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Licorice

Medically reviewed by Drugs.com. Last updated on Oct 22, 2018.

Scientific Name(s): Glycyrrhiza glabra (L.).
Common Name(s): Bois doux, Gan Cao, Glycyrrhizae extractum crudum, Glycyrrhizae radix, Kanzo, Lakrids, Lakritzenwurzel, Licochalcone-A, Licorice, Liquiriti radix, Russian licorice, Shao-yao-gan-cao-tang, Spanish licorice, Succens liquiritiae

Clinical Overview

Use

Used historically for GI complaints, licorice is primarily used as a flavoring agent in the tobacco and candy industries and to some extent in the pharmaceutical and beverage industries today. The chemical compounds found in licorice have been investigated for a variety of uses including cancer therapy as well as for their antiviral activity.

Dosing

Licorice root has been used in daily doses from 760 mg to 15 g for ulcer and gastritis. Higher doses given for extended periods of time may pose a risk of hyperkalemia. The acceptable daily intake (ADI) for glycyrrhizin is suggested to be 0.2 mg/kg/day.

Contraindications

Contraindications have not yet been identified.

Pregnancy/Lactation

Use during pregnancy should be avoided. Licorice exhibits estrogenic activity and has reputed abortifacient effects. There is no clinical evidence to support the use of licorice tea as a galactogogue. Negative effects on pubertal maturation, neuroendocrine function, cognition, and behavior of children born to women who consumed high amounts of licorice during pregnancy have been documented.

Interactions

See Drug Interactions section.

Adverse Reactions

At lower dosages or normal consumption levels, few adverse reactions are evident. Ocular effects and hypersensitivity have been described. Hypertension and hypokalemia are recognized effects of excessive licorice consumption.

Toxicology

Toxicity from excessive licorice ingestion is well established. Mutagenicity and teratogenicity studies have generally shown no ill effects.

Scientific Family

  • Fabaceae (bean)

Botany

G. glabra is a 1.5 m shrub that grows in subtropical climates in rich soil. The name glycyrrhiza is derived from Greek words meaning "sweet roots." The roots of the plant are harvested to produce licorice. Most commercial licorice is extracted from several varieties of G. glabra. The most common variety, G. glabra var. typica (Spanish or European licorice), is characterized by blue flowers, while the variety G. glabra var. glandulifera (Russian licorice) has violet blossoms. Turkey, Greece, Iran, and Iraq supply most commercial licorice. The variety grown in the United States is G. glabra var. lepidota, while that grown in Iran and Iraq is var. violacea. Chinese licorice is derived from the related species G. uralensis and G. pallidiflora.1, 2

History

Therapeutic use of licorice dates back to the Roman Empire. The Greek physician Hippocrates (460 BC) and botanist Theophratus (371 BC) extolled its uses, and Roman naturalist Pliny the Elder (23 AD) recommended it as an expectorant and carminative. Licorice also figures prominently in Chinese herbal medicine. It is used in modern medicinals chiefly as a flavoring agent that masks bitter agents, such as quinine, and in cough and cold preparations for its expectorant activity. Most licorice candy in the United States is actually flavored with anise, not licorice. A sample of licorice from 756 AD was analyzed and found to still contain detectable active principles after 1,200 years.3

Chemistry

Licorice root contains a variety of compounds, including triterpenoids, polyphenols, and polysaccharides (starches, mannose, and sucrose). Polyphenols include certain phenolic acids, such as liquiritin, flavones and flavans; chalcones; and isoflavonoids, such as glabridin.2, 4, 5 The bright yellow color of the root is attributed to the flavonoid content, especially liquiritin and isoliquiritin. Plant gums, resins, and essential oils have been extracted; however, the root is cultivated for the principle active glycoside glycyrrhizin.2, 6 The amount of glycyrrhizin varies from 7% to 10% or more depending on growing conditions.6 Glycyrrhizin, glycyrrhizic acid, and glycyrrhizinate amount to 10% to 25% of the root extract.2 The ammoniated salt of glycyrrhizin is manufactured to specifications from licorice extract and used as a flavoring agent.2 Carbenoxolone, a synthetic analog of glycyrrhetic acid, has been used as a pharmacological agent in the management of peptic ulcers.2 A process has been established to remove glycyrrhizic acid from licorice to eliminate the adverse metabolic effects of licorice. A high-pressure liquid chromotography method to compare the bioavailability of glycyrrhizic acid whether in licorice root or in pure glycyrrhiza extract has been published. These compounds can now be assayed in blood, urine, and bile.6

Uses and Pharmacology

Anti-inflammatory

Glycyrrhetic acid has shown anti-inflammatory and antiarthritic activity in animal studies, which may be due to prostaglandin E2 inhibitory qualities demonstrated by several glycyrrhizin analogs. Japanese researchers found that licorice could aid in the clearance of excess immune complexes in mice with systemic lupus erythematosus.19

