Glycyrrhetinic acid is a bioactive compound derived from glycyrrhizin, the major sweet-tasting constituent of licorice root (Glycyrrhiza glabra). Its relevance to the cortisol body system stems from its ability to inhibit the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which normally converts active cortisol to its inactive form, cortisone. By inhibiting this enzyme, glycyrrhetinic acid can lead to increased levels of active cortisol, particularly in certain tissues such as the kidney.

Several scientific studies have documented this effect. For example, research published in The Lancet and other peer-reviewed journals has shown that glycyrrhetinic acid can raise cortisol activity and, at higher doses or prolonged use, can lead to symptoms resembling hypercortisolism (such as hypertension and hypokalemia). In clinical settings, this property is a double-edged sword: while it can theoretically be used to support cortisol levels in cases of low cortisol, it can also negatively impact blood pressure and electrolyte balance.

While the mechanism by which glycyrrhetinic acid affects cortisol is well understood and scientifically validated, its use as a supplement to "support" the cortisol system is limited by potential side effects and a lack of robust clinical trials specifically evaluating its safety and efficacy for this purpose. Thus, while the scientific basis is established, the clinical utility and safety profile require careful consideration.