licorice

12 Health Benefits and 6 Side Effects of Licorice, with References and Mechanisms

Licorice is mostly associated with candy and has been used in food and medicine for 1000 years. It contains various compounds that help with heartburn, cancer, and a leaky gut. Keep reading to learn more about its health benefits.

Introduction

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811453/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4811453/

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

Licorice many components that have proven health benefits. It has been used in herbal and folk medicines 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 such as hypertension (R).

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

Without glycyrrhizin, DGL is not associated with any adverse effects but still retains some of its beneficial properties. Treatment with DGL can help avoid the side effects of glycyrrhizin and glycyrrhizic acid (R). DGL is typically used to treat stomach ulcers and other digestive problems.

Health Benefits of Licorice

1) Licorice Is Anti-inflammatory

In an analysis of 93 papers, licorice extract was observed to have anti-inflammatory activities (R).

Licorice extract promotes regulatory T cells in mice, suggesting that licorice can protect against autoimmune and inflammatory diseases (R).

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 (R).

Ethanol extract of licorice also prevented against alcohol-induced liver injury in mice by reducing key liver inflammation markers (R).

2) DGL Licorice Helps Reduce Risks of Cardiovascular Diseases

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In patients with high cholesterol, a year of deglycyrrhizinated licorice consumption decreased total cholesterol, LDL cholesterol, and blood pressure levels (R).

In a mouse model of heart attack, the anti-inflammatory and anti-oxidative effects of licorice help mitigate damage to the heart tissue and also facilitate faster recovery (R).

However, regular licorice that contains glycyrrhizin and glycyrrhizic acid can cause the body to excrete more potassium and increase blood pressure, which can worsen heart conditions (R).

3) Licorice May Help with Weight Loss

In mice and rats, licorice flavonoid oil helps weight loss by enhancing fat oxidation during light exercise (R).

Licorice root powder was also effective in reducing body weight gain and fat deposition in mice (R).

4) Licorice Protects the Brain

Glabridin, a major flavonoid of Glycyrrhiza glabra (licorice), can help protect the brain from stroke-related injuries (R).

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 (R).

Licorice flavonoids can also prevent oxidative damage in the brain. Its antioxidant effects help decrease seizure-induced brain cell death in mice (R).

Diabetes can cause memory and learning problems. In diabetic mice, glabridin extract from licorice helps preserve cognitive function (R).

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 (R).

Inflammation in the brain can lead to many diseases like Alzheimer’s, dementia, and multiple sclerosis. Stopping pro-inflammatory activities can help protect the brain (R).

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

5) Licorice May Help Prevent Cancer Growth

Components of licorice are effective against several hallmarks of cancer, including cell proliferation, inflammation, cell death resistance, and making its own blood vessels. Most studies that evaluate anti-cancer activities of licorice are cell-based studies. Additional clinical studies are necessary to confirm its safety and effectiveness as a cancer treatment.

In an oral cancer cell line, a polysaccharide from licorice promotes apoptosis and prevents cancer cells from growing (R).

In a human cancer cell line, licorice is specifically toxic to human cancer cells, but not healthy cells (R, R2).

Licochalcone A and liquiritigenin blocking inflammatory and proliferative pathways (R, R2).

Licochalcone A also inhibits cancer cells from generating its own blood vessel (angiogenesis) by blocking the VEGF receptor (R).

Licorice flavonoids prevented colitis-associated cancer and reduced tumor formation in mice (R).

Bad estrogens can cause cancer. Liquiritigenin may act like good estrogen and prevent cancer by binding to estrogen receptor beta (R).

6) Licorice Helps Heal Gut Inflammation and Ulcers

Licorice is a good adjunctive treatment to standard clarithromycin triple therapy in the treatment of Helicobacter pylori as it increases the eradication rate of H. pylori by about 20% (R).

In patients with dyspepsia, licorice helped symptoms of nausea, indigestion, and stomach pains (R).

In rats with stomach ulcers caused by aspirin, licorice decreased the number and size of the ulcers (R).

