As I was searching for inspiration for my next article, I came across the National Day Calendar. As I was browsing through the list for this month, I saw that April 12th was National Licorice Day and that sparked my inspiration for this article.
One of the things that I regularly do as a practicing Dietitian is to review patient medication lists. You may wonder why a Dietitian would be reviewing patient medications and that is a fair question, after all I’m not a physician or a pharmacist. The reason that I have to review each patient’s medications list is because medications can have interactions with foods, supplements, and the metabolism of various nutrients. Those interactions can range from those of negligible concern to life-threatening interactions. So, I would be remiss if I didn’t keep an eye out for potential issues.
As I have spent time reviewing medications over the years, I quickly noticed that there were certain foods, herbs, and supplements that interact with medications more frequently than others. One food that frequently appears as an item of concern is licorice (usually listed as natural licorice, or black licorice). My patients are also usually confused regarding what is and isn’t licorice as some popular brands thought of as licorice are technically not.
So what exactly is licorice? The common answer I would expect to receive to that question would be “a type of candy””. There is a type of candy referred to as licorice, but the name actually comes from an ingredient that is used as a flavoring agent in the candy. That ingredient being licorice extract.
Licorice and licorice root are common names that refer to three species of plants in the genus Glycyrrhiza: Glycyrrhiza uralensis, Glycyrrhiza glabra, and Glycyrrhiza inflata [1]. Some other common names of for these plants are: sweet root, liquorice, Chinese licorice, gan zao, and gan cao [1]. An extract made from the plant can be used as a flavoring agent, and the plants are also used in various forms of traditional medicines [1].
Okay, so we now know that licorice is an herb and that an extract made from that herb is sometimes used as an ingredient, but why does it interact with medications? The short answer is that it is complicated and while we don’t currently have all of the answers as to specifically why it interacts with various medications, some things are known.
The substance that gives licorice its characteristic flavor and sweetness is called glycyrrhizin [2]. It turns out that glycyrrhizin itself has significant effects on the body. When glycyrrhizin is consumed it can be converted to the compounds 8β-glycyrrhetinic acid (GA) and 3β-monoglucuronyl-18β-glycyrrhetinic acid (3MGA) in the GI tract [3]. Both compounds, GA and 3MGA, inhibit an enzyme (11-β-hydrogenase type II) which results in the hormone cortisol not being oxidized to cortisone [3]. Thus, consuming glycyrrhizin can result in elevated levels of cortisol. Should cortisol levels become sufficiently elevated, the cortisol can interact with certain receptors resulting in a mineralocorticoid excess state in the kidneys [3]. Excess consumption of glycyrrhizin can thus lead to hypokalemia (low potassium level in the blood), hypernatremia (high sodium level in the blood), and hypervolemia (excess fluid volume in the blood) [3]. GA, 3MGA, and other bioactive substances from licorice are eventually metabolized by the liver, where they appear to also impact liver function [3].
Essentially, we do know that licorice contains (possibly several) bioactive substances that can impact the functioning of multiple organ systems throughout the body. However, more research will be needed before we can determine the entirety of licorice’s effect on the body. Unfortunately, that means that we can’t fully answer the “why” part of why does licorice interact with medications. However, we do know that it does, and we have the research to know that licorice intake should be limited or avoided entirely with certain medications.
Earlier, I mentioned the confusion with determining what is and isn’t licorice. I am referring specifically to candy here. Licorice can be used to flavor other foods and beverages, but the only place that I ever come across it here in the US is in candy. Speaking of which, there is a type of candy that has been flavored with licorice for so long that “licorice” has become the name of the candy.
This is where things start to get confusing for consumers. You would think that a candy called licorice would contain licorice or licorice extract in some form. However, if you made that assumption you could actually be wrong. Some candies commonly thought of as licorice, contain no licorice or licorice extract at all. They may contain another ingredient such as anise oil, that has a similar taste profile to licorice [1] or have a completely different flavor profile altogether.
