Glycyrrhizin, a major active compound found in licorice root (Glycyrrhiza glabra), has been studied for its effects on the hypothalamic-pituitary-adrenal (HPA) axis, which regulates cortisol production in the body. The primary scientific rationale for its use in supporting the "cortisol body system" is based on glycyrrhizin’s ability to inhibit the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This enzyme converts active cortisol into its inactive form, cortisone. By inhibiting 11β-HSD2, glycyrrhizin can increase the levels of active cortisol in tissues, thereby potentiating the effects of endogenous cortisol.

Several clinical and preclinical studies have demonstrated that consumption of licorice or glycyrrhizin can lead to increased cortisol activity. This mechanism is linked to the well-documented side effect of licorice-induced pseudoaldosteronism (manifesting as hypertension and hypokalemia), which occurs due to excessive mineralocorticoid receptor activation by cortisol. While this property is sometimes harnessed in traditional and integrative medicine for conditions thought to involve low cortisol or adrenal fatigue, robust clinical trials directly supporting its use for improving HPA axis function or treating adrenal insufficiency are limited.

In summary, while there is a clear scientific mechanism by which glycyrrhizin can influence cortisol levels and activity, the clinical application for "supporting the cortisol body system" should be approached cautiously due to potential adverse effects. The evidence is moderate, primarily mechanistic and observational, rather than based on high-quality clinical trials.