Meridian Medica — Licorice

01

Identity

Botanical Profile

Glycyrrhiza glabra L. — Root and stolon (dried, peeled or unpeeled). Native to southern Europe, Middle East, and Central Asia. Cultivated in Mediterranean region, China, Turkey, Iran, and Russia. One of the most extensively documented herbs in both Western and Eastern medicine for over 4,000 years.

Root: distinctively sweet (50x sweeter than sugar), earthy, and slightly anise-like with a lingering sweetness. Dried root is woody, fibrous, and yellow internally. Tincture has a rich, sweet, slightly bittersweet character. The sweetness is from glycyrrhizin, not sugars.

Species Integrity

Glycyrrhiza glabra (European/Mediterranean licorice) and Glycyrrhiza uralensis (Chinese licorice/Gan Cao) are the primary medicinal species. Both contain glycyrrhizin but differ in secondary compound profiles.

02

Compounds

Active Compound Profile

Glycyrrhizin (glycyrrhizic acid)

2–12% of dried root

Inhibits 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2), prolonging cortisol half-life in tissues; anti-inflammatory via NF-κB inhibition; antiviral; hepatoprotective; 50x sweeter than sucrose

Glycyrrhetinic acid (metabolite of glycyrrhizin)

Generated from glycyrrhizin by gut microbiota

Active 11β-HSD2 inhibitor; the primary systemic metabolite responsible for both therapeutic adrenal effects and mineralocorticoid side effects

Liquiritigenin / Isoliquiritigenin (flavanones)

0.5–2% of dried root

Selective estrogen receptor modulator (SERM); estrogenic and anti-estrogenic depending on tissue; antispasmodic; anti-inflammatory

Glabridin

0.1–0.5% of dried root

Antioxidant (100x more potent than vitamin E in some assays); skin-lightening (tyrosinase inhibitor); anti-inflammatory; anti-atherogenic

Licoricidin and other isoflavonoids

Variable

Antimicrobial; anti-H. pylori; anti-Candida; anti-inflammatory

Absorption

Gut microbiome-dependent activation: Glycyrrhizin is hydrolyzed to the active glycyrrhetinic acid by intestinal bacteria. Healthy gut flora is required for optimal conversion and therapeutic effect.

03

Pathways

Mechanism of Action

★★★☆☆ 11β-HSD2 Inhibition / Cortisol Prolongation Glycyrrhetinic acid inhibits the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 that inactivates cortisol to cortisone in peripheral tissues. This effectively prolongs cortisol activity without increasing adrenal output.

★★★☆☆ NF-κB / Anti-Inflammatory Axis Glycyrrhizin and glycyrrhetinic acid inhibit NF-κB activation, reducing TNF-α, IL-6, and other inflammatory cytokines. Anti-inflammatory potency comparable to hydrocortisone in some assays.

★★★☆☆ Mucosal Healing / Demulcent Licorice polysaccharides and flavonoids promote gastric mucosal healing by increasing mucus production, improving mucosal blood flow, and inhibiting H. pylori adhesion

★★★☆☆ Antiviral / Immune Modulation Glycyrrhizin has direct antiviral activity (inhibits viral replication and membrane fusion) and modulates immune response (enhances interferon production while reducing excessive inflammatory response)

★★★☆☆ Estrogen Receptor Modulation Liquiritigenin acts as a selective estrogen receptor modulator (SERM), with estrogenic activity in some tissues and anti-estrogenic activity in others

04

Biomarkers

What It Moves in Your Labs

Biomarker	Direction	Target	Mechanism
Morning Cortisol (salivary)	↑ Increase (functional)	Normalize diurnal cortisol curve	11β-HSD2 inhibition prolongs cortisol half-life, effectively increasing functional cortisol availability without increased adrenal production
hs-CRP	↓ Decrease	<1.0 mg/L	NF-κB inhibition by glycyrrhizin reduces systemic inflammatory marker production
Blood Pressure	Monitor — do not allow excessive increase	Maintain <140/90 mmHg	11β-HSD2 inhibition causes mineralocorticoid effect: sodium retention, potassium excretion, water retention. MUST MONITOR.
Serum Potassium	Monitor — do not allow decrease	Maintain >3.5 mEq/L	Pseudo-aldosteronism from glycyrrhizin can cause hypokalemia. MUST MONITOR with prolonged use.

05

Extraction

Extraction & Preparation

Decoction (simmered 20–30 min): 90%+ glycyrrhizin; good polysaccharide extraction; good flavonoid extraction

Solubility · Water-soluble; also soluble in ethanolMenstruum · 50% ethanol / 50% waterPlant material · Dried licorice root (Glycyrrhiza glabra), sliced or coarsely groundMaceration time · 4–6 weeks (agitate daily)Ratio · 1:5 (dried)

07

Dosing

Dosing Framework

Morning dose is most important: take licorice in the morning to align cortisol prolongation with the natural morning cortisol peak.