Antiviral

Historically, licorice and its extracts have been used in China and Japan to treat chronic viral hepatitis.2 In in vitro experiments, glycyrrhizin inhibited certain pathogenic viruses by an undetermined mechanism. Inhibition of viral binding to host cell membranes and viral replication, as well as interference with cellular signal transduction have been suggested. Animal and human studies suggest a more complex mechanism involving induction of interferon production via effects of T-cell function.2

Although the mechanism is unclear, glycyrrhizic acid inhibited the reactivation of latent Kaposi sarcoma-associated herpes virus7, 8 and showed efficacy against SARS-associated coronavirus.9

Increased survival times for mice have been demonstrated with glycyrrhizin administration for influenza virus A2 and herpes simplex.2

In clinical trials in chronic hepatitis, Stronger Neo-Minophagen C (an intravenous [IV] glycyrrhizin solution produced in Japan) normalized serum transaminase levels and improved liver function but demonstrated no effect on hepatitis C RNA levels.2

Cancer

Interest in the potential for licorice extracts in the prevention of cancer continues, but in vitro and human clinical data are lacking.

Chemical compounds including glabridin, liquiritin, isoliquiritin, glycyrrhizin, glycyrrhizinic acid, and carbenoxolone have been studied for their effects on mice, rat, and human cancer cell lines, with most studies indicating a dose-dependent action on cell/tumor proliferation and apoptosis. Prostate, breast, colon, liver, and lung cancer cell lines have been investigated.2, 4, 5, 10, 11, 12, 13, 14

Various mechanisms of action have been suggested for licorice compounds, including antioxidant activity, DNA-protective activity, suppressive action, cyclooxygenase inhibition, and phytoestrogenic and progesterone antagonist activity.2, 4 In one experiment, glabridin demonstrated growth-promoting activity at low concentrations but inhibitory activity at higher concentrations.11 The authors suggest the various chemical compounds in licorice extracts may act to modulate one another's effects. Another experiment compared activity of different esters of glycyrrhetinic acid indicating structure activity relationships for licorice compounds.14

In a large retrospective study in Japan (N = 1,249), difference in progression to hepatocellular carcinoma was found in patients with chronic hepatitis C unresponsive to interferon treatment. After adjustment for many variables, those patients who received IV glycyrrhizinic acid 4 mg showed a decrease in the rate of progression to liver cancer, possibly irrespective of length of treatment.15 The same authors had earlier demonstrated a protective effect of long-term glycyrrhizin administration in hepatocellular cancer.4

Cardiac

Carbenoxolone and a traditional licorice preparation Zhigancao may slow myocardial conduction.20, 21 An open-label, randomized, controlled trial (n = 50) assessed the hemodynamic effects of licorice supplementation (glycyrrhizin 290 to 370 mg/day) in normotensive volunteers. After 2 weeks, extracellular volume as well as systolic and diastolic blood pressure (periphery and central) increased significantly in the licorice group compared to the control group. Licorice ingestion also significantly decreased plasma aldosterone and potassium concentrations.57 A systematic review and meta-analysis of 26 clinical trials (N=985) published from 2002 to 2017 found an overall statistically significant increase in diastolic blood pressure (DBP; P<0.001) with short-term use of licorice compared to control; heterogeneity, however, was high. The effect was considered likely due to the significant hypernatremia induced by licorice. Subgroup analysis revealed a significant increase in systolic blood pressure (SBP) when the intervention duration was 2 and 8 weeks, and a significant increase in both SBP and DBP in healthy patients, women with polycystic ovary syndrome, and for each dosage of licorice/day. Pooled data reflected no significant effect on overall lipid parameters (ie, HDL, LDL, total cholesterol, triglycerides).91

Dental

Glycyrrhizin may reduce the growth and acid production of oral bacteria, but results have varied. Other experiments suggest that inhibition of bacterial adherence and inhibition of the enzyme required for plaque formation may be alternative mechanisms for the anticariogenic action of licorice.2

Diabetes

Carbenoxolone and glycyrrhizin have been investigated in animal experiments for use in diabetes. Results have varied and the mechanism by which they might act is unclear.22, 23, 24

GI

As a result of licorice's extensive folk use for gastric irritation, multiple studies in the 1970s and 1980s explored the efficacy of licorice, glycyrrhizinated compounds, deglycyrrhizinated licorice, and carbenoxlone in gastric/peptic ulcers.2, 16, 17, 18 The studies largely showed inconclusive results and efficacy lower than other pharmaceutical agents, such as cimetidine.2 A more recent randomized controlled study, however, conducted in 120 Helicobacter pylori-positive patients observed a significant increase in negative seroconversions among those who received supplemental licorice (380 mg twice daily × 2 weeks) as an adjunct to H. pylori triple therapy (83%) compared to triple therapy alone (62.5%; P=0.018). This response rate was significant only in patients with peptic ulcer disease and not in those with non-ulcer dyspepsia.68

Hepatoprotection

Animal experiments and studies in liver cancer suggest a protective role for licorice in hepatotoxicity.2, 13 A small (n = 66), randomized, double-blind, 2-month study in adults with nonalcoholic fatty liver disease found that 2 g of aqueous extract of licorice root per day produced a significant reduction from baseline in ALT and AST levels.50 There was no histologic evaluation in this study.

