History and Folklore
The first thing you may think of when considering licorice--or “liquorice,” if you are in Europe--is that it is candy, but historically it is better known as an herb. The candy is traditionally prepared from the sweet-tasting root of the licorice plant, a member of the bean family (Fabaceae or Leguminosae). It is native to the Mideast and has been recommended by ancient healers, such as the Greek Dioscorides, who used it as a wound healer. Perhaps signifying its value, it was found at Tutankhamen’s burial site. Konrad von Megenberg, one of the most prolific German writers of the fourteenth century, who wrote Das Buch der Natur (The Book of Nature), called licorice “bear’s droppings,” which remains a good name if you want to keep your friends away from your candy. Napoleon himself was reportedly addicted to licorice, which theoretically could have hampered his sex life (see below.)
Commercial licorice is mainly harvested from the Mediterranean, Spain, Asia, and the former USSR. Millions of pounds are imported to the United States, not so much for candy, as you might think, but 90 percent is used in flavoring cigarettes and other tobacco products. Real licorice is far more popular in Europe. Licorice candy in the United States often has no licorice at all but is flavored with anise oil. However, real licorice candy is now being sold more often in the United States, too.
Licorice has traditionally been used for ages around the world, for congestion, sore throats and cough, digestive problems, ulcers, arthritis, and constipation. Some of these uses appear valid, but the herb contains a potent drug that produces both benefits and dangerous side effects. As such, licorice should be used with care.
How Scientists Think Licorice Works
Licorice temporarily shuts down some members of a family of enzymes called short-chain dehydrogenase reductases (SDRs). This does both good and bad things to you. SDR enzymes are a large family of enzymes that accomplish a wide variety of chemical transformations in the body. Some SDR enzymes that licorice hampers break down stomach-protecting molecules, and other SDR enzymes that licorice inhibits help keep blood pressure low by balancing sodium and potassium concentrations. SDR enzyme inhibition by licorice can thus protect your stomach but raise your blood pressure.
This disabling of SDRs occurs by glycyrrhizinic acid or its salt, glycyrrhizin, the molecules that give licorice root its mild sweetness. Their structures somewhat resemble human steroids, yet unlike steroids they are also attached to sugar molecules. Both licorice molecules have the ability to impersonate your own steroids, and this enables them to “competitively” inhibit your SDR enzymes, meaning that an SDR enzyme temporarily docks with these imposters instead of its customary targets, which prevents the enzyme from performing its usual task.
After you eat licorice, glycyrrhizinic acid or glycyrrhizin reaches your gut, and the bond between the steroid part and the sugars is cleaved, yielding just the sugar-free and unsweet steroid mimic, glycyrrhetinic acid. If the names of these licorice molecules all look like Welsh to you at this point, you are not alone. The thing to remember is that they are all biologically active. The sugar-free metabolite also inhibits short chain reductases, and it can get absorbed into your bloodstream. That’s where the trouble starts. Before we go there, let’s discuss the nice thing licorice does for your gut.
By raising your supply of gut-protecting prostaglandins, licorice increases mucous and decreases acid. You have many sorts of different prostaglandins, each of which has varied and even opposing effects, yet they have acquired negative connotations in popular health articles, because many prostaglandins promote damaging inflammation. However, not all of your prostaglandins are bad. Some of your gut prostaglandins decrease acid secretion and increase the production of protective mucous, which coats your stomach, shielding it from acid and protein-degrading enzymes. Stomach mucous creates a slimy barrier that literally prevents acid and digestive enzymes from digesting the stomach lining itself, which would cause sores on the lining of the stomach that are otherwise known as ulcers. Aspirin, in fact, blocks the synthesis of these gut-protecting prostaglandins, initiating the classic gastric distress associated with aspirin, sometimes causing ulcers. Licorice, on the other hand, inhibits the SDR enzymes that break these gut-protecting prostaglandins down. This allows the prostaglandins to hang around for a longer period of time, consequently enhancing the safeguarding of your stomach lining.
What helps your stomach may help your throat, too. The mucous that licorice increases protects not only your digestive tract, but may help with coughs and sore throats, too; however, that idea is more controversial. Some think it is simply the pleasant, sweet taste that encourages salivation and swallowing, which suppresses a cough reflex.
