Welcome to the Evolution of Medicine podcast! On this episode, James sits down with Christopher Mote, DO, DC, IFMCP, and Tom Guilliams, PhD to discuss HPA axis dysfunction and stress. Dr. Guilliams talks about some updates in his latest edition of The Standard Road Map Series, The Role of Stress and the HPA Axis in Chronic Disease Management (Second Edition), comparing what he focused on five years ago for the first edition to what he has found in more recent research. Dr. Mote discusses how he implements cortisol awakening response (CAR) testing and set a more accurate care plan for his patients. If you are a practitioner looking to implement CAR testing into your or practice or want to know more about how stress affects the body, then click play below!

Highlights include:

  • The cortisol awakening response, how its executed, and how the information can be facilitated in your practice
  • Comparing Dr. Guilliams’ first edition of the Stress Road Map to what is added in the second edition
  • How social isolation has caused stress in 2020 and how group visits are a great way to get patients talking and sharing with one another
  • And so much more!

Resources mentioned in this episode:

James Maskell: Welcome to the Evolution of Medicine podcast, the place health professionals come to hear from innovators and agitators leading the charge. We cover the latest clinical breakthroughs in health technology, as well as practical tools to help you transform your practice and the health of your community. This podcast is brought to you by the Lifestyle Matrix Resource Center, who provide a range of options to help you deliver successful, effective, functional, and integrative medicine. To find out more and to get started, go to goevomed.com/lmrc. That’s goevomed.com/lmrc.

James Maskell: So a warm welcome to the podcast, Dr. Tom Guilliams and Dr. Christopher Mote. Welcome, gentlemen.

Tom Guilliams: Thank you, James.

Christopher Mote: Thank you.

James Maskell: So yeah, we’re here to talk about HPA axis dysfunction, but maybe we should just start with going back five years. Tom, I know that five years ago, you released the first version of this book on HPA dysfunction. And back then, there was a thing that was called adrenal fatigue, and it was something that a lot of functional medicine doctors and practitioners thought they knew a lot about. And I would say in early 2016, I was made aware of that, that this was not based in science, and yet it still maintains a little bit. Do you think that this second version of your book might kill it off for good?

Tom Guilliams: Well, thanks James. Five years ago, when I first wrote this roadmap, it was like putting a mirror up to the functional medicine community, and the mirror was the science and the published data, and especially the laboratory testing. And the big gorilla in the room at the time, of course, was the notion that HPA axis, or stress, created adrenal fatigue and the adrenal glands just can’t make it anymore and they can’t produce cortisol, and you eventually have all these symptoms. And while, of course, the adrenal gland is really important for the stress response, and I don’t want to diminish that, the whole idea of adrenal fatigue needed to be confronted. And so our first book… And I wasn’t the only one. There were others as well who were on the bandwagon in trying to alter the nomenclature, let’s call it, of HPA axis dysfunction away from not only just focusing on the adrenaline glands, but the idea that the adrenal glands themselves were the cause of all the problem.

Tom Guilliams: And I would say that we have put a big dent in it. I don’t know that we’ve created a mortal wound completely and killed off adrenal fatigue. There’s so many books that were written by so many influential people over the last 15 years with adrenal fatigue in the topic and so many websites that I think we have made a dent. I’ve seen a lot of people writing about taking my material and other people’s material and talking about it in a bigger sphere. So I’m glad to be part of that, but I think it might still take a few more years. The second edition probably won’t do too much more except for get more people talking about it. And I think that’s going to be important,

James Maskell: Dr. Mote, as someone who’s been in clinical practice across those years, what does the nomenclature mean to you as far as your own clinical understanding, and then how you educate patients on this topic?

Christopher Mote: Yeah. Ironically, I was one of the early adopters of the notion of adrenal fatigue and one of its biggest proponents back in the year 2002 and 2003. I worked for a laboratory, and my job was to teach clinicians that adrenal fatigue and cortisol steal was this actual entity. And I believed it until Tom and others demonstrated the research that actually showed that the problem was in the brain. And what really we focus on now is deemphasizing the notion of the adrenal gland as the problem.

