement may antagonize or exacerbate the drug’s clinical effects without changing the drug’s concentration. 

Most ADME mechanism fall under four large gene superfamilies comprising more then 1,000 proteins: the cytochrome P450 (CYP) drug metabolism enzymes, the uridine diphosphate-glucuronosyltransferase (UGT) enzymes, the adenosine triphosphate binding cassette (ABC) and the organic anion transporting polypeptide (OATP).

Based on different studies some important interactions have been found, some examples of the more commons ones are: 

  • Goldenseal: used for common cold, upper respiratory tract infections, digestive disorders, gastritis, colitis, UTIs. It has been shown to inhibit two major metabolic enzymes, CYP2D6 and CYP3A4, which are responsible for metabolism of more than one-half of currently used pharmaceutical agents. Strongly recommended to avoid in combination with most over the counter and prescription medications.
  • St. John’s wort: commonly used for depression and mood disorders. It has been shown in multiple human studies to be a potent inducer of CYP3A3 and P-gp. It can reduce effectiveness of cyclosporine, tacrolimus, warfarin, protease inhibitors, theophylline, digoxin, venlafaxine, oral contraceptives and other over the counter and prescription medications.
  • Black cohosh: commonly used for symptoms of menopause, premenstrual syndrome (PMS), painful menstruation and osteoporosis. It may reduce the effectiveness of statins, amiodarone, and fexofenadine (allegra).
  • Ginkgo biloba: used due to its antioxidant properties. It improves blood flow to the brain. Some studies have found that it might modestly boost memory and cognitive speed. It can potentially increase bleeding risk with warfarin (coumadin).
  • Ginseng: some studies have found that it may boost the immune system and decrease glucose blood levels. It may reduce the international normalized ratio by 0.2.
  • Milk thistle: sometimes used as a natural treatment for conditions like cirrhosis, jaundice, hepatitis and gallbladder disorders. It may decrease concentrations of medications metabolized by CYP2C9, such as warfarin, phenytoin and diazepam (valium).

As we can see many supplements can have a negative effect when taking prescription medications. If there is no data available on the potential for specific herb-drug interactions, the conservative approach is to recommend against supplement use.


Asher GN, Corbett AH, Hawke RL. Common Herbal Dietary Supplement-Drug Interactions. Am Fam Physician. 2017 Jul 15;96(2):101-107.

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