# Glycyrrhetinic acid **Canonical URL:** https://ingredients.hermeticasuperfoods.com/ingredients/glycyrrhetinic-acid **Data Source:** Hermetica Superfoods Ingredient Encyclopedia **Updated:** 2026-03-28 **Evidence Score:** 2 / 10 **Category:** Compound **Also Known As:** 18β-glycyrrhetinic acid, Enoxolone, Glycyrrhetic acid, 18β-Glycyrrhetic acid, 3β-Hydroxy-11-oxoolean-12-en-30-oic acid, Licorice acid, GA, Glycyrrhetenic acid ## Overview Glycyrrhetinic acid is the primary bioactive aglycone of glycyrrhizin, a triterpenoid saponin derived from licorice root (Glycyrrhiza glabra). It exerts its principal effects by inhibiting 11β-hydroxysteroid dehydrogenase (11β-HSD), the enzyme responsible for interconverting active [cortisol](/ingredients/condition/stress) and inactive cortisone in peripheral tissues. ## Health Benefits • Acts as a nonselective inhibitor of 11β-hydroxysteroid dehydrogenase, potentially increasing [cortisol](/ingredients/condition/stress) activity (preclinical evidence). • Exhibits antioxidative properties (preclinical evidence). • Demonstrates [anti-inflammatory](/ingredients/condition/inflammation) effects (preclinical evidence). • Shows [antimicrobial](/ingredients/condition/immune-support) activity (preclinical evidence). • Possesses anti-ulcerative properties (preclinical evidence). ## Mechanism of Action Glycyrrhetinic acid nonselectively inhibits both isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD1 and 11β-HSD2), reducing the conversion of [cortisol](/ingredients/condition/stress) to cortisone in peripheral tissues and thereby amplifying local glucocorticoid activity. It also suppresses NF-κB signaling and inhibits prostaglandin-synthesizing enzymes such as cyclooxygenase-2 (COX-2) and phospholipase A2, contributing to its [anti-inflammatory](/ingredients/condition/inflammation) profile. Additionally, glycyrrhetinic acid scavenges [reactive oxygen species](/ingredients/condition/antioxidant) (ROS) and upregulates endogenous antioxidant enzymes including superoxide dismutase (SOD) and catalase. ## Clinical Summary Most evidence for glycyrrhetinic acid derives from in vitro cell studies and rodent models rather than large randomized controlled trials in humans. Small human studies on topical glycyrrhetinic acid formulations (0.5–2%) have demonstrated measurable reductions in skin [inflammation](/ingredients/condition/inflammation) and eczema severity, though sample sizes typically range from 20–60 participants. Oral licorice root extracts standardized to glycyrrhizin/glycyrrhetinic acid content have shown modest [blood pressure](/ingredients/condition/heart-health)-elevating and potassium-lowering effects in controlled human trials, consistent with its 11β-HSD2 inhibition mechanism. Overall, clinical evidence remains preliminary, and well-powered, placebo-controlled trials specifically isolating glycyrrhetinic acid are lacking. ## Nutritional Profile Glycyrrhetinic acid is a pure bioactive triterpenoid compound (pentacyclic oleanane-type), not a whole food ingredient, and therefore contains no macronutrients (protein, fat, or carbohydrates), micronutrients, vitamins, minerals, or dietary fiber. As an isolated compound, it is typically studied and used in doses ranging from 50–500 mg/day in clinical and preclinical contexts. Molecular weight: 470.68 g/mol. It exists in two stereoisomeric forms: 18α-glycyrrhetinic acid and 18β-glycyrrhetinic acid, with the 18β form being the predominant biologically active isomer derived from hydrolysis of glycyrrhizin (the primary saponin of licorice root, Glycyrrhiza glabra). Bioavailability: Oral bioavailability is moderate; when derived from dietary glycyrrhizin, gut microbiota convert glycyrrhizin to glycyrrhetinic acid via hydrolysis of the glucuronide moieties, with peak plasma concentrations typically reached 8–24 hours post-ingestion. It undergoes significant hepatic first-pass [metabolism](/ingredients/condition/weight-management) and enterohepatic recirculation, contributing to a prolonged plasma half-life of approximately 10–32 hours. Plasma protein binding is high (>99%, primarily to albumin). Lipophilicity (log P ≈ 5.7) facilitates membrane permeability but limits aqueous solubility (~0.04 mg/mL in water). No significant vitamin, mineral, or fiber content is applicable to this isolated compound. ## Dosage & Preparation No clinically studied dosage ranges or standardization details are specified for glycyrrhetinic acid. Consult a healthcare provider before starting any new supplement. ## Safety & Drug Interactions Chronic or high-dose consumption of glycyrrhetinic acid can cause pseudoaldosteronism—characterized by sodium retention, hypokalemia, and hypertension—due to excessive inhibition of 11β-HSD2 in the kidneys; the European Food Safety Authority (EFSA) has flagged daily intakes above 100 mg glycyrrhizin as a concern. It may potentiate the effects of corticosteroids and antihypertensive drugs, and can reduce serum potassium when combined with diuretics or cardiac glycosides such as digoxin. Glycyrrhetinic acid is