Licorice may induce uterine contractions. Licorice does not increase all prostaglandins. Licorice specifically hampers the SDR enzyme 15-hydroxyprostaglandin dehydrogenase. This enzyme breaks down prostaglandin F2-alpha and prostaglandin E2. Therefore, licorice raises the concentrations of these two prostaglandins by slowing their metabolic conversion to less active forms. Both prostaglandins are used medically to induce either labor or abortion, because they contract the uterus. Increasing these prostaglandins is worrisome for women who are prone to painful uterine contractions, better known as menstrual cramps, and even more troublesome for pregnant women. Increasing these specific prostaglandins by using licorice could induce premature labor; thus most reputable sources advise you should not take licorice if you are pregnant. Don’t panic if you are pregnant and have innocently eaten one licorice candy. To my knowledge, cases of single doses of licorice inducing acute abortion have not been documented, but heavy use of licorice (500 mg per week) has been positively linked to premature delivery.1
Eating an inordinate amount of licorice causes a potentially dangerous syndrome called apparent mineralocorticoid excess. It’s a common story: a person with high blood pressure innocently enjoys a lavish amount of licorice on a regular basis and winds up in the emergency room. It may surprise you to know that this scenario is quite familiar to medical professionals. In repeated tests of people taking large doses of licorice, all volunteers begin to show signs of apparent mineralocorticoid excess after twenty-four hours, beginning with potassium loss, sodium retention, and water retention, which is then followed by gradually climbing blood pressure. Thankfully, it takes a lot of licorice to cause these side effects, and these symptoms go away after licorice is discontinued. Prolonged consumption (weeks or months) of licorice exceeding a products’ suggested serving size leads to more severe symptoms, however, such as lethargy, paralysis, and heart failure.
It’s called “apparent mineralocorticoid excess,” because a specific hormone classified as a mineralocorticoid appears to be overactive. The most striking effects of licorice overdose--potassium loss, sodium retention, and high blood pressure--are all classically associated with a hormone called aldosterone. Aldosterone is in the category of hormones known as a mineralocorticoid, because it affects mineral balance, specifically potassium and sodium, and because it is produced by the outer core of the adrenal glands, the adrenal cortex. It appears as though licorice increases aldosterone, based on the symptoms it causes; however, in people who overdose on licorice, aldosterone remains low and may even be suppressed. Since aldosterone appears to be in excess, the term apparent mineralocorticoid excess is used for the syndrome that it causes. Here is what licorice really does.
It isn’t aldosterone that licorice increases, but cortisol, which looks like aldosterone to your kidneys. At first scientists postulated that licorice simply mimicked the hormone aldosterone, which certainly seemed reasonable, because aldosterone is a steroid, and licorice contains steroid mimics. You can still find many old herb books that say that licorice binds to aldosterone’s receptor and acts like aldosterone. That theory, however reasonable, proved incorrect. Researchers in the late 1980s were puzzled by this, until a link was made with people who had apparently identical symptoms to licorice toxicity but instead possessed a rare genetic disease rendering them with a defective version of the enzyme 11-beta-dehydroxysteroid reductase type 2 (11-beta HSD2). Since this enzyme is in the family of SDR enzymes that licorice inhibits, researchers made the connection that licorice inhibits this enzyme. This theory has withstood testing in test tubes, isolated cell cultures, animals, and humans, and is now the currently accepted mechanism for licorice causing apparent mineralocorticoid excess.
In the kidney this 11-beta HSD2 normally inactivates cortisol, another steroid hormone. Cortisol (called hydrocortisone when used therapeutically) has a wide range of different actions, such as quelling inflammation and altering blood sugar levels. Normally cortisol’s action on the kidney is blocked, however, because an SDR enzyme in the kidney turns cortisol into a less active form called cortisone. If left active, cortisol works on the kidney just like aldosterone, binding to aldosterone’s receptor and triggering the same effects as aldosterone: potassium wasting through the urine, sodium retention, water retention, and hypertension. The problem with cortisol acting just like aldosterone in your kidney is that cortisol is several times more concentrated than aldosterone in your plasma, and if cortisol remains unchecked at your kidney, it will appear as though your kidney is flooded with aldosterone when it is actually cortisol doing all of this. Normally, the 11-beta HSD2 enzyme inactivates cortisol in the kidney, preventing it from impersonating a flood of aldosterone hormone. This explains why aldosterone appears out of control but remains low in both licorice overdose and 11-beta HSD2 deficiency; it is actually surplus cortisol acting like aldosterone.
In normal circumstances in the kidney, the SDR enzyme 11-beta HSD2 turns cortisol into the less active cortisone, which is not capable of binding to the aldosterone receptor and is thus not capable of acting like aldosterone. When licorice inactivates 11-beta HSD2, cortisol is no longer deactivated in your kidney, and a flood of cortisol binds to your kidney’s aldosterone receptor, mimicking aldosterone.
