Licorice Safety

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Licorice Side Effects and Caution

High doses of licorice when used daily over a prolonged period can cause a

fluid imbalance in the body, involving salt, potassium, and water

metabolism. Licorice-associated hypertension is thought to be due to

increased renal sodium retention. The active compound of licorice,

glycyrrhetinic acid, inhibits renal 11beta-hydroxysteroid dehydrogenase

type 2 and by that mechanism increases access of cortisol to the

mineralocorticoid receptor that causes renal sodium retention and potassium

loss. Basically this means that too much licorice used for prolonged

periods leads to loss of potassium in the urine and the retention of

sodium. Sometimes this is described as pseudoaldosteronism.

Another reported side effect of chronic high dose licorice use is

rhabdomyolisis which is damage to muscle tissue.

Licorice Human Research Update

Licking latency with licorice.

J Clin Invest. 2005 Mar;115(3):591-3.

Numerous viruses cause latent infections in humans, and reactivation often

results in pain and suffering. While vaccines for several of these viruses

are available or currently being studied in clinical trials, and antiviral

therapies have been successful in preventing or treating active infection,

therapy to eradicate latent infection has lagged behind. A new study

reported in this issue of the JCI shows that treatment of cells latently

infected with Kaposi sarcoma-associated herpes virus (KSHV) with

glycyrrhizic acid, a component of licorice, reduces synthesis of a viral

latency protein and induces apoptosis of infected cells. This finding

suggests a novel way to interrupt latency.

Memory-strengthening activity of Glycyrrhiza glabra in exteroceptive and

interoceptive behavioral models.

J Med Food. 2004 Winter;7(4):462-6.

In the traditional system of medicine, the roots and rhizomes of

Glycyrrhiza glabra - licorice plant - have been employed clinically for

centuries for their anti-inflammatory, anti-ulcer, expectorant,

antimicrobial, and anxiolytic activities. The present study was undertaken

to investigate the effects of G. glabra, popularly known as licorice

(Mulathi), on learning and memory. The elevated plus-maze and passive

avoidance paradigm were employed to evaluate learning and memory

parameters. Three doses (75, 150, and 300 mg/kg p.o.) of aqueous extract of

Glycyrrhiza glabra were administered for 7 successive days in separate

groups of mice. The dose of 150 mg/kg of the aqueous extract of licorice

significantly improved learning and memory of mice. Furthermore, this dose

reversed the amnesia induced by diazepam (1 mg/kg i.p.), scopolamine (0.4

mg/kg i.p.), and ethanol (1 g/kg i.p.). Anti-inflammatory and antioxidant

properties of licorice may be contributing favorably to the memory

enhancement effect. Since scopolamine-induced amnesia was reversed by

licorice, it is possible that the beneficial effect on learning and memory

may be because of facilitation of cholinergic transmission in brain.

However, further studies are necessitated to identify the exact mechanism

of action. In the present investigation, licorice has shown promise as a

memory enhancer in both exteroceptive and interoceptive behavioral models

of memory.

Pharmacokinetic and pharmacodynamic profiles of the antitussive principles

of Glycyrrhizae radix (licorice), a main component of the Kampo preparation

Bakumondo-to (Mai-men-dong-tang).

Eur J Pharmacol. 2005 Jan 10;507(1-3):163-8.

We examined the pharmacokinetic and pharmacodynamic properties of

liquiritin apioside, a main antitussive component of Glycyrrhizae radix (

licorice ), with regard to its antitussive effect in guinea pigs. The

present results suggest that G. radix ( licorice ) may produce a persistent

antitussive effect, and that liquiritin apioside plays an important role in

the earlier phase, while liquiritigenin, which is a metabolite of

liquiritin apioside and liquiritin, plays an important role in the late phase.

Licorice reduces serum testosterone in healthy women.

Steroids. 2004 Oct-Nov;69(11-12):763-6.