contraindicated in individuals with hypertension, hypokalemia, renal insufficiency, liver cirrhosis, or hyperaldosteronism. Pregnant women should avoid supplemental doses, as glycyrrhizin and its metabolites have been associated with adverse fetal neurodevelopmental outcomes in epidemiological studies. ## Scientific Research No specific human clinical trials or meta-analyses directly on glycyrrhetinic acid were found in the research. The evidence is primarily preclinical or inferred from studies on glycyrrhizin. ## Historical & Cultural Context Glycyrrhetinic acid is derived from licorice root, which has been used traditionally in various cultures, though specific historical uses or practices are not detailed in the research. ## Synergistic Combinations Licorice root extract, Ashwagandha, Turmeric, Ginseng, Green tea extract ## Frequently Asked Questions ### What is glycyrrhetinic acid and where does it come from? Glycyrrhetinic acid is a pentacyclic triterpenoid saponin aglycone produced when gut bacteria and hepatic enzymes hydrolyze glycyrrhizin, the major sweet compound in licorice root (Glycyrrhiza glabra and Glycyrrhiza uralensis). It is the primary systemically active metabolite responsible for most of licorice root's pharmacological effects following oral ingestion. ### How does glycyrrhetinic acid affect cortisol levels? Glycyrrhetinic acid inhibits 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in the kidneys and other tissues, blocking the inactivation of cortisol to cortisone and allowing cortisol to bind mineralocorticoid receptors. This produces a pseudoaldosteronism-like state with sodium and water retention, elevated blood pressure, and reduced serum potassium, even without changes in circulating aldosterone levels. ### What are the side effects of glycyrrhetinic acid supplements? The most clinically significant side effects include hypertension, hypokalemia (low serum potassium), edema, and in severe cases, muscle weakness or cardiac arrhythmias stemming from pseudoaldosteronism. These effects are dose-dependent and typically emerge with daily glycyrrhizin equivalents above 100–200 mg; they are generally reversible upon discontinuation of the supplement. ### Is topical glycyrrhetinic acid effective for skin conditions? Topical formulations containing 0.5–2% glycyrrhetinic acid have been studied for eczema, contact dermatitis, and rosacea, showing anti-inflammatory effects attributed to COX-2 inhibition and local 11β-HSD1 modulation, which enhances glucocorticoid activity in skin tissue. Small clinical trials report reductions in redness, itching, and lesion severity, though evidence is limited to short-duration studies with fewer than 60 participants. ### Can glycyrrhetinic acid interact with blood pressure medications? Yes, glycyrrhetinic acid can blunt the efficacy of antihypertensive drugs—including ACE inhibitors, ARBs, and diuretics—by promoting sodium retention and raising blood pressure via 11β-HSD2 inhibition. It also risks additive hypokalemia when combined with thiazide or loop diuretics, and can elevate digoxin toxicity risk by lowering serum potassium, which sensitizes cardiac tissue to glycoside effects. ### What is the difference between glycyrrhetinic acid and licorice root extract? Glycyrrhetinic acid is the active metabolite derived from licorice root, created when the body metabolizes glycyrrhizin. While licorice root extract contains multiple compounds including glycyrrhizin, glycyrrhetinic acid is the purified form that directly inhibits 11β-hydroxysteroid dehydrogenase. Supplementing with glycyrrhetinic acid may provide more targeted effects with potentially fewer unwanted compounds from whole licorice preparations. ### How does glycyrrhetinic acid dosage affect cortisol activity differently than licorice root? Glycyrrhetinic acid has a more direct mechanism of action on 11β-hydroxysteroid dehydrogenase inhibition compared to licorice root, potentially resulting in more predictable cortisol-modulating effects at lower doses. The conversion of glycyrrhizin to glycyrrhetinic acid in licorice root is variable and dependent on gut flora, whereas isolated glycyrrhetinic acid provides consistent bioavailability. This makes dosage adjustments potentially more precise with the purified compound, though clinical dosing protocols remain limited. ### Who should avoid glycyrrhetinic acid due to its cortisol effects? Individuals with hypertension, kidney disease, or hormonal imbalances should avoid glycyrrhetinic acid due to its potent effects on cortisol activity and potential to increase sodium retention. Those taking corticosteroid medications should consult a healthcare provider before use, as additive cortisol-enhancing effects may occur. Pregnant and nursing women should avoid this ingredient due to insufficient safety data and the systemic nature of its endocrine effects. --- *Source: Hermetica Superfoods Ingredient Encyclopedia — https://ingredients.hermeticasuperfoods.com* *License: CC BY-NC-SA 4.0 — Attribution required. Commercial use: admin@hermeticasuperfoods.com*