Hormonal effects

Reductions in serum testosterone have been demonstrated in several studies in healthy men consuming glycyrrhizin 0.5 g/day for 7 days. Another trial did not find a reduction; however, methodology between the 2 studies varied.2, 25

In women, licorice has been used in conjunction with spironolactone in the treatment of polycystic ovary syndrome.26 The estrogenic activity of licorice, as well as compounds glabridin and glabrene, has been documented.26, 27

Hot flashes

A randomized, double-blind clinical trial enrolling 60 menopausal women compared the effect of licorice with hormone replacement therapy (HRT) for 90 days for hot flashes. Patients receiving licorice 1,140 mg/day experienced significant reductions in duration and number of hot flashes within the group compared with the HRT (conjugated estrogen 0.312/medroxyprogesterone 2.5 mg daily) group; however, the difference between groups was insignificant. On the other hand, HRT produced a significant reduction in severity of hot flashes compared with licorice (P = 0.008 and P = 0.019). No significant differences were identified based on contextual or demographic factors.53

Metabolic effects

A systematic review and meta-analysis of 26 clinical trials (N=985) published from 2002 to 2017 found an overall statistically significant reduction in body weight of −0.433 kg (less than 1 pound) and BMI of −0.15 kg/m2 (P=0.001 for each) with short-term use of licorice compared to controls; heterogeneity was moderate and high, respectively. Other significant effects included reductions in some liver enzymes (eg, ALP, γ-GTP) and BUN. Overall, lipid parameters were not changed significantly.91

Prevention Postoperative Sore Throat/Cough

In a double-blind, placebo-controlled trial enrolling 236 adult inpatients undergoing elective thoracic surgery, gargling for 1 minute with licorice solution (0.5 g per 30 mL water) approximately 5 minutes prior to anesthetic induction significantly reduced the incidence of postoperative sore throat and coughing compared with sugar water (5 g per 30 mL water).49 A dose-response randomized controlled study (n=144) found a 1 g licorice solution used to gargle 5 minutes prior to intubation to be significantly more effective than lower doses (ie, 0.5 g, 0.25 g) or controls for managing postoperative sore throat, postextubation coughing, and patient satisfaction (P<0.05 each).69

Dosing

Licorice has a poor oral bioavailability, requiring 10 hours to reach maximum glycyrrhizic acid concentrations in healthy volunteers from the ammoniated salt and 12 hours for licorice extract. The lipophilic components of licorice extract have been shown to reduce the gastric emptying rate and absorption of glycyrrhizic acid, and neither glycyrrhizin nor the acid accumulate in tissues. Extensive saturable albumin binding has been demonstrated in humans. Plasma clearance is decreased in patients with chronic hepatitis C and liver cirrhosis.2

Licorice root has been used in daily doses from 760 mg to 15 g for ulcer, gastritis, and nonalcoholic fatty liver disease. Higher doses given for extended periods may pose a risk of hyperkalemia. Deglycyrrhizinated licorice extracts are available.16, 17, 18, 50

A "No-Observed Effects Level" has been proposed as purified glycyrrhizin 2 mg/kg/day, and the ADI for glycyrrhizin is suggested at 0.2 mg/kg/day.2

Pregnancy / Lactation

Use during pregnancy should be avoided. Licorice exhibits estrogenic activity and has reputed abortifacient effects.28, 29 Glycyrrhetic acid has been demonstrated to cross the placental barrier in rats.2 Research suggests a risk factor for preterm delivery when excessive licorice is consumed; however, the data used to support this observation were heterogeneous and retrospectively gathered via questionnaire.30 A propsective cohort study from Korea suggest that licorice increased the risk of stillbirth, but investigators did not see a statistically significant increase in risk for major malformation.51

Despite herbal texts suggesting the use of licorice tea as a galactogogue, there is no clinical evidence.

Consumption of high amounts of licorice during pregnancy has been shown to negatively affect the pubertal maturation, neuroendocrine function, cognition, and behavior of offspring. A follow-up study on the impact of maternal consumption of licorice on pubertal maturation of offspring was conducted subsequent to initial results compiled from a Finnish cohort (N=1,049) that revealed children born to women who consumed high amounts of licorice during pregnancy exhibited significantly worse intelligence, memory, risk of behavior problems, and physiological stress at the age of 8 years than children born to women who consumed little to no licorice during pregnancy. Of the 451 women who participated in the pubertal maturation follow-up study, 327 had consumed zero to low glycyrrhizin (up to 249 mg/week; mean 47 mg/week) and 51 had high maternal consumption (glycyrrhizin 500 mg/week or more; mean, 845 mg/week). After adjustments for covariates, significant variations in standard-deviation scores in the adolescents (mean age, 12.5 years) were observed in a number of pubertal maturation characteristics that were associated with high licorice consumption, including higher weight-for-age and body mass index-for-age as well as advanced pubertal stage in girls. However, in boys, a lower weight-for-age, height-for-age, and height were observed. Cognition problems (ie, lower general, verbal, and performance IQ scales) and risk of attention deficit/hyperactivity disorder problems were also significantly higher among adolescents in the high-exposure group.64

