Licorice root (Glycyrrhiza glabra) has a long history of use in traditional medicine systems, but there is also a scientific basis for its use in supporting the hypothalamic-pituitary-adrenal (HPA) axis, commonly associated with cortisol regulation. The key active compound in licorice root, glycyrrhizin, inhibits the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is responsible for converting active cortisol to its inactive form, cortisone. By inhibiting this enzyme, licorice root can increase the bioavailability of cortisol in the body.

Several studies have demonstrated that glycyrrhizin and licorice extracts can raise cortisol levels and prolong its activity, which has led to their use in adrenal fatigue formulas and for conditions where cortisol support is desired. However, the evidence is largely based on small clinical studies and biochemical analyses rather than large-scale, robust clinical trials. Furthermore, chronic use of licorice can result in side effects such as hypertension, hypokalemia, and fluid retention due to its mineralocorticoid-like effects, indicating that its use must be carefully monitored.

In summary, while licorice root is traditionally used for a variety of ailments, its ability to affect cortisol metabolism is supported by scientific mechanisms and limited clinical evidence. Its use for supporting the cortisol body system has a moderate level of scientific validation, but safety concerns must be considered.