Extracts from the three types of liquorice used most often in supplements inhibited liver enzymes involved with the metabolism of prescription and over-the-counter drugs, discovered a the research team from the University of Illinois College of Pharmacy, Chicago.
“The three liquorice species commonly used in botanical dietary supplements have varying potential for drug-botanical interactions as inhibitors of cytochrome P450 (CYP) isoforms. Each species of liquorice displays a unique profile of constituents with potential for drug interactions,” concluded lead researcher Richard van Breemen.
Although it is widely recognised that consuming excess liquorice may raise blood pressure (due to the saponin glycyrrhizin), this is the first in-depth analysis of how individual species-specific liquorice compounds impact on the main CYP enzymes.
"Consuming too much liquorice can be harmful, but in our lab, we wondered whether the small amounts in dietary supplements might also cause problems by interfering with drug metabolism or transportation," said van Breemen. "The liver has enzymes that process medications, and if these enzymes are induced or inhibited, the drugs will either be processed too quickly or too slowly, respectively."
The findings highlight the need to label the species of liquorice used in individual supplement formulations, thereby minimising possible drug interactions.
“It is important that the liquorice raw materials used for the production of dietary supplements be botanically identified to the species level with a full disclosure of both the species identity and mode of preparation/extraction on the product labels, ” recommended the team.
Species-specific compounds
Previous research has reported that liquorice root extract may have a number of beneficial effects including liver protective, anti-inflammatory, anti-viral and relief of hot flushes during menopause.
The liquorice family (genus Glycyrrhiza) has around 30 different species, of which G. glabra, G. uralensis and G. inflata are the most commonly used in supplements. This study identified 14 specific constituents present in one or more of these species, which had an effect on CYP enzymes.
The researchers analysed the effects of the different types of liquorice on the enzymes set out in the Food & Drug Administration guidelines for drug interactions. Additionally they included CYP2A6 and CYP2E1. The former enzyme is responsible for metabolism of nicotine, while the latter is involved with processing of alcohol, caffeine, and the painkillers paracetamol and chlorzoxazone.
The scientists explained that different species are used interchangeably in European and Chinese Pharmacopoeias, and that a lack of disclosure exists regarding individual formulation content. Each species has differing amounts of each active ingredient and the inhibitory effect on each enzyme is compound specific. Thus, it becomes difficult to predict the extent of interaction of a given supplement brand with medicinal drugs, alcohol or nicotine, they argued.
The six most potent CYP inhibitors were lichochalcone A (found primarily in G. inflata), licoricidin glycoumarin, glabridin, isoliquiritigenin, and 18β-glycyrrhetinic acid.
“Several liquorice characteristic compounds responsible for inhibiting these enzymes were identified, and among them were the species-specific compounds glabridin, glycycoumarin and more importantly licochalcone A. Because each of the liquorice species showed a unique pattern of enzyme inhibition, different drug-botanical interactions may be expected for each,” they stated.
The scientists plan to use their knowledge of the species-specific interactions to develop a safe and effective liquorice therapy for hot flushes in menopausal women. Clinical trials are planned for their G. glabra-derived supplements in 2018.
Source: European Journal of Pharmaceutical Sciences
Volume 109, pp 182-190 Published online ahead of print. DOI: 10.1016/j.ejps.2017.07.034
“Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents”
Authors: Guannan Li, Richard B van Breemen et al.