Licorice root glycyrrhizin: the pseudoaldosteronism risk people keep missing

Real (non-deglycyrrhizinated) licorice root remains a leading cause of severe hypokalemia, secondary hypertension, and cardiac arrhythmia in patients who consume it as a tea, candy, or 'adrenal support' supplement. The mechanism is well characterized, the dose threshold is low, and the case reports continue to accumulate across emergency departments worldwide.

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 mineralocorticoid excess: sodium retention, potassium wasting, hypertension, and metabolic alkalosis.

The threshold is lower than people expect

EFSA's 2006 opinion identified that regular consumption of more than 100 mg/day of glycyrrhizin is associated with adverse cardiovascular and metabolic effects in susceptible individuals [1]. Black licorice candies often contain 100–200 mg glycyrrhizin per ounce; licorice teas vary widely; 'adrenal support' supplements may contain 200–500 mg of glycyrrhizin per daily dose. Doses 'safe' for short-term peptic ulcer use in classical pharmacology (carbenoxolone 100–300 mg/day) overlap with the dietary toxicity range.

The case-report literature

Cases of life-threatening hypokalemia, including ventricular arrhythmia and rhabdomyolysis, have been reported in association with licorice consumption from teas, candy, chewing tobacco substitutes, and 'natural cortisol modulator' supplements [2]. A pivotal case series from the Netherlands documented hospitalizations from licorice intake as low as 50–100 g of candy per day for several weeks [3]. An FDA consumer advisory exists specifically for black licorice candy after Halloween.

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 HSD11B2 cause some individuals to be highly sensitive. Pregnancy is a particular concern — high gestational glycyrrhizin exposure has been associated with adverse cognitive and behavioral outcomes in offspring in Finnish cohort studies [4].

Drug interactions

Licorice potentiates antihypertensive and antiarrhythmic effects opposingly via the mineralocorticoid mechanism. Concurrent diuretics, corticosteroids, digoxin, or QT-prolonging agents are dangerous combinations. Hormonal contraceptive interaction is documented but variable. The interaction with antihypertensive therapy is the most clinically important — patients with treated hypertension may experience refractory pressure rise with concurrent licorice.

DGL is safer because glycyrrhizin is removed

Deglycyrrhizinated licorice (DGL) — manufactured by extracting glycyrrhizin — is sold for gastric ulcer use and does not carry the same hypertension risk because the active mineralocorticoid-mimicking molecule has been removed. The two preparations should not be conflated in clinical conversations.

What clinicians should ask

In any patient presenting 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 1–4 weeks; severe cases require active potassium repletion.

The bottom line

Whole licorice root containing glycyrrhizin should be avoided in anyone with hypertension, cardiac disease, kidney disease, low body weight, pregnancy, or on diuretic therapy. The supplement-marketing claim of 'adrenal support' has no controlled evidence behind it and a substantial safety case against it. DGL is the appropriate form for gastric mucosal use; whole licorice is the appropriate form for nothing widely indicated.