Remember, however, that licorice also can protect the stomach lining by preventing an SDR enzyme from breaking down gut-protecting prostaglandins. It’s a shame that a potentially good ulcer medication has such serious side effects, which begin when licorice’s molecules enter your blood stream. If some smart chemist out there wants to synthesize a nonabsorbable form of these licorice molecules, which remain in the gut, there might be a new ulcer medication on the market.
Good Effects . . . And Not So Good
Licorice overdose is a thoroughly documented and common occurrence. Licorice toxicity is more common in Europe, where more licorice is consumed, and the licorice that is eaten there is real licorice. In the United States licorice often has the syndrome-causing ingredient, glycyrrhizin, removed, and it is called deglycyrrhizinized licorice. It is flavored with similar-tasting anise oil, which does not have this problem. In fact, many U.S. “licorice” products contain no licorice, mimicking its taste with anise oil. Demand for real licorice in the United States is growing, however, so check the label to be sure.
If you don’t have a condition that precludes eating licorice, you can use it to treat ulcers, gastrointestinal upset, cough, and sore throats. Just use it cautiously. There is reasonable evidence that real licorice helps in treating these conditions. Multiple serving sizes of licorice per day for a period on the order of a week or more are usually required for licorice overdose symptoms to show up in healthy people, and the occasional dose of licorice can certainly help people who have ulcers. Be sure you have actual licorice, since many so-called licorice products don’t contain any, and make sure the licorice has not been deglycyrrhizinized. Don’t take too much of the product, and don’t take it for too long. Most pharmaceutical references suggest limiting your treatment to less than four to six weeks, and avoid taking more than 100 grams a day. If you feel any strange symptoms coming on, like weakness, dizziness, water retention, headache, or heart palpitations, stop using it.
Certain people should avoid licorice. Do not take licorice if you have high blood pressure, heart disease, low potassium (hypokalemia), kidney disease, or are pregnant. Certain hormonal disorders may be exacerbated by licorice. This includes adrenal disease, Cushing’s disease, primary hyperaldosteronism (Conn’s disease), secondary hyperaldosteronism, and pseudohyperaldosteronism. Since licorice may have estrogenic action, those with estrogen-sensitive conditions (breast, uterine, and ovarian cancers, endometriosis, and uterine fibroids) may find it helpful to avoid excess licorice, too.
Licorice may not be the most romantic treat for your male partner. If you are male, recent evidence suggests licorice could have a downside for your love life. In some small studies it decreased testosterone levels of both male and female volunteers, and because of this it was suggested as a possible culprit in male sexual dysfunction.
You may be surprised at how many products contain licorice. If you take the time to read labels, you will see that many herbal teas, for example, contain licorice as a sweetening agent, even though they are not labeled “licorice” tea. One case report describes a man who drank 100 grams of licorice in an herbal tea daily for three years, and he had to be hospitalized for extremely low potassium and muscle weakness, which developed into paralysis. His symptoms retreated slowly, even after his licorice was discontinued.2
The literature is replete with similar cases. For example, one woman habitually chewed licorice-flavored gum and developed serious symptoms;3 another did so after she ate five licorice sticks a day for a month.4 Licorice is of course found in licorice candy, but it is also present in some candies that don’t have “licorice” in the name. Some licorice candies sport festive titles like “Turkish Pepper” or “Fisherman’s Friend,” and though they contain licorice, their names do not make that obvious. Licorice is also added to many tobacco and smoking products. There is a case report of a man who chewed roughly ten bags of chewing tobacco a day and swallowed the juice. The resulting paralyzing weakness that he suffered was attributed to the licorice content of the tobacco.5 He recovered when his chew was taken away from him. Many other tobacco products contain licorice as flavoring agent, but it is unlikely that licorice-laced tobacco will affect someone who smokes it. When burned, physiologically active licorice molecules most likely degrade. (What tobacco molecules transform into after they are burned is more of a concern for cancer doctors.) Licorice is also added to certain cough drops, lozenges, and syrups for flavoring.
An occasional small dose of licorice won’t kill you, but you should limit it, especially if you have any of the conditions listed above. Overdosing on licorice takes some effort, as evidenced by the existing case reports, and the occasional bit of licorice won’t kill you. However, if you have condition that could be worsened by licorice, there is no sense in aggravating it either; you should reasonably limit your licorice consumption to amounts far less than what most people would consume. Better yet, treat yourself with deglycyrrhizinized licorice, which has had most of its active ingredient removed.
