Licorice Root (Glycyrrhiza glabra)

Glycyrrhiza glabra / uralensis
Evidence Level
Moderate
2 Clinical Trials
4 Documented Benefits
3/5 Evidence Score

Licorice root is one of the most widely used herbs in both Eastern and Western herbal medicine traditions — the third most prescribed herb in Traditional Chinese Medicine and a staple of European phytotherapy for digestive, respiratory, and hormonal conditions. Its dual-component pharmacology requires understanding: glycyrrhizin (the primary saponin) produces significant hormonal and blood pressure effects, while deglycyrrhizinated licorice (DGL) removes glycyrrhizin to allow safe use for digestive conditions without endocrine side effects.

Studied Dose DGL for GI: 380–760 mg chewable before meals; whole licorice: 200–600 mg/day (limit to 4–6 weeks); glycyrrhizin: maximum 100 mg/day
Active Compound Glycyrrhizin (glycyrrhizic acid, 2–9%) and glycyrrhetinic acid for hormonal effects; deglycyrrhizinated licorice (DGL) extract for GI applications without hormonal effects

Digestive and GI mucosal protection (DGL form)

Deglycyrrhizinated licorice (DGL) is one of the most evidence-based natural treatments for peptic ulcer disease, gastritis, and GERD — protecting gastric mucosa by stimulating mucus production, increasing mucosal cell turnover, and inhibiting H. pylori adhesion. Multiple clinical trials show DGL heals gastric ulcers comparable to antacid and H2-blocker therapy without the side effects of glycyrrhizin.

Adrenal support and cortisol prolongation

Glycyrrhizin inhibits 11-beta-hydroxysteroid dehydrogenase (11β-HSD2) — the enzyme that inactivates cortisol. This prolongs cortisol half-life in tissues, providing an adrenal-supportive effect used therapeutically in adrenal fatigue and Addison's disease protocols. Low-dose glycyrrhizin effectively extends the action of endogenous cortisol.

Antiviral activity

Glycyrrhizin has documented antiviral activity against influenza, herpes viruses (HSV-1, HSV-2, VZV), hepatitis C, and HIV in laboratory and clinical studies. IV glycyrrhizin has been used in Japan for decades as a treatment for chronic hepatitis C. The mechanism involves interference with viral entry, replication, and inflammatory signaling.

Respiratory and anti-inflammatory effects

Licorice root is among the most used herbs for respiratory conditions — reducing mucous membrane inflammation, acting as an expectorant, and soothing irritated airways. Anti-inflammatory mechanisms include NF-κB inhibition, COX-2 suppression, and cortisol potentiation in airways — explaining traditional use for cough, bronchitis, and asthma.

1

11β-HSD2 inhibition and cortisol/aldosterone potentiation

Glycyrrhizin and glycyrrhetinic acid inhibit 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) — the enzyme that converts active cortisol to inactive cortisone in kidney, cardiovascular, and other tissues. Inhibition increases local cortisol activity, producing mineralocorticoid-like effects (sodium retention, potassium excretion, blood pressure elevation) that are both therapeutic (in adrenal insufficiency) and adverse (in excess or prolonged use).

2

DGL mucus stimulation and cytoprotection

DGL stimulates mucosal protective mechanisms in the GI tract independently of glycyrrhizin — increasing mucus gel layer thickness, stimulating prostaglandin E2 production (cytoprotective in mucosa despite being inflammatory elsewhere), and promoting epithelial cell turnover. These effects repair and protect GI mucosa from acid, NSAID, and H. pylori damage.

3

NF-κB and inflammatory pathway suppression

Glycyrrhetinic acid inhibits NF-κB, reduces TNF-α and IL-6 production, and suppresses 5-LOX and COX-2 — providing broad anti-inflammatory effects that contribute to GI, respiratory, and systemic anti-inflammatory applications.

1
DGL and Peptic Ulcer Healing — RCT
PubMed

Randomized trial of chewable DGL (380 mg three times daily) vs. antacid vs. cimetidine in 100 patients with gastric ulcer confirmed by endoscopy for 12 weeks.

100 gastric ulcer patients. 12-week comparative trial.

DGL produced equivalent ulcer healing rates to antacid and cimetidine (H2 blocker) at 12 weeks by endoscopic assessment. No side effects with DGL vs. expected antacid and cimetidine adverse effects. Supports DGL as effective, well-tolerated ulcer treatment.

2
Glycyrrhizin and Chronic Hepatitis C — Long-Term Clinical Study
PubMed

Long-term observational and clinical study of IV glycyrrhizin (Stronger Neo-Minophagen C) in chronic hepatitis C patients in Japan over 10+ years.

Japanese chronic hepatitis C patients. Long-term IV glycyrrhizin treatment.

Long-term IV glycyrrhizin significantly reduced liver enzyme levels, reduced progression to cirrhosis, and reduced hepatocellular carcinoma development compared to untreated controls. Established glycyrrhizin as standard hepatitis C supportive treatment in Japan.

Common Potential side effects

Whole licorice (glycyrrhizin-containing): hypertension, hypokalemia (low potassium), edema with doses >100 mg glycyrrhizin/day or >4–6 weeks use
DGL form: very well tolerated; glycyrrhizin removed eliminates hormonal side effects
Contraindicated in hypertension, heart failure, kidney disease, or hypokalemia if using whole licorice

Important Drug interactions

Antihypertensive medications — glycyrrhizin raises blood pressure; counteracts antihypertensives; avoid whole licorice in hypertensive patients
Diuretics — glycyrrhizin causes potassium loss; potentially serious hypokalemia with loop or thiazide diuretics
Corticosteroids — glycyrrhizin potentiates corticosteroid activity; may enhance or prolong steroid effects
Digoxin — hypokalemia from glycyrrhizin increases digoxin toxicity risk; dangerous combination with whole licorice