Liquorice

(USAN, rINNM)
Synonyms: Alcaçuz; Édesgyökér; Gancao; Glycyrrhiza; Korzeń lukrecji; Lakritsijuuri; Lakritsrot; Lékořicový kořen; Licorice; Liquiritiae radix; Liquorice Root; Orozuz; Raiz de Regaliz; Regaliz; Réglisse, racine de; Saldymedžiu šaknys; Süssholzwurzel.
Cyrillic synonym: Лакрица.

💊 Chemical information

Description.

Liquorice is the dried rhizome and roots of Glycyrrhiza glabra. Those of G. glabra var. typica are known in commerce as Spanish Liquorice, those of G. glabra var. glandulifera as Russian Liquorice, and those of G. glabra var. β -violacea as Persian Liquorice.

Pharmacopoeias.

In Chin., Eur., Jpn, and US. Eur. also includes Liquorice Dry Extract for Flavouring Purposes. US also includes Powdered Licorice and Powdered Licorice Extract. Br. also includes Liquorice Root for use in Traditional Herbal Medicine and Processed Liquorice Root for use in Traditional Herbal Medicinal Product.

Ph. Eur. 6.2

(Liquorice Root; Liquorice

BP 2008). The dried unpeeled or peeled, whole or cut root and stolons of Glycyrrhiza glabra and/or G. inflata and/or G. uralensis. It contains not less than 4% of glycyrrhizic acid. Protect from light.

USP 31

(Licorice). The roots, rhizomes, and stolons of Glycyrrhiza glabra or G. uralensis. It contains not less than 2.5% of glycyrrhizic acid, calculated on the dried basis. Store in a cool, dry place.

BP 2008 (Liquorice Root for use in THM). It is the dried unpeeled root and rhizome of Glycyrrhiza uralensis, G. inflata, or G. glabra. For use in traditional Chinese medicines. It contains not less than 2.0% of glycyrrhizic acid calculated with reference to the dried material. Protect from moisture.

BP 2008 (Processed Liquorice Root for use in THMP). Liquorice Root for use in THM which has been cleaned, softened, sliced transversely or longitudinally to form uniform pieces, and dried. It contains not less than 2.0% of glycyrrhizic acid calculated with reference to the dried material. Protect from moisture.

💊 Adverse Effects and Precautions

Liquorice has mineralocorticoid-like actions manifesting as sodium and water retention and hypokalaemia (see below). Deglycyrrhizinised liquorice is not usually associated with such adverse effects.

Mineralocorticoid effects.