Christopher Mote: But when we talk about stress, it seems as if most of the practitioners I talk to relate it to hormones. Stress is the brain. And what’s interesting to me as I’ve sat in on conferences where one speaker would get up and talk about brain health and another one would get up and talk about adrenal health, and never make the equation between the two of them. So I just think before we’re done here, I really would like every practitioner to understand that if we’re all excited about brain health, and many of us are now, we need to be talking about the notion of the HPA axis, because that is where stress manifests, in the brain.

James Maskell: Awesome. So Tom, why don’t you just, for the practitioners who are listening to this who just need a two minute primer on what is the real physiology, what’s going on, and then what could they have learned in that first book? And then a little bit into what’s happened in the last five years and why you decided to make a second edition.

Tom Guilliams: Well, in two minutes, I think one of the things that we need to realize is the HPA axis is a threat surveillance system that not only is looking outside our body and anticipating things that could harm us, but internal. So inflammation, glycemic control, circadian signals, these kinds of things. And the brain has to put all that together and organize a strategy for energy management. What do I need in the next few hours to survive whatever challenges are coming my way? And so the brain is very good at consolidating all that information. It does it on a circadian, also a circadian overlap. And of course, that triggers the classic HPA axis, which everybody’s learned, the CRH ACTH cortisol, and then the cortisol feedback inhibition.

Tom Guilliams: And one of the things that I did in the first book was I, of course, explain that in much more detail than I just did now. But I also explained that just the production of cortisol alone doesn’t tell us what is happening at the tissue level, because there’s so many different ways that the body manages that signal. It’s a very powerful signal, cortisol, as an internal steroid hormone. And so the body can manage it, it can convert it to an inactive form, it can modify this. All kinds of excellent research now being published on the nuanced changes in how the body produces the receptor for glucocorticoids, or cortisol, and how it modulates the sensitivity of the cortisol at different tissues.

Tom Guilliams: And so I go into that in the book and I teach through it step-wise, and then I talk about the laboratory testing. And of course, Dr. Mote knows a lot about this in the idea that you can measure cortisol, and that tells you something about what the brain is doing by producing cortisol levels at a certain level. But that doesn’t tell you exactly what to do with the patient. There’s a lot more going on in understanding the patient. And we try to bring some of that in.

Tom Guilliams: In the second edition, we update as much as we can of that information. I expand. There’s a small chapter on the effects of stress on memory, because neuroplasticity is affected by stress and cortisol. I talk a little bit about the effects of the thyroid hormone and how cortisol and the HPA axis affects thyroid hormone production. And also, I bring in the endocannabinoid system, which they endocannabinoid system we’re all excited about, but it also affects the stress response as well. So I’ve updated the references that I’ve made sure things are updated and I talk a little bit about what’s happened in the laboratory. When I published the book in 2015, none of the laboratories that I knew of in the United States were incorporating the cortisol awakening response, which we’ll talk about. Now several of them do, because essentially, we exposed how important that was.

Tom Guilliams: So in the last five years, the updating of this book, we wanted to keep it as close to the original as far as a teaching manual as possible, so we didn’t expand it. I think it’s expanded about 30% from the first edition. But I’m really glad in how it turned out. So that’s essentially in two minutes. I think I may have gone over two minutes there.

James Maskell: No, I think that’s a really useful summation. I think helps everyone just get on the same page about it. Over the last year, we featured a lot of content on the causes of the awakening response. If this is the first podcast that you’ve listened to, last year, we did a series of three with Dr. Carrie Jones about the causes of the awaking response. You can go back and listen to that. But Dr. Mote, as someone who’s in clinical practice doing this, why don’t we just jump into what it looks like with doing cortisol awakening response testing in practice. Give us a baseline of how you actually execute this, and how you take information from that test and then start to start to actually try and facilitate health reclamation in your practice.

