Glycyrrhizic acid

Glycyrrhizic acid is the primary bioactive triterpenoid saponin extracted from licorice root (Glycyrrhiza glabra), comprising up to 24% of the root's dry weight. It exerts its effects primarily by inhibiting 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and suppressing NF-κB signaling, driving its anti-inflammatory, antiviral, and hepatoprotective properties.

Origin & History

Glycyrrhizic acid is a triterpene glycoside extracted from the root of the licorice plant, Glycyrrhiza glabra. It is produced through hydrolysis of glycyrrhizin under acidic or alkaline conditions, resulting in a white to light yellow solid used in food, cosmetics, and pharmaceuticals.

Historical & Cultural Context

Glycyrrhizic acid is the main sweet component of Glycyrrhiza glabra root, historically utilized in food and cosmetic products. However, specific traditional medicine systems or uses are not detailed in the provided research.

Health Benefits

• Exhibits potential anti-inflammatory effects, as indicated by preclinical studies.[3] • Shows promise against viral infections, though human studies are lacking.[4] • May offer liver protection based on pharmacological data from non-human studies.[4] • Demonstrates potential anti-tumor activities in preclinical settings.[4] • Enhances drug solubility and stability, increasing the bioavailability of lipophilic drugs.[3]

How It Works

Glycyrrhizic acid inhibits 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), preventing the conversion of cortisol to cortisone and thereby potentiating glucocorticoid activity at mineralocorticoid receptors. It also suppresses the NF-κB signaling pathway, reducing transcription of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Additionally, glycyrrhizic acid undergoes hydrolysis in the gut to its active metabolite glycyrrhetinic acid, which inhibits phospholipase A2 and 15-hydroxyprostaglandin dehydrogenase, further modulating the arachidonic acid cascade.

Scientific Research

Currently, there are no specific human clinical trials or meta-analyses directly cited in the research for glycyrrhizic acid. The evidence is primarily based on preclinical studies and pharmacological reviews.[3][4]

Clinical Summary

Most evidence supporting glycyrrhizic acid comes from in vitro and rodent studies, with limited robust human clinical trials. A small number of Japanese clinical studies using intravenous glycyrrhizin (a glycyrrhizic acid formulation) at doses of 40–240 mg/day demonstrated reductions in liver enzyme levels (ALT, AST) in chronic hepatitis C patients, though sample sizes were generally under 200 participants. Antiviral activity against SARS-CoV, HIV, and herpes simplex virus has been demonstrated in cell culture models, but no phase III human trials confirm these effects. Anti-tumor data remains exclusively preclinical, limiting any efficacy claims for human oncological applications.

Nutritional Profile

Glycyrrhizic acid is a purified triterpenoid saponin compound, not a whole food ingredient, and therefore lacks conventional macronutrient or micronutrient composition. Key chemical and bioactive profile includes: Molecular formula C42H62O16, molecular weight approximately 822.93 g/mol. It is the primary bioactive glycoside of licorice root (Glycyrrhiza glabra), constituting roughly 2–25% of dried licorice root by weight depending on species and extraction method. Structurally, it consists of a glycyrrhetic acid aglycone (an oleanane-type pentacyclic triterpene) linked to two glucuronic acid moieties, which confer its amphiphilic surfactant properties responsible for enhanced drug solubility and bioavailability as a pharmaceutical excipient. Caloric contribution is negligible at standard pharmacological doses (typically 50–500 mg/day in studied contexts). Bioavailability: Oral bioavailability is low in its intact form (~2–3%) due to poor intestinal absorption; gut microbiota hydrolyze it to the more bioavailable aglycone 18β-glycyrrhetic acid, which reaches systemic circulation more readily and is considered the primary active metabolite. It contains no vitamins, dietary minerals, fiber, or protein in its isolated compound form. Sweetness potency is approximately 50 times that of sucrose, though this is an organoleptic property rather than a nutritional one. At doses exceeding 100 mg/day chronically, it inhibits 11β-hydroxysteroid dehydrogenase type 2, leading to pseudohyperaldosteronism, hypokalemia, and elevated blood pressure, which are important safety-relevant pharmacological properties.

Preparation & Dosage

No clinically studied dosage ranges for glycyrrhizic acid in extract, powder, or standardized forms are available. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

Arabinogalactan, carotenoids, lipophilic drugs

Safety & Interactions

Chronic intake exceeding 100 mg/day of glycyrrhizic acid can cause pseudohyperaldosteronism, characterized by sodium retention, hypokalemia, hypertension, and edema due to 11β-HSD2 inhibition. It is contraindicated in individuals with hypertension, hypokalemia, chronic kidney disease, liver cirrhosis, and during pregnancy, as it may elevate fetal cortisol exposure and has been linked to preterm birth in epidemiological data. Glycyrrhizic acid may potentiate corticosteroid drugs, interact with antihypertensives by counteracting their effects, and increase the toxicity of cardiac glycosides such as digoxin through potassium depletion. The European Scientific Committee on Food established a tolerable daily intake of 100 mg glycyrrhizic acid for adults, recommending that food and supplement sources be combined when assessing exposure.