Further studies on the mechanism of the mineralocorticoid action of licorice in humans

Abstract

The pathogenesis of pseudohyperaldosteronism from licorice has been evaluated in 6 male volunteers taking daily 7 g of a commercial preparation of licorice for 7 days, corresponding to an intake of 500 mg/day of glycyrrhizic acid. Pseudohyperaldosteronism was evident during the treatment (increase of body weight, suppression of plasma renin activity and plasma aldosterone, reduction of serum potassium). The ratio (tetrahydrocortisol + allo tetrahydrocortisol)/tetrahydrocortisone in urine increased in 5 cases after 3 days of treatment, without an increase of plasma mineralocorticoid activity (PMA). In the 6th case the urinary ratio was unchanged and PMA increased from the pretreatment value. After 7 days of therapy the ratio remained high and PMA was not measurable in 3 cases, while in the other 3 cases the ratio returned to pretreatment and PMA was higher than pretreatment value. We conclude that the pseudohyperaldosteronism from licorice is initially related to decreased activity of 11 beta-hydroxysteroid-dehydrogenase and afterwards also a direct effect of licorice derivatives on mineralocorticoid receptors becomes evident in some cases. In other cases however the effect on the enzyme is prevailing probably due to individual factors.

Grapefruit juice and licorice increase cortisol availability in patients with Addison's disease

“…11b-HSD type 1 is highly expressed in the liver and also acts as pre-receptor modulator of cortisol effects in most tissues. Reports suggest that licorice inhibits 11b-HSD type 1 (18,30), but this is not in agreement with our findings. As expected, if 11b-HSD type 1 was indeed inhibited, reduced hepatic first pass activation of CA would decrease cortisol C max and increase T max .…”

“…It is possible that inhibition of 11b-HSD type 1 requires larger concentration of glycyrrhetinic acid than 11b-HSD type 2. In the report by Armanini et al (30), 500 mg glycyrrhetinic acid/day was administered for 3 days, which is more than three times the dose used in our study.…”

Licorice Extract Does Not Impair the Male Reproductive Function of Rats

“…The endocrine effects of licorice haved been observed, and it has been demonstrated that licorice can produce pseudoaldosteronism by inactivating 11b-hydroxysteroid dehydrogenase (11b-HSD) and binding to mineralocorticoid receptors, leading to vasoconstriction and hypertension [4,5,7,11,12,15,43].…”

Licorice abuse: time to send a warning message

“…to its plasma concentration being more than 5000 fold the concentration of aldosterone [Armanini et al 1996]. Patients with postural hypotension caused by diabetic autonomic neuropathy have also shown improvement with licorice ingestion [Basso et al 1994].…”