I appreciated the RCT on the efficacy of ginseng for preventing upper respiratory tract infections.1 I suggest cortisol evolved as the natural antagonist of dehydroepiandrosterone (DHEA) activity and is the basis of the “fight or flight mechanism.” This is derived from my hypothesis that the major pathway of adrenal hormone production is the “dehydroepiandrosterone pathway,” which consists of DHEA and cortisol. Increased cortisol may affect many tissues.2 Ginseng reduces cortisol production.3 By reducing the amount of cortisol, and hence the cortisol to DHEA ratio, ginseng increases the relative effectiveness of available DHEA. DHEA is known to exert protection from many infectious agents, including viruses. I suggest ginseng lowers the incidence of upper respiratory tract infections because it decreases the cortisol to DHEA ratio.