Licorice has been considered a medicinal plant for thousands of years. The

most common side effect is hypokalemic hypertension, which is secondary to

a block of 11beta-hydroxysteroid dehydrogenase type 2 at the level of the

kidney, leading to an enhanced mineralocorticoid effect of cortisol. We

have investigated the effect of licorice on androgen metabolism in nine

healthy women 22-26 years old, in the luteal phase of the cycle. They were

given 3.5 g of a commercial preparation of licorice (containing 7.6% W.W.

of glycyrrhizic acid) daily for two cycles. CONCLUSIONS: Licorice can

reduce serum testosterone probably due to the block of 17-hydroxysteroid

dehydrogenase and 17-20 lyase. Licorice could be considered an adjuvant

therapy of hirsutism and polycystic ovary syndrome.

Licorice Flavonoids Suppress Abdominal Fat Accumulation and Increase in

Blood Glucose Level in Obese Diabetic KK-A(y) Mice.

Biol Pharm Bull. 2004 Nov;27(11):1775-8.

Licorice, the root of the Glycyrrhiza species, is one of the most

frequently employed botanicals in traditional medicines. In this study, we

investigated the effects of hydrophobic flavonoids from licorice on

abdominal fat accumulation and blood glucose level in obese diabetic mice.

In order to enrich a fraction of hydrophobic flavonoids, licorice flavonoid

oil was prepared by further extracting licorice ethanolic extract with

medium-chain triglycerides (MCT), and adjusting the concentration of

glabridin, the major flavonoid of licorice, to 1.2% in oil. Mice aged 6

weeks were assigned to 5 groups, and fed a high-fat diet containing 0

(control), 0.5%, 1%, or 2% licorice flavonoid oil, or 0.5% conjugated

linoleic acid (CLA) for 4 weeks. Compared with the control, body weight

gain and weights of abdominal adipose tissues were suppressed by feeding

the diet containing 2% licorice flavonoid oil , and blood glucose levels

after 2 and 4 weeks were suppressed by all of the diets containing licorice

flavonoid oil. Although CLA feeding suppressed body weight gain, it

increased blood glucose level after 2 weeks compared with the control

level. Furthermore, licorice flavonoid oil and licorice ethanolic extract

stimulated human adipocyte differentiation in vitro. These results indicate

that licorice hydrophobic flavonoids have abdominal fat-lowering and

hypoglycemic effects, possibly mediated via activation of peroxisome

proliferator-activated receptor-gamma (PPAR-gamma).

Inhibition of serotonin re-uptake by licorice constituents.

J Mol Neurosci. 2003 Apr;20(2):135-40.

The aim of this study was to test the effect of compounds of the licorice

isoflavan and isoflavene groups, subclasses of the flavonoids family, on

serotonin re-uptake and to compare the results with the effect of other

known phytoestrogens like genistein and daidzein to relate the activity of

these compounds to their structure. The results demonstrated that the

isoflavans glabridin and 4'-O-methylglabridin (4'-OMeG) and the isoflavene

glabrene inhibited serotonin re-uptake, whereas resorcinol, the isoflavan

2'-O-methylglabridin (2'-OMeG), and the isoflavones genistein and daidzein

were inactive. In conclusion, this study showed that several licorice

isoflavans are unique phytoestrogens, which like estradiol, affects the

serotonergic system and inhibits serotonin re-uptake and, thus, potentially

may be beneficial for mild to moderate depression in pre- and

postmenopausal women.

Effect of licorice on the reduction of body fat mass in healthy subjects.

J Endocrinol Invest. 2003 Jul;26(7):646-50.

The history of licorice, as a medicinal plant, is very old and has been

used in many societies throughout the millennia. The active principle,

glycyrrhetinic acid, is responsible for sodium retention and hypertension,

which is the most common side-effect. We show an effect of licorice in

reducing body fat mass. We studied 15 normal-weight subjects (7 males, age

22-26 yr, and 8 females, age 21-26 yr), who consumed for 2 months 3.5 g a

day of a commercial preparation of licorice. Body fat mass (BFM, expressed

as percentage of total body weight, by skinfold thickness and by

bioelectrical impedance analysis, BIA) and extracellular water (ECW,

percentage of total body water, by BIA) were measured. Body mass index

(BMI) did not change. ECW increased. BFM was reduced by licorice; plasma

renin activity and aldosterone were suppressed. Licorice was able to reduce

body fat mass and to suppress aldosterone, without any change in BMI. Since

the subjects were consuming the same amount of calories during the study,

we suggest that licorice can reduce fat by inhibiting 11beta-hydroxysteroid

dehydrogenase Type 1 at the level of fat cells.

