Licorice: Clinical Use. Dosage

PEPTIC ULCER AND DYSPEPSIA

The anti-inflammatory, mucoprotective and anti-ulcer activities of licorice make it an attractive treatment for peptic ulcer. While these effects have been attributed to the glycyrrhizin (GL) and glycyrrhetinic acid (GA) constituents, the deglycyrrhizinated licorice (DGL), which contains <3% GL, has also been investigated and appears to produce the most promising results when used long term. DGL also promotes differentiation of undifferentiated cells to mucous cells and stimulates mucus production and secretion.

In an uncontrolled trial of 32 patients with chronic duodenal ulcer, 3800 mg/day of DGL (in five divided doses) produced signs of healing in all cases and total restoration of mucosa in a majority of subjects. Although treatment continued for 24 weeks, considerable improvement was seen in 56% of patients by week 12 and in 78% by week 16. A shorter 4-week trial of 96 patients with gastric ulcer failed to produce the same positive results.

DGL plus antacid (Caved-S; 2 tablets chewed three times daily between meals) was as effective as cimetidine (200 mg three times daily plus 400 mg at night) after 6 weeks, according to one randomised single-blind trial of 100 volunteers with peptic ulcer. The two treatments continued to produce similar results after 12 weeks and recurrence rates after both medications were reduced were also similar.

Commission E approves the use of licorice for the treatment of gastric and duodenal ulcers.

DERMATITIS

The anti-inflammatory effect induced by glycyrrhetinic acid provides a theoretical basis for its use as a topical anti-inflammatory agent (much like hydrocortisone) in the treatment of dermatitis.

In practice, glycyrrhetinic acid has been used to potentiate the effects of weak steroids (such as hydrocortisone) in order to increase pharmacological effects without the need for stronger corticosteroids. It is assumed that increasing corticosteroid activity in this way will not attract an increase in adverse effects; however, no studies have yet confirmed this.

An early study comparing the effects of hydrocortisone- and GA-containing ointments in dermatitis found that hydrocortisone was usually superior in acute and infantile eczemas, whereas GA was superior for chronic and subacute conditions.

It should be noted that glycyrrhetinic acid is many times more powerful an inhibitor of 11 HSD than glycyrrhizin and therefore should theoretically induce far stronger anti-inflammatory effects. GA is not present in licorice but is produced in the gastrointestinal tract from glycyrrhizin; therefore, it is uncertain whether topical preparations containing pure licorice are likely to produce significant anti-inflammatory effects.

VIRAL INFECTIONS

The antiviral activity demonstrated in animal and in vitro trials provide a theoretical basis for its use in the treatment of SARS-associated CV, HIV, influenza, EBV and HSV-1. Until controlled studies are available, the clinical effectiveness of this treatment remains unknown.

RESPIRATORY TRACT INFECTIONS

Licorice increases mucous production within the respiratory tract and exerts an expectorant action. When combined with its anti-inflammatory, antiviral and possible immune-enhancing effects, it is a popular treatment for upper and lower respiratory tract infections. In practice, it is often used to treat coughs (especially productive types) and bronchitis.

Commission E approves the use of licorice for catarrhs of the upper respiratory tract.

CHRONIC STRESS

Traditionally, licorice is viewed as an ‘adrenal tonic’, most likely due to its ability to slow cortisol breakdown. It may be of benefit in patients experiencing allostatic load due to chronic stress and who are therefore unable to mount a healthy stress response. This is also known as adrenocorticoid insufficiency. Currently, controlled trials are not available to determine its effectiveness in this situation.

Whether this effect is desirable in patients without adrenocorticoid insufficiency and for whom increased cortisol levels may prove problematic is open to conjecture. Chronically high cortisol levels have been associated with desensitisation of the HPA axis, insulin resistance, depression and immunosuppression. In the initial stages of stress, increased cortisol levels trigger negative feedback mechanisms to keep stress under control and, therefore, short-term use may be warranted but is unlikely to be beneficial unless some adrenocorticoid insufficiency exists.

(For more information see ‘Clinical note — Allostasisand adaptation to stress’ in the Siberian ginseng.)

Licorice: Other Uses

Licorice has also been used traditionally as a sweetener and aromatic flavouring agent.

Although controlled trials are lacking, licorice is also used for a number of other conditions, largely based on evidence of pharmacological activity.

CHRONIC FATIGUE SYNDROME

The ability of licorice to slow cortisol catabolism may provide a theoretical basis for its use in cases of CFS accompanied by low cortisol levels. A case report exists of a patient experiencing improved physical and mental stamina and recovery from CFS following use of licorice dissolved in milk (2.5 g/500 mL/day).

POLYCYSTIC OVARY DISEASE

The possibility that licorice may lower testosterone levels in women provides a theoretical basis for its use in PCOS. While trials using licorice as a stand-alone treatment are lacking, studies of licorice in combination with other herbal medicines such as peony have produced promising results, showing reductions in LH:FSH ratio, ovarian testosterone production and improvements in ovulation.

PREVENTING DIABETIC COMPLICATIONS

In diabetic patients with neuropathy, retinopathy or nephropathy, sorbitohglucose ratios are significantly higher than in those without these complications and ratios increase as complications become more severe. As licorice and its component isoliquiritigenin have been shown to inhibit aldolase reductase and suppress sorbitol accumulation in red blood cells in vitro, a theoretical basis exists for its use in the prevention of diabetic complications.

MENOPAUSE

Inhibition of serotonin reuptakeand possible oestrogenic activity provide a theoretical basis for its use in pre- and postmenopausal women with mild to moderate depression.

Constituents in licorice may bind to oestrogen receptors, enhance osteoblast function and attenuate vascular injury and atherosclerosis suggesting a possible role in the prevention of bone disorders and cardiovascular diseases in postmenopausal women.

WEIGHT LOSS

The action of GA in blocking 11HSD type 1 at the level of fat cells may help to explain preliminary evidence suggesting an ability to reduce body fat mass and the thickness of thigh fat.

ADDISON’S DISEASE

The ability of licorice to reduce cortisol breakdown provides a theoretical basis for its use in Addison’s disease, either as a stand-alone treatment, when adrenocortical function is not severely impaired, or as an adjunct to cortisone therapy. While studies in the 1950s confirm this use, recent studies are not available. A case report exists of an 11 -year-old boy with hypoparathyroidism and Addison’s disease developing hypermineralocorticoidism following excessive intake of licorice (300-400 g/day, equiv. 600-800 mg glycyrrhizin) concurrently with hydrocortisoneand 9-alpha-fluorocortisol. Pseudohyperaldosteronism persisted after treatment with 9-alpha-fluorocortisol was withdrawn and hydrocortisonewas reduced; however, symptoms only diminished after the complete withdrawal of licorice. It was suggested that inhibition of 11HSD by licorice was responsible due to increased levels of free cortisol.

Licorice: Dosage Range

• Fluid extract (1:1): 2-4 mL three times daily or 15-40 mL/week (USA, UK, and Australian manufacturer recommendations).

• Root: 5-15 g/day (equivalent to 200-600 mg of glycyrrhizin).

Tea: pour 150 mL boiling water over 1 teaspoon (2-4 g) licorice root, simmer for 5 minutes and filter through a tea strainer after cooling.

• Chronic gastritis: 1 cup of licorice tea after each meal.

ACCORDING TO CLINICAL STUDIES

• Chronic duodenal ulcers: 3800 mg/day of DGL (in five divided doses) before meals and at bedtime.

• Ideally, licorice extracts should contain >30 mg/mL GL.