Glycyrrhetinic acid is a bioactive compound derived from glycyrrhizin, found in licorice root (Glycyrrhiza glabra). Its use to support the adrenal cortex is based primarily on scientific observations. Glycyrrhetinic acid inhibits the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which normally converts active cortisol to inactive cortisone. By inhibiting this enzyme, glycyrrhetinic acid increases local cortisol levels, especially in the kidneys and potentially in other tissues, including the adrenal cortex. This mechanism can mimic the action of mineralocorticoids, leading to increased sodium retention and potassium excretion.

While glycyrrhetinic acid does not directly stimulate adrenal hormone production, its ability to potentiate endogenous cortisol activity has led to its use in some protocols aimed at "supporting" adrenal function, particularly in cases of adrenal insufficiency or so-called "adrenal fatigue." However, clinical evidence for its efficacy in improving adrenal cortex health or function is limited and largely extrapolated from its effects on cortisol metabolism. There are some animal and human studies that document its endocrine effects, but robust clinical trials supporting its use for adrenal support in humans are lacking. Its use is more scientifically reasoned based on mechanism rather than confirmed therapeutic outcomes.

Of note, long-term or excessive use can cause side effects related to mineralocorticoid excess, such as hypertension and hypokalemia. Thus, while there is a scientific basis for its influence on steroid hormone metabolism, evidence for its use as an adrenal cortex support supplement is moderate and should be approached with caution.