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Licorice root

Licorice root

This perennial belongs to the papilionaceous family. It can grow up to 2 m high. The yellow, woody, finger-thick roots produce stolons several meters long, from which upright, round-stemmed to angular shoots grow above ground. They bear alternate, 3-7 unpaired, pinnate leaves with sticky undersides (glands recognizable as dots). The flowers are borne in the leaf axils in multi-flowered racemes. The individual flowers have a pale purple banner. The brownish seeds develop in bare pods.

  • Collection time: March, April and September, October
  • What to collect: Roots

The licorice root was of outstanding importance in the major Asian and European cultures. In China, it is still one of the ten most important medicinal plants (1). Romans and Greeks used it for asthma. The Scythians used its water-retaining effect when crossing deserts to get by for up to 12 days without any fluid intake. In the Arab world, a thirst-quenching drink made from licorice root is still very popular today. In Russia, licorice root extracts were used to treat adrenal insufficiency. The anti-inflammatory effects were first used by the Dutch doctor Revers to treat stomach ulcers. In Japan, a combination of licorice root and peony is used to induce ovulation in hyperandrogenic women. Israeli studies show an effect on various herpes viruses, and in Houston, Texas, a team led by Prof. Vogel conducted research into anti-carcinogenic effects. And last but not least, licorice root enjoys great popularity as a raw material for liquorice, particularly in northern and central Europe. However, the broad spectrum of effects of licorice root is far from exhausted.

Deglycyrrhizinated licorice root/licorice vs. regular licorice root

Glycyrrhizin is one of the active compounds found in licorice root that has a number of health effects, but also some significant side effects such as an increase in blood pressure (2). In deglycyrrhizinated licorice root or licorice, the glycyrrhizin has been removed to prevent its effects. Without glycyrrhizin, licorice root is not associated with any adverse side effects, but retains some of its desirable properties. Supplements made from deglycyrrhizinated licorice root have none of the side effects of glycyrrhizin or glycyrrhizic acid (2). Deglycyrrhizinated licorice root is typically used to treat stomach ulcers and other digestive problems.

Active ingredients

Glycyrrhizin

Glycyrrhizin is the primary active compound in licorice root, which is converted to glycyrrhizic acid in the digestive tract. Glycyrrhizic acid is a potent inhibitor of an enzyme (11-ß-HSD) that converts cortisol into a less active form (cortisone), which means that glycyrrhizin contained in licorice root increases cortisol levels (2, 3). The liver breaks down glycyrrhizic acid, but ingestion of too much licorice root can lead to toxic accumulation of glycyrrhizic acid.

Glabridin

Glabridin is the flavonoid found in the largest quantities in licorice root. Initial studies suggest that glabridin is an antioxidant, anti-inflammatory and neuroprotective agent. This flavonoid is well absorbed by the human body, but further studies are needed to fully understand its effects (4).

Licochalcone A

Licochalcone A (LicoA) is a polyphenol that has potential antiparasitic, antibacterial and anticancer effects (5). It counteracts inflammation by inhibiting lipopolysaccharide signaling, COX-2 and UV light-induced damage. It may also protect against cancer by inhibiting Akt/mTOR pathways (5).

Isoliquiritigenin

Isoliquiritigenin has potential antioxidant, anti-inflammatory and antitumor effects. It has a high affinity for the liver, kidneys and intestines (6). It is well absorbed by rats, but only has a bioavailability of 12%, which is probably due to the fact that the liver and digestive tract break down most of it (6).

Glabrene

Glabrene is an isoflavonoid found in licorice root extract. It binds to oestrogen receptors and activates oestrogen-regulated genes (7). Glabrene can mimic estrogen (7), suggesting that it may prevent bone loss and slow cardiovascular decline in menopausal women. However, further clinical studies are needed to determine whether Glabrene is safe and effective.

Coumarins

Coumarins are compounds that have a sweet odor. The primary coumarin found in licorice root is glycycoumarin, which is well absorbed by animals (8, 9).

Other compounds

  • Formononetin (10)
  • Glisoflavones (11)[
  • Hispaglabridins A and B (12)
  • Rutin (13)
  • Isoanguston A (14)
  • Prunetin (15)
  • Dehydroglyasperin C (16)

Possible health benefits of licorice root

Licorice root could reduce inflammation

In an analysis of 93 clinical and cell-based studies, it was observed that licorice root has anti-inflammatory properties (1). Licorice root promoted the activity of regulatory T cells in mice, suggesting that this medicinal plant may protect against autoimmune and inflammatory diseases (17). Lipopolysaccharide (LPS) activity, TNF-alpha production and NF-kB activity all lead to inflammation in the brain. Treatment with dehydroglyasperin C (a flavonoid found in licorice root) stops pro-inflammatory activity in the brain and helps prevent neuronal cell death (16). An ethanol extract of licorice root also reduced alcohol-induced liver damage in mice by reducing key markers of liver inflammation (18).

