WASHINGTON, Aug. 21, 2017 -- Licorice roots have a diverse and flavorful history, having been used in ancient Egyptian times as a tea and in traditional Chinese medicines, all the way to today as a flavoring agent and as an ingredient in some licorice candies. Some women now take licorice extracts as supplements to treat hot flashes and other menopausal symptoms. But scientists caution that the substance could pose a health risk by interacting with medications.
The researchers are presenting their results today at the 254th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features nearly 9,400 presentations on a wide range of science topics.
"Concerns about the risk of stroke and breast cancer associated with conventional hormone therapy are prompting women to seek alternatives," Richard B. van Breemen, Ph.D., says. "Some take botanical dietary supplements, such as licorice, to treat menopausal symptoms like hot flashes."
But just because a substance is sold as a supplement in a health food store doesn't mean it is completely safe for all people to take. And on its own, even as a candy, licorice can be harmful in some cases. The U.S. Food and Drug Administration recommends that licorice not be eaten in large amounts during one sitting, and warns that excessive consumption can lead to irregular heart rhythm and muscle fatigue.
"Consuming too much licorice 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," says van Breemen, who is at the University of Illinois at Chicago. "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." He points out that these changes could pose a significant safety risk to those who take a daily licorice dietary supplement along with other medication.
Van Breemen's team analyzed how three types of licorice -- two North American species, Glycyrrhiza uralensis and G. inflata, and a European species called G. glabra -- affected liver enzymes involved in drug metabolism. They found that all three species inhibit several of these enzymes. Only G. uralensis and G. inflata extracts were found to induce some of these enzymes. Therefore, the researchers say that G. uralensis and G. inflata are more likely to interfere with drug metabolism when compared to G. glabra.
Consumers would have a difficult time using this information, however, because most supplements don't list the species on their labels. But the researchers are using this knowledge to develop their own licorice therapy that would be safe and effective for women experiencing menopausal symptoms, such as hot flashes. They plan to start clinical trials on their G. glabra-based supplements next year.
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Van Breemen's work was funded by the National Institutes of Health.
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Title
Pharmacokinetic interactions between drugs and licorice botanical dietary supplements used by menopausal women
Abstract
Concerns regarding increased risks of stroke and breast cancer have prompted many women to consider botanical dietary supplements instead of conventional hormone therapy for the management of menopausal symptoms such as hot flashes. Among botanical supplement alternatives to hormone therapy, licorice (Glycyrrhiza sp.) is an increasingly popular alternative and has a long history of use in Traditional Chinese Medicine as well as in Western pharmacopeias. To ensure the safe use of licorice dietary supplements, we investigated their potential for drug interactions. Standardized licorice extracts of Glycyrrhiza glabara, G. inflata, and G. uralensis, the three most common species used in dietary supplements, were studied for possible inhibition or induction of cytochrome P450 enzymes involved in drug metabolism. In studies using human liver microsomes and a cocktail probe substrate assay, all three licorice species showed inhibition of CYP2B6, CYP2C8, CYP2C9 and CYP2C19. G. inflata also inhibited CYP1A2, CYP2D6, and CYP3A4. Cryopreserved human hepatocytes were used to predict effects of the extracts and individual licorice compounds on cytochrome P450 enzyme induction. CYP3A4 was unaffected by all Glycyrrhiza sp, and CYP1A2 and CYP2B6 were induced in hepatocytes by G. uralensis and G. inflata. Due to these data, dietary supplements containing G. uralensis and G. inflata are more likely than G. glabra to cause clinically relevant drug interactions.