licorice

Licorice

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 is a plant native to southern Europe and Asia and is used to flavor candies, sweeteners, and tobacco products.

Licorice contains glycyrrhizin and glabridin, which have proven health effects on the body. It has been used in herbal and folk medicines for its anti-inflammatory properties.

While licorice is mainly found to have positive health benefits, excessive intake of glycyrrhizin may increase high blood pressure and muscle weakness.

The Licorice that I Recommend

Licorice Pills

  • Heart Health/10
  • Inflammation/10
  • Brain/10
  • Antioxidant/10
  • Energy/Endurance/10

Pros

  • Is anti-inflammatory
  • Protects against cancer
  • Protects the heart and brain
  • Reduces fatigue
  • Benefits the gut

Cons

  • Raises blood pressure
  • Interferes with drug metabolism
  • Lowers potassium levels
  • Causes muscle weakness
  • Might lower testosterone levels in males

Constituents of Licorice and their Pharmacokinetics

1) Glycyrrhizin/ Glycyrrhetinic Acid

The main active component of licorice is glycyrrhizin. It is metabolized (changed) into glycyrrhetinic acid by the body’s metabolism (R).

After oral ingestion of licorice, bacteria in the body changes glycyrrhizin’s main constituent, glycyrrhizic acid, into glycyrrhetinic acid. Glycyrrhetinic acid is a very potent inhibitor of the 11-ß-HSD enzyme (R).

Carrier molecules absorb and transport glycyrrhetinic acid to the liver, where it is metabolized to different conjugates. It then circulates in the blood and the intestines. Repeated intake of licorice might lead to the accumulation of glycyrrhetinic acid and can cause toxicity (R).

In one human study, glycyrrhizin administration by itself has a lower intestinal absorption rate when it is a component of licorice root extract in comparison to when it is administered alone (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 both female and male subjects, 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-tumor 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 are not dose dependent. Its affinity is high in 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 the intestinal tract rapidly absorbs the flavonoid. The M1 and M2 conjugates 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 and its beneficial effects in bone and heart tissues (R).

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

Deglycyrrhizinated Licorice (DGL) vs Regular Licorice

Glycyrrhizin is an active compound in licorice. Consuming large amounts of licorice can increase cortisol levels and blood pressure, reduce testosterone, and even cause pseudo-hyperaldosteronism (R).

People manufactured deglycyrrhizinated licorice (DGL) by removing glycyrrhizin to prevent its side effects. DGL is available in wafers, capsules, liquids, and lozenges (R).

DGL is not associated with any adverse effects. Treatment with DGL can help avoid complications from glycyrrhizin and glycyrrhizic acid (R).

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. This protects 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 and helps prevent neuron cell death (R).

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

2) Licorice Helps Prevent Heart Disease

bigstock-medical-stethoscope-head-and-r-104167844-min

High cholesterol, obesity, and high blood pressure can all lead to heart disease (R).

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

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).

3) 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) stops lipopolysaccharide (LPS) activity in mice cell culture. It prevented LPS from inducing TNF-α production. It also reduced NF-kB activity, which helps stop neuron cell death and inflammation (R).

4) Licorice May Help Prevent Cancer Growth

In a human cancer cell line, licorice increased tumor-specific cytotoxicity (R).

Licochalcone, a licorice polyphenol, may be a skin cancer chemopreventive agent by blocking certain biochemical pathways (R).

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

Angiogenesis, or blood vessel formation, can become abnormal during the production of tumors. Licohalcone A (LicoA), the main active compound from Glycyrrhiza inflate (licorice), inhibits tumor angiogenesis (R).

The VEGF signaling pathway helps control angiogenesis. LicoA blocks VEGF signaling and the expression of its primary receptor. Thus, LicoA was able to stop blood vessel formation in both human skin cell culture and mice (R).

Liquiritigenin, a flavanone from Radix glycyrrhiza (licorice), shows the same effects on human cancer cell culture. It also reduced VEGF signaling, which helped stop angiogenesis (R).

5) Licorice Benefits the Gut

In patients with peptic ulcer disease, clarithromycin treatment with licorice helped reduce H. pylori bacteria. The bacteria is associated with poor gut health (R).

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

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

In rats, licorice decreased the number and size of gastric ulcers more than aspirin-treated rats (R).

Also, licorice may be able to treat drug poisoning by increasing metabolizing enzymes and other mechanisms (R).

6) Licorice Helps Improve Women’s Health

Glabridin and glabrene, both licorice flavonoids, have estrogen-like activities. This can help women who have low estrogen levels (R).

Glabridin has a similar effect on human cell culture as estradiol-17beta (a form of estrogen). It was able to stimulate the DNA synthesis and formation of certain cells. Like estradiol-17beta, it also blocked creatine kinase activity (R).

On the other hand, glabrene can bind to estrogen receptors and also stimulate muscle cell formation (R).

Licorice chalcones also have estrogen-like effects. They induced the expression of an estrogen responsive gene TFF1 in an Ishikawa cell line (human cancer cell culture) (R).

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

The glycyrrhetinic acid from licorice 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).

In menopausal women, licorice is more effective than hormone replacement therapy (HRT) by reducing hot flash duration, but not hot flash severity (R).

7) Licorice Helps Prevent the Growth of Microbes

bigstock-146401415-min

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

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

Licorice has antiviral and antimicrobial properties by preventing virus gene replication and stopping bacterial gene expression (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).

8) Licorice Prevents Fatigue

Glabridin, a polyphenolic flavonoid from licorice extract, prevented 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 exercise period lasted (R).

High blood lactic acid levels are a good indicator of fatigue. Exercising mice treated with glabridin had significantly lower blood lactic acid levels in comparison to the control group. Glabridin can slow down and lower the amount of blood lactic acid produced after exercise (R).

Blood urea nitrogen (BUN) levels usually increase significantly after exercise and are related to fatigue.  Glabridin also lowered BUN formation in exercising mice (R).

Glycogen is an important energy source during exercise. Glabridin increased the amount of glycogen stored in the muscles of exercising mice, thus increasing their endurance (R).

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

9) Licorice Helps You Sleep

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

The GABA-BZD receptor is an important target for inducing sleep. Licorice ethanol extract induces sleep in mice via the GABA receptor. This decreased the time required to fall asleep and increased the length of non-REM sleep (R).

10) Licorice May Benefit Male Infertility

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

Side Effects of Licorice Intake

Although licorice may have its benefits, chronic or excess consumption can cause unwanted complications and health problems. Since these effects mostly come from glycyrrhizic acid, DGL can help avoid these side effects (R).

1) Licorice Increases Cortisol Levels

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).

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

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).

The inactivation of 11β-HSD2 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).

2) 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).

3) 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).

4) 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 a shorter pregnancy term. 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 have caused premature delivery (R).

In one review, women who consumed licorice during pregnancy had children with behavioral problems associated with HPA axis dysfunction (R).

5) Other Rare Side Effects

Licorice consumption may reduce testosterone levels in healthy men. However, these results vary 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 not many studies have shown these results (R).

Technical

  • Glycyrrhetic acid can also bind to mineralocorticoid receptors, but its affinity is less than that of aldosterone (R).
  • LicoA binds with PI3K and MEK1, as well as B-Raf, to suppress COX-2 enzyme expression (R).
  • Liquiritigenin, isoliquiritigenin, glycycoumarin, semilicoisoflavone B, licoisoflavone A, licoricone, glycyrol, licoflavonol, and licoisoflavone B may be the key compounds responsible for licorice–P450 interactions (R).
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889530/

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

Buy Licorice

Leave a Reply