Licorice root

Synonym(s): glabridine, Glycyrrhiza glabra, glycyrrhetinic acid

Nutrient group: plant extracts & active ingredients

Sources and physiological effects

Dietary sources
Licorice root belongs to the family of legumes within the subfamily of the papilionaceous plants (Faboideae). Key components of the root are triterpene saponins - especially the sweet-tasting glycyrrhizinic acid, as well as coumarins and flavonoids. In the diet, the licorice root is mainly found in the form of sweets, teas and spirits. However, it is best known as an ingredient of licorice, which is particularly popular in the northern countries of Europe.
Physiological effects
Hormone balance	Delayed excretion of corticosteroids and extension of the biological half-life of cortisol and aldosterone by inhibition of the enzyme 11ß-hydroxysteroid dehydrogenase
Antioxidant	Increased formation of paraoxonase 2 (PON2), which contributes intracellularly to antioxidative protection especially under inflammatory conditions
Mucosa	Antibacterial properties Anti-ulcerative effects through reduction of gastric acid formation

Detailed information

Licorice root ingredients - combination of glabridin and glycyrrhizinic acid

The licorice root contains triterpene saponins (such as glycyrrhinzic acid), flavonoids (such as galbridin) and coumarins. So far, researchers have discovered a total of around 400 different components. Due to its metabolically active effects, licorice root is of particular interest in the treatment of metabolic syndrome. The ingredients glabridin and glycyrrhizinic acid have different biochemical targets in the same indication range. In order to be able to use these therapeutically, preparations should contain both the extract and the oil extract preparation of the licorice root.

11β-Hydroxysteroid dehydrogenases (11β-HSD1) as key enzymes of metabolic syndrome

18α-glyceric acid is a naturally occurring metabolite of the glycyrrhizinic acids contained in the licorice root. It has been shown to inhibit the activity of 11β-HSD1 and is already being discussed as a promising substance with therapeutic relevance (1). Animal studies have shown that increased activity of 11β-HSD1 leads both to increased fat storage in the abdomen and to increased formation of the stress hormone cortisol from cortisone (2). In return, the enzyme 11β-HSD2 reduces cortisol to cortisone (3). The metabolic effect of cortisol also consists of the differentiation of preadipocytes into adipocytes (3). The resulting visceral fat forms 11β-HSD1, which increases the cortisol level. The disturbed formation of mineralocorticoids as well as the increased inflammatory readiness and insulin resistance, combined with increased oxidative stress, can ultimately lead to diseases typical of metabolic syndrome such as arteriosclerosis, high blood pressure and diabetes (4) (5).

Glabridin and Metabolic Syndrome

The flavonoid glabridin acts as an agonist on peroxisome proliferator-activated receptor gamma (PPAR-gamma) ligand. This nuclear receptor plays a central role as a transcription factor in metabolic processes in metabolic syndrome. Activation of the PPAR-gamma receptor seems to be an important factor in the treatment of metabolic syndrome. The oily licorice root extract Glavonoid® shows PPAR-gamma-activating effects. This explains the reduction of abdominal fat formation and the hypoglycemic effects of this preparation (6).

Antioxidative protective effects of glabridin in hyperglycemia

The flavonoid glabridin is also associated with strong anti-atherogenic properties, especially in cases of elevated blood sugar levels. It increases the formation of PON2, which contributes intracellularly to antioxidative protection especially under inflammatory conditions (7). Among other things, this prevents LDL oxidation, which occurs at the start of arteriosclerotic changes. For the oily licorice root extract Glavonoid® these effects were demonstrated in a mouse (8).

Glavonoid® reduces visceral fat formation

The prevention of the formation of new visceral adipose tissue is a therapeutic interest. Animal studies have shown that Glavonoid® intensifies the expression of genes that play a central role in β oxidation in lipid metabolism. Pyruvate kinase is also inhibited in the liver, which is important for glycolytic lipogenesis (9). Both in animal studies and clinical studies with obese people, Glavonoid® reduced fat deposits in the abdomen. A Japanese double-blind and placebo-controlled study with 103 overweight patients was able to show that after 12 weeks of supplementation with 300 mg Glavonoid®, there was a significant weight loss caused by a reduction of fatty tissues (10). Pharmacological tests also showed that a daily intake of 300 – 1200 mg is safe and free of side effects (11).

Antimicrobial and antiulcerative properties of licorice root

Licorice root contains not only the plant-typical components glabridin and glabrol but also natural salicylic acid, for which significant antimicrobial effects have been demonstrated (12). In addition, polysaccharide fractions of Glycyrrhizia glabra can reduce the adhesion of Helicobacter pylori, Campylobacter jejuni and Porphyromonas gingivalis to potential host cells by 60 – 70 % (13), thereby reducing bacterial infection. In addition, licorice root has demonstrated anti-ulcer properties by reducing gastric acid production, increasing mucus formation and promoting cytokine balance (14).