7) Licorice Helps with Menopausal Symptoms

In menopausal women, licorice is more effective than hormone replacement therapy (HRT) by reducing hot flash duration, but not hot flash severity (R). In a phase II clinical trial, liquiritigenin is part of MF101, an herbal extract formula that helped with menopausal hot flashes (R).

Glabridin, liquiritigenin, and glabrene have estrogen-like activities, which can help women who have low estrogen levels (R, R2), such as in the case of menopause.

Glabridin has a similar effect on human cell culture as estradiol-17beta (the most potent form of estrogen) (R). Glabrene can bind to estrogen receptors and also stimulate muscle cell formation (R).

8) Licorice Helps with Polycystic Ovarian Syndrome (PCOS)

Treatment with spironolactone (a mineralocorticoid and androgen receptor antagonist) and licorice can help reduce polycystic ovary syndrome (PCOS) symptoms in women (R).

In women with PCOS, glycyrrhetinic acid can reduce testosterone levels while inducing regular ovulation. Two other licorice metabolites (glabridin and glabrene) have estrogen-life effects that can help treat PCOS (R).

9) Licorice May Help with Infections

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Licorice stimulates the immune system and has antioxidant properties (R).

Licorice has antiviral, antibacterial, and anti-fungal properties (R).

In a cell-based study, glycyrrhizic acid (from licorice extract) was effective in controlling the growth of bacteria (R). 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. (R).

10) Licorice Helps with Fatigue

Licorice increases cortisol levels and activities 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) (R). The increase in cortisol may somewhat help with energy levels. In addition, it also increases DHEA and testosterone levels (R).

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 (R). In comparison to untreated mice, swimming mice treated with glabridin had lower markers of fatigue, including significantly lower blood lactic acid levels and blood nitrogen urea, and higher glycogen levels (R).

However, clinical trials are needed to determine glabridin’s effects on humans.

11) Licorice Helps You Sleep

Glycyrrhiza glabra, one type of licorice root, can help induce sleep and increase sleep duration (R).

The GABA receptor is an important target for inducing sleep. Gabrol and liquiritigenin induces 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 (R).

12) Licorice May Benefit Male Infertility

In mice, licorice extract increased sperm production, which may benefit male infertility (R).

Side Effects of Licorice

Although licorice may have its benefits, chronic or excess consumption can cause unwanted complications and health problems. Since these side effects mostly come from glycyrrhizic acid, using DGL can help avoid these side effects (R), except when the desired benefit is directly associated with glycyrrhizic acid itself.

1) Licorice Increases Cortisol

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498851/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498851/

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 (R).

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

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 (R).

2) Licorice Causes High Blood Pressure

A longer half-life for cortisol means that it takes longer for the concentration of cortisol in the blood to decrease. Excess cortisol can contribute to hypertension (high blood pressure). These effects from glycyrrhizic acid are greater in women than in men (R, R).

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

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 (R, R).

3) Licorice Slows 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 (R).

4) Excess Licorice Consumption Can 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, excess licorice consumption caused hypokalemia (low potassium) and muscle weakness (R).

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

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 (R).

Glycyrrhetic acid can also bind to mineralocorticoid receptors, but its affinity is less than that of aldosterone (R).

5) Licorice Can Cause Problems During Pregnancy

In a survey of 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 can cause an increase in prostaglandin levels in the uterus. This may lead to contractions (R).

However, these results may not necessarily be caused solely by licorice consumption. Because this information was collected retrospectively, other factors may also have contributed to the premature delivery (R).

The inactivation of 11β-HSD2 by licorice can cause HPA axis dysfunction. In one review, pregnant women who consumed licorice had lower placental 11β-HSD2 levels. Their children had behavioral problems associated with HPA axis dysfunction (R).

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 (R, R).

Some rare side effects include heart attack and stroke, but few studies have shown these results (R).