Mineralocorticoid effects have been reported after excessive or prolonged ingestion of liquorice. The liquorice may be ingested in confectionery (including liquorice-flavoured chewing gum), tea, soft drinks, herbal medicines, cough mixtures, or by chewing tobacco. The enzyme 11β-hydroxysteroid dehydrogenase (cortisol oxidase) converts cortisol to cortisone, preventing cortisol gaining access to non-specific mineralocorticoid receptors. This enzyme is inhibited by glycyrrhetinic acid (produced by the hydrolysis of glycyrrhizic acid, a natural constituent of liquorice), resulting in increased concentrations of cortisol in the body, enhancing its physiological effects.1-3 Clinical manifestations include consequences of sodium retention such as hypertension,4-10 and hypokalaemia, which can result in neuromuscular disturbances ranging from muscle weakness,11 myoclonus,12 and myopathy10 to paralysis13-15 and rhabdomyolysis.15-17 Arrhythmias16,18 and fatal cardiac arrest19have also been reported. Increased amounts of cortisol in vascular smooth muscle may cause vasoconstriction. Vasospasm of vessels supplying the optic nerve may have caused transient visual disturbances reported after liquorice ingestion.2 Other reported effects of liquorice include growth retardation in a boy with Addison’s disease;20 liquorice was thought to have potentiated the effect of hydrocortisone. Endocrine effects of liquorice have been reviewed.21 Conflicting effects on testosterone and prolactin have been reported. Components of liquorice root (which has been tried for menopausal symptoms) have both oestrogenic and anti-oestrogenic activity, and it has reportedly caused gynaecomastia. Individuals vary markedly in their susceptibility to liquoriceinduced adverse effects.1 Those consuming 400 mg glycyrrhetinic acid daily generally experience adverse effects, but a regular daily intake of no more than 100 mg of glycyrrhetinic acid (about 50 g of liquorice sweets) has produced adverse effects in some who appear more sensitive to its effects. Some consider a daily intake of 10 mg glycyrrhetinic acid to be a safe daily dose for adults; the amount of salt consumed needs to be considered as even a low dose of liquorice may induce sodium overload in those consuming high amounts of sodium chloride.3
1. Walker BR, Edwards CR. Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess. Endocrinol Metab Clin North Am 1994; 23: 359–77
2. Dobbins KRB, Saul RF. Transient visual loss after licorice ingestion. J Neuroophthalmol 2000; 20: 38–41
3. Frey FJ, Ferrari P. Pastis and hypertension—what is the molecular basis? Nephrol Dial Transplant 2000; 15: 1512–14
4. van Uum SH. Liquorice and hypertension. Neth J Med 2005; 63: 119–20
5. Dellow EL, et al. Pontefract cakes can be bad for you: refractory hypertension and liquorice excess. Nephrol Dial Transplant 1999; 14: 218–20
6. Woywodt A, et al. Turkish pepper (extra hot). Postgrad Med J 2000; 76: 426–8
7. Janse A, et al. The old lady who liked liquorice: hypertension due to chronic intoxication in a memory-impaired patient. Neth J Med 2005; 63: 149–50
8. Russo S, et al. Low doses of liquorice can induce hypertension encephalopathy. Am J Nephrol 2000; 20: 145–8
9. Hall RC, Clemett RS. Central retinal vein occlusion associated with liquorice ingestion. Clin Experiment Ophthalmol 2004; 32: 341
10. Hussain RM. The sweet cake that reaches parts other cakes can’t! Postgrad Med J 2003; 79: 115–16
11. Yoshida S, Takayama Y. Licorice-induced hypokalemia as a treatable cause of dropped head syndrome. Clin Neurol Neurosurg 2003; 105: 286–7
12. Ishiguchi T, et al. Myoclonus and metabolic alkalosis from licorice in antacid. Intern Med 2004; 43: 59–62
13. Elinav E, Chajek-Shaul T. Licorice consumption causing severe hypokalemic paralysis. Mayo Clin Proc 2003; 78: 767–8
14. Lin S-H, et al. An unusual cause of hypokalemic paralysis: chronic licorice ingestion. Am J Med Sci 2003; 325: 153–6
15. van den Bosch AE, et al. Severe hypokalaemic paralysis and rhabdomyolysis due to ingestion of liquorice. Neth J Med 2005; 63: 146–8
16. Bauchart J-J, et al. Alcohol-free pastis and hypokalaemia. Lancet 1995; 346: 1701
17. Firenzuoli F, Gori L. Rabdomiolisi da liquirizia. Recenti Prog Med 2002; 93: 482–3
18. Eriksson JW, et al. Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia. J Intern Med 1999; 245: 307–10
19. Haberer JP, et al. Severe hypokalaemia secondary to overindulgence in alcohol-free “pastis”. Lancet 1984; i: 575–6
20. Doeker BM, Andler W. Liquorice, growth retardation and Addison’s disease. Horm Res 1999; 52: 253–5
21. Armanini D, et al. History of the endocrine effects of licorice. Exp Clin Endocrinol Diabetes 2002; 110: 257–61.

Pregnancy.

Studies in Finnish women indicated that heavy consumption of liquorice (equivalent to ≥ 500 mg/week of glycyrrhizic acid) during pregnancy was associated with an increased risk of preterm delivery.1,2 Consumption of large amounts of liquorice was a social habit noted to occur in some northern European countries.
1. Strandberg TE, et al. Birth outcome in relation to licorice consumption during pregnancy. Am J Epidemiol 2001; 153: 1085–8
2. Strandberg TE, et al. Preterm birth and licorice consumption during pregnancy. Am J Epidemiol 2002; 156: 803–5.

💊 Uses and Administration

Liquorice is used as a flavouring and sweetening agent. It has demulcent and expectorant properties and has been used in cough preparations. It has ulcer-healing properties that may result from stimulation of mucus synthesis. It contains constituents that produce mineralocorticoid effects (see above). Liquorice may also possess some antispasmodic and laxative properties. Deglycyrrhizinised liquorice has a reduced mineralocorticoid activity and has been used, usually with antacids, for the treatment of peptic ulcer disease.
1. Fiore C, et al. A history of the therapeutic use of liquorice in Europe. J Ethnopharmacol 2005; 99: 317–24.

💊 Preparations

Ph. Eur.: Liquorice Ethanolic Liquid Extract, Standardised; USP 31: Licorice Fluidextract.

Proprietary Preparations

Braz.: Alcalergin; Brefus†; Cz.: Gallentee†; Fr.: Depiderm; Trio D†; Ger.: Fichtensirup N†; Lakriment Neu†; Suczulen mono†.
Published January 24, 2019.