Interactions

Agents with antiplatelet properties: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of agents with antiplatelet properties. Bleeding may occur. Consider therapy modification.31, 32, 33, 34

Anticoagulants: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of anticoagulants. Bleeding may occur. Consider therapy modification.31, 32, 33, 34

Antihypertensives: Herbs (hypertensive properties) may diminish the antihypertensive effect of antihypertensives agents. Monitor therapy.35

Cardiac glycosides: Licorice may enhance the adverse/toxic effect of cardiac glycosides. Monitor therapy.72, 73, 74, 75, 76

Clozapine: CYP3A4 inducers (weak) may decrease the serum concentration of clozapine. Monitor therapy.77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87

Cortisone: Licorice may increase cortisol serum levels. Monitor therapy.52

Estrogen derivatives: Herbs (estrogenic properties) may enhance the adverse/toxic effect of estrogen derivatives. Monitor therapy.36

Herbs (anticoagulant/antiplatelet properties): Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of other herbs (anticoagulant/antiplatelet properties). Bleeding may occur. Consider therapy modification.31, 32, 33, 34

Loop diuretics: Licorice may enhance the hypokalemic effect of loop diuretics. Monitor therapy.37

Nimodipine: CYP3A4 inducers (weak) may decrease the serum concentration of nimodipine. Monitor therapy.88, 89

Nonsteroidal anti-inflammatory agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of nonsteroidal anti-inflammatory agents. Bleeding may occur. Consider therapy modification.31, 32, 33, 34

Salicylates: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of salicylates. Bleeding may occur. Consider therapy modification.31, 32, 33, 34

Thiazide diuretics: Licorice may enhance the hypokalemic effect of thiazide and thiazide-like diuretics. Monitor therapy.38

Thrombolytic agents: Herbs (anticoagulant/antiplatelet properties) may enhance the adverse/toxic effect of thrombolytic agents. Bleeding may occur. Consider therapy modification.31, 32, 33, 34

Adverse Reactions

At "usual" dosages or normal consumption levels, few adverse reactions are evident. Reports of adverse reactions in the literature are generally due to licorice intoxication or chronic excessive intake, and these effects are described in Toxicology below.

Consumption of as little as 50 g/day can produce mineralocorticoid hypertension and has been demonstrated in a case of a 45-year-old perimenopausal woman who had been consuming up to 6 cups/day of licorice tea for 12 months.39, 59 A case of very early onset pre-eclampsia in an 18-year-old primigravida female was deemed likely aggravated by considerable licorice consumption.62 An open-label, randomized, controlled trial (n = 50) assessed the hemodynamic effects of licorice supplementation (glycyrrhizin 290 to 370 mg/day) in normotensive volunteers. After 2 weeks, extracellular volume as well as systolic and diastolic blood pressure (periphery and central) increased significantly in the licorice group compared to the control group. Licorice ingestion also significantly decreased plasma aldosterone and potassium concentrations.57 Licorice should be used cautiously in patients with hypertension because of potential for mineralocorticoid hypokalemic effects, including severe hypokalemia with secondary polymorphic ventricular tachycardia.40, 54, 56 A case of hypermineralcorticoidism subsequent to consumption of large amounts of licorice cough lozenges (160 lozenges/day; approximately 288 mg/day of glycyrrhizin) for 3 to 4 months resulted in hypokalemia and hypertension that resolved several weeks after cessation of the licorice lozenges. It was noted that although urinary cortisol was elevated during the toxic state, serum cortisol remained normal.61 Similarly, apparent mineralocorticoid excess as a result of drinking licorice tea 3 times daily was reported in a 65-year-old female who presented with frequent paroxysmal palpitations and hypokalemia.66 Mineralocorticoid excess compounded by excessive use of terbutaline (12 to 14 inhalations/day) and high water intake (4 to 5 L/day) was found to be likely related to an unspecified amount of licorice in a 54-year-old man with a history of asthma and hypertension.90

Ocular effects have been described and may be due to the cyclooxygenase-inhibitory effect of glabridin; however, large amounts of licorice are required for this effect. Vasospasm of the optic nerve blood vessels resulting in visual disturbances mimicking ocular migraine (but with no headache) has been reported.41 Additionally, a case of hypertensive retinopathy resulting in acute visual impairment in the presence of pseudohyperaldosteronism in a 57-year-old man was determined to be the result of consumption of at least 900 g/week of liquorice over the last 3 to 4 months. He had an unremarkable medical history and presented with a blood pressure of 250/110 mm Hg and severe hypokalemia. A total of 7 medications were needed to improve his vision at the time of discharge and even after 3 months of not eating any liquorice, he still required 2 antihypertensive medications to maintain a normal blood pressure.63 A better outcome was achieved for a 47-year-old female who developed glycyrrhizin-induced hypertensive retinopathy and nephropathy after long-term consumption of glycyrrhizin 225 mg/day for 3 years. The initial hypertension (230/100 mm Hg), renal dysfunction, and ophthalmodynia that were present upon admission returned to normal within 6 months of discontinuing the compound glycyrrhizin tablets.70

