About Herbs, Botanicals & Other Products

Scientific Name
Glycyrrhiza glabra, Glycyrrhiza uralensis
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Common Name

Gan cao, sweet root, glycyrrhiza, liquorice

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Clinical Summary

Licorice, derived from the root of the plant, has been used as a flavoring and sweetening agent. This herb is also an important component of traditional Chinese medicine used to detoxify and to enhance or balance the effects of other components in herbal formulas; and as a tonic, expectorant and a demulcent in Ayurveda. A number of compounds including glycyrrhizin are thought to account for its biologic activity.
In vitro and animal data show that licorice has antibacterial (2) (27), anticancer (3) (4) (28) (29), anti-inflammatory (30) effects, and estrogenic activity (7) (8) (10). Studies also that suggest licorice can reduce cardiotoxicity associated with doxorubicin (31) and may improve efficiency of chemotherapy (32). However, these effects have not been confirmed in humans.
Licorice demonstrated effectiveness in reducing dyspepsia (1) and hyperlipidemia (33) in clinical studies.

Adverse effects of licorice include hypokalemia, hypernatremia, pseudo-hyperaldosteronism, decreased libido in men (5), and paralysis (6).
Licorice products may interfere with anticoagulants and hormonal therapy.

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Food Sources

Flavoring agent

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Purported Uses
  • Bronchitis
  • Chest congestion
  • Constipation
  • GI disorders
  • Hepatitis
  • Inflammation
  • Menopausal symptoms
  • Microbial infection
  • Peptic ulcers
  • Primary adrenocortical insufficiency
  • Prostate cancer
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Constituents
  • Triterpenoid Saponins: Glycyrrhizin (metabolized in vivo to glycyrrhetinic acid and glycyrrhizinic)
  • Flavonoids: Liquiritin, chalcones, glabridin
  • Isoflavone: Formononetin
  • Amines: Asparagines, betaine, and choline
  • Amino Acids
  • Polysaccharides Sterols: B-sitosterol
  • Coumarins: glycyrol
    (9)
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Mechanism of Action

Licorice contains isoflavone and other constituents that have estrogen receptor modulating activities (8) (10). The flavone and liquiritigenin components selectively activate ER-alpha (11). Glycyrrhizin has been reported to bind to glucocorticoid and mineralocorticoid receptors and exerts its effect via inhibition of 11b-hydroxysteroid dehydrogenase (12). Licorice can reduce serum testosterone by inhibiting 17-hydroxysteriod dehydrogenase (35) (36). Long-term ingestion of licorice has been shown to cause secondary hypertension and hypokalemia, resulting in paralysis (6). The coumarin constituent has antiplatelet activity. Licorice has been shown to have chemopreventive effects by influencing Bcl-2/Bax (3) and via inhibiting carcinogenesis (4).
Licorice inhibited P-glycoprotein (P-gp), resulting in increased intracellular concentration of the chemo agent daunorubicin, which is a substrate of P-gp (34).

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Pharmacokinetics

Administration of licorice after meals delays the time (Tmax) to peak concentration, but does not affect maximum concentration (Cmax) or area-under-the-curve (AUC) (13). Elimination half-life is approximately 5 hours following intravenous administration (14). Primary route of excretion is via bile (15).

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Warnings

Due to the adverse reaction profile of licorice, many studies have been performed using the deglycyrrhizinated licorice (DGL) extract. Deglycyrrhizinated licorice is free of glycyrrhizin and has had no reported significant adverse effects.

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Contraindications

Licorice should not be consumed by those with renal or liver dysfunction, or women who are pregnant or breast-feeding.

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Adverse Reactions

Reported: Hypertension (16), lethargy, muscle pain, sodium retention, hypokalemia (17) (18) (19) (20) (26) (40) (41), adrenal crisis (21), decreased libido in men, ventricular fibrillation (22), cardiac arrythmias (23), carpal tunnel syndrome (24), glycyrrhizic acid poisoning (25), suppression of scalp sebum secretion (5), and leukoderma (42) following use of a skin lightening cream containing licorice extract have been reported.