Anti-atherosclerotic effects of licorice extract supplementation on

hypercholesterolemic patients: increased resistance of LDL to atherogenic

modifications, reduced plasma lipid levels, and decreased systolic blood

pressure.

Nutrition 2002 Mar;18(3):268-73

We previously demonstrated the beneficial effects of dietary flavonoids

derived from the ethanolic extract of licorice root against atherosclerotic

lesion development in association with inhibition of low-density

lipoprotein (LDL) oxidation in atherosclerotic mice. Administration of

licorice extract to normolipidemic subjects also inhibited LDL oxidation.

In the present study, we extended our investigation to analyze the

anti-atherogenic effects of licorice-root extract consumption in moderately

hypercholesterolemic patients. Supplementation of licorice root extract

(0.1 g/d) to patients for 1 mo was followed by an additional 1 mo of

placebo consumption. RESULTS: Licorice consumption reduced patients' plasma

susceptibility to oxidation (by 19%); increased resistance of plasma LDL

against three major atherogenic modifications: oxidation (by 55%),

aggregation (by 28%), and retention, estimated as chondroitin sulfate

binding ability (by 25%); reduced plasma cholesterol levels (by 5%), which

was due to a 9% reduction in plasma LDL cholesterol levels; and reduced (by

14%) plasma triacylglycerol levels. After the 1 mo of placebo consumption,

these parameters reversed toward baseline levels. Licorice extract

supplementation also reduced systolic blood pressure by 10%, which was

sustained during the placebo consumption.ONCLUSIONS: Dietary consumption of

licorice-root extract by hypercholesterolemic patients may act as a

moderate hypocholesterolemic nutrient and a potent antioxidant agent and,

hence against cardiovascular disease.

Effects of prolonged ingestion of graded doses of licorice by healthy

volunteers.

Bernardi M. Patologia Speciale Medica I, University of Bologna.

Life Sci. 1994;55(11):863-72.

Licorice can induce a hypermineralocorticoid syndrome. Current literature

usually refers to the effects of sweets containing glycyrrhizin, but little

is known about the consequences of a prolonged intake of " pure licorice " .

We administered graded daily doses of dried, aqueous extract of licorice

root, containing 108, 217, 380 and 814 mg of glycyrrhizin, to 4 groups of 6

healthy volunteers of both sexes for 4 weeks. No significant effects

occurred in groups 1 and 2. After 2 weeks, side effects leading to

withdrawal from the protocol occurred in a female in group 3 (headache), a

male with a family history of hypertension in group 4 (arterial

hypertension), and a female also taking oral contraceptives in group 4

(hypertension, hypokalaemia and peripheral edema). In group 4, transient

reduction in kalaemia and increase in body weight were found after 1 and 2

weeks, respectively. A depression of plasma renin activity occurred in

groups 3 and 4. In healthy subjects, only the highest doses of licorice led

to untoward effects. These were favored by subclinical disease or oral

contraceptives, and were less common and pronounced than what has been

reported after the intake of glycyrrhizin taken as such or as a flavoring

agent in confectionery products.

Licorice - Dietary consumption of licorice-root extract by

hypercholesterolemic patients may act as a moderate hypocholesterolemic

nutrient and a potent antioxidant agent and, hence against cardiovascular

disease.

Glycyrrhizin, an aqueous extract of licorice root, has anti-inflammatory

activity and has been used for the treatment of chronic viral hepatitis.

Glycyrrhizin inhibited the cytolytic activity of complement via the

activation of both the classical and alternative pathways, while it had no

effect on immune adherence, suggesting that it blocks C5 or a later stage

of the complement cascade. Further analysis revealed that glycyrrhizin

inhibits the lytic pathway in which the membrane attack complex (MAC) is

formed. This mechanism suggests that glycyrrhizin may prevent tissue injury

caused by MAC not only in chronic hepatitis but in many autoimmune and

inflammatory diseases.