Christopher Mote: Yeah, thanks very much. I appreciate that opportunity. We have two tracks in our office, a primary care path where people who enjoy their health can just call us as they need us, and then we have a functional medicine track where everybody who has chronic illness and is looking for transformation is going to get the cortisol awakening response as one of the key core tests to start. And I’ve learned over time that there are really three things that this does for us. Every patient takes this three saliva sample cortisol test in the morning to see the responsiveness of the brain to stress. It is essentially a stress test for the brain. And when we’re talking in terms of cardiovascular health, cardiologists might get a stress test to see if their patient is going to die of sudden death heart attack. But we’ve got patients who are dying from excessive levels of stress. Cortisol is the death hormone. But what we really need to understand is how active, underactive, or overactive is the brain in responding to stress? And the CAR does that for us.

Christopher Mote: So number one, it helps me to assess the brain health of my patient. And specifically, then, there are nutritional protocols and lifestyle management that can support that stress response. Number two, it gives me a prognosis. If your CAR has flattened and the neuro-transmitters are depleted and your body’s lacking the ability to respond to stress, everything I try to do with you in my office in terms of transforming your health and putting you through additional protocols or treating your gut or things like that, they’re not going to go smooth. In fact, it’s going to take me as much as twice as long to help you get your health back if you have a flattened CAR. So it’s a marker of prognosis for me, and for setting patients’ expectations.

Christopher Mote: And number third, practically, it’s the entry point for our patients to see that they have a problem with stress and to get into at least two of our group health visits, one to talk about hormones and stress, and the other one is dedicated just towards teaching patients the implementation of lifestyle habits to reset the circadian rhythms. Which obviously, then, can support the brain and make them more resilient to stress. So it is assessment, prognosis, and an entry point into our group health strategies.

James Maskell: Yeah. Let me just go a little deeper into that, because I would say one of the reasons why you’ve been a frequent guest on the Evolution of Medicine in the last year and a half is just because of your innovative use of group visits. And I guess I just want to ask you about social isolation as a stressor. What have the CAR tests in 2020 showed you about social stress? And how has that reinforced your dedication to group delivered health?

Christopher Mote: Well, two things have conspired to give me an awakening here, James. One is that I’ve never seen such incredible mental emotional stress levels in my patients, and myself, frankly. And I think we all understand where the majority of that’s coming from. But the second is you’ve had so many guests on your podcast, and recently I saw you on Dr. Hyman’s podcast, and just talking about all of the facets that come with group health visits. And one of the key ones being that you bring people together and get them out of isolation. And I’ve never seen us more isolated than we are right now, partly out of necessity. But it is dangerously difficult, then, to help patients to transform their health. And so many are getting stuck.

Christopher Mote: And listening to you and looking at our patients, we’ve decided to move away from group health visits merely as a vehicle to deliver lab results and education, but now as a way to do ongoing group health visits, like some of the other people you’ve talked to, where we can bring people in and get them out of isolation. We are still doing that through Zoom, but now the purpose of some of our visits is purely just to get people together and to get them talking and sharing with one another.

James Maskell: Tom, I just want to come back to you before we go back into some of those things. I think that’s really interesting. Have you been aware of emerging research on social stress as a driver of overall stress?

Tom Guilliams: Yeah, if we think of… In the book, I have this wheel, we call them the four categories of stress. And I’ve upgraded the graphic in this last edition to really emphasize the perceived stress component. Because stress, as you know, is not… It’s when it comes to perceived stress. And this is unlike circadian signals and glycemic signals and inflammatory signals, which are very direct to the brain. There’s this indirect effect of their perceived stress. And it has to be interpreted because it’s really the body anticipating an event, not really reacting to an event, it’s really anticipating an event.

