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NCCIH Clinical Digest

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Herb-Drug Interactions:
What the Science Says

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September 2015
Clinical Guidelines, Scientific Literature, Info for Patients: 

Black Cohosh

Black cohosh has a history of use for rheumatism (arthritis and muscle pain) but has been used more recently as a folk or traditional remedy for hot flashes, night sweats, vaginal dryness, and other symptoms that can occur during menopause. Black cohosh has also been used for menstrual irregularities and premenstrual syndrome, and to induce labor.

Potential for Herb-Drug Interactions

  • Although concerns have been raised about possible interactions between black cohosh and various medications, based on the available clinical data, the risk of herb-interactions appears to be small.
  • A 2012 review concluded that standardized black cohosh supplements, when taken at recommended doses, pose little risk for herb-drug interactions.

Efficacy

  • Study results are mixed on whether black cohosh effectively relieves menopausal symptoms. A 2012 Cochrane review of 16 randomized controlled trials involving 2027 perimenopausal or postmenopausal women found insufficient evidence to support the use of black cohosh for menopausal symptoms.
  • A 2008 systematic review of six studies with a total of 1112 peri- and postmenopausal women had similar findings; however, the authors concluded that the beneficial effect of black cohosh on perimenopausal women cannot be excluded.
  • There are not enough reliable data to determine whether black cohosh is effective for rheumatism or other uses.

Safety

  • A safety review by the Dietary Supplement Information Expert Committee of the U.S. Pharmacopeia’s Council of Experts determined that products containing black cohosh should be labeled to include the following cautionary statement: Discontinue use and consult a health care practitioner if you have a liver disorder or develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice. The safety review analyzed 30 reports on use of black cohosh products concerning liver damage. All were assigned possible causality; none were determined probable or certain causality.
  • There have been some reports of side effects such as stomach discomfort, headache, or rash. In general, clinical trials of black cohosh for menopausal symptoms have not found serious side effects.

Echinacea

Echinacea has traditionally been used for colds, flu, and other infections, based on the idea that it might stimulate the immune system to more effectively fight infection.

Potential for Herb-Drug Interactions

  • Supplements formulated with standardized echinacea extracts appear to have minimal risk of interacting with most conventional medications. A 2012 review concluded that standardized echinacea extracts, when consumed according to label recommendations, are not likely to dramatically modulate human CYP, ABC, and SLCO isoforms in vivo; the review labelled the interaction risk as low.
  • Similarly, a 2012 systematic review found limited clinical evidence of echinacea as a perpetrator of pharmacokinetic drug interactions. However, it found weak effects in terms of either induction or inhibition for Echinacea (presystemic/hepatic CYP3A4 inhibition/induction, CYP1A2 and CYP2C9 inhibition at high doses).
  • However, a 2014 review found that echinacea can induce drug metabolism mediated by CYP3A, but most likely relevant when administered with substances with a narrow therapeutic index or low oral bioavailability.

Efficacy

  • Evidence is mixed on whether echinacea can prevent or effectively treat upper respiratory tract infections. For example, a 2014 Cochrane review of 24 trials of more than 4,000 participants concluded that echinacea has not been shown to provide benefits for treating colds; however, it is possible there is a small, non-significant benefit from some echinacea products in prophylaxis trials.
  • However, a 2007 meta-analysis of 14 studies evaluating the effects of echinacea on the common cold found evidence that supports echinacea’s benefit in decreasing the incidence and duration of the common cold.

Safety

  • When taken orally, echinacea usually does not cause side effects. However, some people experience allergic reactions, including rashes, increased asthma, and anaphylaxis. In clinical trials, gastrointestinal side effects were most common.
  • People are more likely to experience allergic reactions to echinacea if they are allergic to related plants in the daisy family, which includes ragweed, chrysanthemums, marigolds, and daisies. Also, people with asthma or atopy may be more likely to have an allergic reaction when taking echinacea.

Garlic

Garlic’s most common folk or traditional uses as a dietary supplement are for high cholesterol, heart disease, and high blood pressure.

