Licorice Root

High-dose or prolonged licorice root use causes pseudoaldosteronism via inhibition of 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2). This enzyme normally inactivates cortisol in mineralocorticoid-sensitive tissues; its inhibition allows cortisol to activate mineralocorticoid receptors, causing sodium and water retention, hypokalemia, and hypertension. This pharmacological effect directly opposes antihypertensive medications and can render them ineffective.

Advise hypertensive patients to avoid licorice root supplements; limit to deglycyrrhizinated licorice (DGL). Monitor blood pressure carefully in patients who consume licorice confectionery regularly. If pseudoaldosteronism is suspected (uncontrolled hypertension, hypokalemia), discontinue licorice and re-evaluate antihypertensive regimen.

Glycyrrhizinic acid in licorice inhibits 11-beta-HSD2 and also inhibits 11-beta-HSD1, prolonging the plasma half-life of prednisolone and cortisol. This effectively potentiates corticosteroid activity and may amplify both therapeutic and adverse effects including Cushingoid features, osteoporosis, adrenal suppression, and hyperglycemia. Glycyrrhizin has been studied as a pharmacokinetic potentiator of prednisolone.

Patients on systemic corticosteroids must be cautioned against regular licorice root supplementation. Use only deglycyrrhizinated licorice (DGL) which lacks glycyrrhizinic acid. If co-administration has occurred, monitor for Cushingoid features, blood pressure, blood glucose, and potassium levels.

Both licorice (via pseudoaldosteronism) and potassium-wasting diuretics cause hypokalemia through different mechanisms. Licorice promotes renal potassium excretion via mineralocorticoid activation while loop and thiazide diuretics also promote renal potassium loss. Concurrent use produces synergistic potassium depletion with risk of severe hypokalemia, cardiac arrhythmias, and muscle weakness.

Avoid regular licorice root supplementation in patients on potassium-wasting diuretics. Monitor serum electrolytes regularly. Use DGL formulation if licorice is needed for GI indications. Advise adequate dietary potassium intake.

High-dose licorice induces hypokalemia through pseudoaldosteronism via 11-beta-HSD2 inhibition. Hypokalemia dramatically increases myocardial sensitivity to digoxin by reducing competitive displacement of digoxin from Na+/K+ ATPase, amplifying positive inotropic and electrophysiological effects. This can precipitate life-threatening digoxin toxicity even at previously well-tolerated digoxin doses.

Avoid licorice root entirely in patients on digoxin. If a patient on digoxin has been consuming licorice, check serum potassium and digoxin levels urgently. Correct hypokalemia before adjusting digoxin dose. Monitor ECG for signs of digoxin toxicity including AV block and ventricular arrhythmias.

Glycyrrhiza glabra extracts demonstrated inhibition of CYP2C9, CYP2C8, and CYP2C19 in preclinical studies. CYP2C9 is the primary enzyme metabolizing S-warfarin; inhibition could increase warfarin plasma levels and INR. A Phase I clinical trial with standardized DGL extract found no clinically significant CYP interactions at therapeutic doses, suggesting the concern applies primarily to high-glycyrrhizin whole-root preparations.

High-dose, high-glycyrrhizin licorice preparations should be avoided with warfarin. DGL formulations appear lower risk. If a patient uses whole licorice root, monitor INR. Advise patients to report changes in bleeding tendency or INR values.

Glycyrrhizic acid (GA) and its metabolite glycyrrhetinic acid (GA) inhibit 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), allowing excess cortisol to activate mineralocorticoid receptors in the kidney, causing sodium/water retention, hypertension, and hypokalemia — a state of pseudohyperaldosteronism. Spironolactone and eplerenone are mineralocorticoid receptor antagonists prescribed to counteract aldosterone excess. When licorice simultaneously activates mineralocorticoid pathways, these drugs are functionally antagonised. A clinical study in 32 women with PCOS showed that combining spironolactone with 3.5 g/day licorice significantly modulated the renin-aldosterone axis.

High-dose or long-term licorice use will antagonise spironolactone and eplerenone. Patients with heart failure, primary hyperaldosteronism, or PCOS prescribed potassium-sparing diuretics should avoid significant licorice intake. Monitor potassium levels and blood pressure. Deglycyrrhizinated licorice (DGL) lacks glycyrrhizin and is safe for these patients.

Licorice root contains components (including liquiritigenin and isoliquiritigenin) that have demonstrated monoamine oxidase inhibitory properties in preclinical assays, potentially increasing monoamine neurotransmitter levels. When combined with pharmaceutical MAOIs, additive or synergistic inhibition could amplify serotonergic, dopaminergic, and adrenergic activity, increasing the risk of hypertensive crisis, serotonin syndrome, and other monoamine-related adverse effects.

Avoid combining licorice root with MAOI antidepressants. This combination carries risk of serotonin syndrome and hypertensive crisis — both potentially life-threatening. At minimum, a 14-day washout period after MAOI discontinuation should precede licorice supplementation, and vice versa. Patients must be counselled to disclose all botanical use to their prescribers.

Glycyrrhetinic acid inhibits 17β-hydroxysteroid dehydrogenase and 5-alpha reductase, enzymes involved in androgen biosynthesis. Clinical studies have demonstrated that licorice consumption (7 g/day for one week) significantly reduced serum testosterone in healthy men. This anti-androgenic activity could antagonise the therapeutic effect of exogenous testosterone replacement therapy or androgenic medications. Glabridin also has anti-androgenic properties.

Advise male patients on testosterone replacement therapy to avoid significant licorice intake. Monitor testosterone levels if licorice cannot be avoided. Female patients using DHEA supplements should also be aware of this interaction. Effects are reversible upon licorice discontinuation.