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Licorice

Licorice

Common Names

  • Gan cao
  • Sweet root
  • Glycyrrhiza
  • Liquorice

For Patients & Caregivers

How It Works Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

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 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.

Purported Uses Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.
  • 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 including 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. Human data are lacking.
  • To treat microbial infections
    Studies in animals suggest that licorice has antimicrobial activity, but human data are lacking.
  • 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.
Do Not Take If Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.
  • You take cardiac glycosides: Licorice may increase their effects and cause toxicity.
  • You take insulin: Licorice may increase the sugar lowering effect.
  • You take diuretic drugs: Licorice may lower the blood potassium level.
  • You take warfarin or other blood thinners: Licorice may increase the risk of bleeding.
  • You take MAO-inhibitors (MAOIs): 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 cytochrome P450 substrates: Licorice may affect the actions of these drugs.
  • You are taking cyclosporine: Licorice greatly reduced the oral bioavailability of cyclosporine by activating P-gp and CYP3A4, which can make it less effective.
  • You are taking cortisol acetate: Licorice increased cortisol availability in tissues, which may increase its side effects.
  • You are taking metformin: Pre-administration of licorice juice reduced the efficacy of metformin, in a rat model. Whether similar effect occurs in humans is not known
Side Effects Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.
  • High blood pressure
  • Lethargy
  • Muscle pain
  • Cardiac arrhythmias
  • High sodium retention
  • Low blood levels of potassium
  • Decreased libido in men
  • Suppression of scalp sebum secretion
  • Low blood platelet count
Special Point Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

Due to the adverse reaction profile of licorice, many studies have been performed using the deglycyrrhizinated licorice (DGL) extract that is free of glycyrrhizin.

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For Healthcare Professionals

Scientific Name Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.
Glycyrrhiza glabra, Glycyrrhiza uralensis
Clinical Summary Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

Derived from the root of the plant, licorice has been used as a flavoring and sweetening agent. This herb is an important component of traditional Chinese medicine used to detoxify and 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 be responsible for its biologic effects.

In vitro and animal studies show that licorice has antibacterial (2) (27), antiviral (48), anticancer (3) (4) (28) (29), anti-inflammatory (30), and hepatoprotective (49) properties. Licorice also demonstrated estrogenic effects (10), reduced cardiotoxicity associated with doxorubicin (31), and improved the antitumor effects of cyclophosphamide (32). However, these effects have not been confirmed in humans.

Clinical data suggest utility of licorice in lowering dyspepsia (1) and hyperlipidemia (33), and concurrent intake of a glycyrrhizin-containing product during alcohol consumption was shown to afford hepatoprotection (50). In another study, preoperative gargling with licorice solution affected significant reductions in postoperative sore throat when compared to gargling with sugar water (51). Licorice solution was also reported to improve xerostomia in hemodialysis patients (52); and had comparable efficacy as triamcinolone in the management of oral mucositis during radiotherapy (53). But chronic ingestion of even moderate doses of licorice has been associated with hypertension and hypokalemia (54).

Purported Uses Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.
  • Bronchitis
  • Chest congestion
  • Constipation
  • GI disorders
  • Hepatitis
  • Inflammation
  • Menopausal symptoms
  • Microbial infection
  • Peptic ulcers
  • Primary adrenocortical insufficiency
  • Prostate cancer
Mechanism of Action Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

Glycyrrhizin, one of the bioactive compounds of licorice, has been shown to bind to glucocorticoid and mineralocorticoid receptors, and exert its effects via inhibition of 11b-hydroxysteroid dehydrogenase (12). Licorice can reduce serum testosterone by inhibiting 17-hydroxysteriod dehydrogenase (35) (36). It also contains isoflavones and other constituents that have estrogen receptor-modulating activities (10). The flavone and liquiritigenin components selectively activate ER-alpha (11).