The ingestion of licorice, and/or its active metabolites, can sometimes

produce an acquired form of apparent mineralocorticoid excess (AME)

syndrome, expressed as sodium retention, potassium loss and suppression of

the renin-angiotensin-aldosterone system, in addition to clinical

consequences such as raised blood pressure and oedema.

Licorice Animal Studies

Memory enhancing activity of Glycyrrhiza glabra in mice.

J Ethnopharmacol. 2004 Apr;91(2-3):361-5.

In the traditional system of medicine, the roots and rhizomes of

Glycyrrhiza glabra (family: Leguminosae) have been employed clinically for

centuries for their anti-inflammatory, antiulcer, expectorant,

antimicrobial and anxiolytic activities. The present study was undertaken

to investigate the effects of Glycyrrhiza glabra (popularly known as

liquorice) on learning and memory in mice. Elevated plus-maze and passive

avoidance paradigm were employed to test learning and memory. Three doses

(75, 150 and 300 mg/kg p.o.) of aqueous extract of Glycyrrhiza glabra were

administered for 7 successive days in separate groups of animals. The dose

of 150 mg/kg of the aqueous extract of liquorice significantly improved

learning and memory of mice. Furthermore, this dose significantly reversed

the amnesia induced by diazepam (1 mg/kg i.p.) and scopolamine (0.4 mg/kg

i.p.). Anti-inflammatory and antioxidant properties of liquorice may be

contributing favorably to the memory enhancement effect. Since

scopolamine-induced amnesia was reversed by liquorice, it is possible that

the beneficial effect on learning and memory was due to facilitation of

cholinergic-transmission in mouse brain. However, further studies are

necessitated to identify the exact mechanism of action. In the present

investigation, Glycyrrhiza glabra has shown promise as a memory enhancing

agent in all the laboratory models employed.

Antithrombotic effect of Glycyrrhizin, a plant-derived thrombin inhibitor.

Thromb Res. 2003;112(1-2):93-8.

Glycyrrhizin (GL), an anti-inflammatory compound isolated from licorice

(Glycyrrhiza glabra), has been previously identified as a thrombin

inhibitor. Here we report the in vivo effects of GL upon two experimental

models of induced thrombosis in rats. Intravenous administration of GL

caused a dose-dependent reduction in thrombus size on a venous thrombosis

model that combines stasis and hypercoagulability. It was observed that GL

doses of 180 mg/kg body weight produced 93% decrease on thrombus weight. GL

doses above 90 mg/kg caused significant hemorrhagic effect. In contrast

with heparin, GL did not potentiate the inhibitory activity of antithrombin

III or heparin cofactor II towards thrombin. Altogether, data indicate that

glycyrrhizin is an effective thrombin inhibitor in vivo, which may account

for its other known pharmacological properties.

Glycyrrhizin, an active component of licorice roots, reduces morbidity and

mortality of mice infected with lethal doses of influenza virus.

Licorice Laboratory Studies

A compound derived from licorice root may help slow the effects of aging on

the brain and keep mental skills sharp. Researchers found the compound,

known as carbenoxolone, appears to inhibit an enzyme in the brain that is

involved in making stress-related hormones, which have been associated with

age-related mental decline. The study, published in the online early

edition of the Proceedings of the National Academy of Sciences, showed

daily supplementation with the compound improved verbal fluency in healthy

elderly men and improved verbal memory in older adults with diabetes.

A compound isolated from the root of the licorice plant could be more

effective than current treatments for SARS, the virus that has killed 780

people worldwide. Glycyrrhizin, or licorice root, is already given to

patients suffering from HIV and hepatitis C. Researchers at furt

University Medical School now believe licorice could help to combat SARS.

--The Lancet medical journal.

Licorice Extract 12%~26% Glycyrrhizic Acid

Sous is a drink served in Jordan and Middle Eastern countries with licorice.

Licorice also comes in black licorice and licorice candy

Licorice research licorice benefits licorice side effects