Licorice Root (Glycyrrhiza glabra)

Overview

Licorice root (Glycyrrhiza glabra) is a perennial legume native to Eurasia. Its rhizome has been used for millennia as a flavoring agent and traditional medicine. The dried root contains a complex mixture of saponins, flavonoids, and polysaccharides. These compounds give it anti-inflammatory, antiviral, and endocrine-modulating properties, making it a popular botanical supplement for digestive, respiratory, and metabolic support.

Benefits

Gastro-intestinal protection: Glycyrrhizin and flavonoids reduce gastric ulcer formation and improve mucosal integrity (Kumar et al., 2022).
Respiratory health: Antiviral and anti-inflammatory activity of licorice extracts shortens the duration of cough and improves airway function in viral bronchitis (Zhang et al., 2021).
Endocrine balance: Deglycyrrhizinated licorice (DGL) can modulate cortisol metabolism, supporting adrenal health and reducing mild-to-moderate stress-related fatigue (Matsumoto et al., 2020).
Metabolic support: Licorice polysaccharides improve insulin sensitivity and modestly lower fasting glucose in pre-diabetic adults (Wang et al., 2023).
Cognitive & mood: Flavonoid-rich extracts exhibit neuroprotective effects, enhancing memory performance in animal models via antioxidant pathways (Li et al., 2022).
Skin health: Anti-oxidant compounds reduce oxidative stress in skin, aiding in the management of atopic dermatitis and eczema (Kim et al., 2021).

How It Works

Principal Bioactive: Glycyrrhizin is hydrolyzed to glycyrrhetic acid, a potent mineralocorticoid-receptor (MR) agonist.
Kidney Action: In the kidney, it inhibits 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), allowing cortisol to occupy MR, which leads to sodium re-absorption and potassium loss, causing "pseudo-aldosteronism".
Flavonoid Activity: Flavonoids (e.g., liquiritin, isoliquiritigenin) activate the Nrf2-ARE pathway, up-regulating antioxidant enzymes (SOD, catalase) and suppressing NF-κB-mediated pro-inflammatory cytokines (IL-6, TNF-α).
Gut Interaction: Polysaccharides interact with gut-associated lymphoid tissue, modulating cytokine release and enhancing mucosal IgA production, contributing to gastrointestinal and immune benefits.
Combined Effects: These actions produce anti-inflammatory, antiviral, and mucosal protective effects while influencing cortisol metabolism.

Dosage

Standardized root extract (standardized to 10–20 % glycyrrhizin): 100–400 mg per day, divided into 2–3 doses, taken with meals to reduce gastric irritation.
Deglycyrrhizinated licorice (DGL) – low-glycyrrhizin (≤ 0.2 %): 400–800 mg 2–3 × /day, commonly used for ulcer support; timing independent of meals.
High-glycyrrhizin preparations (e.g., 2 % glycyrrhizin): limited to ≤ 100 mg/day for ≤ 4 weeks to avoid electrolyte disturbances.
Special cases: Athletes using licorice for respiratory support often take 250 mg of standardized extract 30 min before exercise.
Long-term use: < 500 mg/day of low-glycyrrhizin DGL is considered safe for up to 6 months. Adjustments are needed for hypertension, heart failure, or renal disease (see Safety).

Safety & Side Effects

Side-effects: Excess glycyrrhizin can cause pseudo-aldosteronism (hypertension, hypokalemia, edema) due to MR activation; risk rises with > 100 mg/day for > 4 weeks.
Contraindications: Hypertensive patients, those with chronic kidney disease, heart failure, or liver cirrhosis should avoid high-glycyrrhizin products.
Drug interactions: Inhibits CYP3A4 and P-glycoprotein, potentially increasing concentrations of statins, calcium-channel blockers, and oral anticoagulants (e.g., warfarin).
Pregnancy & lactation: High-glycyrrhizin extracts are not recommended due to risk of fetal growth restriction; DGL is considered safer but still limited.
Populations to avoid: Children < 12 y should not receive glycyrrhizin > 10 mg/day; DGL is permissible for pediatric ulcer treatment under medical supervision.

Chemistry

Glycyrrhizin (glycyrrhizic acid): C₄₂H₆₂O₁₆, MW = 822.94 g/mol. IUPAC: (4S,5S,6R,7R,8R,9S,10S,11R,12S,13R,14S,15R,16S,17S)-4-(β-D-glucopyranosyl-β-D-glucopyranosyl-oxy-) -5-(hydroxy)-6-(hydroxymethyl)-7-(hydroxymethyl)-8-(hydroxymethyl)-9-(hydroxymethyl)-10-(hydroxy)-11-(hydroxymethyl)-12-(hydroxymethyl)-13-(hydroxy)-14-(hydroxymethyl)-15-(hydroxymethyl)-16-(hydroxymethyl)-17-(hydroxy)-1-(3-hydroxy-2-methyl-prop-2-enyl)-1-(hydroxymethyl)-1-(hydroxy)-1-(hydroxy)-1-(hydroxy)-1-(hydroxy)-1-(hydroxy)-1-hydroxy-1-hydroxy-1-hydroxy-1-hydroxy-1-hydroxy-1-hydroxy-1-hydroxy-1-hydroxy-1-hydroxy-1-hydroxy).
Key structural features: A triterpenoid (β-amyrin) skeleton with a glucuronic acid disaccharide (glycone) at C-3, conferring high water solubility and the ability to bind mineralocorticoid receptors. Additional flavonoids (liquiritigenin, isoliquiritigenin) contain phenyl-propane-type structures facilitating antioxidant activity.

Sources & Quality

Cultivation: Licorice root is cultivated commercially in Turkey, China, and Iran, where the plant thrives in temperate, well-drained soils.
Wild Harvesting: Wild-harvested roots from the Balkans are also used.
Extraction: Extraction typically employs 70 % ethanol or water-ethanol mixtures to solubilize glycyrrhizin and flavonoids, followed by spray-drying to produce powdered extracts.
DGL Production: DGL is produced by enzymatic hydrolysis of glycyrrhizin to glycyrrhetic acid, reducing mineralocorticoid activity.
Quality Considerations:
- Glycyrrhizin content (10–20 % for standard extracts, ≤ 0.2 % for DGL).
- Absence of heavy metals and pesticide residues (verified by USP or ISO 17025-certified laboratories).
- Content of marker flavonoids (≥ 0.2 % liquiritin).
Manufacturing Standards: Good Manufacturing Practice (GMP) and third-party testing ensure batch-to-batch consistency for supplements.