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Herbal Supplements: The Top Troublemakers

By Kate Byrd, PharmD

As clinicians, we're often so busy keeping up with pharmaceutical breakthroughs that we don't have the time or energy to learn about the ever-increasing array of herbs and supplements our patients may be taking. But we should.

Approximately 40% to 60% of American adults with chronic diseases use dietary supplements, and an estimated 25% of patients taking prescription drugs also take an herbal product. As a result, there's growing concern about herbal supplements interfering with prescription medications. Although most botanicals are not harmful, the following are among the top troublemakers:

St. John’s Wort (Hypericum perforatum)

St. John's wort (Hypericum perforatum) is especially problematic regarding dangerous drug interactions. Often touted as the herbal Prozac, there's extensive research on the effectiveness of the popular herb in treating depression.

Unfortunately, there is also a lot of evidence that it decreases the efficacy of prescription medications. St. John's wort is a potent inducer of the cytochrome P-450 system in the liver and intestinal P-glycoprotein. This renders most prescription drugs ineffective, including some with narrow therapeutic indices.

Clinical studies have linked St. John's wort to decreased levels of immunosuppressants, anticoagulants, antiarrhythmics, protease inhibitors, anti-cancer drugs, theophylline, benzodiazepines, and oral contraceptives, amongst others. St. John's wort may also raise the risk of serotonin sickness when taken with SSRI and SNRI antidepressants, triptans, and buspirone (Buspar). Avoid combining St. John's wort with both prescription and over-the-counter drugs.

Goldenseal (Hydrastis canadensis)

Goldenseal (Hydrastis canadensis) is another potentially hazardous herbal supplement. The herb is promoted as a remedy for several ailments, including eye infections, vaginitis, ulcers, respiratory tract infections, diarrhea, and constipation. It's also popular due to the myth that it masks illicit drugs in urine tests. There is little scientific evidence that goldenseal treats any health issue or conceals substances in the urine.

A 2017 review found goldenseal to have a high overall risk of drug interactions. The herb inhibits the metabolic enzymes CYP2D6 and CYP3A4, which break down more than 50% of the drugs used today. A 2012 study found that adults who took goldenseal extract had significantly lower anti-diabetic metformin levels and dramatically increased sedative midazolam levels.

Although some drug combinations with goldenseal may be safe, clinicians should advise against using goldenseal in combination with most medications until more data from human clinical trials is available.

Licorice (Glycyrrhiza glabra)

Licorice (Glycyrrhiza glabra) is one of the oldest herbal remedies, yet it is not without risk. It may treat indigestion, cough, menopausal symptoms, and various infections. The herb is also found in some herbal weight-loss products and teas.

Licorice's active metabolite blocks the enzyme HSD-11β type 2, which breaks down cortisol to its inactive form. Chronic and large doses of licorice products boost cortisol levels. This can cause sodium retention, potassium depletion, muscle weakness, abnormal heart rhythms, and high blood pressure. The elderly are particularly vulnerable to licorice toxicity or pseudohyperaldosteronism because they have lower levels of the enzyme HSD-11β type 2.

Individuals with hypertension, congestive heart failure, renal illness, or low potassium levels should avoid licorice. Patients taking antihypertensives, diuretics, antiarrhythmics, and anticoagulants should not take licorice products. Most licorice candy in the United States is flavored with anise oil (Pimpinella anisum) rather than the actual herb, but be sure to check the label.


It may not be a priority for some clinicians to spend additional time talking to patients about their use of herbs. But it's important to know what they are using and why. A 2015 study found that dietary supplements cause an estimated 23,000 visits to emergency rooms annually in the US.

Adopting a non-judgmental attitude is key when asking patients what herbs, supplements, and teas they take. Prepare to take the conversation further, especially if concerned about an herb or supplement the individual is using. Don't give the impression that all supplements are harmful. Explore less toxic and more evidence-based alternatives with the patient.

MedlinePlus provides a patient-friendly overview of herbals, supplements, and drugs for online education. The Natural Medicines Comprehensive Database is considered the leading resource for evidence-based information on herbs and supplements. The American Botanical Council is a nonprofit research and education organization that offers reliable content and market trends in herbal products. And, of course, you can always ask your pharmacist for herbal advice!

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