NCCIH Clinical Digest

for health professionals

Herb-Drug Interactions: What the Science Says

July 2021

Clinical Guidelines, Scientific Literature, Info for Patients: 
Herb-Drug Interactions

Black Cohosh

Currently, black cohosh is promoted as a dietary supplement for hot flashes and other menopausal symptoms. It has also been promoted for other conditions, including menstrual cramps and premenstrual syndrome, and to induce labor.

Potential for Herb-Drug Interactions

  • The risk of interactions between black cohosh and medicines appears to be small. A 2017 review found that black cohosh has an overall low risk of drug interactions but may reduce the effectiveness of statins.

Efficacy

  • Research suggests that certain black cohosh extracts and some combination products containing black cohosh may reduce some menopause symptoms. Most of the research has been on the single extract Remifemin. Research on other black cohosh products has had inconsistent results. Guidelines released in 2015 indicate that there is a lack of consistent evidence for any benefit from black cohosh for menopause symptoms. But a 2017 systematic review and network meta-analysis found that black cohosh was more effective than placebo for reducing menopausal symptoms; however, black cohosh was not significantly better than transdermal estradiol and progestogen.

  • The research is inconsistent on whether black cohosh helps to reduce hot flashes that are related to breast cancer treatment. People with breast cancer should avoid using black cohosh before talking with their health care provider.

  • There aren’t enough reliable data to show whether black cohosh is effective for other uses.

Safety

  • In clinical trials, people have taken black cohosh for as long as 12 months with no serious harmful effects.

  • Black cohosh can cause some mild side effects, such as stomach upset, cramping, headache, rash, a feeling of heaviness, vaginal spotting or bleeding, and weight gain.

  • Some commercial black cohosh products have been found to contain the wrong herb or to contain mixtures of black cohosh and other herbs that are not listed on the label.

  • Cases of liver damage—some very serious—have been reported in people taking commercial black cohosh products. These problems are rare, and it is uncertain whether black cohosh was responsible for them.

  • It’s not clear if black cohosh is safe for women who have had hormone-sensitive conditions such as breast cancer.

  • Little is known about whether it’s safe to use black cohosh during pregnancy or while breastfeeding.

  • Black cohosh should not be confused with blue cohosh (Caulophyllum thalictroides), which has different effects and may not be safe. Black cohosh has sometimes been used with blue cohosh to stimulate labor, but this use was linked to severe adverse effects in at least one newborn.

Garlic

Garlic is most commonly promoted as a dietary supplement for high blood cholesterol and high blood pressure.

Potential for Herb-Drug Interactions

  • Studies suggest that garlic supplements may interfere with the effectiveness of some drugs, including saquinavir, a drug used to treat HIV infection. Garlic supplements may also interact with some dietary herbs and other supplements.

Efficacy

  • While there’s conflicting evidence, the most reliable results suggest that taking garlic supplements may reduce total cholesterol and low-density lipoprotein cholesterol levels in people with high levels of these blood lipids. If it does, the effect is small, and it may take more than 8 weeks before noting any improvement. Taking garlic doesn’t appear to improve high-density lipoprotein levels or triglycerides.

  • Garlic supplements may be helpful for high blood pressure, but the evidence is limited.

  • The most reliable research has found that intake of garlic as a food or supplement is not associated with a reduced risk of developing gastric cancer. However, epidemiologic studies suggest a link between higher intakes of vegetables in the garlic family and lower risks of certain cancers, particularly gastrointestinal cancers.

  • There’s not enough evidence to show whether garlic is helpful for the common cold.

Safety

  • Garlic is probably safe for most people in the amounts usually eaten in foods.

  • Little is known about whether it’s safe to use garlic supplements or apply garlic to the skin during pregnancy or while breastfeeding.

  • Side effects include breath and body odor, heartburn, and upset stomach. These side effects can be more noticeable with raw garlic. Some people have allergic reactions to garlic.

  • Taking garlic supplements may increase the risk of bleeding.

Ginkgo Biloba

The extract from ginkgo leaves is promoted as a dietary supplement for many conditions, including anxiety, allergies, dementia, eye problems, peripheral artery disease, tinnitus, and other health problems.

Potential for Herb-Drug Interactions

  • A 2017 review found that Ginkgo biloba has an overall low risk of drug interactions, but there may be a potential increased bleeding risk with warfarin (Coumadin).

Efficacy

  • There’s no conclusive evidence that ginkgo is helpful for any health condition. Although some studies suggest that ginkgo may help to slightly improve some symptoms of dementia, the findings have been described as unreliable. Also, other studies have had conflicting findings. Ginkgo neither helps prevent dementia or cognitive decline nor prevents Alzheimer’s-related dementia from getting worse—this is according to studies that include the long-term Ginkgo Evaluation Memory Study, which enrolled more than 3,000 older adults.