Dose 1

Low: 1–2g dried root daily (tea or powder)

Minimal mineralocorticoid risk at this dose; suitable for longer-term use (8–12 weeks) with monitoring

Dose 2

Moderate: 2–5g dried root daily

Standard therapeutic range; limit to 4–6 weeks; monitor BP weekly; ensure adequate potassium intake

Dose 3

DGL: 380–760mg chewable, 2–3x daily

Safe for long-term use; no mineralocorticoid effects; chew before meals for direct mucosal contact

08

Synergies

Synergy Partners

★★★☆☆ Ashwagandha (Withania somnifera) Licorice cortisol prolongation + ashwagandha HPA axis modulation = comprehensive adrenal support addressing both cortisol availability and adrenal axis regulation

★★★☆☆ Rhodiola (Rhodiola rosea) Rhodiola stimulates stress resistance at the cellular level (heat shock protein induction) + licorice extends cortisol activity = complementary adaptogenic strategies

★★★☆☆ Ginger (Zingiber officinale) Ginger anti-inflammatory synergizes with licorice NF-κB inhibition; ginger enhances circulation and delivery of licorice compounds to tissues

★★★☆☆ Marshmallow Root (Althaea officinalis) Marshmallow demulcent + licorice mucosal healing = synergistic GI mucosal restoration; combined mucilaginous and anti-inflammatory repair

★★★☆☆ Nettle (Urtica dioica) Nettle potassium content partially offsets licorice-induced potassium loss; nettle's mineral profile complements licorice adrenal support

Signature Stack

THE ADRENAL RECOVERY TRIAD
Components: Licorice Root (cortisol prolongation) + Ashwagandha (HPA axis modulation) + Rhodiola (stress resistance) · Multi-pathway convergence: Cortisol half-life extension (licorice 11β-HSD2 inhibition) + HPA axis normalization (ashwagandha) + Cellular stress resistance (rhodiola HSP70 induction) + Synergistic NF-κB inhibition (all three) · The Adrenal Recovery Triad is the most potent adaptogenic stack in the Meridian Medica protocol, reserved for patients with documented adrenal insufficiency or severe HPA axis dysregulation. The three herbs address different aspects of adrenal-stress physiology for comprehensive recovery. · Practical integration: Morning decoction of all three roots (recipe above). Limit full-dose protocol to 4–6 weeks, then transition to ashwagandha maintenance. Monitor blood pressure and potassium throughout. This is a supervised protocol, not a casual daily tonic.

09

Safety

Contraindications & Interactions

Minor Hypertension Glycyrrhizin-mediated 11β-HSD2 inhibition causes pseudo-aldosteronism: sodium retention, potassium excretion, and water retention leading to elevated blood pressure. The effect is dose-dependent and reversible upon discontinuation.

Minor Hypokalemia Potassium wasting from mineralocorticoid effect can cause hypokalemia, potentially leading to muscle weakness, cardiac arrhythmia, and metabolic alkalosis.

Avoid Pregnancy Glycyrrhizin crosses the placenta and may affect fetal cortisol metabolism. Finnish cohort study associated high maternal licorice intake with earlier puberty and cognitive differences in offspring. AHPA Class 2b.

Minor Drug interactions (multiple) Licorice potentiates corticosteroid effects; antagonizes spironolactone and other potassium-sparing diuretics; may reduce efficacy of antihypertensive medications; extends half-life of prednisolone.

Minor Duration of use Prolonged high-dose use (>6 weeks at therapeutic doses) increases risk of pseudo-aldosteronism. Effects are cumulative and dose-dependent. Glycyrrhetinic acid has a long half-life and accumulates.

Minor Liver disease Hepatic insufficiency may impair glycyrrhizin metabolism, leading to accumulation and increased side effect risk.

11

Evidence

Evidence Base

★★★★★ Adrenal Support / 11β-HSD2 Inhibition Definitive — Well-characterized pharmacological mechanism

★★★★☆ GI Mucosal Healing (DGL) Strong — Multiple controlled studies

★★★☆☆ Anti-Inflammatory (Systemic) Moderate — Strong mechanism; limited RCTs for systemic inflammation

★★★☆☆ Antiviral Moderate — In vitro and clinical evidence for specific viruses

★★★☆☆ Anti-H. pylori (Adjunctive) Moderate — Small RCTs showing adjunctive benefit

Evidence Gaps

The highest-value research gap for Meridian Medica: no published RCT has evaluated low-dose licorice root specifically for adrenal insufficiency in Hashimoto's patients with documented low morning cortisol. The 11β-HSD2 inhibition mechanism is definitive, but its clinical application for HPA axis support in autoimmune thyroid disease has never been formally studied. An RCT measuring salivary cortisol diurnal curve, fatigue scores, and thyroid biomarkers before and after 6 weeks of low-dose licorice (2–3g/day) in Hashimoto's women with morning cortisol below the 25th percentile would fill this critical gap.

Quality Alert

Licorice root adulteration concerns include:

12

Protocol

Protocol Integration

Layer 1: Hypothalamic / Autonomic — HPA axis, circadian rhythm, stress response

Layer 2: Systemic Nutritional Repletion — Micronutrient optimization, antioxidant defense

Layer 3: Gut Permeability / Microbiome — Tight junction repair, motility, SIBO management

Recipe Integration

Adrenal Recovery Decoction (signature preparation)

1 tbsp licorice root per 3 cups water, simmered 20–30 min; 2 cups daily (morning + afternoon)

Feed the Markers

Licorice appears in the following Meridian Medica protocol contexts: