Glycyrrhizin

Glycyrrhizin at a Glance

Glycyrrhizin — also called glycyrrhizic or glycyrrhizinic acid — is the principal oleanane triterpenoid saponin of licorice (Glycyrrhiza) and its sweet principle, roughly 50 times sweeter than sucrose. Structurally it is a glycoside: the pentacyclic triterpene aglycone glycyrrhetinic acid carrying two glucuronic-acid sugars. It is the compound that makes licorice root taste sweet, and the compound behind licorice’s best-known medical effects and its best-known hazard ^{1,15Reference 1Sabbadin C et al. · 2019Licorice: from pseudohyperaldosteronism to therapeutic usesView study →Reference 15Wahab S et al. · 2021ReviewGlycyrrhiza glabra (Licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}.

The single most important fact about this molecule is that most of its systemic activity is not its own. Taken by mouth, glycyrrhizin is barely absorbed intact; gut bacteria hydrolyse off its two sugars to release glycyrrhetinic acid (18β-glycyrrhetinic acid), the aglycone that is actually absorbed and that drives the downstream endocrine effects ^{5,6Reference 5Takeda S et al. · 1996AnimalBioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysisView study →Reference 6Ploeger B et al. · 2001The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modelingView study →}. Reading this therefore means reading two molecules at once — the sweet, poorly-absorbed parent, and its active metabolite.

That metabolite is what makes licorice risky. Glycyrrhetinic acid inhibits the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), producing apparent mineralocorticoid excess — a pseudoaldosteronism of high blood pressure, potassium loss and fluid retention that, in heavy or prolonged use, has caused severe hypokalaemia, rhabdomyolysis, dangerous arrhythmias and rare fatal cardiac arrest ^{1,2,11Reference 1Sabbadin C et al. · 2019Licorice: from pseudohyperaldosteronism to therapeutic usesView study →Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →Reference 11Edelman ER et al. · 2020Case 30-2020: a 54-year-old man with sudden cardiac arrestView study →}. The efficacy story (antiviral, hepatoprotective, anti-inflammatory) and the safety story run through the same biochemistry, which is why this molecule carries a moderate flag rather than a benign one.

The Aglycone Connection: Why Most Effects Are Glycyrrhetinic Acid’s

Glycyrrhizin is best understood as a microbiome-activated prodrug. The intact saponin is large, highly polar (two ionised glucuronic acids) and poorly permeable, so little crosses the gut wall unchanged. In the colon, bacterial β-glucuronidases cleave the sugars to yield the lipophilic aglycone glycyrrhetinic acid, which is then absorbed, undergoes enterohepatic recycling, and reaches the systemic circulation ^{5,6Reference 5Takeda S et al. · 1996AnimalBioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysisView study →Reference 6Ploeger B et al. · 2001The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modelingView study →}.

The practical consequences are threefold and run through everything below:

• The active agent for endocrine effects is the aglycone, not the parent. 11β-HSD2 inhibition, and therefore the whole pseudoaldosteronism picture, is chiefly glycyrrhetinic acid’s doing ^{1,2Reference 1Sabbadin C et al. · 2019Licorice: from pseudohyperaldosteronism to therapeutic usesView study →Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →} — see its dedicated page.
• Effect depends on the gut flora. Because absorption requires bacterial hydrolysis, germ-free or antibiotic-suppressed conditions sharply reduce it, and individuals vary — part of why sensitivity to licorice differs so widely between people ^{5Reference 5Takeda S et al. · 1996AnimalBioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysisView study →}.
• The effective half-life is long and cumulative. Glycyrrhetinic acid clears slowly with enterohepatic cycling, so effects accumulate over days of repeated intake — the reason licorice toxicity is characteristically dose- and duration-dependent rather than a single-dose event ^{6Reference 6Ploeger B et al. · 2001The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modelingView study →}.

Apparent Mineralocorticoid Excess: The 11β-HSD2 Mechanism

This is the mechanistic hinge of the entire page — the same action that gives glycyrrhizin a legitimate glucocorticoid-potentiating, anti-inflammatory role at low exposure is what poisons at high exposure.

The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) sits in mineralocorticoid target tissues (kidney, colon) and continuously converts active cortisol into inactive cortisone. Its job is to protect the mineralocorticoid receptor — which binds cortisol and aldosterone with equal affinity — from being swamped by cortisol, which circulates at far higher concentrations than aldosterone. Glycyrrhetinic acid inhibits 11β-HSD2, so cortisol is no longer inactivated locally; it accumulates and illicitly activates the mineralocorticoid receptor exactly as aldosterone would, and glycyrrhetinic acid may also bind the receptor directly as a weak agonist ^{1,2Reference 1Sabbadin C et al. · 2019Licorice: from pseudohyperaldosteronism to therapeutic usesView study →Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →}.

The result is apparent mineralocorticoid excess with a suppressed renin–aldosterone axis (aldosterone is low precisely because the receptor is already being driven): renal sodium and water retention, potassium and hydrogen wasting, and expansion of plasma volume. Clinically that reads as hypertension, hypokalaemia, metabolic alkalosis and oedema ^{1,2,3Reference 1Sabbadin C et al. · 2019Licorice: from pseudohyperaldosteronism to therapeutic usesView study →Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →Reference 3Ceccuzzi G et al. · 2023ReviewLiquorice toxicity: a comprehensive narrative reviewView study →}. Every toxic manifestation later here is a downstream consequence of this one enzyme block.

What It's Used For

Glycyrrhizin’s therapeutic literature is broad but uneven: a genuine human hepatology use (intravenous, in Japan), a large in-vitro/animal antiviral base, and an anti-inflammatory action inseparable from the 11β-HSD2 mechanism above. The honest through-line is that oral bioavailability of the parent is poor, and the marquee human evidence uses the intravenous isolate, not the whole root.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Only the hepatology use has controlled human isolate data; the rest is preclinical or mechanism, so scores stay measured.

01Hepatoprotective / anti-hepatitisPromising52%Double-blind IV glycyrrhizin (SNMC) RCT ↓ALT in chronic hepatitis C + long Japanese clinical record ^{9,10Reference 9Fiore C et al. · 2008Antiviral effects of Glycyrrhiza speciesView study →Reference 10van Rossum TG et al. · 1999RCTIntravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trialView study →}

02AntiviralShaky44%In-vitro SARS-CoV / SARS-CoV-2 (main-protease block) + antiviral review across HBV/HCV/HSV/HIV ^{7,8,9Reference 7Cinatl J et al. · 2003Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirusView study →Reference 8van de Sand L et al. · 2021Glycyrrhizin effectively inhibits SARS-CoV-2 replication by inhibiting the viral main proteaseView study →Reference 9Fiore C et al. · 2008Antiviral effects of Glycyrrhiza speciesView study →}

03Anti-inflammatory / glucocorticoid-potentiatingShaky38%11β-HSD inhibition sparing cortisol; mechanism strong, human efficacy indirect ^{1,2Reference 1Sabbadin C et al. · 2019Licorice: from pseudohyperaldosteronism to therapeutic usesView study →Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →}

04Expectorant / mucosal & anti-ulcerShaky30%Traditional expectorant/demulcent use; aglycone-linked anti-ulcer activity ^{1,15Reference 1Sabbadin C et al. · 2019Licorice: from pseudohyperaldosteronism to therapeutic usesView study →Reference 15Wahab S et al. · 2021ReviewGlycyrrhiza glabra (Licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}

Mechanisms

Pharmacokinetics

Glycyrrhizin is the compound-page’s clearest case of why the metabolite matters more than the molecule. The intact saponin is large and highly polar, so oral absorption of the parent is poor; systemic exposure depends on gut bacterial hydrolysis (β-glucuronidase) to the lipophilic aglycone glycyrrhetinic acid, which is the species actually absorbed — bacterial hydrolysis is indispensable to that absorption in rats ^{5Reference 5Takeda S et al. · 1996AnimalBioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysisView study →}. Glycyrrhizic acid then undergoes extensive presystemic metabolism and enterohepatic cycling, well described by physiologically-based pharmacokinetic modelling ^{6Reference 6Ploeger B et al. · 2001The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modelingView study →}. Two consequences dominate: (1) flora-dependence introduces wide inter-individual variability, and germ-free/antibiotic states blunt the effect ^{5Reference 5Takeda S et al. · 1996AnimalBioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysisView study →}; and (2) the aglycone’s slow clearance and recycling give a long effective half-life, so glycyrrhetinic acid accumulates with repeated dosing — the pharmacological reason licorice toxicity is dose- and duration-dependent, building over days to weeks rather than striking on first exposure ^{6Reference 6Ploeger B et al. · 2001The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modelingView study →}. This is also why the one robust efficacy use is intravenous (bypassing the absorption bottleneck) ^{10Reference 10van Rossum TG et al. · 1999RCTIntravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trialView study →}.

Clinical Trials

Human trials of the isolate are essentially the intravenous hepatology programme; oral licorice/glycyrrhizin sits mostly in observational, toxicological and traditional use.

Last checked: July 2026.

Sweetness & Non-Nutritive Use

Glycyrrhizin is a non-sugar sweetener, roughly 50 times sweeter than sucrose, with a slow onset and a lingering, slightly bitter–anise aftertaste characteristic of licorice ^{15Reference 15Wahab S et al. · 2021ReviewGlycyrrhiza glabra (Licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}. It (and its ammonium salt) is used to flavour confectionery, tobacco, beverages and pharmaceuticals, and to mask bitterness. Crucially, it is not an inert sweetener: unlike sucralose or stevioside, the amount needed to sweeten also delivers a pharmacologically active dose of the 11β-HSD2-inhibiting aglycone, which is exactly why black-licorice confectionery is a recurrent cause of pseudoaldosteronism rather than a harmless sweet (see Toxicity) ^{3,11Reference 3Ceccuzzi G et al. · 2023ReviewLiquorice toxicity: a comprehensive narrative reviewView study →Reference 11Edelman ER et al. · 2020Case 30-2020: a 54-year-old man with sudden cardiac arrestView study →}.

Isolate vs. Plant Studies

The evidence here splits unusually cleanly. The strongest human data are the isolate — intravenously — where SNMC/IV glycyrrhizin was studied as a defined drug in hepatitis C ^{9,10Reference 9Fiore C et al. · 2008Antiviral effects of Glycyrrhiza speciesView study →Reference 10van Rossum TG et al. · 1999RCTIntravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trialView study →}; that is a genuine strength, not the usual whole-plant confound. The antiviral and anti-inflammatory mechanism work is also isolate (glycyrrhizin or glycyrrhetinic acid in cell/animal systems) ^{7,8Reference 7Cinatl J et al. · 2003Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirusView study →Reference 8van de Sand L et al. · 2021Glycyrrhizin effectively inhibits SARS-CoV-2 replication by inhibiting the viral main proteaseView study →}. Where the isolate framing breaks down is oral exposure: swallowed glycyrrhizin behaves as a prodrug requiring gut flora, so real-world oral effect is inseparable from the whole-root matrix, the microbiome and dose accumulation ^{5,6Reference 5Takeda S et al. · 1996AnimalBioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysisView study →Reference 6Ploeger B et al. · 2001The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modelingView study →}. And the safety literature is overwhelmingly whole-licorice — confectionery, teas, root extracts and supplements — where glycyrrhizin content is variable and often unlabelled ^{3,11,12Reference 3Ceccuzzi G et al. · 2023ReviewLiquorice toxicity: a comprehensive narrative reviewView study →Reference 11Edelman ER et al. · 2020Case 30-2020: a 54-year-old man with sudden cardiac arrestView study →Reference 12Yang LY et al. · 2019Case reportLiquorice-induced severe hypokalemic rhabdomyolysis with Gitelman syndrome and diabetes: a case reportView study →}. Net: robust isolate pharmacology intravenously, but oral human reality is a whole-food, flora-dependent exposure.

Prevalence in Nature

Glycyrrhizin is effectively licorice-specific — it is the defining saponin of the genus Glycyrrhiza (Fabaceae) and is not a widespread plant metabolite the way simple terpenes or phenolic acids are. It is concentrated in the root and stolons, where it typically accounts for ~2–6% of dry weight (with reports up to ~15% in some material), the fraction responsible for the root’s sweetness ^{15Reference 15Wahab S et al. · 2021ReviewGlycyrrhiza glabra (Licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}. Content varies substantially with species — Glycyrrhiza glabra (European/Middle-Eastern licorice), G. uralensis (Chinese licorice / Gan Cao) and G. inflata differ in their saponin and flavonoid profiles — and with provenance, age and extraction ^{15Reference 15Wahab S et al. · 2021ReviewGlycyrrhiza glabra (Licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}. It co-occurs in the root with the aglycone glycyrrhetinic acid and with licorice’s characteristic flavonoids such as glabridin and liquiritin.

Major Natural Sources

Source	Plant part	Reported glycyrrhizin content
Licorice (Glycyrrhiza glabra)	dried root / stolon	~2–6% dry wt (up to ~15% reported)
Chinese licorice (Glycyrrhiza uralensis)	dried root	variable; species-dependent saponin profile
Glycyrrhiza inflata	dried root	variable; species-dependent

These are percentages of the dried root, and the ranges shift with species, provenance and extraction method ^{15Reference 15Wahab S et al. · 2021ReviewGlycyrrhiza glabra (Licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}.

Discovery & Synthesis

Glycyrrhizin has been recognised as licorice’s sweet principle for centuries — the name traces to the botanical Glycyrrhiza, from the Greek glykys (“sweet”) and rhiza (“root”), the same root that gives “licorice” through Latin liquiritia. The crystalline saponin was characterised chemically in the nineteenth century, and the structure of its aglycone glycyrrhetinic acid and the two glucuronic-acid sugars was elucidated over the twentieth ^{15Reference 15Wahab S et al. · 2021ReviewGlycyrrhiza glabra (Licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicologyView study →}.

Because glycyrrhizin is a large, complex pentacyclic triterpene glycoside, total synthesis has never been the commercial route — it is obtained by extraction and purification from licorice root, and the food/pharmaceutical article is usually supplied as the pure acid or as mono-ammonium glycyrrhizinate. The related intravenous drug Stronger Neo-Minophagen C (SNMC) is a formulated glycyrrhizin preparation (with cysteine and glycine) manufactured for clinical use in Japan ^{9Reference 9Fiore C et al. · 2008Antiviral effects of Glycyrrhiza speciesView study →}.

Patents: not yet researched.

Toxicity & Safety

Glycyrrhizin earns a moderate flag — well above a typical dietary sweetener — because its aglycone is a bona-fide 11β-HSD2 inhibitor, and in enough quantity, for long enough, it reliably produces pseudoaldosteronism. This is the load-bearing safety point of the whole molecule.

Pseudoaldosteronism (Apparent Mineralocorticoid Excess)

Through the 11β-HSD2 mechanism above, glycyrrhizin/glycyrrhetinic acid causes a syndrome that mimics aldosterone excess while aldosterone and renin are actually suppressed: hypertension, hypokalaemia, sodium and water retention with oedema, and metabolic alkalosis ^{1,2,3Reference 1Sabbadin C et al. · 2019Licorice: from pseudohyperaldosteronism to therapeutic usesView study →Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →Reference 3Ceccuzzi G et al. · 2023ReviewLiquorice toxicity: a comprehensive narrative reviewView study →}. A systematic review and meta-analysis found that consistent licorice ingestion raises blood pressure and lowers serum potassium across studies ^{4Reference 4Penninkilampi R et al. · 2017Meta-analysisThe association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysisView study →}. It is dose- and duration-dependent and cumulative, reflecting the aglycone’s long effective half-life ^{6Reference 6Ploeger B et al. · 2001The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modelingView study →}.

Severe & Fatal Cases

At the heavy end this is not a nuisance effect. Case reports document severe hypokalaemia with rhabdomyolysis (muscle breakdown, dark urine, acute kidney injury) from chronic licorice or licorice-water intake ^{12Reference 12Yang LY et al. · 2019Case reportLiquorice-induced severe hypokalemic rhabdomyolysis with Gitelman syndrome and diabetes: a case reportView study →}, and the syndrome can precipitate dangerous ventricular arrhythmias. A New England Journal of Medicine Case Record described a man who suffered sudden cardiac arrest linked to excessive black-licorice consumption, with the hypokalaemia and apparent mineralocorticoid excess of glycyrrhizin toxicity ^{11Reference 11Edelman ER et al. · 2020Case 30-2020: a 54-year-old man with sudden cardiac arrestView study →}. These are the reason “it’s only candy” is the wrong intuition.

Intake Guidance & Populations at Risk

Regulatory bodies have set conservative thresholds: the EU Scientific Committee on Food suggested a habitual upper intake of about 100 mg glycyrrhizic acid per day, above which adverse mineralocorticoid effects become likely, and reviews echo that regular intake beyond roughly this level — readily reached from confectionery, strong licorice tea or supplements — carries real risk ^{2,3Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →Reference 3Ceccuzzi G et al. · 2023ReviewLiquorice toxicity: a comprehensive narrative reviewView study →}. Risk is higher and reached at lower doses in people with hypertension, cardiac disease, kidney disease, or pre-existing hypokalaemia, in older adults, and in women ^{2,3Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →Reference 3Ceccuzzi G et al. · 2023ReviewLiquorice toxicity: a comprehensive narrative reviewView study →}. Individual susceptibility varies (partly via gut-flora differences in aglycone generation) ^{5Reference 5Takeda S et al. · 1996AnimalBioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysisView study →}.

Drug Interactions

The interactions follow from the mechanism and are potassium-centred ^{2,3Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →Reference 3Ceccuzzi G et al. · 2023ReviewLiquorice toxicity: a comprehensive narrative reviewView study →}:

• Potassium-wasting diuretics (thiazides, loop diuretics) — additive hypokalaemia.
• Cardiac glycosides (digoxin) — hypokalaemia potentiates digoxin toxicity/arrhythmia.
• Corticosteroids — glycyrrhizin potentiates corticosteroid action (cortisol-sparing via 11β-HSD), and can compound their sodium-retaining, potassium-losing effects.
• Antihypertensives — the pressor effect can oppose blood-pressure control.
• Drugs prolonging the QT interval / antiarrhythmics — via hypokalaemia, added arrhythmia risk.

Pregnancy (Prose Note)

Licorice/glycyrrhizin is linked to adverse pregnancy outcomes and is generally avoided in pregnancy. In a Finnish cohort, heavy maternal glycyrrhizin intake (≥500 mg/week) was associated with roughly double the risk of preterm (<37 weeks) delivery ^{13Reference 13Strandberg TE et al. · 2002ObservationalPreterm birth and licorice consumption during pregnancyView study →}; follow-up of exposed offspring reported poorer cognitive performance and more psychiatric (including ADHD-type) problems, consistent with glycyrrhizin lowering placental 11β-HSD2 and increasing fetal glucocorticoid exposure ^{14Reference 14Räikkönen K et al. · 2009ObservationalMaternal licorice consumption and detrimental cognitive and psychiatric outcomes in childrenView study →}. Per site policy, the pregnancy/lactation decision belongs on the herb and product pages where intake is chosen; the finding is stated here as a cited risk, not a molecule-level verdict.