  • For various health conditions, a small amount of evidence suggests a benefit from taking ginkgo, but the overall evidence is not conclusive. These conditions include anxiety, diabetic retinopathy, glaucoma, peripheral artery disease, premenstrual syndrome, schizophrenia, and vertigo.

  • Research seems to suggest that ginkgo doesn’t help with memory enhancement in healthy people, high blood pressure, tinnitus, multiple sclerosis, seasonal affective disorder, or the risk of having a heart attack or stroke.

Safety

  • For most people, ginkgo leaf extract appears to be safe when taken by mouth in moderate amounts.

  • Side effects of ginkgo may include headache, stomach upset, dizziness, palpitations, constipation, and allergic skin reactions. People with a known bleeding risk should be cautious about ginkgo possibly increasing the risk of bleeding.

  • In a 2013 study, rodents given ginkgo leaf extract had an increased risk of developing liver and thyroid cancer at the end of the 2-year tests. Whether these results apply to humans is unclear.

  • Ginkgo taken orally may be unsafe during pregnancy. It might cause early labor or extra bleeding during delivery if used near that time. Little is known about whether it’s safe to use ginkgo while breastfeeding.

  • Fresh (raw) or roasted ginkgo seeds and the unprocessed ginkgo leaves can contain dangerous amounts of a toxic substance.

Ginseng (Asian)

Asian ginseng taken orally is promoted for increasing resistance to environmental stress and as a general tonic to improve well-being. Asian ginseng is also promoted as a dietary supplement for a variety of other reasons—to improve physical stamina, concentration, and memory; stimulate immune function; slow the aging process; and relieve various other health problems, such as respiratory and cardiovascular disorders, depression, anxiety, and menopausal hot flashes. Topical use (applied to the skin) of Asian ginseng as part of a multi-ingredient preparation is promoted for premature ejaculation.

Potential for Herb-Drug Interactions

  • A 2017 review noted that Asian ginseng has been shown (in a single study) to induce CYP3A4, which could decrease the effectiveness of drugs such as calcium channel blockers, some chemotherapeutic and HIV agents, certain antihypertensive and statin medications, and some antidepressants.

  • Studies on the effect of Asian ginseng on the anticoagulant warfarin (Coumadin) have had mixed results.

Efficacy

  • Results from a 2013 systematic review of 65 randomized controlled trials suggest that Asian ginseng may help improve glucose metabolism and lower blood sugar. However, the authors of the review noted that many studies included in the review were not high quality and that ginseng preparations were diverse.

Safety

  • Short-term oral use (up to 6 months) of Asian ginseng in recommended amounts appears to be safe for most people. However, questions have been raised about its long-term safety, and some experts recommend against its use by infants and children, and when pregnant or breastfeeding.

  • When used short-term as part of a specific multi-ingredient topical skin application, Asian ginseng is likely safe. Safety after prolonged repetitive topical use has not been determined.

  • Insomnia is the herb’s most common side effect. Others include menstrual problems, breast pain, increased heart rate, high or low blood pressure, headache, loss of appetite, and digestive problems.

  • Some evidence suggests that Asian ginseng might affect blood sugar.

  • Asian ginseng may be unsafe when taken orally during pregnancy. One of the chemicals in it has been found to cause birth defects in animals.

Goldenseal

Goldenseal is promoted as a dietary supplement for colds and other respiratory tract infections, allergic rhinitis, ulcers, and digestive upsets such as diarrhea and constipation. It is also used as a mouthwash for sore gums and as an eyewash for eye inflammation, and it is applied to the skin for rashes and other skin problems.

Potential for Herb-Drug Interactions

  • A 2021 study found that levels of metformin decreased about 25 percent in healthy adults who were given goldenseal extract plus metformin. This drop was enough to potentially hinder glucose control in people with type 2 diabetes taking metformin.

  • A 2017 review found goldenseal to have an overall high risk of drug interactions because it has been shown to inhibit two major metabolic enzymes, CYP2D6 and CYP3A4, which are responsible for metabolism of more than half of currently used pharmaceutical agents.

Efficacy

  • The scientific evidence does not support the use of goldenseal for any health-related purpose.

  • Berberine, a substance found in goldenseal, has been studied for heart failure, diarrhea, infections, and other health conditions. However, when people take goldenseal orally, very little berberine may be absorbed by the body or enter the bloodstream, so study results on berberine may not apply to goldenseal.

Safety

  • Little information is available on the safety of goldenseal taken alone. Goldenseal might be safe for most adults when taken by mouth in the short term. There is not enough reliable information to know if goldenseal is safe for long-term use.

  • Goldenseal should not be used when pregnant or breastfeeding, and it should not be given to infants. Berberine can cause or worsen jaundice in newborn infants and could lead to a life-threatening problem called kernicterus.