Tom Guilliams: And so when you change so many things about a person’s life, family structure. Are my kids going to school or are they not going to school? Am I going to have to stay at home? What is my job prospects? All these different financial issues. All of these are all new, they’re unpredictable. They all threaten your financial situation and you don’t feel under control. And those are really the quintessential aspects of perception of stress. Are you under control when you have new unpredictable things happening? And we have new unpredictable things happening almost on a weekly basis, it seems.

Tom Guilliams: So yes, and we’re seeing published data. Obviously we’re seeing more and more published data. It’s probably not so much on the HPA axis as we see with depression and in other publications. We are seeing some data, but underlying that, we’re seeing this. And we’re going to see this for, I think, the next generation. Because one of the things in the research that I think is hidden in the HPA axis world dealing with adults is that early life stress has a major effect on the HPA axis, which can have a lifetime effect on stress and the way the HPA axis functions and the way that people respond to events. So all of the stressors that are going on now, which are being experienced by young people, even children in the womb, those are going to be manifesting in the next generation, because it’s really affecting their brain and the way that they perceive events. So yeah, this is going to be a big event and it’s really going to have, I think, a lasting effect. Longer than we think.

James Maskell: Yeah, I totally agree, and have certainly made some decisions about my own life and my family in the last 10 months to reflect that understanding because we’d spoken about it. And I think if you’re in this functional medicine world and you really understand the degree to how stress affects the body, what that predisposes you for chronic disease, and then, as you said, how it affects over a lifetime, it’s a big deal. So Dr. Mote, tell us about these lifestyle measures that can be implemented to improve one’s stress response as a baseline level independent of individualization.

Christopher Mote: Thanks. It was 2017 when Dr. Satchin Panda published his book Circadian Code, and then it dovetailed with what I was learning through Dr. Guilliams’s book on circadian rhythms. And I thought I knew lots about it. As it turned out, I didn’t. But what I’ve done, and much of it does come from Dr. Panda’s book, is shared with patients the need to regulate two primary cues, two primary cues, one being food and one being light. And so as much as the type of food we eat, the timing of it, you’ve heard of things like time restricted eating or intermittent fasting. But certainly, feeding the body and fasting the body are two very powerful cues for the brain, and to regulate things like the production of brain derived neurotrophic factor, BDNF, which helps to grow new neurons.

Christopher Mote: And so we can help our patients to be more resilient to stress without nutritional supplements, without expensive lab testing. Just by helping them understand that whether they get outdoors for 30 to 60 minutes, and safely get their sunglasses off to get the full effect of the outdoor light to energize the brain. And then put on these blue blocking glasses two hours before bed to completely negate any blue spectrum light that would keep the brain awake. Doing just those two things really trains the brain to be fully alert and then fully shut down for sleep and repair. We do the same thing with feeding and fasting. And so I’m just a big believer that there are powerful, powerful mechanisms working either against us, if we’re just not aware of them or won’t do anything about them, or that we can harness to really get the brain in its full capacity for resilience back online.

James Maskell: Yeah, I totally agree. I guess one question I have is it seems to me that some of what you’re talking about gets left behind because so many clinicians want to get into the individualized stuff. The car is sexy and having all the information that comes off the back of it. Whereas ultimately, what you’re talking about there is necessary for getting to that next step of individualization.

Christopher Mote: Yeah. It’s so much easier, despite the people who have trouble swallowing pills or can’t remember them, it is so much easier to swallow a pill, prescription or nutritional supplement, than it is to start to change a habit. And this is, again, where we’ve had to fall back on groups. Because it really takes a commitment on the part of the patient, and then support for them, in order to make these habit changes. But it truly is the habit. The habit, the epigenetics, that changes our genes, that changes our function, and that changes our health.

James Maskell: Beautiful. Okay. So I guess for both of you, and maybe we can start with you, Tom. What would you wish that clinicians would understand in order to better address stress related conditions in their patients?

