Licorice root glycyrrhizin: the pseudoaldosteronism risk people keep missing

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Real (non-deglycyrrhizinated) licorice root remains a leading cause of severe hypokalemia, secondary hypertension, and cardiac arrhythmia in people who consume it as a tea, candy, or "adrenal support" supplement. The mechanism is well characterized, the dose threshold is lower than most people expect, and the case reports continue to accumulate across emergency departments worldwide. It is one of the clearest examples of a "natural" product with a genuinely dangerous, dose-dependent pharmacology.

The Molecule and Its Mineralocorticoid Mimicry

Glycyrrhizin is hydrolyzed in the gut to glycyrrhetinic acid, which inhibits 11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme normally inactivates cortisol to cortisone in mineralocorticoid-target tissues, including the renal collecting tubule. When 11β-HSD2 is inhibited, endogenous cortisol acts on the mineralocorticoid receptor, producing apparent (or "pseudo-") mineralocorticoid excess: sodium retention, potassium wasting, hypertension, and metabolic alkalosis, with suppressed plasma renin and aldosterone confirming the diagnosis.

The Threshold Is Lower Than People Expect

European food-safety review has identified that regular consumption above roughly 100 mg/day of glycyrrhizin is associated with adverse cardiovascular and metabolic effects in susceptible individuals. Black licorice candies often contain 100–200 mg of glycyrrhizin per ounce; licorice teas vary widely; and "adrenal support" supplements may deliver 200–500 mg per daily dose. Doses considered acceptable for short-term peptic-ulcer use in classical pharmacology overlap with the dietary toxicity range, so the line between "flavoring" and "drug" is thinner than the product category suggests.

The Case-Report Literature

Cases of life-threatening hypokalemia, including ventricular arrhythmia, rhabdomyolysis, hypertensive crisis, and acute pulmonary oedema, have been reported in association with licorice from teas, candy, and "natural cortisol modulator" supplements. Published case series of licorice-induced pseudohyperaldosteronism repeatedly show the same triad — hypertension, hypokalemia, and suppressed renin and aldosterone — resolving over weeks once the licorice is stopped, sometimes requiring mineralocorticoid-receptor blockade and potassium repletion in the interim. An FDA consumer advisory specifically warns about black licorice candy. Increasingly, the offending product is an unregulated "liver support" or "adrenal" supplement rather than confectionery, which makes the history even easier to miss.

Who Is Most at Risk

Risk is amplified by older age, female sex, lower baseline body weight, concurrent diuretic use (especially loop or thiazide), low dietary potassium, and existing hypertension. Polymorphisms in the gene encoding 11β-HSD2 make some individuals highly sensitive. Pregnancy is a particular concern: in a Finnish birth-cohort study, children exposed to high maternal glycyrrhizin intake scored lower on tests of cognition and had higher odds of attention problems, alongside altered pubertal timing — a signal serious enough that several authorities advise pregnant women avoid high licorice intake entirely.

Drug Interactions

Licorice works against antihypertensive and antiarrhythmic therapy through its mineralocorticoid mechanism. Concurrent diuretics, corticosteroids, digoxin, or QT-prolonging agents are dangerous combinations, because hypokalemia potentiates digoxin toxicity and arrhythmia risk. The interaction with antihypertensive therapy is the most clinically important: a patient with treated hypertension may experience a refractory pressure rise that resolves only when the licorice is identified and stopped.

DGL Is Safer Because Glycyrrhizin Is Removed

Deglycyrrhizinated licorice (DGL) — manufactured by extracting the glycyrrhizin — is sold for gastric mucosal use and does not carry the same hypertension risk, because the mineralocorticoid-mimicking molecule has been removed. The two preparations should never be conflated. DGL is the appropriate form for gastric use; whole glycyrrhizin-containing licorice is the appropriate form for essentially nothing widely indicated as a supplement.

What Clinicians Should Ask — and What "Adrenal Support" Really Means

In any patient with refractory hypertension, unexplained hypokalemia, metabolic alkalosis, or rhabdomyolysis, ask specifically about licorice candy, teas, traditional-medicine preparations, and "adrenal" or "cortisol" supplements. The history is frequently missed because patients do not think of licorice as a drug. Discontinuation generally restores potassium and pressure over one to four weeks; severe cases need active potassium repletion, sometimes with potassium and magnesium correction under supervision. It is worth being blunt about the "adrenal fatigue" framing that sells these products: there is no controlled evidence that licorice "supports" the adrenal glands, and the adaptogens commonly marketed in the same aisle — ashwagandha, rhodiola, and holy basil — have, at best, modest stress-related data and do not justify a glycyrrhizin load. Products built around DHEA or Panax ginseng raise separate cautions of their own. The safest move for almost everyone is to keep glycyrrhizin out of a daily supplement regimen entirely.