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Herb-Drug Interactions

Cardiac glycosides: Licorice may potentiate toxicity (24).
Diuretics: Chronic use of licorice may increase loss of potassium.
Spironolactone / Amiloride: Licorice should not be used simultaneously due to effects on sodium and potassium excretion.
Corticosteroids: Concomitant use with licorice might potentiate the duration of activity.
Insulin: Licorice may have a synergistic effect possibly causing hypokalemia and sodium retention with concomitant use (38) .
Hormonal therapy: Licorice may interfere with the activity of hormonal therapy due to its estrogenic or anti-estrogenic properties.
Anticoagulants: Licorice may increase the metabolism and clearance of warfarin (19).
MAO-inhibitors (MAO-I): Licorice may potentiate activity of MAO-Is.
(37) (8)
P-Glycoprotein (P-gp) substrates: Licorice inhibited P-gp, resulting in increased intracellular concentration of the chemo agent daunorubicin, which is a substrate of P-gp (34).
Cytochrome P450 substrates: Glycyrrhizin, a major ingredient of licorice, induces CYP3A and can affect the intracellular concentration of drugs metabolized by this enzyme (39).

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Herb Lab Interactions
  • Secondary hypertension.
  • Potassium levels may be decreased.
  • Sodium levels may be elevated.
  • Testosterone levels may be decreased.
  • Blood sugar levels may be decreased.
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Literature Summary and Critique

The only studies in humans showing positive results have used deglycyrrhizinated licorice as a single agent in peptic ulcers. Studies of licorice in combination with other herbs has shown favorable results, such as PC-SPES for prostate cancer.

Madisch A, et al. Treatment of Functional Dyspepsia with a Herbal Preparation. A Double- Blind, Randomized, Placebo-Controlled, Multicenter Trial. Digestion 2004;69:45-52.
This study was aimed at determining the efficacy and safety of STW 5-II, an herbal preparation containing extracts of licorice root as one of the major ingredients as well as matricaria flower, peppermint leaves, caraway, lemon balm, and bitter candy tuft. 120 patients with functional dyspepsia were randomly assigned to 4 treatment groups and treated over a 12-week period. Patients received either STW 5-II or placebo for 8 weeks. Treatment during the last 4-week period was determined by the investigator based on symptom relief in patients. The outcome measure was the standardized gastrointestinal symptom score (GIS). There was a significant decrease in GIS in patients treated with STW 5-II compared to those on placebo during the first 4 weeks. Symptoms improved further in patients who continued treatment during the second 4 weeks. After 8 weeks, 43.3% patients on active treatment and 3.3% patients on placebo reported total symptom relief. The authors suggest that STW 5-II significantly improves symptoms of dyspepsia as compared to a placebo. However, since STW 5-II contains other herbs, the extent to which licorice contributes to relieving dyspeptic symptoms is not clear from this study.

