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Glycyrrhizic acid: the assessment of a no effect level

National Poisons Control Centre, National Institute of Public Health and the Environment, Bilthoven, Netherlands; Department of Intensive Care and Clinical Toxicology, Utrecht University Hospital, Utrecht, Netherlands; Vrijheid 1, 1231 TK Loosdrecht, Netherlands

J A Bijlsma

Department of Intensive Care and Clinical Toxicology, Utrecht University Hospital, Utrecht, Netherlands

W van Dokkum

TNO-Nutrition and Food Research, Zeist, Netherlands

T J F Savelkoull

National Poisons Control Centre, National Institute of Public Health and the Environment, Bilthoven, Netherlands; Department of Intensive Care and Clinical Toxicology, Utrecht University Hospital, Utrecht, Netherlands

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.

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.

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.

Key Words: glycyrrhizic acid • healthy volunteers • no-effect level • acceptable daily intake • atrial natriuretic peptide • renin-angiotensin-aldosterone axis

Human & Experimental Toxicology, Vol. 19, No. 8, 434-439 (2000)
DOI: 10.1191/096032700682694251


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