Safety at a Glance

⚠️ Moderate toxicity

• The sweetness itself is not the problem — the dose is. Trace culinary exposure in flavourings is not the same as habitual heavy licorice, and deglycyrrhizinated licorice (DGL) removes this molecule entirely.
• Pseudoaldosteronism is the defining hazard. Inhibiting 11β-HSD2 causes hypertension, hypokalaemia, fluid retention and metabolic alkalosis — dose- and duration-dependently ^{1,2,4Reference 1Sabbadin C et al. · 2019Licorice: from pseudohyperaldosteronism to therapeutic usesView study →Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →Reference 4Penninkilampi R et al. · 2017Meta-analysisThe association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysisView study →}.
• Heavy or prolonged use can be severe or fatal. Documented severe hypokalaemia with rhabdomyolysis, and rare sudden cardiac arrest from excessive licorice ^{11,12Reference 11Edelman ER et al. · 2020Case 30-2020: a 54-year-old man with sudden cardiac arrestView study →Reference 12Yang LY et al. · 2019Case reportLiquorice-induced severe hypokalemic rhabdomyolysis with Gitelman syndrome and diabetes: a case reportView study →}.
• Avoid in pregnancy. Heavy intake is linked to preterm birth and adverse offspring neurodevelopment ^{13,14Reference 13Strandberg TE et al. · 2002ObservationalPreterm birth and licorice consumption during pregnancyView study →Reference 14Räikkönen K et al. · 2009ObservationalMaternal licorice consumption and detrimental cognitive and psychiatric outcomes in childrenView study →}.
• Higher risk with hypertension, cardiac or renal disease, or existing low potassium — and with potassium-wasting diuretics, digoxin and corticosteroids ^{2,3Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →Reference 3Ceccuzzi G et al. · 2023ReviewLiquorice toxicity: a comprehensive narrative reviewView study →}.
• Effect accumulates over days. The active aglycone has a long effective half-life, so regular intake builds up rather than clearing between doses ^{6Reference 6Ploeger B et al. · 2001The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modelingView study →}.

Dosage

There is no general therapeutic oral dose for glycyrrhizin, and the safety framing dominates. Regulatory guidance (EU Scientific Committee on Food) places a habitual upper intake near 100 mg glycyrrhizic acid per day; regularly exceeding this — easily done with strong licorice confectionery, licorice tea or root extracts — makes dose- and duration-dependent pseudoaldosteronism likely ^{2,3Reference 2Omar HR et al. · 2012Licorice abuse: time to send a warning messageView study →Reference 3Ceccuzzi G et al. · 2023ReviewLiquorice toxicity: a comprehensive narrative reviewView study →}. The one established isolate use is intravenous: the glycyrrhizin preparation Stronger Neo-Minophagen C (SNMC) for chronic hepatitis in Japan, and IV glycyrrhizin in the hepatitis-C trial, both bypassing the poor oral bioavailability of the parent ^{9,10Reference 9Fiore C et al. · 2008Antiviral effects of Glycyrrhiza speciesView study →Reference 10van Rossum TG et al. · 1999RCTIntravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trialView study →}. Where the glycyrrhizin effect is unwanted (e.g. gastric use), deglycyrrhizinated licorice (DGL) is chosen specifically to remove it. These are regulatory thresholds and research/clinical figures, not a personal recommendation.

