Licorice (Glycyrrhizin)
Glycyrrhizin (and its metabolite glycyrrhetinic acid) is the active compound in licorice root. Rather than lowering cortisol, it inhibits the enzyme 11-beta-HSD2 in the kidney, preventing local breakdown of cortisol to inactive cortisone — so cortisol lingers and acts on mineralocorticoid receptors. This raises effective cortisol activity, causing pseudohyperaldosteronism: hypertension, sodium retention and potassium loss. Relevant as something athletes should be careful with, not a cortisol-lowering aid.
01 Overview
Licorice's glycyrrhizin is metabolised to glycyrrhetinic acid, which inhibits renal 11-beta-hydroxysteroid dehydrogenase type 2. Normally this enzyme converts cortisol to inactive cortisone at the kidney, protecting the mineralocorticoid receptor from cortisol; when it is blocked, cortisol activates that receptor like aldosterone. The result is sodium and water retention, high blood pressure and low potassium — a well-documented cause of hypertension in heavy licorice consumers.
Contrary to the intuitive framing, licorice therefore effectively increases glucocorticoid/mineralocorticoid action rather than blunting cortisol. It is included here because it is a common OTC/herbal cortisol-axis modulator, and because athletes using it (for GI or throat remedies, or in some 'adrenal support' products) can develop meaningful hypertension and hypokalaemia. Deglycyrrhizinated licorice (DGL) removes glycyrrhizin and avoids these effects.
02 Mechanism
Glycyrrhetinic acid inhibits renal 11-beta-HSD2, preventing conversion of cortisol to cortisone so cortisol activates mineralocorticoid receptors (apparent mineralocorticoid excess).
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Effect threshold | 100 mg/day | Oral | ~100 mg/day glycyrrhizin can begin to raise BP; effects vary by sensitivity. |
| Typical exposure | 200–400 mg/day | Oral | Heavy licorice/confectionery or supplement intake associated with pseudohyperaldosteronism. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Increased effective cortisol activityProlongs local cortisol action at the kidney rather than lowering cortisol. | mineralocorticoid effect | Clinical | |
| Mild anti-inflammatory / mucosal soothingTraditional use for GI and throat complaints; some soothing effect on mucosa. | modest | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| HypertensionSodium/water retention raising blood pressure with regular glycyrrhizin intake. | Moderate | Dose-dependent | Clinical | |
| HypokalaemiaLow potassium that can cause weakness, cramps and arrhythmia in severe cases. | Severe | With heavy intake | Clinical |