Liquorice Toxicity: A Comprehensive Narrative Review

Abstract

Background: Renowned since ancient times for its medical properties, liquorice is nowadays mainly used for flavoring candies or soft drinks. Continuous intake of large amounts of liquorice is a widely known cause of pseudo-hyperaldosteronism leading to hypertension and hypokalemia. These manifestations are usually mild, although in some cases may generate life-threatening complications, i.e., arrhythmias, muscle paralysis, rhabdomyolysis, and coma. In addition, liquorice has an important estrogenic-like activity. Methods: We summarized the current knowledge about liquorice and reviewed 104 case reports in both the English and Italian languages from inception to June 2023 concerning complications due to an excess of liquorice intake. Results: In contrast to most published data, female sex and old age do not appear to be risk factors. However, hypertension and electrolyte imbalance (mainly hypokalemia) are prevalent features. The detection of glycyrrhetinic acid in blood is very uncommon, and the diagnosis is essentially based on an accurate history taking. Conclusions: Although there is not a significant mortality rate, liquorice toxicity often requires hospitalization and therefore represents a significant health concern. Major pharmaceutical drug regulatory authorities should solicit public awareness about the potentially dangerous effects caused by excessive use of liquorice.

The King of Chinese Medicine——Glycyrrhiza glabra (Licorice): All-round Inquiry in its Chemical Composition, Pharmacodynamics, Traditional and Medicinal Value

“…Studies have found that glycyrrhizic acid has a variety of pharmacological properties, including anti-inflammatory, antiviral, antitumor, antioxidant, and anti-allergic activities that contribute to the recovery and protection of the alimentary, respiratory, nervous, endocrine, and cardiovascular systems. In the human body, glycyrrhizic acid is broken down into glycyrrhizinic acid by intestinal bacteria, which possesses various pharmacological activities and has been widely researched and used for the treatment of various diseases [12,13] .…”

“…Aldosterone regulates Na-K exchangers, epithelial Na channels, renal outer medullary K channels, aquaporins, and bicarbonate-chloride antiporters via MR activation. In vitro studies revealed that both glycyrrhizic acid and GA exhibit inhibitory effects on 11β-hydroxysteroid dehydrogenase-type 2 (11β-HSD2), which leads to an excessive production of mineralocorticoids [87] , with the potency of GA inhibition being approximately 200 times greater than that of glycyrrhizic acid [13] . Within the renal glomeruli, this event elicits a pronounced aldosterone-like response, resulting in enhanced Na reabsorption and K excretion [85,88,89] .…”

“…The toxicity threshold of glycyrrhizic acid as defined by the World Health Organization is 100 mg/day. However, significant variability exists based on factors such as age, sex, concomitant medication use, and comorbidities (eg, essential arterial hypertension, chronic renal failure, and hepatic failure) [13] . After oral intake, licorice is converted into glycyrrhizic acid in the gut, which is hydrolyzed to GA by the β-glucuronidase in gut microbiota.…”

Exploring Influence of Production Area and Harvest Time on Specialized Metabolite Content of Glycyrrhiza glabra Leaves and Evaluation of Antioxidant and Anti-Aging Properties

“…Besides, it is also used as natural sweetener and flavor additive in foods, beverages, functional foods, and food supplements [2,3]. However, excessive consumption of licorice can lead to some side effects such as hypertension and edema [4]. A particularly distinctive feature of Calabrian G. glabra is its lower content of glycyrrhizin [5], which is the compound responsible for the sweet taste of roots but also for the hypertensive effects.…”