References

1. Sabbadin C, Bordin L, Donà G, Manso J, Avruscio G, Armanini D (2019). Licorice: from pseudohyperaldosteronism to therapeutic uses. Frontiers in Endocrinology. https://pubmed.ncbi.nlm.nih.gov/31379750/
2. Omar HR, Komarova I, El-Ghonemi M, Fathy A, Rashad R, Abdelmalak HD, Yerramadha MR, Ali Y, Helal E, Camporesi EM (2012). Licorice abuse: time to send a warning message. Therapeutic Advances in Endocrinology and Metabolism. https://pubmed.ncbi.nlm.nih.gov/23185686/
3. Ceccuzzi G, Rapino A, Perna B, Costanzini A, Farinelli A, Fiorica I, Marziani B, Cianci A, Rossin F, Cesaro AE, Spampinato MD, De Giorgio R, Guarino M (2023). Liquorice toxicity: a comprehensive narrative review. Nutrients. https://pubmed.ncbi.nlm.nih.gov/37764649/
4. Penninkilampi R, Eslick EM, Eslick GD (2017). The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis. Journal of Human Hypertension. https://pubmed.ncbi.nlm.nih.gov/28660884/
5. Takeda S, Ishthara K, Wakui Y, Amagaya S, Maruno M, Akao T, Kobashi K (1996). Bioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysis. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/8910850/
6. Ploeger B, Mensinga T, Sips A, Seinen W, Meulenbelt J, DeJongh J (2001). The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. Drug Metabolism Reviews. https://pubmed.ncbi.nlm.nih.gov/11495500/
7. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW (2003). Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. https://pubmed.ncbi.nlm.nih.gov/12814717/
8. van de Sand L, Bormann M, Alt M, Schipper L, Heilingloh CS, Steinmann E, Todt D, Dittmer U, Elsner C, Witzke O, Krawczyk A (2021). Glycyrrhizin effectively inhibits SARS-CoV-2 replication by inhibiting the viral main protease. Viruses. https://pubmed.ncbi.nlm.nih.gov/33918301/
9. Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J (2008). Antiviral effects of Glycyrrhiza species. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/17886224/
10. van Rossum TG, Vulto AG, Hop WC, Brouwer JT, Niesters HG, Schalm SW (1999). Intravenous glycyrrhizin for the treatment of chronic hepatitis C: a double-blind, randomized, placebo-controlled phase I/II trial. Journal of Gastroenterology and Hepatology. https://pubmed.ncbi.nlm.nih.gov/10574137/
11. Edelman ER, Butala NM, Avery LL, Lundquist AL, Dighe AS (2020). Case 30-2020: a 54-year-old man with sudden cardiac arrest. New England Journal of Medicine. https://pubmed.ncbi.nlm.nih.gov/32966726/
12. Yang LY, Yin JH, Yang J, Ren Y, Xiang CY, Wang CY (2019). Liquorice-induced severe hypokalemic rhabdomyolysis with Gitelman syndrome and diabetes: a case report. World Journal of Clinical Cases. https://pubmed.ncbi.nlm.nih.gov/31183353/
13. Strandberg TE, Andersson S, Järvenpää AL, McKeigue PM (2002). Preterm birth and licorice consumption during pregnancy. American Journal of Epidemiology. https://pubmed.ncbi.nlm.nih.gov/12396997/
14. Räikkönen K, Pesonen AK, Heinonen K, Lahti J, Komsi N, Eriksson JG, Seckl JR, Järvenpää AL, Strandberg TE (2009). Maternal licorice consumption and detrimental cognitive and psychiatric outcomes in children. American Journal of Epidemiology. https://pubmed.ncbi.nlm.nih.gov/19808634/
15. Wahab S, Annadurai S, Abullais SS, Das G, Ahmad W, Ahmad MF, Kandasamy G, Vasudevan R, Ali MS, Amir M (2021). Glycyrrhiza glabra (Licorice): a comprehensive review on its phytochemistry, biological activities, clinical evidence and toxicology. Plants (Basel). https://pubmed.ncbi.nlm.nih.gov/34961221/

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