Glycyrrhizic acid: the assessment of a no effect level

Abstract

<jats:p> Because from earlier experiments in rats and a pilot study in humans a no effect level of glycyrrhizic acid could not be established, a second experiment was performed in healthy volunteers. The experiment was performed in females only, because the effects were most marked in females in the pilot study. Doses of 0, 1, 2 and 4 mg glycyrrhizic acid/kg body weight were administered orally for 8 weeks to 39 healthy female volunteers aged 19-40 years. </jats:p><jats:p> The experimentlasted 12 weeks including an adaptation and a “wash-out” period.Ano-effectlevel of2 mg/kgis proposed from the results ofthis study, from which an acceptable daily intake (ADI) of 0.2 mg/kg body weight can be extrapolated with a safety factor of 10. This means consumption of 12 mg glycyrrhizic acid/day for a person with a body weight of 60 kg. This would be equal to 6 g licorice a day, assuming that licorice contains 0.2% of glycyrrhizic acid. </jats:p><jats:p> The proposed ADI is below the limit advised by the Dutch Nutrition Council of 200 mg glycyrrhizic acid/day. This reflects the relatively mild acute toxicity of glycyrrhizic acid, which is also emphasised by the “generally recognised as safe” (GRAS) status of glycyrrhizic acid in the USA in 1983. However, the long-term effects of a mild chronic intoxication (causing, for example, a mild hypertension), although not immediately lethal, justify special attention to the amount of glycyrrhizic acid used daily. </jats:p>

Inhibition of 11β–hydroxysteroid dehydrogenase type II selectively blocks the tumor COX-2 pathway and suppresses colon carcinogenesis in mice and humans

“…Long-term excessive ingestion of licorice has been reported to induce hypokalemia and elevation of blood pressure in a subset of people (20). Although these side effects were not seen with GA treatment in our experimental animals, nor have they been reported as a substantial limitation in studies of humans treated daily with comparable doses of GA for extended periods (19,45), we did observe that the concentrations of GA used in our studies increased levels of active CS in the kidney ( Figure 5D). Therefore, it is likely that if comparable doses of GA were used in humans, some percentage of patients would develop hypertension and/or hypokalemia, requiring treatment with the potassium-sparing diuretic amiloride.…”

Licorice Flavonoid Oil Effects Body Weight Loss by Reduction of Body Fat Mass in Overweight Subjects

“…LFO is prepared via a sequence of processes: extracting the roots of licorice G. glabra with ethanol, re-extracting with MCT, and standardizing the final concentration of glabridin, a major polyphenol flavonoid, to 1%. The concentration of glycyrrhizic acid, which induces a mineral corticoid action as the major side effect of licorice root, 31,32) is reduced to below 0.005% by the above processing. Licorice root and its extracts are highly safe food ingredients that have been widely consumed since ancient times and also are registered as Generally Recognized As Safe (GRAS) by the FDA in the U.S.…”

Glycyrrhizic acid toxicity caused by consumption of licorice candy cigars

“…13 The licorice candy cigars consumed by this patient each weigh 19 g and contain 0.45 g of GZA according to information obtained directly from the Ontario manufacturer (Maria Miller, consumer representative, The Hershey Company: personal communication, 2007). Based on this, the patient consumed an estimated 1.8-3.2 g of GZA per day, which is significantly below the amount generally believed to cause symptoms.…”

“…Based on this, the patient consumed an estimated 1.8-3.2 g of GZA per day, which is significantly below the amount generally believed to cause symptoms. [13][14][15] Of note, potassium sorbate is an ingredient in the involved candy, and may have contributed to the patient being normokalemic. Additional ingredients of these licorice candy cigars include wheat flour, cooking molasses, liquid sugar, corn starch, salt, mineral oil, soy lecithin, natural flavour, dextrin, artificial colour and potassium sorbate.…”