Evidence Based
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6 Licorice Root Benefits (Powder & Extract) + Side Effects

Written by Carlos Tello, PhD (Molecular Biology) | Last updated:
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Puya Yazdi, MD | Written by Carlos Tello, PhD (Molecular Biology) | Last updated:

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Licorice

Licorice is mostly associated with candy and has been used in food and medicine for 1,000 years. It contains various compounds that may help with heartburn, cancer, and a leaky gut. Keep reading to learn more about its health benefits.

What Is Licorice Root?

Licorice, or liquorice, is a plant native to southern Europe and Asia and used to flavor candies, sweeteners, and tobacco products. It is also a widely-used Chinese herb [1].

Licorice has many components with promising health benefits. It has been used in herbal and folk medicine for its anti-inflammatory properties.

Deglycyrrhizinated Licorice (DGL) vs Regular Licorice

Glycyrrhizin is an active compound in licorice with several health benefits, as well as significant side effects like hypertension [2].

Deglycyrrhizinated licorice (DGL) has glycyrrhizin removed, thus preventing its side effects. DGL is available in wafers, capsules, liquids, and lozenges [2].

Without glycyrrhizin, DGL is not associated with any identified adverse effects but still retains some of its beneficial properties. DGL supplements lack the side effects of glycyrrhizin and glycyrrhizic acid [2]. DGL is typically used to treat stomach ulcers and other digestive problems.

Active Compounds

Glycyrrhizin

The main active component of licorice is glycyrrhizin, which is transformed into glycyrrhizic acid in the gut. Glycyrrhetinic acid is a potent inhibitor of an enzyme (11-ß-HSD) that turns cortisol to a less active form (cortisone) – so, glycyrrhizic acid in regular licorice increases cortisol levels [2, 3].

The liver breaks down glycyrrhetinic acid, but taking too much licorice might lead to toxic glycyrrhetinic acid buildup [2].

Glabridin

Glabridin is the most abundant flavonoid in licorice. Preliminary research suggests it is antioxidant, anti-inflammatory, and neuroprotective. This flavonoid is absorbed well in humans, though more studies are needed. [4, 4].

Licochalcone A

Licochalcone A (LicoA) is a polyphenol. It has potential antiparasitic, antibacterial and anti-cancer properties [5].

It stops inflammation in cells by suppressing the lipopolysaccharide (LPS) signaling, COX-2, and UV light-induced damage. It may also prevent cancer (by suppressing the Akt/mTOR pathways) [5, 5].

Isoliquiritigenin

Isoliquiritigenin has potential antioxidant, anti-inflammatory, and antitumor effects. It has a high affinity for the liver, kidneys, and small and large intestines [6].

It is absorbed well in rats but has a bioavailability of 12%, likely because the liver and gut break most of it down [6].

Glabrene

Glabrene is an isoflavonoid in licorice root extract. It binds to estrogen receptors and activates estrogen-regulated genes [7].

Glabrene can mimic estrogen [7], suggesting that it might slow down bone loss and cardiovascular decline in menopausal women. However, additional clinical studies need to determine whether glabrene is safe and effective.

Coumarins

Coumarins are compounds that have a sweet smell. The main coumarin in licorice is called glycycoumarin and it’s absorbed well in animals [8, 9].

Other Compounds

  • Formononetin [10]
  • Glisoflavone [11]
  • Hispaglabridins A and B [12]
  • Rutin [13]
  • Isoangustone A [14]
  • Prunetin [15]
  • Dehydroglyasperin C [16]

Health Benefits of Licorice Root

Possibly Effective for:

1) Lowering Inflammation

In an analysis of 93 clinical, animal, and cell-based studies, licorice extract was observed to have anti-inflammatory activities [1].

Licorice extract promoted regulatory T cells in mice, suggesting that licorice can protect against autoimmune and inflammatory diseases [17].