Evidence of Action
The evidence for licorice’s producing untoward and even dangerous side effects--high blood pressure and potassium loss--are far more thoroughly documented than its therapeutic actions. Nonetheless, it may promote the healing of ulcers, although because of its side effects, it should only be taken for limited time periods. Licorice was able to prevent ulcer caused by aspirin in rats,6 and licorice increases stomach-protective mucous formation and decreases stomach acid production. Both of these actions shield the stomach from damaging acid, allowing old ulcers to heal and preventing new ulcers from forming.
Carbenoxalone, a semisynthetic derivative of glycyrrhetic acid that releases licorice’s natural glycyrrhetic acid when consumed orally, has been shown to accelerate the healing of ulcers, too.7 Unfortunately, people taking carbenoxalone also experience worrisome blood pressure elevation and potassium loss; it causes the same problems as licorice. It is sold in the United Kingdom, but is not available in the United States.
Deglycyrrhizinized licorice has also been tested as an ulcer aid. This is licorice that has had most of its offending, side effectcausing glycyrrhizin removed (sold commercially as “Caved-S”). Unfortunately, it is the glycyrrhizin and its aglycone metabolite that are responsible for the ulcer-protecting, beneficial effects. Indeed, animal studies show deglycyrrhizinized licorice had no effect on gastric prostaglandins, which are thought to mediate licorice’s protective effects. Consequently, it is not a surprise that most deglycyrrhizinized licorice trials for ulcer have been unimpressive,8, 9 although a few actually boast modest benefits.10, 11 This may be due to the trace glycyrrhizin (about 3 percent remains) in the treatment; or perhaps unknown factors are at work. At any rate, deglycyrrhizinized licorice is certainly safer than licorice, but probably doesn’t help ulcer sufferers either.
Licorice has been tested for other possible benefits on a limited scale. There is preliminary evidence that licorice reduces testosterone in both men12 and women,13 which is usually a detriment for the men, but could theoretically help certain women, such as those with polycystic ovarian syndrome. Licorice might reduce body fat, but small trials testing licorice’s ability to help you lose fat are conflicting, possibly because of the weight gain that it causes through water retention.14 Also, some preliminary studies show that licorice has action against hepatitis B and C,15, 16 but the studies are too small to draw conclusions as of yet. Additionally, a skin preparation using licorice was able to reduce redness and itching in dermatitis.17 More evidence is needed to evaluate licorice for these uses.
The Bottom Line
• Licorice raises blood pressure, causing you to retain sodium and lose potassium, by inactivating an enzyme that normally keeps cortisol from acting on your kidneys. In extreme cases these side effects can be dangerous and have even been fatal.
• Licorice may help those with ulcers or stomach upset, but should not be taken for extended periods of time. Licorice protects your gut by inactivating an enzyme that normally inactivates mucous-producing and acid-decreasing prostaglandins in your gut.
• Deglycyrrhizinized licorice is safer than licorice, although it may be less effective in healing ulcers.
• Don’t use licorice if you are pregnant. It may cause premature delivery.
• Several medical conditions are aggravated by taking licorice, such as hypertension, heart problems, and kidney disease, and estrogen-sensitive diseases, such as certain cancers, endometriosis and uterine fibroids, hyperaldosteronism and pseudohyperaldosteronism, low potassium, and male sexual dysfunction.
What’s in it
Licorice’s active ingredient, which also makes it taste sweet, is due to about 5 to 9 percent glycyrrhizin, the acid salt of a saponin glycoside. The free, acidic version of this molecule is also active, and is called glycyrrhizic acid. Both are bound to two glucuronic acid sugar molecules. Licorice also possesses 1 percent flavonoids, primarily liquiritin and liquiritigenin, and related chalcones isoliquiritin, isoliquiritigenin. Isoflavonoids include formononetin, glabren, glabridin, and glabrol. Hydroxycoumarins include herniarin and umbelliferone, and sterols such as beta-sitosterol and stigmasterol. The root contains trace anethole, estagole (also present in anise and fennel oils), and eugenol (also found in cloves).
Commonly Reported Uses for Licorice*
used for gastrointestinal ulcers, stomach upset, sore throat, cough, congestion, expectorant, sweetener, flavoring
forms available for internal use:
dried whole, chopped, or powdered root, capsule, extract, infusion, tea, powdered extract, tincture, candies, gum, lozenges, syrup, liqueurs
commonly reported dosage:
A typical dose of licorice is 1 to 4 grams of powdered root, or up to three cups of licorice tea, daily, taken for no longer than four weeks.