Indications

Effect	Indication	Dosage
Physiological effects at a low intake	Therapeutic support for metabolic syndrome and obesity	100 mg/d
	To reduce the risk factors of abdominal fat distribution	100 mg/d
	For 11Beta-HSD index (>1,3)	100 mg/d
	To improve performance, concentration and fatigue	100 mg/d
	If the microecological balance is disturbed by bacterial infestation of the body, especially in gastrointestinal tract	150 – 300 mg/d

Administration

General mode of administration
When	Licorice root extract should be taken between meals. Hint: Use during pregnancy and lactation is not recommended, as increased licorice consumption may be accompanied by unfavorable metabolic programming in the child.
Side effects
None; only after prolonged use of very high doses (more than 50 g/day) can the electrolyte concentrations in the body shift, allowing reversible symptoms such as high blood pressure and heart complaints to develop.
Contraindications
Pregnancy, lactation, hypertension, renal failure

Interactions

Drug interactions
NSAIDs (e.g. Diclofenac, ASS, ibuprofen)	Licorice root can reduce the side effects of NSAIDs, especially in the gastrointestinal area.
Corticosteroids (e.g. prednisolone, dexamethasone)	Licorice root has a cortisol saving effect and increases the effect of corticosteroids, side effects can be reduced by lower dosages.
Diuretics (loop diuretics, thiazides)	Simultaneous intake at high doses may lead to increased excretion of potassium.
Nutrient interactions
None	No relevant interactions are known to date.

References

1) Classen-Houben, D. et al. 2009. Selective inhibition of 11beta-hydroxysteroid dehydrogenase 1 by 18alpha-glycyrrhetinic acid but not 18beta-glycyrrhetinic acid. J Steroid Biochem Mol Biol. 113(3-5):248-52.
2) Yin, Y. Y. et al. 2010. Effects of glycyrrhizic acid on 11 β-hydroxysteroid Dehydrogenase (11 βHSD1 and 2) activities and HOMA-IR in rats at different treatment periods. Exp Clin Endocrinol Diabetes.
3) Andres, J. Untersuchungen über Regulationsmechanismen der 11beta-Hydroxysteroid Dehydrogenase Typ 1. Dissertation an der Universität Potsdam, 2008.
4) Masuzaki, H. et al. 2001. A transgenic model of visceral obesity and the metabolic syndrome. Science. 294:2166-70. doi: 10.1126/science.1066285.
5) Mazukaki, H., Flier, J. S. 2003. Tissue specific glucocorticoid reactivating enzyme, 11-β-hydroxysteroid dehydrogensae type 1 (11 βHSD-1) a promising drug target for the treatment of metabolic syndrome. Curr Drug Targets Immune Endocr Metabol Disord. 3(4):255-262(8).
6) Nakagawa, K. et al. 2004. Licorice flavonoids suppress abdominal fat accumulation and increase in blood glucose level in obese diabetic KK-A(y) mice. Biol Pharm Bull. 27(11):1775-8.
7) Yehuda, I. et al. 2011. Glabridin, a phytoestrogen from licorice root, up-regulates manganese superoxide dismutase, catalase and paraoxonase 2 under glucose stress. Phytother Res. 25(5):659-667. doi: 10.1002/ptr.3318.
8) Mae, T. et al. 2003. A licorice ethanolic extract with peroxisome proliferator-activated receptor-gamma ligand-binding activity affects diabetes in KK-Ay mice, abdominal obesity in diet-induced obese C57BL mice and hypertension in spontaneously hypertensive rats. J Nutr. 133(11):3369-77.
9) Aoki, F. et al. 2007. Suppression by licorice flavonoids of abdominal fat accumulation and body weight gain in high-fat diet-induced obese C57BL/6J mice. Biosci Biotechnol Biochem. 71(1):206-14. doi: 10.1271/bbb.60463.
10) Tominaga, Y. et al. 2006. Licorice flavonoid oil effects body weight loss by reduction of body fat mass in overweight subjects. J of Health Science. 52(6): 672–683. doi: doi.org/10.1248/jhs.52.672.
11) Aoki, F. et al. 2007. Clinical safety of licorice flavonoid oil (LFO) and pharmacokinetics of Glabridin in healthy humans. J Am Col Nutr. 26(3):2009-218.
12) Mitscher, L. A. et al. 1980. Antimicrobial agents from higher plants. Antimicrobial isoflavanoids and related substances from Glycyrrhiza glabra L. var. typical. J Nat Prod. 43(2):259-69.
13) Wittschier, N. et al. 2007. Large molecules as anti-adhesive compounds against pathogens. J Pharm Pharmacol. 59(6):777-86.
14) Khayyal, M. T. et al. 2001. Antiulcerogenic effect of some gastrointestinally acting plant extracts and their combination. Arzneimittelforschung. 51(7):545-53. doi: 10.1055/s-0031-1300078.

References Interactions
Stargrove, M. B. et al. Herb, Nutrient and Drug Interactions: Clinical Implications and Therapeutic Strategies, 1. Auflage. St. Louis, Missouri: Elsevier Health Sciences, 2008.
Gröber, U. Mikronährstoffe: Metabolic Tuning –Prävention –Therapie, 3. Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2011.
Gröber, U. Arzneimittel und Mikronährstoffe: Medikationsorientierte Supplementierung, 3. aktualisierte und erweiterte Auflage. Stuttgart: WVG Wissenschaftliche Verlagsgesellschaft Stuttgart, 2014.