Hypersensitivity reactions to glycyrrhiza-containing products have also been noted.2

In the 2016 Scientific Statement by the American Heart Association regarding drugs that may cause or exacerbate heart failure, licorice has been recognized as a product with antiplatelet and anticoagulant effects, which may increase bleeding risk when used with anticoagulants. Additionally, it exhibits possibly harmful cardiovascular effects, such as hypertension and fluid retention (pseudohyperaldosteronism), which may be harmful in patients with heart failure. The guidelines noted that naturoceuticals are not recommended for the management of heart failure symptoms or for the secondary prevention of cardiovascular events, and that nutritional supplements are not recommended for the treatment of heart failure [Low-quality; Limited].60

Toxicology

Many case reports of hypokalemic paralysis, pseduoaldosteronism, and cardiac myopathy due to hypokalemia are found in the literature. Symptoms including severe hypokalemia, mineralocorticoid hypertension, cardiac arrhythmias, paralysis of the extremities, metabolic alkalosis, hypoxemia, and hypercapnea have been reported. Several authors suggest that licorice intoxication might be a more commonplace cause for these states considering the widespread availability of licorice-containing traditional and herbal medicines.42, 43, 44, 45, 46, 47, 48, 55, 67 A rare case of licorice-induced thyrotoxic periodic paralysis was reported in a 43-year-old man recently diagnosed with Graves’ disease who presented with hypokalemia, a hyperthyroid state, and paralysis. His symptoms were suspected to have been induced secondarily to excess licorice consumption (400 mL/day licorice tea for the previous 12 days). Paralysis symptoms resolved completely upon stabilizing his potassium levels.67

Although several cases of posterior reversible encephalopathy syndrome-induced licorice hypertension in adults have been reported,58, 65 one case in a 10-year-old child has been documented. The boy was hospitalized following a cluster of generalized unexplained tonic-clonic seizures. General, neurological, and lab tests were unremarkable except for elevated blood pressure (135/88 mm Hg) and low blood potassium (3.5 mmol/L). Persistently high cortisol levels with normal circadian rhythm were also observed and suggested an association between an endocrine disorder and hypertension. Medical history and observation of black teeth during a follow-up examination revealed the boy had been eating 20 licorice sweets a day for a period of 4 months; consuming an estimated 2,400 mg licorice per day (corresponding to 72 mg of glycyrrhizic acid/day; equivalent to 2.88 mg/kg). Blood pressure normalized and vasogenic edema was reduced considerably within 2 weeks after stopping the licorice.58

The mechanism by which the glycyrrhizinates exert their effect on the renin-angiotensin-aldosterone system has been elucidated.2, 39, 40, 46 Competitive (and reversible) inhibition of the enzyme 11-beta-hydroxysteroid dehydrogenase results in the suppression of cortisol conversion to inactive cortisone. Consequent suppression of plasma renin activity and aldosterone levels is evident. Exchangeable sodium levels increase and cortisol occupation of mineralocorticoid receptors in the distal kidney tubules is enhanced. The condition responds to administration of spironolactone, potassium supplementation, and discontinuation of licorice.

The majority of mutagenicity studies in animals show no genotoxic effects for licorice or glycyrrhizinates.2 Teratogenicity studies in mice, rats, hamsters, and rabbits at a range of doses show no treatment-related effects.2 A study on fetal rat lung development explored the effect of glycyrrhizinates on 11-beta-hydroxysteroid dehydrogenase due to its involvement in surfactant synthesis. In the highest dosage group, a reduction in the enzyme was observed but with no increase in fetal malformation or fetal death rate.2

Index Terms

  • G. glabra var. typica
  • G. glabra var. glandulifera
  • G. glabra var. lepidota
  • G. glabra var. violacea
  • G. pallidiflora
  • G. uralensis
  • European Licorice
  • Spanish Licorice

