Glycyrrhiza glabra L. (Licorice Root Extract)

Licorice root extract (Glycyrrhiza glabra L.) contains glycyrrhizin and its aglycone glycyrrhetinic acid as primary bioactives, which modulate cortisol metabolism, inhibit 11β-hydroxysteroid dehydrogenase, and exert anti-inflammatory effects on gastrointestinal mucosa. Deglycyrrhizinated licorice (DGL) formulations like GutGard® are specifically used to support digestive comfort and insulin sensitivity without the blood pressure-raising effects of glycyrrhizin.

Origin & History

Glycyrrhiza glabra L. (licorice) is a perennial herb native to southern Europe, the Mediterranean, and parts of Asia, belonging to the Fabaceae family. The extract is derived from dried roots and rhizomes through hydroalcoholic or water-based extraction methods, yielding standardized extracts rich in flavonoids and glycyrrhizin. Branded forms like GutGard® are standardized to contain ≥10% total flavonoids including ≥3.5% glabridin by HPLC.

Historical & Cultural Context

Licorice root has been used for millennia in Traditional Chinese Medicine, Ayurveda, and Greco-Arabic medicine for gastrointestinal issues, respiratory conditions, and as an anti-inflammatory agent. Traditional preparations include root beverages at 30 mg/mL concentrations, and it continues to play a role in TCM formulations for harmonizing herbs and treating inflammatory conditions.

Health Benefits

• Supports healthy insulin metabolism and weight management - RCT (n=58) showed significant reductions in HOMA-IR and body weight with 1,500 mg/day (moderate evidence)
• Promotes digestive comfort and functional dyspepsia relief - Two RCTs (n≈100) demonstrated symptom improvements with GutGard® 150 mg/day (moderate evidence)
• Supports H. pylori eradication - Clinical trial showed efficacy with GutGard® via COX/LOX inhibition (moderate evidence)
• Enhances wound healing - Preclinical studies showed 5% topical extract optimized burn recovery (preliminary evidence)
• Reduces inflammatory markers - RCT (n=89) in COVID-19 patients showed improved CRP and ALT levels (moderate evidence)

How It Works

Glycyrrhetinic acid inhibits 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that converts inactive cortisone to active cortisol in peripheral tissues, thereby reducing local glucocorticoid activity and improving insulin sensitivity as measured by HOMA-IR. Flavonoids such as liquiritin and isoliquiritigenin activate PPARγ receptors and suppress NF-κB signaling, reducing pro-inflammatory cytokine production in the gastric and intestinal mucosa. DGL fractions specifically inhibit H. pylori adhesion to gastric epithelium and stimulate mucin secretion, reinforcing the mucosal barrier and alleviating functional dyspepsia symptoms.

Scientific Research

Clinical evidence includes a randomized double-blind trial (PMID: 29670847) showing licorice extract (1,500 mg/day) significantly reduced insulin resistance and body weight in 58 overweight subjects. Two RCTs on GutGard® (150 mg/day) demonstrated efficacy for functional dyspepsia and H. pylori eradication through anti-inflammatory mechanisms. A recent COVID-19 trial (PMID: 37847472, n=89) found licorice improved CRP and ALT markers without affecting mortality.

Clinical Summary

A randomized controlled trial (n=58) demonstrated that 1,500 mg/day of licorice root extract produced statistically significant reductions in HOMA-IR and body weight compared to placebo, providing moderate-quality evidence for metabolic benefits. Two additional RCTs (combined n≈100) using the standardized DGL preparation GutGard® at 150 mg/day reported meaningful improvements in functional dyspepsia symptom scores versus control groups. Evidence quality is moderate overall, limited by relatively small sample sizes and short intervention durations; larger, longer trials are needed to confirm durability of effects. No head-to-head trials currently compare licorice root extract to standard pharmacological agents for dyspepsia or insulin resistance.

Nutritional Profile

Licorice root extract is a concentrated botanical preparation with negligible macronutrient content at typical supplemental doses (150–1,500 mg/day). Key bioactive compounds include: Triterpenoid saponins — glycyrrhizin (glycyrrhizinic acid) is the primary marker compound at approximately 2–25% by dry weight in root material, though deglycyrrhizinated licorice (DGL) formulations reduce this to <3% to minimize mineralocorticoid side effects; glycyrrhizin is hydrolyzed in the gut to its aglycone glycyrrhetinic acid (18β-glycyrrhetinic acid), which exhibits the primary pharmacological activity with estimated oral bioavailability of ~15–30% due to hepatic first-pass metabolism. Flavonoids — glabridin (0.1–0.3% in root extract) and liquiritin (liquiritigenin glucoside, approximately 0.5–2%) are major polyphenolic constituents; glabridin bioavailability is enhanced by lipid-based delivery. Chalcones — isoliquiritigenin and licochalcone A are present at trace concentrations (<0.1%) with anti-inflammatory and metabolic activity. Coumarins — licopyranocoumarin and glycycoumarin at minor concentrations (<0.05%). Polysaccharides — water-soluble glycyrrhizan (pectic polysaccharides) contribute to mucosal-soothing properties; content varies by extraction method. Minerals — naturally contains trace potassium (relevant to glycyrrhizin-mediated pseudoaldosteronism risk at high doses), calcium, and magnesium at nutritionally insignificant levels in supplemental doses. Standardized commercial extracts (e.g., GutGard®) are typically standardized to ≥15% glabridin or total flavonoids. Fat-soluble constituents such as glabridin exhibit improved absorption when taken with food containing dietary fat.

Preparation & Dosage

Clinically studied doses include: dried licorice extract at 1,500 mg/day for metabolic support; GutGard® (standardized flavonoid extract) at 150 mg/day for 60 days for digestive health; topical preparations at 5-20% w/w in hydrogels for wound care. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

Probiotics, Zinc carnosine, Slippery elm, Ginger extract, Curcumin

Safety & Interactions

Whole licorice extracts containing glycyrrhizin can cause pseudohyperaldosteronism at doses above approximately 100 mg glycyrrhizin/day, leading to sodium retention, hypokalemia, elevated blood pressure, and edema, particularly with prolonged use exceeding 4–6 weeks. Licorice root may potentiate antihypertensive drugs (reducing efficacy), interact with corticosteroids (amplifying mineralocorticoid effects), and increase risk of hypokalemia when combined with diuretics or stimulant laxatives. DGL formulations with glycyrrhizin removed carry significantly lower cardiovascular risk but are still not recommended during pregnancy due to evidence linking glycyrrhizin exposure to adverse fetal neurodevelopmental outcomes. Individuals with hypertension, kidney disease, liver cirrhosis, or those taking warfarin, digoxin, or hormonal contraceptives should consult a healthcare provider before use.