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References
  1. Madisch A, Holtmann G, Mayr G, et al. Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial. Digestion. 2004;69(1):45-52.
  2. Gupta VK, Fatima A, Faridi U, et al. Antimicrobial potential of Glycyrrhiza glabra roots. J Ethnopharmacol. Mar 5 2008;116(2):377-380.
  3. Jo EH, Hong HD, Ahn NC, et al. Modulations of the Bcl-2/Bax family were involved in the chemopreventive effects of licorice root (Glycyrrhiza uralensis Fisch) in MCF-7 human breast cancer cell. J Agric Food Chem. Mar 24 2004;52(6):1715-1719.
  4. Takahashi T, Takasuka N, Iigo M, et al. Isoliquiritigenin, a flavonoid from licorice, reduces prostaglandin E2 and nitric oxide, causes apoptosis, and suppresses aberrant crypt foci development. Cancer Sci. May 2004;95(5):448-453.
  5. De Smet PAGM. Adverse Effects of Herbal Drugs. Vol 3. New York: Springer: 1997.
  6. Lin SH, Yang SS, Chau T, et al. An unusual cause of hypokalemic paralysis: chronic licorice ingestion. Am J Med Sci. Mar 2003;325(3):153-156.
  7. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy (OR): Eclectic Medical Publications; 1998.
  8. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-Care Professionals. 1st ed. London: Pharmaceutical Press; 1996.
  9. Blumenthal M, Goldberg A, Brinckmann J, et al. Herbal Medicine, Expanded Commission E Monographs. Austin: American Botanical Council; 2000.
  10. Somjen D, Knoll E, Vaya J, et al. Estrogen-like activity of licorice root constituents: glabridin and glabrene, in vascular tissues in vitro and in vivo. J Steroid Biochem Mol Biol. Jul 2004;91(3):147-155.
  11. Mersereau JE, Levy N, Staub RE, et al. Liquiritigenin is a plant-derived highly selective estrogen receptor beta agonist. Mol Cell Endocrinol. Feb 13 2008;283(1-2):49-57.
  12. Tyler V. Herbs of Choice, the Therapeutical Use of Phytomedicinals. Binghamton: Pharmaceutical Press; 1994.
  13. Miyamura M, Ono M, Kyotani S, et al. [Properties of glycyrrhizin in Kampo extracts including licorice root and changes in the blood concentration of glycyrrhetic acid after oral administration of Kampo extracts]. Yakugaku Zasshi. Mar 1996;116(3):209-216.
  14. Stormer FC, Reistad R, Alexander J. Glycyrrhizic acid in liquorice—evaluation of health hazard. Food Chem Toxicol. Apr 1993;31(4):303-312.
  15. Ichikawa T, Ishida S, Sakiya Y, et al. Biliary excretion and enterohepatic cycling of glycyrrhizin in rats. J Pharm Sci. Jul 1986;75(7):672-675.
  16. Breidthardt T, Namdar M, Hess B. A hypertensive urgency induced by the continuous intake of a herbal remedy containing liquorice. J Hum Hypertens. 2006 Jun;20(6):465-6.
  17. Yasue H, Itoh T, Mizuno Y, Harada E. Severe hypokalemia, rhabdomyolysis, muscle paralysis, and respiratory impairment in a hypertensive patient taking herbal medicines containing licorice. Intern Med. 2007;46(9):575-8.
  18. Mumoli N, Cei M. Licorice-induced hypokalemia. Int J Cardiol. 2008 Mar 14;124(3):e42-4.
  19. Mu Y, Zhang J, Zhang S, Zhou HH, Toma D, Ren S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther. 2006 Mar;316(3):1369-77.
  20. Templin C, Westhoff-Bleck M, Ghadri JR. Hypokalemic paralysis with rhabdomyolysis and arterial hypertension caused by liquorice ingestion. Clin Res Cardiol. 2009 Feb;98(2):130-2.
  21. Isaia GC, Pellissetto C, Ravazzoli M, Tamone C. Acute adrenal crisis and hypercalcemia in a patient assuming high liquorice doses. Minerva Med. 2008 Feb;99(1):91-4.
  22. Gerritsen KG, Meulenbelt J, Spiering W, et al. An unusual cause of ventricular fibrillation. Lancet. 2009 Mar 28;373(9669):1144.