Potential for Herb-Drug Interactions

  • Based on available evidence, short-term use of garlic supplements pose only a limited risk of clinically important herb-drug interactions. However, prolonged exposure to concentrated garlic extracts may reduce the efficacy of drugs whose disposition depends on the human efflux transporter ABCB1. There has been some evidence that garlic may have an effect on the metabolism of the HIV antiviral drug saquinavir, but a 2012 review concluded that, overall, the herb-drug interaction risk for garlic is low.
  • A 2012 systematic review supports these findings and suggests that at commonly recommended doses, garlic does not act as potent or moderate inhibitor or inducer of cytochrome P450 (CYP) enzymes or P-glycoprotein (ABCB1).

Efficacy

  • A 2014 Cochrane review concluded that there is insufficient clinical evidence on the effects of garlic for preventing or treating the common cold.
  • Some evidence indicates that garlic supplementation can slightly lower blood cholesterol levels over the short term (1 to 3 months). However, a 2007 randomized controlled trial on the safety and effectiveness of three garlic preparations for lowering blood cholesterol levels found no statistically or clinically significant effects.

Safety

  • Garlic supplements appear to be safe for most adults. Side effects include breath and body odor, heartburn, upset stomach, and allergic reactions. These side effects are more common with raw garlic.
  • Garlic can thin the blood in a manner similar to aspirin, which may be a problem during or after surgery.

Ginkgo Biloba

Numerous studies of ginkgo have been done for a variety of conditions. Among the most widely researched are dementia, memory impairment, intermittent claudication due to peripheral vascular disease, and tinnitus.

Potential for Herb-Drug Interactions

  • There are some data from animal research to suggest that ginkgo can have an effect on the pharmacokinetics of several drugs; however, current available clinical evidence suggests that low doses do not pose a risk for clinically relevant herb-drug interactions.
  • A 2012 review concluded that the interaction risk of ginkgo biloba is small, if taken at low doses. Higher daily doses may increase the potential for interactions with other medications.

Efficacy

  • A 2008 randomized controlled trial of more than 3,000 older adults found the well-characterized ginkgo product EGb–761 ineffective in lowering the overall incidence of dementia and Alzheimer's disease. Further analysis of the same data also found ginkgo to be ineffective in slowing cognitive decline, lowering blood pressure, or reducing the incidence of hypertension.
  • Some smaller studies of ginkgo for memory enhancement have had promising results, but a 2002 randomized controlled trial sponsored by the National Institute on Aging of more than 200 healthy adults over age 60 found that ginkgo taken for 6 weeks did not improve memory.
  • A 2013 Cochrane review of four trials involving more than 1,500 participants found that the evidence does not demonstrate ginkgo biloba’s effectiveness for tinnitus.
  • Overall, the evidence on ginkgo for symptoms of intermittent claudication has not yet shown a significant benefit for this condition, although several small studies have found modest improvements.

Safety

  • Side effects of ginkgo may include headache, nausea, gastrointestinal upset, diarrhea, dizziness, or allergic skin reactions. More severe allergic reactions have occasionally been reported.
  • Some data suggest that ginkgo may affect platelet aggression, but the significance of increased bleeding risk is inconclusive.

Ginseng (Asian)

Treatment claims for Asian ginseng are numerous and include the use of the herb to support overall health and boost the immune system. Traditional and folk uses of ginseng include improving the health of people recovering from illness; increasing a sense of well-being and stamina; improving both mental and physical performance; treating erectile dysfunction, hepatitis C, and symptoms related to menopause; and lowering blood glucose and controlling blood pressure.

Potential for Herb-Drug Interactions

  • Most herb-drug interactions with Asian ginseng are based on preclinical studies and mechanisms of action. Current evidence suggests that ginseng induces activity of the drug-metabolizing enzyme CYP3A in the liver and possibly the gastrointestinal tract. A 2012 open-label study concluded that patients taking Asian ginseng in combination with CYP3A substrates with narrow therapeutic ranges should be closely monitored for adequate therapeutic response to the substrate medication.

Efficacy

  • Although Asian ginseng has been widely studied for a variety of conditions, clinical evidence to date do not conclusively support health claims associated with the herb. Only a few large, high-quality clinical trials have been conducted. Most evidence is preliminary.