In the US, the most common licorice candy that I come across is red licorice. The two most popular brands of red licorice in the US appear to be Twizzlers and Red Vine. According to Hershey’s website, original Twizzlers Twists do contain licorice but their most popular flavors (strawberry and cherry) do not contain licorice extract [4]. As far as Red Vine goes, their website says that Red Vine Twists do not contain licorice extract [5]. So it would appear that red licorice generally does not contain licorice extract and should be safe for individuals who need to avoid licorice due to their medications, but what about black licorice?
Both Twizzlers and Red Vine do produce a black licorice product and per their respective web sites, both do contain licorice extract [4, 5]. Does all black licorice contain licorice extract then? Supposedly no, you can find black licorice that is flavored with another ingredient (like anise oil) that does not contain any licorice extract. However, after searching for quite awhile I was unable to actually find one of these products. Upon review, each of the products that I saw listed licorice extract on their ingredients panels. Searching for “anise oil licorice” resulted in products that contained both anise oil and licorice extract. So while licorice-free black licorice is said to exist, it may be difficult to find.
So people taking certain medications need to avoid black licorice, or any product that contains licorice extract, but what about the rest of us? How safe is licorice for the general population? The answer is that the safety of licorice consumption seems to be dose dependent. Small amounts consumed infrequently appear unlikely to cause issues for the average person, but consuming large amounts at once or even relatively small amounts frequently can cause issues. According to the American Heart Association, consuming even two ounces per day for two weeks or more can cause irregular heart rhythms in individuals over 40 [2]. There is also at least one case of an individual passing away from cardiac arrest from consuming excessive amounts of black licorice [6].
In summary, licorice is an herb and licorice extract can be used as a flavoring agent. There are bioactive substances in licorice that interact with many medications, making it a food of concern that many people need to limit or avoid. The effects of licorice consumption seem to be dose dependent, so it should be safe for an otherwise healthy person to consume in moderation. However, consuming large amounts of black licorice at once, or consuming small amounts regularly can still cause issues for some people. Red licorice and other licorice-type candies may not actually contain any licorice extract at all (confirm this by reading the ingredients label) and should be safe for individuals who need to avoid licorice.
Personally, I don’t eat much candy. I don’t dislike the flavor of black licorice, but I don’t really buy it either. Here in the US there are many types and flavors of candy to choose from (which you should consume in moderation if you are choosing to eat candy) so avoiding licorice isn’t much of a sacrifice for most individuals.
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Sources:
NIH National Center for Complementary and Integrative Health. Licorice Root. NIH NCCIH Web site. https://www.nccih.nih.gov/health/licorice-root. Last Updated August 2020. Accessed April 16, 2023.
M. Merschel. “Black licorice is a candy that should inspire caution”. American Heart Association News. https://www.heart.org/en/news/2022/10/28/black-licorice-is-a-candy-that-should-inspire-caution. Published October 28, 2022. Accessed April 20, 2023.
Deutch MR, Grimm D, Wehland M, Infanger M, Krüger M. “Bioactive Candy: Effects of Licorice on the Cardiovascular System”. Foods. 2019 Oct 14;8(10):495. doi: 10.3390/foods8100495. PMID: 31615045; PMCID: PMC6836258. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836258/. Accessed April 20, 2023.
“About Twizzlers Candy” Hersheyland web site. https://www.hersheyland.com/twizzlers/about#:~:text=Yes%2C%20the%20original%20TWIZZLERS%20Twists,TWIZZLERS%20Twists%20a%20healthy%20snack%3F. Accessed April 21, 2023.
“FAQ” Red Vines web site. https://redvines.com/faq/#:~:text=Do%20Red%20Vines%C2%AE%20Original,Licorice%20Twists%20contain%20licorice%20extract. Accessed April 21, 2023.
Elazer R. Edelman, M.D., Ph.D., Neel M. Butala, M.D., M.B.A., Laura L. Avery, M.D., Andrew L. Lundquist, M.D., Ph.D., et al. “Case 30-2020: A 54-Year-Old Man with Sudden Cardiac Arrest” The New England Journal of Medicine. 2020; 383:1263-1275. DOI: 10.1056/NEJMcpc2002420. https://www.nejm.org/doi/full/10.1056/NEJMcpc2002420. Accessed April 22, 2023.