  23. Tacconi P, Paribello A, Cannas A, Marrosu MG. Carpal tunnel syndrome triggered by excessive licorice consumption. J Peripher Nerv Syst. 2009 Mar;14(1):64-5.
  24. Yorgun H, Aksoy H, Sendur MA, et al. Brugada syndrome with aborted sudden cardiac death related to liquorice-induced hypokalemia. Med Princ Pract. 2010;19(6):485-9.
  25. Caubet-Kamar N, Tubery M, Garrouste C, Lauque D, Kamar N. Harmful effect of saline infusion in a patient with glycyrrhizic acid poisoning. CJEM. 2010 May;12(3):224-5.
  26. Støving RK, Lingqvist LE, Bonde RK, Is glycyrrhizin sensitivity increased in anorexia nervosa and should licorice be avoided? Case report and review of the literature. Nutrition. 2010 Aug 24. [Epub ahead of print]
  27. Badr AE, Omar N, Badria FA. A laboratory evaluation of the antibacterial and cytotoxic effect of Liquorice when used as root canal medicament. Int Endod J. 2010 Aug 31.
  28. Kim YH, Shin EK, Kim DH, et al. Antiangiogenic effect of licochalcone A. Biochem Pharmacol. 2010 Oct 15;80(8):1152-9.
  29. Park SY, Lim SS, Kim JK, et al. Hexane-ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells. Br J Nutr. 2010 May 21:1-11.
  30. Chandrasekaran CV, Deepak HB, Thiyagarajan P, et al. Dual inhibitory effect of Glycyrrhiza glabra (GutGard™) on COX and LOX products. Phytomedicine. 2010 Sep 21.
  31. Choi HJ, Seon MR, Lim SS, et al. Hexane/ethanol extract of Glycyrrhiza uralensis licorice suppresses doxorubicin-induced apoptosis in H9c2 rat cardiac myoblasts. Exp Biol Med (Maywood). 2008 Dec;233(12):1554-60.
  32. Gol'dberg ED, Amosova EN, Zueva EP, et al. Licorice preparations improve efficiency of chemotherapy and surgical treatment of transplanted tumors. Bull Exp Biol Med. 2008 Feb;145(2):252-5.
  33. Hasani-Ranjbar S, Nayebi N, Moradi L, et al. The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Curr Pharm Des. 2010;16(26):2935-47.
  34. Nabekura T, Yamaki T, Ueno K, Kitagawa S. Inhibition of P-glycoprotein and multidrug resistance protein 1 by dietary phytochemicals. Cancer Chemother Pharmacol. 2008 Oct;62(5):867-73.
  35. Armanini D, Mattarello MJ, Fiore C, et al. Licorice reduces serum testosterone in healthy women. Steroids. 2004 Oct-Nov;69(11-12):763-6.
  36. Armanini D, Bonanni G, Mattarello MJ, et al. Licorice consumption and serum testosterone in healthy man. Exp Clin Endocrinol Diabetes. 2003 Sep;111(6):341-3.
  37. Hatano T, Fukuda T, Miyase T, Noro T, Okuda T. Phenolic constituents of licorice. III. Structures of glicoricone and licofuranone, and inhibitory effects of licorice constituents on monoamine oxidase. Chem Pharm Bull (Tokyo). 1991 May;39(5):1238-43.
  38. Eu CH, Lim WY, Ton SH, bin Abdul Kadir K. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats. Lipids Health Dis. 2010 Jul 29;9:81.
  39. Tu JH, He YJ, Chen Y, et al. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol. 2010 Aug;66(8):805-810.
  40. Yorgun H, Aksoy H, Sendur MA, et al. Brugada syndrome with aborted sudden cardiac death related to liquorice-induced hypokalemia. Med Princ Pract. 2010;19(6):485-9.
  41. Pant P, Nadimpalli L, Singh M, Cheng JC. A case of severe hypokalemic paralysis and hypertension. Licorice-induced hypokalemic paralysis. Am J Kidney Dis. 2010 Jun;55(6):A35-7.
  42. Madhogaria S, Ahmed I. Leucoderma after use of a skin-lightening cream containing kojic dipalmitate, liquorice root extract and Mitracarpus scaber extract. Clin Exp Dermatol. 2010 Jun;35(4):e103-5.
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How It Works