Licorice root could relieve intestinal inflammation and help with gastric ulcers

In a clinical trial involving120 subjects, licorice root was shown to be a good adjunctive treatment in combination with standard clarithromycin triple therapy in the treatment of Helicobacter pylori bacteria. Licorice root was able to increase the killing rate of H. pylori bacteria by about 20% (19). In another study of 50 subjects with dyspepsia - a variant of indigestion - licorice root helped to reduce symptoms of nausea, stomach upset and stomach pain (20). In rats suffering from aspirin-induced gastric ulcers, licorice root reduced the number and size of ulcers (21).

Although the evidence is limited, it suggests that licorice root may help with indigestion and gastric ulcers.

Licorice root could help with symptoms of menopause

In a clinical trial of 60 menopausal women, licorice root was more effective than hormone therapy in reducing the duration of hot flashes, but had no effect on the intensity of hot flashes. In another study of over 200 women, a plant extract containing liquiritigenin helped with hot flushes during the menopause (22, 23). Glabridin, liquiritigenin and glabrene have estrogen-like activities that may help women who have low estrogen levels, as is the case during menopause (24, 25). In cell cultures, glabridin had similar effects to estradiol-17beta (the most potent form of estrogen). Glabrene docked onto the estrogen receptors and stimulated the formation of muscle cells (24).

Licorice root could reduce the risk of heart disease

In a clinical study of nearly 100 subjects with high cholesterol levels, one year of consuming deglycyrrhizinated licorice root reduced total cholesterol levels, LDL cholesterol levels and blood pressure levels (26). In a mouse model of myocardial infarction, the anti-inflammatory and antioxidant effects of licorice root helped reduce damage to heart tissue and promote faster recovery (27). The available studies are insufficient to support the role of deglycyrrhizinated licorice root in reducing the risk of heart disease. Further clinical studies are needed. In addition, both licorice root containing glycyrrhizin and glycyrrhizic acid may stimulate the body to excrete more potassium and also increase blood pressure, which could ultimately exacerbate heart disease (2).

Licorice root could help in the treatment of polycystic ovary syndrome

In a clinical study of 32 women suffering from polycystic ovary syndrome, glycyrrhetinic acid reduced testosterone levels while inducing regular ovulation. Two other licorice root metabolites (glabridin and glabrene) have estrogen-like effects that may help in the treatment of polycystic ovary syndrome (28). These preliminary research results still need to be confirmed by larger, more robust studies.

Licorice root could reduce fatigue

Licorice root increased cortisol levels and activity in a study of 20 healthy volunteers by inhibiting the 11-beta-HSD enzyme - the enzyme that converts cortisol to the less active cortisone - and inhibiting the SULT2A1 enzyme - the enzyme that marks steroid hormones, including cortisol, for elimination. The increase in cortisol levels may help to increase energy levels. In addition, this increase also results in increased levels of DHEA and testosterone (3). Glabridin, a polyphenol flavonoid found in licorice root extract, reduced exercise-induced fatigue in mice. Mice treated with glabridin swam longer than mice in the control group. The higher the glabridin dose, the longer the mice lasted in the swimming test. Glabridin-treated mice also had lower markers of fatigue such as blood lactate levels and blood nitrogen-urea levels, as well as higher glycogen levels (29). As these are the only studies on the topic to date, further studies are needed to determine the effects of licorice root on fatigue. Other potential health benefits that have so far only been observed in cellular and animal studies. The potential benefits of licorice root listed in the following sections are not yet supported by clinical research, so the studies listed should not be considered proof of efficacy in humans.

Licorice root could support weight loss

In mice and rats, licorice root flavonoid oils helped with weight loss by increasing fat oxidation during light exercise (30). Licorice root powder was also effective in reducing body weight and fat storage in mice (31).

Licorice root could protect the brain

Glabridin, a primary flavonoid of Glycyrrhiza glabra (licorice root), may help protect the brain from stroke-related damage. In rats that had suffered a stroke, an injection of glabridin (25mg per kilogram of body weight) significantly reduced brain damage, prevented neuronal death and reduced DNA damage. At the same time, the injection increased antioxidant levels in the brain (32). Licorice root flavonoids may also protect against oxidative damage in the brain. These antioxidant effects helped to reduce seizure-induced brain cell death in mice (33). Oral administration of glabridin at doses of 25 and 50 mg per kilogram of body weight was able to reduce learning and memory deficits in diabetic rats. In addition, such administration helped to improve brain function in non-diabetic rats (34). Inflammation in the brain can lead to many diseases such as Alzheimer's, dementia and multiple sclerosis. Stopping pro-inflammatory activities could therefore help to protect the brain (16). Treatment with dehydroglyasperin C (a licorice root flavonoid) prevented LPS (a bacterial toxin) from inducing TNF-alpha production in a cell study. This treatment also reduced NF-kB activity, which may help stop neuronal cell death and inflammation (16).