References

1. Glycyrrhiza glabra L. USDA, NRCS. 2007. The PLANTS Database (http://plants.usda.gov, Dec 2007). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Isbrucker RA, Burdock GA. Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Regul Toxicol Pharmacol. 2006;46(3):167-192.16884839
3. Shibata S. Int J Pharmacog. 1994;32(1):75-89.
4. Wang ZY, Nixon DW. Licorice and cancer. Nutr Cancer. 2001;39(1):1-11.
5. Chin YW, Jung HA, Liu Y, et al. Anti-oxidant constituents of the roots and stolons of licorice (G. glabra ). J Agric Food Chem. 2007;55(12):4691-4697.17516657
6. Raggi MA, Bugamelli F, Nobile L, et al. HPLC determination of glycyrrhizin and glycyrrhetic acid in biological fluids, after licorice extract administration to humans and rats. Bollettino Chimico Farmaceutico. 1994;133(11):704-708.7654308
7. Curreli F, Friedman-Kien AE, Flore O, et al. Glycyrrhizic acid alters Kaposi sarcoma-associated herpesvirus latency, triggering p53-mediated apoptosis in transformed B lymphocytes. J Clin Invest. 2005;115(3):642-652.15765147
8. Cohen JI. Licking latency with licorice. J Clin Invest. 2005;115(3):591-593.15765143
9. Cinatl J, Morgenstern B, Bauer G, et al. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003;361(9374):2045-2046.12814717
10. Jung JI, Lim SS, Choi HJ, et al. Isoliquiritigenin induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells. J Nutr Biochem. 2006;17(10):689-696.16517140
11. Dong S, Inoue A, Zhu Y, et al. Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root. Food Chem Tox. 2007;45(12):2470-2478.17664038
12. Adams LS, Seeram NP, Hardy ML, Carpenter C, Heber D. Analysis of the interactions of botanical extract combinations against the viability of prostate cancer cell lines. eCAM. 2006;3(1):117-124.16550232
13. Lee CK, et al. Effects of the licorice extract against tumor growth and cisplatin-induced toxicity in a mouse xenograft model of colon cancer. Bio Pharm Bull. 2007;30(11):2191-2195.17978499
14. Chintharlapalli S, Papineni S, Jutooru I, et al. Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator-activated receptor [gamma] agonists in colon cancer cells. Mol Cancer Ther. 2007;6(5):1588-1598.17513608
15. Ikeda K, Arase Y, Kobayashi M, et al. A long-term glycyrrhizin injection therapy reduces hepatocellular carcinogenesis rate in patients with interferon-resistant active chronic hepatitis C: a cohort study of 1249 patients. Dig Dis Sci. 2006;51(3):603-609.
16. Kassir ZA. Endoscopic controlled trial of four drug regimens in the treatment of chronic duodenal ulceration. Ir J Med. 1985;78:153-156.3891678
17. Morgan AG, McAdam WA, Pacsoo C, Damborough A. Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy. Gut. 1982;23(6):545-551.7042486
18. Morgan AG, Pacsoo C, McAdam WA. Maintenance therapy: a two year comparison between Caved-S and cimetidine treatment in the prevention of symptomatic gastric ulcer recurrence. Gut. 1985;26(6):599-602.4007604
19. Chen R, Yuan C. China Journal of Chinese Materia Medica. 1991;16(10):617-619.1820795
20. Kojodjojo P, Kanagaratnam P, Segal OR, Hussain W, Peters NS. The effects of carbenoxolone on human myocardial conduction: a tool to investigate the role of gap junctional uncoupling in human arrhythmogenesis. J Am Coll Cardiol. 2006;48(6):1242-1249.16979013
21. Matsumoto T, Tanaka M, Yamada H, Cyong JC. Effect of licorice root on Carrageenan-induced decrease in immune complex clearance in mice. J Ethnopharm. 1996;53(1):1-4.
22. Sandeep TC, Andrew R, Homer NZ, et al. Increased in vivo regeneration of cortisol in adipose tissue in human obesity and effects of the 11beta-hydroxysteroid dehydrogenase type 1 inhibitor carbenoxolone. Diabetes. 2005;54(3):872-879.15734867
23. Tomlinson JW, Sherlock M, Hughes B, et al. Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 activity in vivo limits glucocorticoid exposure to human adipose tissue and decreases lipolysis. J Clin Endocrinol Metab. 2007;92(3):857-864.17200165
24. Andrews RC, Rooyackers O, Walker BR. Effects of the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes. J Clin Endocrinol Metab. 2003;88(1):285-291.12519867
25. Arimanini D, Mattarello MJ, Fiore C, et al. Licorice reduces serum testosterone in healthy women. Steroids. 2004;69(11-12):763-766.
26. Armanini D, Castello R, Scaroni C, et al. Treatment of polycystic ovary syndrome with spironolactone plus licorice. Eur J Obstet Gynecol Reprod Biol. 2007;131(1):61-67.17113210
27. Oerter Klein K, Janfaza M, Wong JA, Chang RJ. Estrogen bioactivity in fo-ti and other herbs used for their estrogen-like effects as determined by a recombinant cell bioassay. J Clin Endocrinol Metab. 2003;88(9):4077-4079.12970265
28. Newall CA, Anderson LA, Phillipson JD, eds. Herbal Medicines: A Guide for Health-Care Professionals. London: Pharmaceutical Press; 1996.
29. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109:227-235.11950176
