Liquorice abuse causes a syndrome of pseudohyperaldosteronism. Much less commonly, glucocorticoid-like effects have been reported. The electrolyte-active principle of liquorice is glycyrrhizic acid (GI), which can be hydrolyzed to glycyrrhetinic acid (GE). Previous studies have reported that GE, but not GI, may occupy mineralocorticoid and glucocorticoid receptors. We here report that both GE and GI can bind to both mineralocorticoid and glucocorticoid receptors. The affinity of GI for mineralocorticoid receptors is four orders of magnitude lower than aldosterone and for glucocorticoid receptors five orders of magnitude lower than dexamethasone. The affinity, though low, is sufficient to explain the mineralocorticoid-like side effects, given the large amount of liquorice required to produce such a syndrome.

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 (males: 41.8+/-2.0 before vs 47.0+/-2.3 after, p<0.001; females: 48.2+/-1.4 before vs 49.4+/-2.1 after, p<0.05). BFM was reduced by licorice: (male: before 12.0+/-2.1 vs after 10.8+/-2.9%, p<0.02; female: before 24.9+/-5.1 vs after 22.1+/-5.4, p<0.02); plasma renin activity (PRA) 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.

Alzheimer's disease is often characterized by an increase in plasma cortisol without clinical evidence of hypercorticism. Twenty-three consecutive patients with Alzheimer's disease and 23 age- and sex-matched healthy controls were studied by measuring plasma cortisol and dehydroepiandrosterone sulfate (DHEAS) (by enzyme immunoassay), the number of type I and type II corticosteroid receptors in mononuclear leukocytes (by radio-receptor-assay), and the lymphocyte subpopulations (by cytofluorimetry). Results are expressed in terms of median and range. In Alzheimer's disease, plasma cortisol was higher than in controls (median 0.74, range 0.47-1.21 vs 0.47, 0.36-0.77 mmol/L; p < 0.001). Plasma DHEAS, the DHEAS/cortisol ratio, and the number of type II corticosteroid receptors were significantly lower in AD than in controls (DHEAS: median 1.81, range 0.21-3.69 vs 3.51, 1.35-9.07 micromol/L; DHEAS/ cortisol: 2.04, range 0.3-5.8 vs 6.8, range 2.7-24 and type II receptors: 1219, 1000-2700 vs 1950, 1035- 2750 receptors per cell; p < 0.001). No correlation was found between the hormonal parameters, age, and mini-mental test score. These data support the hypothesis of a dysregulation of the adrenal pituitary axis in Alzheimer's disease, which is probably the consequence of damage to target tissues by corticosteroids.

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Carbenoxolone is a derivative of glycyrrhetinic acid used for the treatment of peptic ulcer and gastritis, with salt and water retention a very common side-effect. To investigate this drug-induced pseudohyperaldosteronism we have studied 6 male volunteers before, during and after treatment with carbenoxolone for 7 days. Serum, urinary and sweat electrolytes values were consistent with a mineralocorticoid-like effect of drug administration. PRA was suppressed, and plasma cortisol and aldosterone progressively decreased over treatment. We have also determined by radioreceptor assay the plasma levels of factors which bind to mineralocorticoid receptors in rat kidney cytosol. The levels of these factors were decreased significantly at day 3 of treatment, suggesting a local renal effect of carbenoxolone to amplify endogenous steroid action. At day 7 the radioreceptor assay values were still decreased but significantly higher than at day 3, suggesting in addition a direct mineralocorticoid effect of the drug. We conclude that the drug is initially effective by amplifying the effect of endogenous steroids, and then when the plasma concentrations of the drug or its metabolites reach a higher plasma concentration, there may also be in addition a direct mineralocorticoid-like effect.