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Licorice - Glycyrrhiza glabra

Licorice is a perennial herb with a rich history in traditional medicine across various cultures. Modern scientific research has investigated many of its purported benefits, revealing a complex profile of therapeutic potential alongside important safety considerations.

Image source and license: https://commons.wikimedia.org/wiki/File:Glycyrrhiza_glabra_Y03.jpg.
Modified by Peter Jorgensen.

Botanical Classification and Common Names

The primary medicinal licorice plant is Glycyrrhiza glabra (European licorice or Spanish licorice), belonging to the Fabaceae family. Other species with medicinal properties include Glycyrrhiza uralensis (Chinese licorice) and Glycyrrhiza inflata (Ural licorice). These are collectively referred to as "true licorice." Common names include liquorice (British spelling), sweet root, and gan cao (in Traditional Chinese Medicine).

Plants sometimes confused with true licorice but botanically distinct include American licorice (Glycyrrhiza lepidota), which has different phytochemical properties, and anise (Pimpinella anisum), fennel (Foeniculum vulgare), and star anise (Illicium verum), which merely share a similar flavor profile due to the compound anethole but are not related to true licorice.

Active Compounds

The primary bioactive component in licorice is glycyrrhizin (also called glycyrrhizic acid), a triterpene glycoside that comprises 2-25% of dried licorice root. Other important compounds include flavonoids (liquiritin, isoliquiritin), isoflavonoids (glabridin, galbrene), chalcones, and various polyphenols. Most research focuses on glycyrrhizin and glabridin as the compounds responsible for the majority of therapeutic effects.

Evidence-Based Health Benefits

• Gastric and Duodenal Ulcers: Multiple clinical trials have demonstrated licorice's effectiveness in treating peptic ulcers. Licorice extracts have been found to accelerate ulcer healing when compared to placebo.
• Functional Dyspepsia: Studies show improvement in symptoms of indigestion and stomach discomfort with standardized licorice extracts.
• Gastroesophageal Reflux Disease (GERD): Research indicates that deglycyrrhizinated licorice (DGL) may help manage GERD symptoms by enhancing mucus production and protecting the esophageal lining.
• Viral Hepatitis: Several Japanese and Chinese clinical trials have demonstrated that glycyrrhizin injections can reduce liver enzyme levels in chronic hepatitis C patients.
• Respiratory Conditions: Licorice extracts have shown mucolytic, expectorant, and anti-inflammatory properties useful in bronchitis and asthma.
• Oral Health: Studies support antimicrobial effects against bacteria responsible for dental caries and periodontal disease.
• Dermatological Conditions: Topical licorice preparations have shown efficacy for atopic dermatitis, eczema, and melasma due to anti-inflammatory and tyrosinase-inhibiting properties.
• Menopausal Symptoms: Limited evidence suggests potential benefits for vasomotor symptoms in menopausal women.
• Anti-inflammatory Properties: Glycyrrhizin demonstrates corticosteroid-like effects by inhibiting 11-beta-hydroxysteroid dehydrogenase, the enzyme that converts cortisol to inactive cortisone.

Conditions with Insufficient Evidence

• Cancer Prevention/Treatment: Despite promising in vitro and animal studies showing anti-cancer properties, human clinical evidence remains preliminary.
• COVID-19: Some in vitro studies suggest antiviral activity against SARS-CoV-2, but clinical evidence is limited and inconclusive.
• Cognitive Function: Animal studies suggest neuroprotective effects, but human studies are lacking.
• Weight Loss: Claims regarding appetite suppression or metabolism enhancement lack substantial clinical support.

Recommended Dosages

Dosages vary based on preparation and indication:

• Whole Root: Typically 1-5g daily of dried root.
• Standardized Extracts: 200-600mg daily, standardized to contain 20-25% glycyrrhizic acid.
• Deglycyrrhizinated Licorice (DGL): 380-1140mg, taken 20 minutes before meals for digestive concerns.
• Glycyrrhizin: For hepatitis management (clinical settings only), 40-200mg daily, typically administered intravenously in specialized formulations.
• Topical Preparations: 1-2% licorice extract in creams or gels for dermatological applications.

For most conditions, treatment durations of 4-6 weeks are common in clinical trials, with reassessment recommended before continuing longer-term use.

