Licorice

Metadata

Approved Indications

Commission E (Germany)

• Approved: Catarrhs of the upper respiratory tract
• Approved: Gastric/duodenal ulcers
• Duration limited to 4-6 weeks without medical supervision

ESCOP

• Gastric and duodenal ulcers
• Gastritis
• Expectorant for coughs and bronchial catarrh

EMA/HMPC

• Traditional use: Relief of digestive symptoms including burning sensation and dyspepsia
• Traditional use: Expectorant in cough associated with cold
• Well-established use: Under evaluation for certain indications
• Short-term use (not more than 4-6 weeks) considered safe

Agreement/Disagreement Analysis

Strong agreement across all bodies on both GI (ulcers, gastritis) and respiratory (expectorant, catarrh) indications. All bodies also agree on the need for duration limitation (4-6 weeks). The EMA assessment report provides the most detailed safety framework, including specific glycyrrhizin thresholds.

Conditions Treated

Approved/Monographed

• Peptic ulcers (gastric and duodenal)
• Gastritis
• Dyspepsia with burning sensation
• Catarrhs of the upper respiratory tract
• Cough and bronchial catarrh (expectorant)

Traditional/Additional Uses

• Sore throat and pharyngitis (demulcent)
• Adrenal insufficiency support (traditional; related to mineralocorticoid activity)
• Viral hepatitis (glycyrrhizin preparations; primarily Asian medicine)
• Aphthous ulcers (topical)
• Eczema/dermatitis (topical glycyrrhetinic acid)

Mechanism of Action

Key Active Compounds

• Glycyrrhizin (glycyrrhizic acid): 2-15% of root dry weight (PhEur: min 4%)
  • A triterpene saponin; the principal bioactive compound
  • Hydrolyzed by gut bacteria to glycyrrhetinic acid (the active metabolite)
• Glycyrrhetinic acid (enoxolone): The aglycone of glycyrrhizin; more potent
• Flavonoids: Liquiritin, liquiritigenin, isoliquiritigenin, glabridin
  • Antioxidant, estrogenic, and anti-inflammatory properties
• Coumarins: Minor component
• Polysaccharides: Immunomodulatory activity
• Essential oil: Minor component

GI Protective Mechanisms

• Prostaglandin enhancement: Glycyrrhetinic acid inhibits prostaglandin-metabolizing enzymes (15-hydroxyprostaglandin dehydrogenase and delta-13-prostaglandin reductase), thereby increasing local prostaglandin levels in gastric mucosa
• Mucus secretion: Stimulates gastric mucus production and secretion
• Cytoprotection: Protects gastric mucosal cells from damage
• Anti-Helicobacter: Some evidence for activity against H. pylori
• Acid suppression: Weak anti-secretory activity

Respiratory Mechanisms

• Expectorant: Stimulates tracheal mucus secretion
• Demulcent: Soothes irritated mucous membranes of the throat
• Anti-inflammatory: Reduces airway inflammation
• Antitussive: Some cough-suppressant activity

The Mineralocorticoid Problem (Safety-Critical)

• 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2) inhibition: Glycyrrhetinic acid is a potent inhibitor of this enzyme
• 11-beta-HSD2 normally converts active cortisol to inactive cortisone in the kidney
• Inhibition allows cortisol to bind to mineralocorticoid receptors
• Result: Pseudoaldosteronism — sodium retention, potassium excretion, water retention
• Clinical consequences: Hypertension, hypokalemia, edema, metabolic alkalosis

DGL (Deglycyrrhizinated Licorice)

Rationale

DGL was developed to provide the GI protective benefits of licorice while eliminating the mineralocorticoid side effects of glycyrrhizin.

Manufacturing

• Glycyrrhizin is removed from licorice extract through processing
• The remaining extract retains flavonoids, polysaccharides, and other non-glycyrrhizin compounds

Efficacy

• DGL was shown to be effective in alleviating peptic ulcer disease symptoms
• Some evidence suggests DGL may actually be more effective than glycyrrhetinic acid itself for ulcer healing
• Mechanism may involve stimulation of salivary compounds that promote growth and regeneration of stomach and intestinal cells

Critical Administration Note

• DGL must be taken as chewable tablets: Mixing with saliva appears essential for efficacy
• Chewable form may promote release of salivary compounds that stimulate GI mucosal repair
• DGL in capsule form has NOT been shown to be effective — this is an important clinical pearl

DGL Safety

• Can be used safely with all diuretics (no glycyrrhizin-related potassium loss)
• No hypertension risk
• Can be used long-term (no 4-6 week time limit)
• One study found 350 mg chewable DGL taken with each dose of aspirin reduced aspirin-induced GI bleeding

Clinical Evidence Summary

Peptic Ulcer Disease

• Historical significance: Glycyrrhetinic acid (as carbenoxolone) was the first drug proven to promote healing of gastric and duodenal ulcers, predating H2-blockers and PPIs
• Modern systematic review and meta-analysis (2025): G. glabra showed efficacy in peptic ulcer disease management
• Most modern evidence is for DGL rather than whole licorice
• DGL dosing: 380 mg chewable tablets, 3 times daily before meals, for 8-16 weeks

