How Much Is Too Much? Exploring Pseudohyperaldosteronism in Glycyrrhizic Acid Toxicity From Chronic Licorice Root Consumption

Abstract

Licorice has been around for centuries and has been commercialized in the food, tobacco, and healthcare industry. Historically, its therapeutic benefits have been reaped in countless ways, including as a thirst sensation suppressor in battlefields, flavoring agent in medicinal preparations, antacid for gastric discomfort and peptic ulcers, and even as an estrogenic agent in postmenopausal women. Licorice and its derivatives are recognized safe by the US Food and Drug Administration (FDA). Though FDA recognized the licorice to be a food additive in certain concentrations, it has issued warnings against its use in at-risk group and in larger amount. However, it is a lesser known fact that glycyrrhizic acid, the active component in licorice, can cause a metabolic syndrome presenting as pseudohyperaldosteronism. Chronic consumption leads to the development of hypertension, metabolic alkalosis, and hypokalemia. We present a patient who developed a sinus pause on telemetry and subsequent syncope after presenting for evaluation of hypertension and hypokalemia. The patient had been ingesting a significant quantity of deglycyrrhizinated licorice for many years to alleviate postprandial epigastric pain. Although seemingly benign electrolyte disturbance, it is crucial to recognize that chronic consumption of licorice without strict regulation can lead to supraventricular and ventricular ectopics and tachyarrhythmias with the potential to develop lifethreatening arrhythmias including ventricular tachycardia, ventricular fibrillation, and Torsades de Pointes.

Lethal Arrhythmia Induced by Licorice

“…A daily consumption of glycyrrhetinic acid of 95 mg or more may cause an increase in blood pressure. 3 4 5 In the present case, long-term use of licorice may induce pseudoaldosteronism with intractable hypokalemia, resulting in lethal polymorphic ventricular arrhythmias. As licorice could be taken without any prescription, final diagnosis was delayed due to unawareness of taking licorice.…”

Close Call From a Sweet Twist: A Case of Licorice-Induced Torsades De Pointes

“…Pseudohyperaldosteronism is a clinical condition characterized by sodium retention, hypertension, metabolic alkalosis, potassium wasting, and suppression of plasma renin and aldosterone levels [ 2 ]. The main active constituent of licorice is the prodrug glycyrrhizin, which is converted to 3β-monoglucuronyl-18β-glycyrrhetinic acid (3MGA) and 18β-glycyrrhetinic acid (GA) by intestinal bacteria possessing specialized β-glucuronidases [ 7 ].…”

“…The US Food and Drug Administration (FDA) recognizes licorice and its derivatives as safe; however, they have issued warnings about larger consumption in at-risk groups. Pseudohyperaldosteronism is one of its lesser-known side effects [ 2 ]. It is a clinical condition characterized by sodium retention, hypertension, metabolic alkalosis, potassium wasting, and suppression of plasma renin and aldosterone levels [ 2 ].…”

“…Pseudohyperaldosteronism is one of its lesser-known side effects [ 2 ]. It is a clinical condition characterized by sodium retention, hypertension, metabolic alkalosis, potassium wasting, and suppression of plasma renin and aldosterone levels [ 2 ]. This can be due to prolonged intake of products flavored with licorice such as licorice roots, teas, tobacco, herbal products, candies, breath fresheners, and even laxatives [ 3 ].…”

Severe Hypokalemia and Metabolic Alkalosis Caused by Licorice Discovered During the Treatment of Intraoperative Hypoxemia

“…Glycyrrhizin, the main component of licorice, inhibits 11-β-HSD2. It results in a relative increase in cortisol, leading to excess sodium reabsorption and potassium excretion, which can cause hypertension, hypokalemia, metabolic alkalosis, low plasma renin activity, and low plasma aldosterone levels (Figure 3 ) [ 4 - 7 ]. This may be the reason the elevated blood pressure persisted after the induction of anesthesia.…”