30. Strandberg TE, Andersson S, Järvenpää AL. Risk factors for preterm delivery. Lancet. 2003;361(9355):436.12573415
31. Mousa SA. Antithrombotic effects of naturally derived products on coagulation and platelet function. Methods Mol Biol. 2010;663:229-240.20617421
32. Stanger MJ, Thompson LA, Young AJ, et al. Anticoagulant activity of select dietary supplements. Nutr Rev. 2012;70(2):107-117.22300597
33. Spolarich AE, Andrews L. An examination of the bleeding complications associated with herbal supplements, antiplatelet and anticoagulant medications. J Dent Hyg. 2007;81(3):67.17908423
34. Ulbricht C, Chao W, Costa D, et al. Clinical evidence of herb-drug interactions: a systematic review by the Natural Standard Research Collaboration. Curr Drug Metab. 2008;9(10):1063-1120.19075623
35. Jalili J, Askeroglu U, Alleyne B, et al. Herbal products that may contribute to hypertension. Plast Reconstr Surg. 2013;131(1):168-173.23271526
36. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med. 1998; 217(3):369-78.9492350
37. Lasix (furosemide) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; September 2010.
38. Hukkanen J, Ukkola O and Savolainen MJ. Effects of low-dose liquorice alone or in combination with hydrochlorothiazide on the plasma potassium in healthy volunteers. Blood Press. 2009;18(4):192-195.19562574
39. Quinkler M, Stewart PM. Hypertension and the cortisol-cortisone shuttle. J Clin Endocrinol Metab. 2003;88(6):2384-2392.12788832
40. 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):575-578.17473492
41. Santaella RM, Fraunfelder FW. Ocular adverse effects associated with systemic medications: recognition and management. Drugs. 2007;67(1):75-93.17209665
42. Sigurjonsdottir HA, Ragnarsson J, Franzson L, Sigurdsson G. Is blood pressure commonly raised by moderate consumption of liquorice?J Human Hyperten1995;9(5):345-348.7623371
43. Bielenberg J. Pharm Ztg. 1989;134(12):9-12.
44. Farese RV, Biglieri EG, Shackleton CH, Irony I, Gomez-Fontes R. Licorice-induced hypermineralocorticoidism. N Engl J Med. 1991;325(17):1223-1227.1922210
45. Hsu YJ, Lin YF, Chau T, et al. Electrocardiographic manifestations in patients with thyrotoxic periodic paralysis. Am J Med Sci. 2003;326(3):128-132.14501227
46. Elinav E, Chajek-Shaul T. Licorice consumption causing severe hypokalemic paralysis. Mayo Clin Proc. 2003;78(6):767-768.12934789
47. Schapera CH. Potential causes of secondary hypertension. Am Fam Physician. 2003;68(1):42.12887112
48. Lin SH, Yang SS, Chau T, Halperin ML. An unusual cause of hypokalemic paralysis: chronic licorice ingestion. Am J Med Sci. 2003;325(3):153-156.12640291
49. Ruetzler K, Fleck M, Nabecker S, et al. A randomized, double-blind comparison of licorice versus sugar-water gargle for prevention of postoperative sore throat and postextubation coughing. Anesth Analg. 2013;117(3):614-621.23921656
50. Hajiaghamohammadi AA, Ziaee A, Samimi R. The efficacy of licorice root extract in decreasing transaminase activities in non-alcoholic fatty liver disease: a randomized controlled clinical trial. Phytother Res. 2012;26(9):1381-1384.22308054
51. Choi JS, Han JY, Ahn HK, et al. Fetal and neonatal outcomes in women reporting ingestion of licorice (Glycyrrhiza uralensis) during pregnancy. Planta Med. 2013;79(2):97-101.23299757
52. 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;165(5):761-769.2189661910.1530/EJE-11-0518
53. Menati L, Khaleghinezhad K, Tadayon M, Siahpoosh A. Evaluation of contextual and demographic factors on licorice effects on reducing hot flashes in postmenopause women. Health Care Women Int. 2014;35(1):87-99.23663094
54. Panduranga P, Al-Rawahi N. Licorice-induced severe hypokalemia with recurrent torsade de pointes. Ann Noninvasive Electrocardiol. 2013;18(6):593-596.24303973
55. Bisogni V, Rossi GP, Calo LA. Apparent mineralcorticoid excess sysndrome, an often forgotten or unrecognized cause of hypokalemia and hypertension: case report and appraisal of the pathyophysiology. Blood Press. 2014;23(3):189-192.24053336
56. Ozturk S, Karaman K, Cetin M, Erdem A. Polymorphic ventricular tachycardia (torsades de pointes) due to licorice root tea. Arch Turk Soc Cardiol. 2013;41(3):241-244.23703562
57. Leskinen MH, Hautaniemi EJ, Tahvanainen AM, et al. Daily liquorice consumption for two weeks increases augmentation index and central systolic and diastolic blood pressure. PLoS ONE. 2014;9(8):e105607.25153328
58. Tassinari D, Bergamaschi R, Corsini I, Landini S, Romanin B, Ballarini E, De Ponti F, Carfagnini F, Toni F, Bernardi F. Posterior reversible encephalopathy syndrome associated with licorice consumption: a case report in a 10-year-old boy. Pediatr Neurol. 2015;52:457-459.25680999
59. Allcock E, Cowdery J. Hypertension induced by liquorice tea [published online June 15, 2015]. BMJ Case Rep.2607780510.1136/bcr-2015-209926
60. Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2016;134(6):e32-69.27400984