Lipopolysaccharide (LPS) activity, TNF-α production, and NF-kB activity all lead to inflammation in the brain. Treatment with dehydroglyasperin C (a licorice flavonoid) stops the pro-inflammatory activity in the brain and helps prevent neuron cell death [16].

Ethanol extract of licorice also reduced alcohol-induced liver injury in mice by reducing key liver inflammation markers [18].

You may use licorice for your inflammatory issues if your doctor determines that it may help in your case.

2) Gut Inflammation & Ulcers

Licorice was a good adjunctive treatment to standard clarithromycin triple therapy in the treatment of Helicobacter pylori in a clinical trial on 120 people. It increased the eradication rate of H. pylori by about 20% [19].

In another trial on 50 people with dyspepsia, licorice helped symptoms of nausea, indigestion, and stomach pains [20].

In rats with stomach ulcers caused by aspirin, licorice decreased the number and size of the ulcers [21].

The evidence is limited but suggests that licorice may help with dyspepsia and ulcers.

3) Menopausal Symptoms

In a clinical trial on 60 menopausal women, licorice was more effective than hormone replacement therapy (HRT) at reducing hot flash duration, but had no effect on hot flash severity. In another trial on over 200 women, an herbal extract formula with liquiritigenin helped with menopausal hot flashes [22, 23].

Glabridin, liquiritigenin, and glabrene have estrogen-like activities, which may help women who have low estrogen levels, such as in the case of menopause [24, 25].

Glabridin had a similar effect on human cell culture to estradiol-17beta (the most potent form of estrogen). Glabrene bound to estrogen receptors and also stimulated muscle cell formation in cell-based studies [24].

Insufficient Evidence for:

1) Reducing Heart Disease Risk

In a clinical trial on almost 100 people with high cholesterol, a year of deglycyrrhizinated licorice (DGL) consumption decreased total cholesterol, LDL cholesterol, and blood pressure levels [26].

In a mouse model of heart attack, the anti-inflammatory and anti-oxidative effects of licorice helped mitigate damage to the heart tissue and also facilitate faster recovery [27].

The available evidence is insufficient to support the role of DGL in reducing the risk of heart disease. More clinical trials are needed.

In addition, regular licorice that contains glycyrrhizin and glycyrrhizic acid can cause the body to excrete more potassium and increase blood pressure, which may ultimately worsen heart conditions [2].

2) Polycystic Ovarian Syndrome (PCOS)

In a clinical trial on 32 women with PCOS, glycyrrhetinic acid reduced testosterone levels while inducing regular ovulation. Two other licorice metabolites (glabridin and glabrene) have estrogen-like effects that may also help treat PCOS [28].

These preliminary finding needs to be validated in larger, more robust clinical studies.

3) Fatigue

Licorice increased cortisol levels and activity by inhibiting 11-beta-HSD (the enzyme that converts cortisol to the less active cortisone) and SULT2A1 (the enzyme that tags steroid hormones, including cortisol, for elimination) in 20 healthy volunteers. The increase in cortisol may help with energy levels. In addition, it also increases DHEA and testosterone levels [3].

Glabridin, a polyphenolic flavonoid from licorice extract, reduced exercise-induced fatigue in mice. Mice treated with glabridin swam for a longer period of time compared to control mice. The larger the dose of glabridin, the longer the mice could swim. Mice treated with glabridin also had lower markers of fatigue, such as blood lactic acid levels and blood nitrogen urea, and higher glycogen levels [29].

A single clinical trial and a study in mice cannot be considered sufficient evidence to claim that licorice reduces fatigue. Further clinical research is needed.

Animal and Cell Research (Lack of Evidence)

No clinical evidence supports the use of licorice for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed should not be interpreted as supportive of any health benefit.

Weight Loss

In mice and rats, licorice flavonoid oil helps weight loss by enhancing fat oxidation during light exercise [30].

Licorice root powder was also effective in reducing body weight gain and fat deposition in mice [31].