*These uses and dosages are from historic use and are not necessarily tested nor recommended.
1 Strandberg TE, Andersson S, Jarvenpaa AL, McKeigue PM. Preterm birth and licorice consumption during pregnancy. Am J Epidemiol. 2002 Nov 1;156(9):803-5.
2 Lin SH, Yang SS, Chau T, Halperin ML. An unusual cause of hypokalemic paralysis: chronic licorice ingestion. Am J Med Sci. 2003 Mar;325(3):153-6.
3 Michaux L, Lefebvre C, Coche E. Perverse effects of an apparently harmless habit. Rev Med Interne. 1993 Feb;14(2):121-2.
4 Berlango Jimenez A, Jimenez Murillo L, Montero Perez FJ, Munoz Avila JA, Torres Murillo J, Calderon de la Barca Gazquez JM. Acute rhabdomyolysis and tetraparesis secondary to hypokalemia due to ingested licorice.
An Med Interna. 1995 Jan;12(1):33-5.
5 Blachley JD, Knochel JP. Tobacco chewer’s hypokalemia: licorice revisited. N Engl J Med. 1980 Apr 3;302(14):784-5.
6 Dehpour AR, Zolfaghari ME, Samadian T, Vahedi Y. The protective effect of liquorice components and their derivatives against gastric ulcer induced by aspirin in rats. J Pharm Pharmacol. 1994 Feb;46(2):148-9.
7 Bianchi Porro G, Petrillo M, Lazzaroni M, Mazzacca G, Sabbatini F, Piai G, Dobrilla G, De Pretis G, Daniotti S. Comparison of pirenzepine and carbenoxolone in the treatment of chronic gastric ulcer. A double-blind endoscopic trial. Hepatogastroenterology. 1985 Dec;32(6):293-5.
8 Bardhan KD, Cumberland DC, Dixon RA, Holdsworth CD. Clinical trial of deglycyrrhizinised liquorice in gastric ulcer. Gut. 1978 Sep;19(9):779-82.
9 Nussbaumer U, Landolt M, Rothlisberger G, Akovbiantz A, Keller H, Weber E, Blum AL, Peter P. Postoperative stress hemorrhage: ineffective prevention with pepsin inhibitor and deglycyrrhizinized licorice extract. Prospective study. Schweiz Med Wochenschr. 1977 Feb 26;107(8):276-9.
10 Morgan AG, McAdam WA, Pacsoo C, Darnborough A. Comparison between cimetidine and Caved-S in the treatment of gastric ulceration, and subsequent maintenance therapy.
Gut 1982 Jun; 23(6): 545-51.
11 Turpie AG, Runcie J, Thomson TJ.Clinical trial of deglydyrrhizinized liquorice in gastric ulcer. Gut. 1969 Apr; 10(4): 299-302.
12 Armanini D, Bonanni G, Mattarello MJ, Fiore C, Sartorato P, Palermo M. Licorice consumption and serum testosterone in healthy man. Exp Clin Endocrinol Diabetes. 2003 Sep;111(6):341-3
13 Armanini D, Mattarello MJ, Fiore C, Bonanni G, Scaroni C, Sartorato P, Palermo M. Licorice reduces serum testosterone in healthy women. Steroids. 2004 Oct-Nov;69(11-12):763-6.
14 Armanini D, De Palo CB, Mattarello MJ, Spinella P, Zaccaria M, Ermolao A, Palermo M, Fiore C, Sartorato P, Francini-Pesenti F, Karbowiak I. Effect of licorice on the reduction of body fat mass in healthy subjects. J Endocrinol Invest. 2003 Jul;26(7):646-50.
15 Eisenburg J.Treatment of chronic hepatitis B. Part 2: Effect of glycyrrhizic acid on the course of illness. Fortschr Med. 1992 Jul 30;110(21):395-8.
16 Abe Y, Ueda T, Kato T, Kohli Y. Effectiveness of interferon, glycyrrhizin combination therapy in patients with chronic hepatitis C. Nippon Rinsho. 1994 Jul;52(7):1817-22.
17 Saeedi M, Morteza-Semnani K, Ghoreishi MR. The treatment of atopic dermatitis with licorice gel. J Dermatolog Treat. 2003 Sep;14(3):153-7.