Bottom Line: Licorice may be helpful in treating peptic ulcers, but it has not been shown effective in treating cancer.

In traditional Chinese medicine, licorice is often used in herbal formulas to harmonize the effects of other herbs. Experiments in animals and humans show licorice can mimic the effects of steroid hormones such as aldosterone and estrogen. The substance in licorice that scientists think is responsible for these effects is called glycyrrhizin. However, because glycyrrhizin causes undesirable side effects, it is often removed from licorice products during processing.

Physiologic activity has also been reported for several other compounds in licorice. Isoflavone compounds also mimic estrogens in the human body, and can kill several strains of bacteria and viruses on contact. Other compounds act as blood thinners and inhibit the process of inflammation. In humans, the compound, carbenoxolone, has been used to treat stomach and esophageal ulcers with positive effects. Scientists think that it increases blood flow to and amount of mucus lining the stomach.

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Purported Uses
  • To treat bronchitis and chest congestion
    No scientific evidence supports this use.
  • To relieve constipation
    This claim is not backed by research.
  • To treat gastrointestinal disorders such as peptic ulcers
    A substance in licorice called carbenoxolone decreased pain and heartburn and increased healing in patients with peptic ulcers, but major side effects (e.g., edema or fluid accumulation, low potassium, and high blood pressure) were reported.
  • To treat hepatitis
    Clinical trials in Japan have used a licorice extract (containing glycyrrhizin) to treat hepatitis B and C, and have shown that glycyrrhizin reduces liver disease. However, there is no proof that deglycyrrhizinated licorice would have the same effect.
  • To reduce inflammation
    Studies in animals support this use, but there is no proof from clinical trials that this effect occurs in humans.
  • To relieve menopausal symptoms
    Studies in animals show that licorice has estrogenic effects, and some of the components of licorice bind estrogen receptors. However, there is no proof from clinical trials that this effect occurs in humans.
  • To treat microbial infections
    Studies in animals suggest that licorice has anti-microbial activity, but there is no proof from clinical trials that this effect occurs in humans.
  • To treat prostate cancer
    No scientific evidence supports this use. Licorice is an ingredient in PC-SPES, which has been studied in patients with prostate cancer.
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Research Evidence

Most clinical trials studying licorice have used it in combination with other herbs, such as PC-SPES for prostate cancer.

A number of clinical trials have used deglycyrrhizinated licorice to treat stomach ulcers, with favorable results.

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Patient Warnings
  • Glycyrrhizin, one of the active compounds in licorice, is known to cause many side effects (see Side Effects for details). Therefore, many clinical trials use deglycyrrhizinated licorice (DGL) extract, and have found side effects to be greatly reduced.
  • This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
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Do Not Take If
  • You have liver or kidney problems.
  • You are pregnant or breast-feeding.
  • You have existing heart disease.
  • You take cardiac glycosides (Licorice may increase their effects and cause toxicity).
  • You take stimulant laxatives (Long-term use of licorice may increase your loss of potassium in the urine, causing dangerously low blood potassium levels).
  • You take diuretics (Long-term use of licorice may increase your loss of potassium in the urine, causing dangerously low blood potassium levels).
  • You take spironolactone or amiloride (Licorice should not be used at the same time as these medications because it can alter the body's retention of sodium and loss of potassium in the urine).
  • You take corticosteroids (Licorice may have additive effects).
  • You take insulin (Licorice may have additive effects, possibly causing low blood levels of potassium and high levels of sodium retention in the body).
  • You take hormonal therapy such as hormone replacement therapy or birth control pills (Because it alters the effects of sex hormones such as estrogen, licorice may interfere with hormonal therapy).
  • You take warfarin or other blood thinners (Licorice may increase the risk of bleeding).
  • You take MAO-inhibitors (MAO-Is) (Licorice may have additive effects).
  • You take daunorubicin: Licorice intake can result in increased intracellular concentration of daunorubicin, which may increase its toxic effects.
  • You are taking drugs that are substrates of Cytochrome P450 3A (Licorice may increase the risk of side effects of these drugs).
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Side Effects
  • High blood pressure
  • Lethargy
  • Muscle pain
  • Cardiac arrhythmias
  • Sodium retention
  • Hypokalemia (low blood levels of potassium)
  • Hyper-mineralcorticoidism
  • Pseudo-hyperaldosteronism (causing low blood levels of potassium and high sodium retention)
  • Decreased libido in men
  • Suppression of scalp sebum secretion
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Dosage (Inside MSKCC Only)
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Aliases
Gan Cao
Glycyrrhiza Glabra
Glycyrrhiza Uralensis
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E-mail your questions and comments to aboutherbs@mskcc.org.
Last updated: August 16, 2011