Brain Protection

Glabridin, a major flavonoid of Glycyrrhiza glabra (licorice), may help protect the brain from stroke-related injuries. In stroke-induced rats, glabridin injection (at 25mg/kg) significantly decreased brain damage, prevented nerve cell death, and lowered DNA damage. It also increased antioxidant levels in the brain [32].

Licorice flavonoids may also prevent oxidative damage in the brain. Its antioxidant effects help decrease seizure-induced brain cell death in mice [33].

Diabetes can cause memory and learning problems. In diabetic mice, glabridin extract from licorice helped preserve cognitive function [34].

Oral glabridin administration at 25 and 50 mg/kg reversed learning and memory deficits in diabetic rats. Additionally, it helped improve brain function in non-diabetic rats [34].

Inflammation in the brain can lead to many diseases like Alzheimer’s, dementia, and multiple sclerosis. Stopping pro-inflammatory activities could help protect the brain [16].

Treatment with dehydroglyasperin C (a licorice flavonoid) prevented LPS (a bacterial toxin) from inducing TNF-α production in a cell-based study. It also reduced NF-kB activity, which may help stop neuron cell death and inflammation [16].

Sleep Quality

The GABA receptor is an important target for inducing sleep. Gabrol and liquiritigenin from licorice root extract induced sleep in mice via the GABA receptor. This decreased the time required to fall asleep and increased the length of non-REM sleep without decreasing deep sleep [35].

Male Infertility

In mice, licorice extract increased sperm production, which may benefit male infertility [36].

Cancer

Components of licorice were effective against several hallmarks of cancer, including cell proliferation, inflammation, cell death resistance, and making its own blood vessels in cell-based studies.

However, many substances have anti-cancer effects in cells, including downright toxic chemicals like bleach. This doesn’t mean that they have any medical value. On the contrary, most substances (natural or synthetic) that are researched in cancer cells fail to pass further animal studies or clinical trials due to a lack of safety or efficacy.

In an oral cancer cell line, a polysaccharide from licorice promoted apoptosis and prevented cancer cells from growing. Licorice was specifically toxic to human cancer cells, but not healthy cells [37, 38, 39].

Licochalcone A and liquiritigenin block inflammatory and proliferative pathways in cells [40, 41].

Licochalcone A also inhibited cancer cells from generating its own blood vessels (angiogenesis) by blocking the VEGF receptor [42].

Licorice flavonoids prevented colitis-associated cancer and reduced tumor formation in mice [43].

“Bad” estrogens can cause cancer. Liquiritigenin may act as a “good” estrogen and prevent cancer by binding to estrogen receptor beta [25].

Infections

Preliminary research suggests that licorice stimulates the immune system and has antioxidant properties. Its active compounds also had antiviral, antibacterial, and anti-fungal properties in test tubes [44, 45].

In a cell-based study, glycyrrhizic acid (from licorice extract) was effective in controlling the growth of bacteria [46]. Alcoholic licorice root extract inhibited two types of bacteria in cell culture (S. mutans and L. acidophilus). These two types of bacteria can damage teeth [47].

Note, however, that these are very preliminary results that haven’t been validated in humans or even in animals. Further research is needed to determine if licorice may help fight the infections caused by these microorganisms.

Side Effects & Precautions

Deglycyrrhizinated Licorice (DGL)

Chronic or excessive consumption of regular licorice can cause unwanted complications and health problems. Since these side effects mostly come from glycyrrhizic acid, using DGL can help avoid these side effects, except when the desired benefit is directly associated with glycyrrhizic acid itself [2].

Regular Licorice

1) May Increase Cortisol

In large doses, licorice can increase cortisol levels.

Cortisol is a steroid hormone and is also known as the “stress hormone.” It can increase or decrease blood pressure, glucose levels, immune responses, etc. in response to stress [48].