Licorice root could improve sleep quality

GABA receptors are an important target for inducing sleep. Gabrol and liquiritigenin from a licorice root extract induced sleep in mice via the Gaba receptor. This reduced the time it took to fall asleep and increased the duration of non-REM sleep without reducing the depth of sleep (35).

Licorice root could improve male fertility

In mice, a licorice root extract increased sperm production, which could promote male fertility (36).

Licorice root could have anti-cancer effects

Licorice root components have been shown in cell studies to be effective against several hallmarks of cancer including cell proliferation, inflammation, resistance to cell death and production of its own blood vessels. However, there are many substances that have anti-cancer effects in cells, including toxic chemicals such as bleach. This does not mean that they have any medicinal value. Quite the opposite - most substances (natural or synthetic) that have been studied in cancer cells fail in subsequent animal studies or clinical trials due to lack of safety or efficacy. In an oral cancer cell line, a polysaccharide from licorice root promoted apoptosis (cell death) of cancer cells and prevented cancer cell growth. Licorice root was specific for human cancer cells but was not toxic to healthy cells (37, 38, 39). Licochalcone A and liquiritigenin blocked inflammatory and proliferative pathways in cells (40, 41). Licochalcone A also inhibited cancer cells from forming their own blood vessels by blocking the VEGF receptor (42). Licorice root flavonoids prevented collitis-related cancer in mice and reduced tumor formation (43). "Bad" estrogens can cause cancer. Liquiritigenin could act as a "good" estrogen and prevent cancer by binding to the estrogen receptor beta (25).

Licorice root could protect against infections

Preliminary research suggests that licorice root can stimulate the immune system and has antioxidant properties. The active compounds it contains also showed antiviral, antibacterial and antifungal properties in test tube studies (44, 45). In a cell-based study, glycyrrhizic acid was effective in controlling the growth of bacteria (46). An alcoholic licorice root extract inhibited two types of bacteria in cell cultures (S. mutans and L. acidophilus). These two types of bacteria can damage teeth (47). However, these preliminary results have not yet been validated in humans or even in animals. Further research is therefore needed to determine whether licorice root can help fight the infections caused by these bacteria. Recent research shows that the licorice sugar contained in licorice (approx. 20% in licorice syrup) is an excellent protection against viruses - both in the active stage and during the period of inactivity. Many viruses can remain hidden in cells for years before they cause a (new) infection. Liquorice sugar is the only substance that removes the camouflage of the viruses and thus triggers the suicide program of the infected cell. (Journal of Clinical Investigation, Vol. 115, No. 3, p. 650) An effectiveness against Heptatis C has also been proven recently. This justifies the assumption that licorice can also successfully combat other viruses.

Glycyrrhetinic acid as a cream

A study showed that glycyrrhetinic acid also breaks down the fat that is directly under the skin. To do this, it must be applied directly to the skin as a cream. In a corresponding trial, women had to treat their thighs with the cream for a month. The result: they only lost subcutaneous fat on the top layer, so absorption into the internal organ system could be ruled out and no side effects occurred. None of the study participants were obese. The researchers assume that the cream has a much stronger effect on overweight people.

Need in sport

Clycyrrhetinic acid-based cream can therefore help people who want to lose weight on their thighs or stomach, for example. It also benefits bodybuilders who have problems reducing fat in exposed areas. The use of glycyrrhetinic acid cream can pay off, especially before a competition.

Dosages and dosage forms

Liquid extracts

Licorice root extracts are the most widely used form of licorice root products. They are used as commercial sweeteners in sweets and drinks. The glycyrrhizic acid content of licorice root extracts should not exceed 30 mg glycyrrhizic acid per ml. Higher doses may have undesirable side effects (61).

Powder

Licorice root is available in powder form on the Internet and in drugstores. In combination with a gel base, it can be mixed into an ointment for application to the skin to cleanse the skin. In powder form, licorice root is particularly helpful in the treatment of eczema and acne. The powder can also be put into capsules and taken orally. According to the World Health Organization (WHO) guidelines, the recommended daily dose of licorice root powder is less than 75 mg per day (62).

Tea

The leaves of the licorice root plant are very popular in dried form as a tea. These teas are used to promote digestion, respiration and adrenal gland health. Herbal teas advertised as bronchial teas or detox teas usually contain some form of licorice root. It is not recommended to consume more than 250 ml of licorice root tea per day.