Liquiritigenin was also shown to have neuroprotective effects in scopolamine-induced mice likely via increasing expression of brain-derived neurotrophic factor (BDNF), and phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP response element binding (CREB) in the hippocampus (55). In addition, glycyrrhizic acid, a triterpene glycoside, demonstrated anti-allerigic property by restoring the immune balance of subsets 1 and 2 of T helper cells in a dose-dependent manner. It also siginificantly reduced B cells producing allergen-specific IgE and IgG1 (56).

In other studies, licorice demonstrated chemo-preventive effects by modulating expression of Bcl-2/Bax proteins, which act as apoptotic regulatory factors (3); and via inhibiting carcinogenesis (4). The most common side effect of licorice is hypokalemic hypertension, which occurs secondary to inhibition of 11beta-hydroxysteroid dehydrogenase, a renal enzyme responsible for converting cortisol to cortisone. This inhibition results in enhancing the mineralocorticoid effects of cortisol (36) that include sodium retention and excretion of potassium.

Warnings Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

Due to the adverse reaction profile of licorice, many studies have been performed using the deglycyrrhizinated licorice (DGL) extract that is free of glycyrrhizin.

Adverse Reactions Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

Hypertension (16) (45) (57), lethargy, muscle pain, sodium retention, hypokalemia (17) (18) (19) (20) (26)  (41), adrenal crisis (21), ventricular fibrillation (22), cardiac arrythmias (23), carpal tunnel syndrome (24), glycyrrhizic acid poisoning (25), leukoderma (42), and thrombocytopenia (43)have been reported following ingestion of licorice or licorice containing products.

Herb-Drug Interactions Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

Cardiac glycosides: Licorice may potentiate toxicity (24).
Diuretics: Licorice may increase the risk of hypokalemia (17) (18).
Insulin: Licorice may increase insulin sensitivity (38) .
Anticoagulants: Licorice may increase the metabolism and clearance of warfarin (19).
MAO-inhibitors (MAOIs): Licorice may potentiate activity of MAOIs (37)
P-Glycoprotein (P-gp) substrates: Licorice inhibited P-gp, resulting in increased intracellular concentration of the chemotherapy agent daunorubicin, which is a substrate of P-gp (34).
Cytochrome P450 substrates: Glycyrrhizin, a major constituent of licorice, induces CYP3A (39) and CYP2D6 (44), and can affect the intracellular concentration of drugs metabolized by this enzyme. However, other constituents, like glabridin, glycycoumarin and licochalcone A from different species of licorice can inhibit these enzymes (40).
Cyclosporine: Licorice greatly reduced the oral bioavailability of cyclosporine by activating P-gp and CYP3A4 (46).
Cortisol acetate: Licorice increased cortisol availability in tissues in the hours following oral cortisone acetate administration (47).
Metformin: Pre-administration of licorice juice reduced the efficacy of metformin, in a rat model (58). The clinical relevance in humans has yet to be determined.

Dosage (OneMSK Only) Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.
References Minus iconIcon indicating subtraction, or that the element can be closed. Plus IconIcon indicating addition, or that the element can be opened. Arrow (down) icon.An arrow icon, usually indicating that the containing element can be opened and closed.

  1. Gupta VK, Fatima A, Faridi U, et al. Antimicrobial potential of Glycyrrhiza glabra roots. J Ethnopharmacol. Mar 5 2008;116(2):377-380.

  2. De Smet PAGM. Adverse Effects of Herbal Drugs. Vol 3. New York: Springer: 1997.

  3. 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.

  4. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy (OR): Eclectic Medical Publications; 1998.

  5. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines: A Guide for Health-Care Professionals. 1st ed. London: Pharmaceutical Press; 1996.

  6. Blumenthal M, Goldberg A, Brinckmann J, et al. Herbal Medicine, Expanded Commission E Monographs. Austin: American Botanical Council; 2000.

  7. 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.

  8. 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.

