Practice Essentials
Natural licorice is an extract from the root of Glycyrrhiza glabra, a 4- to 5-foot woody shrub that contains glycyrrhizic acid (GZA) and grows in subtropical climates in Europe, the Middle East, and Western Asia. Licorice extracts and its principal component, glycyrrhizin, have extensive use in foods, tobacco products, and snuff, and in traditional and herbal medicine.
As a result of these extensive applications, estimated consumption of licorice and glycyrrhizin in the United States is high: 0.027-3.6 mg glycyrrhizin per kilograms per day. [1] However, many candies marketed as licorice (eg, red licorice) have artificial licorice flavoring and do not contain glycyrrhizin. Licorice root that is sold as a dietary supplement can be found with the glycyrrhizin removed, resulting in a product known as deglycyrrhizinated licorice, or DGL. [2]
Licorice poisoning is rare. However, regular licorice ingestion can result in hypokalemia, hypernatremia, and water retention (see Presentation and Workup). Emergency treatment of licorice poisoning is largely supportive and consists primarily of monitoring for electrolyte abnormalities (especially of potassium) and other complications, with correction if necessary (see Treatment).
Background
Licorice (or liquorice) is a plant of ancient origin and steeped in history. Licorice has been used as a medicinal agent in a number of cultures, [3] dating back to ancient Egypt and China. Medicinal uses have included the following:
Licorice flavor is found in a wide variety of licorice candies. Licorice is also found in some soft drinks (eg, root beer) and is in some herbal teas where it provides a sweet aftertaste. [11]
Licorice extract (block, powder, or liquid) may be applied to cigarette tobacco at levels of about 1-4% to enhance and harmonize the flavor characteristics of smoke, improve moisture-holding characteristics of tobacco, and act as a surface-active agent for ingredient application. [12]
Pathophysiology
Natural licorice possesses both mineralocorticoid properties and glucocorticoid properties. Most licorice-flavored foods available in the United States do not contain GZA, and they do not produce the hypermineralocorticoid syndromes observed with the long-term consumption of moderate-to-significant amounts of natural licorice.
Consumption of large doses of GZA in licorice extract can lead to hypokalemia and serious hypertension, a syndrome known as hypermineralocorticoidism. [13, 14] Biochemical studies indicate that glycyrrhizinates inhibit 11-beta-hydroxysteroid dehydrogenase (type 2), the enzyme responsible for inactivating cortisol through conversion to cortisone. As a result, a continuous, high-level exposure to glycyrrhizin compounds can produce hypermineralocorticoid-like effects in both animals and humans. These effects are reversible upon withdrawal of licorice or glycyrrhizin. [1]
In the kidney, cortisol activation of mineralocorticoid receptors alters renal tubular exchange of sodium (retained), potassium (excreted), and hydrogen ions (excreted); producing an increased extracellular volume (hypertension, [15] edema), hypokalemia (weakness, muscle spasm), [16] and metabolic alkalosis. [17]
Pseudoprimary aldosteronism from chronic licorice ingestion is characterized by low serum and urinary aldosterone levels and decreased serum renin activity. This differs from true primary hyperaldosteronism caused by aldosterone-producing adenomas or primary adrenal hyperplasia, which is characterized by elevated urine and serum aldosterone levels.
Licorice can reduce the serum testosterone level, probably by blocking 17-hydroxysteroid dehydrogenase and 17,20 lyase. [18] Licorice has therefore been considered an adjuvant therapy of hirsutism and polycystic ovary syndrome. [19]
The exact amount of ingested GZA that produces mineralocorticoid toxicity is unclear. A meta-analysis to assess the effect of chronic ingestion of licorice found the mean daily dose of glycyrrhizic acid across 18 studies was 377.9 mg, which is approximately 189 g of black licorice a day, assuming 2.0 mg g−1 (0.2% w/w) glycyrrhizic acid in black licorice. However, the concentration of glycyrrhizic acid changes significantly dependent on the product. Licorice findings range between 0.26 and 7.9 mg g−1, while in health products the range was 0.30 to 7.9 mg g−1. A typical pack of Liquorice Allsorts was found to contain 91.0 mg, a serving of licorice tea contained 20.0 mg and a single licorice pipe contained 4.6 mg. With only limited and sporadic consumption of licorice, it would be difficult to ingest more than 500 mg of glycyrrhizic acid per day. Assuming an average concentration of 2.0 mg g−1 for black licorice confectionery, it would require consumption of 250 g per day to reach 500 mg of glycyrrhizic acid daily. While this quantity is relatively high, but as evidenced by numerous case reports, a small portion of the population does consume licorice at these levels. [20]
Prognosis
Patients generally fully recover with discontinuation of exposure. After licorice exposure is discontinued, spontaneous correction of hypertension and hypokalemia generally occur within several weeks; however, months may pass before the renin-aldosterone system becomes active again. [21] Muscle weakness/paralysis may resolve within days of potassium replacement.
Severe, and sometimes fatal, complications following ingestion of licorice can occur. In these cases, significant quantities of licorice have typically been consumed in the short- to medium-term. Reported complications include rhabdomyolysis, hypertensive encephalopathy and cardiac arrest and death. [20]