DGL (deglycyrrhizinated licorice root)

DGL is licorice root from which the glycyrrhizin has been removed and is a safer form of licorice root. DGL should not contain more than 2% glycyrrhizin. This dosage form is recommended for the treatment of indigestion and other digestive tract problems where prolonged use may be necessary. DGL is available in the form of chewable tablets, capsules, tea and powder. Consumption of DGL should not exceed 5 grams per day.

Side effects & precautions

Deglycyrrhizinated licorice root (DGL)

Chronic or excessive consumption of regular licorice root can cause unwanted complications and health problems. Since these side effects are primarily caused by glycyrrhizic acid, DGL can help prevent these side effects, but this is not useful if the desired effects of taking licorice root products are directly related to glycyrrhizic acid itself (2).

Possible side effects of regular licorice root

Licorice root can increase cortisol levels

In high doses, licorice root can increase cortisol levels. Cortisol is a steroid hormone also known as the stress hormone. It can increase or decrease blood pressure and glucose levels in response to stress, affect immune response, etc. (48). Glycyrrhizic acid and glycyrrhetinic acid - two active metabolites of licorice root extracts - act like aldosterone. They inhibit the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) and thus prevent it from converting cortisol into cortisone. This leads to a longer half-life of cortisol and increases cortisol activity (2, 49). The hypothalamic-pituitary-adrenal axis is an important response system to stress. Normal cortisol levels help to maintain the balance of this regulatory system. However, excessive cortisol levels can cause dysfunction of this regulatory circuit and lead to chronic stress, depression, alcoholism and other disorders (50).

Licorice root could increase blood pressure

A longer half-life of cortisol means that it takes longer for cortisol concentrations in the blood to fall. Excessive cortisol levels can contribute to high blood pressure. One study found that these effects were stronger in women than in men (51). An increase in cortisol concentration locally in the adrenal glands can increase the levels of mineral corticoids, which can increase blood pressure. In people who do not suffer from hypertension, the increase in blood pressure (3.1 to 14.4 mgHg) depends on the amount of licorice root consumed (52, 53). The increase in cortisol levels can also cause pseudo-hyperaldosteronism. This condition is characterized by increased blood pressure, reduced potassium concentrations and water and sodium retention (2, 51).

Licorice root could slow down drug metabolism

Several components contained in licorice root, including liquiritigenin and isoliquiritigenin, inhibit the CYP3A4 gene and the cytochrome P450 enzyme. Inactivation of the P450 enzyme could slow down drug metabolism and increase the concentration of these drugs in the bloodstream, which in turn could increase the risk of drug side effects (54).

Licorice root could lower potassium levels

When licorice root inhibits the 11-βHSD2 enzyme, it also causes excessive mineral corticoid production and a decrease in potassium levels. In several case studies, excessive licorice root consumption caused low potassium levels and muscle weakness (55). Low potassium levels caused by licorice root can lead to irregular heartbeat and cause heart problems (56). These effects can vary from person to person. The full effect of licorice root on potassium levels depends on the person's health, medications taken and other factors, according to an observational study of 360 people (55). Glycyrrhetinic acid can also bind to mineralcorticoid receptors, but its affinity is weaker than that of aldosterone (2).

Licorice root could cause problems during pregnancy

In a survey of 100 Finnish women who had experienced a premature birth, a high consumption of licorice root was associated with a shorter duration of pregnancy. The glycyrrhizic acid contained in licorice root increases cortisol levels, which can lead to an increase in prostaglandin levels in the uterus. This can trigger contractions of the uterus (57).

In addition, inactivation of the 11β-HSD2 enzyme by licorice root can cause dysfunction of the hypothalamic-pituitary-adrenal axis. In a study of over 300 pregnant women, it was observed that those who consumed higher amounts of licorice root had lower levels of 11β-HSD2 in the placenta. Their children tended to have behavioral disturbances associated with dysfunction of the hypothalamic-pituitary-adrenal axis (58). However, these effects were investigated in cohort studies. This type of study may link factors to specific health problems but not establish them as a cause. It is possible that other genetic or environmental factors may have contributed to the observed effects.

Other rare side effects Licorice root may lower testosterone levels in healthy men. However, these results vary from study to study. Further research is needed before definitive conclusions can be drawn (59, 60). Some rare side effects include heart attack and stroke, although there are few studies showing these results (2).

Interactions with medications

Some compounds contained in licorice root may interact with medications. To avoid such interactions, the use of licorice root should be discussed with the attending physician if medication is being taken. Glabridin can, for example, inhibit cytochrome 3A4 and 2B6 - P450 enzymes, which are involved in the breakdown of certain active pharmaceutical ingredients. This could influence the effect of these drugs. Below is a table of different drug compounds on the left and licorice root compounds on the right that may interact with these drugs.

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