During the discussion of the DUTCH Hormone Test, you mentioned that gut issues can contribute to low free cortisol levels. Can you go over that connection again?

Chris Kresser:  Sure. Gut issues could contribute to high cortisol, low cortisol, a combination of high and low cortisol, dysregulation of the diurnal cortisol rhythm, and there are several possible mechanisms. One is that gut issues often provoke a chronic low-grade inflammatory response, and inflammation affects the regulation of the HPA axis in several different ways. It can affect the sensitivity of cells to cortisol. It can affect the production of cortisol itself because cortisol is an anti-inflammatory hormone, as we went over, so you can see an increase in cortisol production in the face of inflammation as the body’s attempt to deal with that. Over time, if the tissue-specific and brain central nervous system mechanisms for regulating cortisol are affected by the gut issues, then you could potentially see a decrease in cortisol. So there are multiple different mechanisms, and you can’t really predict what exactly the expression of the dysfunction will be based on the particular gut issue. For example, you can’t say, oh, people with SIBO, they have low cortisol, or people with parasites have high cortisol. You can’t even say that cortisol, in general, will be low or high with gut issues. All you can say is that we know that gut issues can lead to HPA axis dysregulation, and we know that HPA axis dysregulation can lead to gut issues. It’s a bidirectional relationship. That’s why we end up addressing both gut issues and HPA axis issues simultaneously in many cases, it’s why we include HPA axis assessment and gut assessment in the case review for every new patient, and it’s why in this ADAPT Framework Level One Course we’re starting with the gut and the HPA axis as well as functional blood chemistry as the core things that we want to focus on with every patient. If you treat gut issues successfully and the cortisol doesn’t resolve—cortisol remains low or high—then you have to go on and start doing specific therapies for cortisol, which we talked about in the HPA axis unit, or you have to search for other things that could be contributing to HPA axis dysregulation. Remember the four primary triggers of HPA-D, which are perceived stress, glycemic dysregulation, inflammatory signalling, and … Why am I forgetting the fourth one right now? Circadian disruption. So if you’ve looked at all of those and addressed all of those, that’s pretty time consuming. It can take a long time, but the solution is probably in one of those four areas.