  9. Tyler V. Herbs of Choice, the Therapeutical Use of Phytomedicinals. Binghamton: Pharmaceutical Press; 1994.

  10. Stormer FC, Reistad R, Alexander J. Glycyrrhizic acid in liquorice—evaluation of health hazard. Food Chem Toxicol. Apr 1993;31(4):303-312.

  11. 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.

  12. 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.

  13. Mumoli N, Cei M. Licorice-induced hypokalemia. Int J Cardiol. 2008 Mar 14;124(3):e42-4.

  14. 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.

  15. 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.

  16. Gerritsen KG, Meulenbelt J, Spiering W, et al. An unusual cause of ventricular fibrillation. Lancet. 2009 Mar 28;373(9669):1144.

  17. 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.

  18. 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.

  19. 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.

  20. Kim YH, Shin EK, Kim DH, et al. Antiangiogenic effect of licochalcone A. Biochem Pharmacol. 2010 Oct 15;80(8):1152-9.

  21. Chandrasekaran CV, Deepak HB, Thiyagarajan P, et al. Dual inhibitory effect of Glycyrrhiza glabra (GutGard™) on COX and LOX products. Phytomedicine. 2010 Sep 21.

  22. 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.

  23. 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.

  24. 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.

  25. Armanini D, Mattarello MJ, Fiore C, et al. Licorice reduces serum testosterone in healthy women. Steroids. 2004 Oct-Nov;69(11-12):763-6.

  26. 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.

  27. 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.

  28. Li G, Simmler C, Chen L, et al. Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci. 2017 Jul 31;109:182-190. doi: 10.1016/j.ejps.2017.07.034. [Epub ahead of print]

  29. 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.

  30. Celik M, Karakus A, Zeren C, et al. Licorice induced hypokalemia, edema, and thrombocytopenia. Hum Exp Toxicol. 2012 Dec;31(12):1295-8.

  31. Pandit S, Ponnusankar S, Bandyopadhyay A, et al. Exploring the possible metabolism mediated interaction of Glycyrrhiza glabra extract with CYP3A4 and CYP2D6.Phytother Res. 2011 Oct;25(10):1429-34.

  32. Ruiz-Granados ES, Shouls G, Sainsbury C, Antonios T. A salty cause of severe hypertension. BMJ Case Rep. 2012 Feb 25;2012. doi:pii: bcr1220115336. 10.1136/bcr.12.2011.5336.

  33. Hou YC, Lin SP, Chao PD. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP 3A. Food Chem. 2012 Dec 15;135(4):2307-12.

  34. Methlie P, Husebye EE, Hustad S, Lien EA, Løvås K. Grapefruit juice and licorice increase cortisol availability in patients with Addison’s disease.Eur J Endocrinol. 2011 Nov;165(5):761-9.

  35. Kuo KK, Chang JS, Wang KC, et al. Water extract of Glycyrrhiza uralensis inhibited enterovirus 71 in a human foreskin fibroblast cell line. Am J Chin Med. 2009;37(2):383-94.

  36. Penninkilampi R, Eslick EM, Eslick GD. The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis.J Hum Hypertens. 2017 Jun 29. doi: 10.1038/jhh.2017.45. [Epub ahead of print]

  37. Ko YH, Kwon SH, Lee SY, Jang CG. Liquiritigenin ameliorates memory and cognitive impairment through cholinergic and BDNF pathways in the mouse hippocampus. Arch Pharm Res. 2017 Sep 22. doi: 10.1007/s12272-017-0954-6. [Epub ahead of print]

  38. Foster CA, Church KS, Poddar M, Van Uum SH, Spaic T. Licorice-induced hypertension: a case of pseudohyperaldosteronism due to jelly bean ingestion. Postgrad Med. 2017 Apr;129(3):329-331.

  39. Awad R, Mallah E, Khawaja BA, et al. Pomegranate and licorice juices modulate metformin pharmacokinetics in rats. Neuro Endocrinol Lett. 2016 Jul;37(3):202-206.

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