  • A study funded by the National Center for Complementary and Integrative Health (NCCIH) found that some commercial goldenseal dietary supplements didn’t contain much goldenseal and instead included ingredients not listed on their labels.

St. John’s Wort

St. John’s wort is promoted for depression, menopausal symptoms, attention-deficit hyperactivity disorder (ADHD), somatic symptom disorder, obsessive-compulsive disorder, and other conditions. Topical use of St. John’s wort is promoted for various skin conditions, including wounds, bruises, and muscle pain.

Potential for Herb-Drug Interactions

  • A 2017 review found St. John’s wort to have an overall high risk of drug interaction because it is a potent inducer of both cytochrome P-450 enzymes and intestinal P-glycoprotein.

  • 2012 review has documented clinically significant interactions with St. John’s wort and the immunosuppressant drug cyclosporine, the antiretroviral agent indinavir, oral contraceptives, coumadin, digoxin, and benzodiazepines, among others.

Efficacy

  • 2009 Cochrane systematic review of 29 international studies suggested that St. John’s wort may be better than a placebo and as effective as standard prescription antidepressants for major depression of mild to moderate severity. St. John’s wort also appeared to have fewer side effects than standard antidepressants. The studies conducted in German-speaking countries—where St. John’s wort has a long history of use by medical professionals—reported more positive results than those done in other countries, including the United States. It’s uncertain whether this is true for severe depression and for time periods longer than 12 weeks.

  • St. John’s wort has also been studied for conditions other than depression. For some, such as irritable bowel syndrome, chronic hepatitis C virus infection, HIV infection, and social anxiety disorder, current evidence suggests that St. John’s wort isn’t helpful.

  • St. John’s wort might be helpful for menopausal symptoms, wound healing, and somatic symptom disorder, but there’s not enough evidence to know for certain.

  • There’s not enough reliable evidence to know whether St. John’s wort might be beneficial for quitting smoking or improving memory or for many conditions, including anxiety, ADHD, and seasonal affective disorder.

Safety

  • St. John’s wort may cause increased sensitivity to sunlight, especially when taken in large doses. Other side effects can include insomnia, anxiety, dry mouth, dizziness, gastrointestinal symptoms, fatigue, headache, or sexual dysfunction.

  • Taking St. John’s wort with certain antidepressants may lead to increased serotonin-related side effects, which may be potentially serious.

  • There isn’t enough reliable information available to know if St. John’s wort is safe when used topically. It may cause severe skin reactions to sun exposure.

  • It may not be safe to use St. John’s wort during pregnancy or while breastfeeding. It has caused birth defects in laboratory animals. Infants breastfed by mothers who take St. John’s wort can experience colic, drowsiness, and fussiness.

References

  • Asher GN, Corbett AH, Hawke RL. Common herbal dietary supplement–drug interactions. American Family Physician. 2017;96(2):101-107.
  • DeKosky ST, Williamson JD, Fitzpatrick AL, et al. Ginkgo biloba for prevention of dementia: a randomized controlled trial. JAMA. 2008;300(19):2253-2262.
  • Gurley BJ, Fifer EK, Gardner Z. Pharmacokinetic herb-drug interactions (part 2): drug interactions involving popular botanical dietary supplements and their clinical relevance. Planta Medica. 2012;78(13):1490-1514.
  • Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database of Systematic Reviews. 2008;4:CD000448.
  • Nguyen JT, Tian D-D, Tanna RS, et al. Assessing transporter-mediated natural product-drug interactions via in vitro-in vivo extrapolation: Clinical evaluation with a probe cocktail. Clinical Pharmacology and Therapeutics. 2021;109(5):1342-1352.
  • Piscitelli SC, Burstein AH, Welden N, et al. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clinical Infectious Disease. 2002;34(2):234-238.
  • Rider CV, Nyska A, Cora MC, et al. Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets. Toxicologic Pathology. 2014;42(5):830-843.
  • Sarri G, Pedder H, Dias S, et al. Vasomotor symptoms resulting from natural menopause: a systematic review and network meta-analysis of treatment effects from the National Institute for Health and Care Excellence guideline on menopause. BJOG. 2017;124(10):1514-1523.
  • Shergis JL, Zhang AL, Zhou W, et al. Panax ginseng in randomised controlled trials: a systematic review. Phytotherapy Research. 2013;27(7):949-965.
  • Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism. 2015;100(11):3975-4011.

NCCIH Clinical Digest is a service of the National Center for Complementary and Integrative Health, NIH, DHHS. NCCIH Clinical Digest, a monthly e-newsletter, offers evidence-based information on complementary health approaches, including scientific literature searches, summaries of NCCIH-funded research, fact sheets for patients, and more.

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