Licorice has been known to cause hypertension, hypokalemia, and edema.  It is contraindicated in people who have chronic liver diseases, hypokalemia, hypertonia, and renal disease. 

A well-documented adverse effect of Licorice ingestion is the Syndrome of Apparent Mineralocorticoid Excess (AME).  Aldosterone is the main mineralocorticoid in the human body and is made in the adrenal gland.  Its effects are sodium and water retention and potassium loss in the kidney leading to increased blood pressure and hypokalemia, respectively.  This link was first made with the description of children in whom this syndrome was discovered.  They developed hypertension with signs of hypokalemia, metabolic alkalosis and suppression of the intrinsic renin-angiotensin-aldosterone system, which partially controls the body’s blood pressure regulation. Much research has been done to determine the mechanism responsible for these effects.  Apparently, the glycyrrhetinic acid in Licorice inhibits the enzyme 11-beta-hydroxysteroid dehydrogenase, which is responsible for metabolizing endogenous glucocorticoids (steroids) to an inactive form.  This leads to increased levels of active glucocorticoids in the body. Glucocorticoids are made in the adrenal gland as well and have activity at mineralocorticoid (Aldosterone) receptors, leading to the syndrome of apparent mineralocorticoid excess.

A 2001 study published in the Journal of Human Hypertension by Sigurjonsdottir, demonstrated a linear dose-response relationship to licorice-induced rise in blood pressure.  Healthy volunteers consumed licorice in variable doses, 50-200 g/day, for 2-4 weeks, corresponding to a daily intake of 75-540 mg of glycyrrhetinic acid.  The individual response to the licorice followed a normal distribution, systolic blood pressure increased by 3.1-14.4 mm Hg and demonstrated a dose-dependant response, but not a time-response relationship.  Even the lowest doses of 50 g of licorice consumed daily for two weeks was found to cause a significant increase in blood pressure from baseline. These findings could have important implications to patients already being treated for hypertension.

Numerous case reports have been released documenting these adverse effects in patients who have consumed Licorice.  Cumming et al. reported a case of a 70-year-old woman who was admitted to the hospital with a flaccid quadriplegia caused by severe hypokalemia.  The effect was attributed to the intake of relatively small amounts of licorice taken in combination with antihypotensive treatment.  Similar symptoms have been reported after the ingestion of 20 to 40 grams of licorice daily over two years, which resolved quickly when potassium was replaced and licorice was discontinued.

One case reported by Eriksson et al. in the Journal of Internal medicine, was of a 44-year-old female who presented to the hospital with a life-threatening ventricular tachycardia.  She displayed repeated episodes of Torsades de Pointes, a cardiac arrhythmia that is fatal if not treated immediately.  Her serum potassium was low at 2.3 mmol/L.  After being treated with potassium and magnesium infusions, her arrhythmias ceased.  Her work up showed no evidence of Cushing’s syndrome or hyperaldosteronism as the cause of her electrolyte abnormalities. It then was revealed that the patient had been ingesting moderately large amounts of licorice every day for four months.  After discontinuing the licorice, the patient remained symptom free after more than a year later.

In the American Journal of Nephrology, Russo described two cases of hypertensive encephalopathy from low-dose, daily intake of licorice.  Although this complication had not been previously documented, it has been proposed that some people may be more susceptible to low doses of glycyrrizic acid because of an already deficient level of 11 beta-hydroxysteroid dehydrogenase.