Constituents of Licorice, their Properties and Pharmacokinetics (Technical)

1) Glycyrrhizin/Glycyrrhetinic Acid

The main active component of licorice is glycyrrhizin. After oral ingestion of licorice, our gut bacteria changes glycyrrhizin’s main constituent, glycyrrhizic acid, into glycyrrhetinic acid, which is a very potent inhibitor of the 11-ß-HSD enzyme. 11-ß-HSD converts cortisone (the less active form of cortisol) to cortisol, so glycyrrhizic acid increases cortisol levels (R, R2).

Carrier molecules absorb and transport glycyrrhetinic acid to the liver, where it is metabolized to different conjugates (various molecules of similar, but not identical, chemical structures). It then circulates in the blood and the intestines. Repeated intake of licorice might lead to the accumulation of glycyrrhetinic acid, which can cause toxicity (R).

In humans, glycyrrhizin administration by is better absorbed as a pure extract than as part of a whole licorice root (R).

2) Glabridin

Glabridin is the most abundant flavonoid in licorice. It is anti-oxidative, anti-inflammatory and neuroprotective. It is absorbed in the intestine (R, R).

In humans, daily 300-1200 mg licorice flavonoid oil (LFO) administration showed nearly linear pharmacokinetics. Glabridin levels reach steady state levels around 2 weeks of LFO dosage (R).

Glabridin inhibits cytochromes 3A4 and 2B6 (P450 enzymes that help metabolize drugs) in humans. It inhibits these enzymes at a concentration, time, and NADPH-dependent manner (R).

However, glabridin’s bioavailability, metabolism, and absorption in the body is unclear due to conflicting studies (R).

3) Licochalcone A

Licochalcone A (LicoA) is a licorice polyphenol. It has antiparasitic, antibacterial and anti-cancer properties (R).

LicoA stops inflammation in humans and cell culture by suppressing the lipopolysaccharide (LPS) signaling pathway. It also prevents cancer by suppressing the Akt/mTOR and ERK1/2/p90RSK signaling pathways (R).

LicoA binds with various enzymes to suppress COX-2 enzyme expression and stop UV light-induced inflammation (R).

4) Isoliquiritigenin and Liquiritigenin

Isoliquiritigenin is a chalcone that has antioxidative, anti-inflammatory, and antitumor effects. In rats, its pharmacokinetics is not dose-dependent. It has a high affinity for the liver, kidneys, and small and large intestines (R).

Although more than ninety percent of the oral isoliquiritigenin is absorbed in rats, it has a bioavailability of 11.8%. This may be due to its high metabolism in the liver and small intestines (R).

Liquiritigenin is a metabolite of isoliquiritigenin. There are no studies of liquiritigenin pharmacokinetics in humans available. However, scientists have used studies done on mice, rats, rabbits, and dogs to estimate some results (R).

Oral administration of liquiritigenin in animals showed that it is rapidly absorbed in the intestine. The M1 and M2 conjugates (modified forms) of liquiritigenin rapidly form in all species (R).

5) Glabrene

Glabrene is an isoflavonoid found in licorice root extract. It binds to human cell estrogen receptors (R).

In human cell culture, glabrene activates the expression of estrogen-regulated genes. In rats, glabrene causes a significant increase in creatine kinase activity. Glabrene can mimic estrogen in terms of its beneficial effects in bone and heart tissues (R), suggesting that it might slow down bone loss or cardiovascular decline in menopausal women. However, additional clinical studies would be necessary to determine whether glabrene is safe and effective for menopausal symptoms.

6) Coumarins

Coumarins are organic chemical compounds that have a sweet smell. Some coumarins found in licorice include licopyranocoumarin, licoarylcoumarin, and glycycoumarin (R).

Glycycoumarin is a major coumarin of licorice. After oral administration, it is readily absorbed in the blood and urine. In rats, P450 enzymes catalyze glycycoumarin into different metabolites (R).

7) Other Compounds in Licorice

Technical

  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889530/

    http://pubmedcentralcanada.ca/pmcc/articles/PMC3795865/
    http://pubmedcentralcanada.ca/pmcc/articles/PMC3795865/

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