Side Effects and Safety Concerns

• Pseudoaldosteronism: The most significant concern with glycyrrhizin consumption is a syndrome characterized by hypertension, hypokalemia (low potassium), sodium and water retention, and suppression of the renin-angiotensin-aldosterone system.
• Hypertension: Regular consumption of glycyrrhizin above 100mg daily can cause significant blood pressure elevation within two weeks.
• Hypokalemia: Potassium depletion can lead to muscle weakness, cardiac arrhythmias, and increased sensitivity to digoxin and other medications.
• Edema: Fluid retention, particularly evident in the lower extremities.
• Hormonal Effects: May affect estrogen and testosterone levels, potentially causing menstrual irregularities in women and decreased libido or erectile dysfunction in men.
• Drug Interactions: Known to interact with diuretics, digoxin, corticosteroids, antihypertensives, and certain diabetes medications.

Deglycyrrhizinated licorice (DGL) preparations, specifically designed to remove glycyrrhizin, avoid most of these side effects while retaining benefits for digestive conditions.

High-Dose Studies and Knowledge Gaps

Research into doses exceeding the recommended therapeutic range has primarily focused on toxicity rather than enhanced benefits. Studies have confirmed that doses of glycyrrhizin exceeding 400mg daily consistently produce adverse effects without corresponding increases in therapeutic value. A comprehensive safety review by Omar et al. (2012) concluded that doses above 100mg/day of glycyrrhizin should be avoided except in controlled clinical settings.

Significant knowledge gaps include: 1) long-term safety data beyond 6 months of continuous use; 2) standardized preparation methods across different licorice species; 3) reliable biomarkers for individualized dosing; and 4) comparative efficacy between different licorice species and preparation methods.

Contraindications

Licorice (particularly glycyrrhizin-containing preparations) should be avoided by individuals with:

• Hypertension
• Heart failure
• Kidney disease
• Liver cirrhosis
• Hypokalemia
• Pregnancy (may increase risk of preterm birth)
• Estrogen-sensitive conditions (e.g., breast cancer, uterine fibroids)

Pharmaceutical Products Containing Licorice

• Glycyron: Glycyrrhizin preparation used for chronic hepatitis management.
• Stronger Neo-Minophagen C: A standardized intravenous formulation containing glycyrrhizin, used primarily in Japan for hepatitis treatment.
• Iberogast: A multi-herb preparation containing licorice, used for functional dyspepsia and IBS.
• CarbenoxoIone: A synthetic derivative of glycyrrhizic acid, historically used for peptic ulcers but now largely discontinued due to side effects.

References

Ceccuzzi, G., Rapino, A., Perna, B., Costanzini, A., Farinelli, A., Fiorica, I., ... & Guarino, M. (2023). Liquorice toxicity: a comprehensive narrative review. Nutrients, 15(18), 3866.

Farag, M. A., Porzel, A., & Wessjohann, L. A. (2012). Comparative metabolite profiling and fingerprinting of medicinal licorice roots using a multiplex approach of GC–MS, LC–MS and 1D NMR techniques. Phytochemistry, 76, 60-72.

Omar, H. R., Komarova, I., El-Ghonemi, M., Fathy, A., Rashad, R., Abdelmalak, H. D., ... & Camporesi, E. M. (2012). Licorice abuse: time to send a warning message. Therapeutic advances in endocrinology and metabolism, 3(4), 125-138.

Wahab, S., Annadurai, S., Abullais, S. S., Das, G., Ahmad, W., Ahmad, M. F., ... & Amir, M. (2021). Glycyrrhiza glabra (Licorice): A comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicology. Plants, 10(12), 2751.

Yasui, S., Fujiwara, K., Tawada, A., Fukuda, Y., Nakano, M., & Yokosuka, O. (2011). Efficacy of intravenous glycyrrhizin in the early stage of acute onset autoimmune hepatitis. Digestive diseases and sciences, 56, 3638-3647.

Zhang, Y., Sheng, Z., Xiao, J., Li, Y., Huang, J., Jia, J., ... & Li, L. (2023). Advances in the roles of glycyrrhizic acid in cancer therapy. Frontiers in Pharmacology, 14, 1265172.

Zhao, H., Zhang, X., Chen, X., Li, Y., Ke, Z., Tang, T., ... & Yang, J. (2014). Isoliquiritigenin, a flavonoid from licorice, blocks M2 macrophage polarization in colitis-associated tumorigenesis through downregulating PGE2 and IL-6. Toxicology and applied pharmacology, 279(3), 311-321.

Zheng, Y., Hua, R., Bian, H., Li, Y., Su, X. and Wang, X. (2023) 'Molecular mechanisms underlying the anticancer, anti-inflammatory, and neuroprotective effects of glycyrrhizic acid: A meta-analysis and systematic review', Frontiers in Pharmacology, 14, pp. 1133294-1133316.