Glycyrrhizic acid and glycyrrhetinic acid, active metabolites (products of metabolism) of licorice extract, act like aldosterone. They inhibit the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enzyme and stop it from converting cortisol to cortisone. This causes an increase in cortisol half-life and an increase in cortisol activity [2, 49].

The hypothalamic–pituitary–adrenal (HPA) axis is an important response system to stress. Normal cortisol levels help maintain the HPA axis. However, excess cortisol can cause HPA axis dysfunction and lead to chronic stress, depression, alcoholism, and other disorders [50].

2) May Cause High Blood Pressure

A longer half-life of cortisol means that it takes longer for the concentration of cortisol in the blood to decrease. Excess cortisol can contribute to high blood pressure. A study found that these effects of glycyrrhizic acid were greater in women than in men [51].

The increase in cortisol locally in the adrenals can increase mineralocorticoids, which can increase blood pressure. Among non-hypertensive people, the increase in blood pressure (3.1 – 14.4 mgHg) is dependent on the amount of licorice consumed [52, 53].

The increase in cortisol can also cause pseudo-hyperaldosteronism. This condition is characterized by elevated blood pressure, decreased blood potassium concentration, and the retention of water and sodium [2, 51].

3) May Slow Down Drug Metabolism

Multiple components of licorice, including liquiritigenin and isoliquiritigenin, inhibit the CYP3A4 gene and cytochrome P450 enzymes. Inactivation of P450 enzymes could also slow down drug metabolism, enhance their concentration in the blood, and increase the risk of drug side effects [54].

4) May Lower Potassium Levels

When licorice metabolites inhibit the 11-βHSD2 enzyme, it also causes excess mineralocorticoid production and a decrease in potassium levels. In multiple case studies, excessive licorice consumption caused hypokalemia (low potassium) and muscle weakness [55].

Licorice-induced hypokalemia can lead to arrhythmia (irregular heartbeat) and cause heart problems [56].

Still, this effect seems to vary among patients. The full effect of licorice on potassium depends on the person’s health, the medication they are taking, and other factors according to an observational study on 360 people [55].

Glycyrrhetic acid can also bind to mineralocorticoid receptors, but its affinity is less than that of aldosterone [2].

5) May Cause Problems During Pregnancy

In a survey of over 100 Finnish women who gave birth to premature babies, heavy licorice consumption was significantly associated with shorter pregnancy terms. The glycyrrhizic acid from licorice increases cortisol levels, which may cause an increase in prostaglandin levels in the uterus. This may trigger contractions [57].

The inactivation of 11β-HSD2 by licorice can cause HPA axis dysfunction. In a study on over 300 pregnant women, those who consumed high amounts of licorice had lower placental 11β-HSD2 levels. Their children tended to have behavioral problems associated with HPA axis dysfunction [58].

However, these effects were investigated in cohort studies. These types of studies can associate factors with certain health conditions but not establish them as their cause. Other genetic and environmental factors may have contributed to the effects observed.

6) Other Rare Side Effects

Licorice consumption may reduce testosterone levels in healthy men. However, these results are mixed between studies. More tests need to be done before any definite conclusions are reached [59, 60].

Some rare side effects include heart attack and stroke, but few studies have shown these results [2].

Drug Interactions

Some compounds in licorice can interact with drugs. To help avoid interactions, be sure to tell your doctor about all medications, vitamins, or herbs you’re taking to find out how licorice might interact with something else you are taking.

Glabridin, for example, inhibits cytochromes 3A4 and 2B6 – P450 enzymes that help metabolize drugs. This means that it could affect how your prescription drugs work.

Licorice Root Supplements

Both licorice root and DGL are available as supplements. The FDA doesn’t approve them for any conditions due to the lack of solid clinical research. Regulations set manufacturing standards for supplements but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing

DGL is safer and may be a better choice for most people.

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About the Author

Carlos Tello

PhD (Molecular Biology)
Carlos received his PhD and MS from the Universidad de Sevilla.
Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.

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