61. Dai DW, Singh I, Hershman JM. Lozenge-induced hypermineralcorticoid state – a unique case of licorice lozenges resulting in hypertension and hypokalemia. J Clin Hypertens (Greenwich). 2016;18(2):159-160.26212733
62. Hauksdottir D, Sigurjonsdottir HA, Arnadottir M, Geirsson RT. Severe, very early onset pre-eclampsia associated with liquorice consumption. Hypertens Pregnancy. 2015;34(2):221-226.25774453
63. Schroder T, Hubold C, Muck P, Lehnert H, Haas CS. A hypertensive emergency with acute visual impairment due to excessive liquorice consumption. Neth J Med. 2015;73(2):82-85.25774453
64. Raikkonen K, Martikainen S, Pesonen A-K, et al. Maternal licorice consumption during pregnancy and pubertal, cognitive, and psychiatric outcomes in children. Am J Epidemiol. 2017 Feb 3:1-12.28158597
65. O’Connell K, Kinsella J, McMahon C, Holian J, O’Riordan S. Posterior reversible encephalopathy syndrome (PRES) associated with liquorice consumption. Ir J Med Sci. 2016;185(4):945-947.25342161
66. Gallacher SD, Tsokolas G, Dimitropoulos I. Liquorice-induced apperent mineralocorticoid excess presenting in the emergency department. Clin Med (Lond). 2017;17(1):43-45.28148579
67. Sayiner ZA, Abiyev A, Eraydin A, Ozkaya M. A rare cause of thyrotoxic periodic paralysis: liquorice consumption. Postgrad Med J. 2017;93(1099):295-296.28258118
68. Hajiaghamohammadi AA, Zargar A, Oveisi S, Samimi R, Reisian S. To evaluate the effect of adding licorice to the standard treatment regimen of Helicobacter pylori. Braz J Infect Dis. 2016;20(6):534-538.27614124
69. Honarmand A, Safavi M, Arani AS, Shokrani O. The efficacy of different doses of liquorice gargling for attenuating postoperative sore throat and cough after tracheal intubation. Eur J Anaesthesiol. 2016;33(8):588-609.26716864
70. Li J, Fan X, Wang Q. Hypertensive crisis with 2 target organ impairment induced by glycyrrhizin. Medicine (Baltimore). 2018;97(11):e0073.29538199
71. Luis A, Domingues F, Pereira L. Metabolic changes after licorice consumption: a systematic review with meta-analysis and trial sequential analysis of clinical trials. Phytomedicine. 2018;39:17-24.29433679
72. Digoxin [prescribing information]. Columbus, OH: Roxane Laboratories Inc; September 2012.
73. Francini-Pesenti F, Puato M, Piccoli A, Brocadello F. Liquorice-induced hypokalemia and water retention in the absence of hypertension. Phytother Res. 2008;22(4):563-565.18386259
74. Murphy SC, Agger S, Rainey PM. Too much of a good thing: a woman with hypertension and hypokalemia. Clin Chem. 2009;55(12):2093-2096.19946064
75. 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;55(6):A35-A37.20497832
76. 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):485-489.20881418
77. Clozaril (clozapine) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; September 2015.
78. Jerling M, Lindstrom L, Bondesson U, Bertilsson L. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit. 1994;16(4):368-374.7974626
79. Joos AA, Frank UG, Kaschka WP. Pharmacokinetic interaction of clozapine and rifampicin in a forensic patient with an atypical mycobacterial infection. J Clin Psychopharmacol. 1998;18(1):83-85.9472849
80. Junghan U, Albers M, Woggon B. Increased risk of hematological side-effects in psychiatric patients treated with clozapine and carbamazepine? Pharmacopsychiatry. 1993;26(6):262.8127933
81. Langbehn DR, Alexander B. Increased risk of side-effects in psychiatric patients treated with clozapine and carbamazepine: a reanalysis. Pharmacopsychiatry. 2000;33(5):196.11071023
82. Miller DD. Effect of phenytoin on plasma clozapine concentrations in two patients. J Clin Psychiatry. 1991;52(1):23-25.1988414
83. Muller T, Becker T, Fritze J. Neuroleptic malignant syndrome after clozapine plus carbamazepine. Lancet. 1988;2(8626-8627):1500.2904624
84. Peritogiannis V, Pappas D, Antoniou K, Hyphantis T, Mavreas V. Clozapine-rifampicin interaction in a patient with pulmonary tuberculosis. Gen Hosp Psychiatry. 2007;29(3):281-282.17484952
85. Raitasuo V, Lehtovaara R, Huttunen MO. Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics. A case report. Psychopharmacology (Berl). 1994;116(1):115-116.7862923
86. Tiihonen J, Vartiainen H, Hakola P. Carbamazepine-induced changes in plasma levels of neuroleptics. Pharmacopsychiatry. 1995;28(1):26-28.7746842
87. Van Strater AC, Bogers JP. Interaction of St Johns wort (Hypericum perforatum) with clozapine. Int Clin Psychopharmacol. 2012;27(2):121-124.22113252
88. Nimodipine [prescribing information]. Montvale, NJ: Ascend Laboratories LLC; April 2015.
89. Tartara A, Galimberti CA, Manni R, et al. Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients. Br J Clin Pharmacol. 1991;32(3):335-340.1777370
90. Buhl LF, Pedersen FN, Andersen MS, Glintborg D. Licorice-induced apparent mineralocorticoid excess compounded by excessive use of terbutaline and high water intake. BMJ Case Rep. 2018; 2018:bcr-2017-223918 [epub ahead of print].29674401

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