Safety

  • Patients using oral hypoglycemics or insulin should be cautious about hypoglycemia when taking Asian ginseng.
  • Short-term use of ginseng at recommended doses appears to be safe for most people. Some sources suggest that prolonged use might cause side effects.
  • The most common side effects are headaches and sleep and gastrointestinal problems.

Goldenseal

Historically, Native Americans have used goldenseal for various health conditions such as skin diseases, ulcers, and gonorrhea. Currently, folk or traditional uses of goldenseal include colds and other respiratory tract infections, infectious diarrhea, eye infections, vaginitis, and occasionally, cancer.

Potential for Herb-Drug Interactions

  • Goldenseal is a potent inhibitor of both CYP3A4 and CYP2D6 enzyme activity. A 2012 review concluded that that goldenseal’s herb-drug interaction risk is high.
  • The CYP enzyme interactions are thought to be due to the two most common isoquinoline alkaloids found in goldenseal, berberine and hydrastine.

Efficacy

  • Only a few studies have been published on the safety and efficacy of goldenseal, and there is scant scientific evidence to support using it for any health problem.

Safety

  • Goldenseal is considered safe for short-term use in adults at recommended dosages. Rare side effects may include nausea and vomiting. However, there is little information about the safety of high dosages or the long-term use of goldenseal.
  • Other herbs containing berberine, including Chinese goldthread (Coptis trifolia) and Oregon grape (Mahonia aquifolium), are sometimes substituted for goldenseal. These herbs may have different effects, side effects, and drug interactions than goldenseal.
  • Women who are pregnant or breastfeeding should avoid using goldenseal. Berberine can cause or worsen jaundice in newborns and could lead to kernicterus. Goldenseal should not be given to infants and young children.

Kava

Historically, kava was used to help people fall asleep and fight fatigue, as well as to treat asthma and urinary tract infections. It also had a topical use as a numbing agent. More recent folk or traditional uses include anxiety, insomnia, and menopausal symptoms.

Potential for Herb-Drug Interactions

  • Only a few clinical studies have examined the interaction potential of kava, and the results have been mixed. There is some evidence that concomitant use of kava and CNS depressants can increase risk of drowsiness and motor reflex depression. However, a 2012 review concluded that kava supplements, when consumed per product label recommendations, are not likely to affect the efficacy or toxicity of medications.

Efficacy

  • Although a few clinical studies provide some evidence that kava may be beneficial for the management of anxiety, the U.S. Food and Drug Administration has issued a warning that using kava supplements has been linked to a risk of severe liver damage.
  • There is no evidence to support the use of kava for any other condition.

Safety

  • Kava has been reported to have hepatotoxic effects. Kava has been associated with several cases of dystonia.
  • Long-term and/or heavy use of kava may result in jaundice.

St. John’s Wort

Historically, St. John’s wort has been used for centuries to treat mental disorders and nerve pain. St. John’s wort has also been used for malaria, as a sedative, and as a balm for wounds, burns, and insect bites. Today, St. John’s wort is used as a folk or traditional remedy for depression, anxiety, and/or sleep disorders.

Potential for Herb-Drug Interactions

  • St. John’s wort is a potent inducer of both cytochrome P-450 enzymes and intestinal P-glycoprotein. A 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

  • Data on benefits of St. John’s wort for depression have been inconsistent. A 2002 study of 340 patients found that St. John’s wort was no more effective than placebo in treating major depression of moderate severity, and a 2011 study found that neither St. John’s wort nor citalopram relieved symptoms of minor depression better than a placebo.
  • However, a 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.

Safety

  • St. John’s wort may cause increased sensitivity to sunlight. Other side effects can include 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.

References

Black Cohosh

Echinacea

Garlic

Ginkgo Biloba

Asian Ginseng

Goldenseal

Kava

St. John’s Wort

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.

The National Center for Complementary and Integrative Health is dedicated to exploring complementary health products and practices in the context of rigorous science, training complementary health researchers, and disseminating authoritative information to the public and professionals. For additional information, call NCCIH's Clearinghouse toll-free at 1-888-644-6226, or visit the NCCIH Web site at nccih.nih.gov. NCCIH is 1 of 27 institutes and centers at the National Institutes of Health, the Federal focal point for medical research in the United States.

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This page last modified June 25, 2018