Respiratory Conditions

• Limited modern RCT data
• Commission E and ESCOP approval based primarily on traditional evidence and pharmacological plausibility
• Expectorant and demulcent effects well-established pharmacologically
• Licorice is a component of many European cough preparations

Gastritis and Dyspepsia

• Traditional use well-documented
• Mechanism well-characterized (prostaglandin enhancement, mucus secretion)
• Modern RCT data limited for these specific indications

Anti-Helicobacter Activity

• In vitro evidence for activity against H. pylori
• [NEEDS-RESEARCH] Clinical significance as adjunctive anti-H. pylori treatment unclear

European vs. US/Anglophone Consensus

Safety Profile

Contraindications (Commission E)

• Cholestatic liver disorders
• Liver cirrhosis
• Hypertension (pre-existing)
• Hypokalemia
• Severe renal insufficiency
• Pregnancy (contraindicated)

Drug Interactions (Significant)

• Cardiac glycosides (digoxin): Hypokalemia from glycyrrhizin potentiates digoxin toxicity — potentially life-threatening
• Diuretics (thiazides, loop diuretics): Additive potassium loss; increased hypokalemia risk
• Corticosteroids: May potentiate corticosteroid effects (11-beta-HSD2 inhibition)
• Antihypertensives: May antagonize blood pressure control
• Spironolactone: Glycyrrhizin may antagonize spironolactone’s potassium-sparing effect
• Oral contraceptives: May increase sensitivity to glycyrrhizin effects
• Warfarin and anticoagulants: Theoretical interaction via coumarin content

Side Effects (Dose and Duration Dependent)

• At therapeutic doses for <=4-6 weeks: Generally safe
• With regular use >3 g root/day or >100 mg glycyrrhizin/day for >6 weeks:
  • Sodium and water retention
  • Hypertension (can be severe)
  • Hypokalemia (can be severe; risk of cardiac arrhythmias)
  • Edema
  • Metabolic alkalosis
  • Headache, lethargy
• Susceptible individuals: Even 80-100 mg/day glycyrrhizin may provoke severe hypertension
• WHO and EFSA recommendation: Maximum 100 mg glycyrrhizin per day

Pregnancy/Lactation

• Contraindicated in pregnancy (Commission E)
• Glycyrrhizin may cross the placenta; associated with preterm birth and lower birth weight in epidemiological studies
• Glycyrrhizin may affect fetal cortisol levels via 11-beta-HSD2 inhibition in placenta
• Lactation: Avoid; insufficient safety data

Clinical Dosage

Whole Licorice Root (With Glycyrrhizin) — Time-Limited

• Dried root (tea/decoction): 1.5-5 g root, 2-3 times daily
• Fluid extract (1:1): 2-4 mL, 3 times daily
• Dry extract: Various ratios; standardized to glycyrrhizin content
• Maximum duration: 4-6 weeks without medical supervision
• Maximum glycyrrhizin: 100 mg/day (WHO, EFSA)
• Monitor blood pressure and potassium levels with prolonged use

DGL (Deglycyrrhizinated Licorice) — No Time Limit

• Chewable tablets: 380 mg, chewed and swallowed 20 minutes before meals or between meals
• Frequency: 3 times daily (for peptic ulcer: 3x/day for 8-16 weeks)
• Must be chewable form (capsule form is ineffective)
• Can be used long-term
• No hypertension or hypokalemia concerns
• Can reduce aspirin-induced GI bleeding (350 mg chewed with each aspirin dose)

Key Products (European Market)

• Various Suessholz (licorice) root teas and extracts
• Component of numerous European cough and bronchial preparations
• Liquiritiae extractum fluidum (fluid extract, PhEur)
• DGL chewable tablets (more common in US/UK market)

Sources

• Commission E Monograph: Liquiritiae radix (Bundesanzeiger)
• ESCOP Monograph: Liquiritiae radix (2003)
• EMA/HMPC Assessment Report on Glycyrrhiza glabra L. and/or G. inflata Bat. and/or G. uralensis Fisch., radix (Final)
• EMA/HMPC: Liquiritiae radix herbal medicinal product page
• WHO: Monographs on Selected Medicinal Plants — Radix Glycyrrhizae
• EFSA/SCF: Scientific Opinion on glycyrrhizic acid
• BfR (German Institute for Risk Assessment): Glycyrrhizin in licorice
• VKM Norway (2018): Hazard assessment of glycyrrhizic acid from liquorice
• Altmeyers Encyclopedia: Liquiritiae radix monograph
• Pastorino et al. (2018) “Liquorice: A Comprehensive Review” PMC8703329
• Morgan et al. (2019) “Bioactive Candy: Effects of Licorice on the Cardiovascular System” PMC6836258
• PeaceHealth: Licorice monograph
• Efficacy.pro: Licorice and DGL Scientific Monograph

Connections

• Turmeric Curcumin: Both have GI protective properties; turmeric via choleretic mechanism, licorice via prostaglandin/mucus mechanism
• Ginger: Both used for GI conditions; can be combined
• Fenugreek: Both have GI indications; fenugreek as demulcent, licorice as mucosal protector
• Cinnamon: Both have traditional GI use; both have significant safety considerations
• Respiratory herbs module: Licorice as expectorant/demulcent overlaps with ivy, thyme, marshmallow
• Cardiovascular herbs module: Licorice-induced hypertension is a cardiovascular safety concern