Tom Guilliams: Well, I think following up with what Chris was just saying is when you think of personalized medicine or personalized lifestyle medicine, you really are helping prioritize. All you’re doing, when you’re talking about assessment, when you’re using the car, you’re using many of these different aspects of trying to get some nuance and try to figure out what’s going wrong with the patient. But then you’re really helping prioritize those things in their life which they can change, which they have the ability to change, and then empowering them to make those changes.

Tom Guilliams: And I think a lot of clinicians, Chris can speak to this, sometimes it’s easier to send them home with a prescription and say, they’ll pick this up in the pharmacy, they’ll take this for a month, and we’ll see. But really, how do you empower someone who has never exercised? How do you empower someone who has bad eating habits and they don’t even really know how to cook? Or these kinds of things. Or they’re on a swing shift and you’re trying to figure out a way to get them back on a circadian pattern. And these things can be extremely frustrating for our clinicians, and sometimes they just give up. And I think really understanding how important these big levers are. These are the big levers. And if the patient can move them, not only will they have a physiological effect that’ll benefit them, but they will feel empowered by the ability that they changed something.

Tom Guilliams: And then, of course, you can use a course of nutrition and sometimes nutraceuticals, not necessarily pharmaceuticals [inaudible] to bridge the gap, but very rarely will completely alter the patient. What you really want is something that they can do that really alters. We talk about epigenetics, we talk about these things that really repattern their phenotype. And those are going to be those big things and they’re going to be difficult, and they’re oftentimes things that you never learned in medical school. And so if I can tell clinicians there’s a lot more power in the patient if you can figure out how to do what that person’s been figuring out how to do. And I’m sure he can add on to what I just said.

James Maskell: Why don’t you add on, Dr. Mote?

Christopher Mote: So we shifted the conversation with Dr. Guilliams’ book from adrenal stress, and then we started talking about adrenal hormones, and now we’re talking about stress. But where I want this conversation ultimately to go with clinicians is how do we support the brain? In 2013, when David Perlmutter came out with his book The Grain Brain, that was the first strategy that I ever had in clinical practice to help my patients with their brain health. And that was to change their diet to remove gluten. And then in 2017, we had Dale Bredesen’s book, and Dr. Bredesen had a very comprehensive way of addressing brain health. And it was the first time that clinicians were truly empowered to really get in and make changes to support a patient’s brain, and again, their stress response.

Christopher Mote: Well, now what we’re learning is we’re not intimidated as clinicians anymore about supporting and affecting brain health, and many of us are looking for tools. And I just want to say that with the cortisol awakening response, we have a true stress test for the brain. And then we have actual protocols, both lifestyle and nutraceutical, to support brain health. And we can have clinical outcomes that genuinely help to put back a patient’s mood, energy, sleep, tissue repair, their immune function, and really make changes to their overall health.

Christopher Mote: And the one thing I want to say is that if we’re going to make that change, and especially if we’re going to use a test to drive our thinking in our patients’ plans, we have to run this test on ourselves. And this, to me, is a key. If a clinician is serious about wanting to set up a stress response or a stress support practice, if they want to help their patients with stress related illness and with brain health, they have to run this test on themselves. A cortisol awakening response should be mandatory for any doctor, any physician, any provider who says they’re really serious about wanting to help patients with their brain health. Because then it becomes personal. You get to see how stress is affecting you, us, personally. And to me, those are the things I would want most clinicians to understand. That we are truly talking about assessing and supporting the brain, and to start with ourselves.

James Maskell: Beautiful.

Tom Guilliams: Can I just add something, James?

James Maskell: Yeah.

Tom Guilliams: I know we’ve talked about this in previous podcasts, but for me, it also goes back to that idea of metabolic reserve. That if you can build… When it comes to stress, stress is a depleter of metabolic resources, just like diabetes is a depleter of… It depletes so many different aspects of the metabolic function of so many tissues. So when we think about this, when we’re thinking about diet, we’re thinking about circadian rhythm, we’re thinking about physical activity. All of these things that we know are good are really rebuilding the antioxidant capacity, the mitochondrial function, plasticity in the brain. All of these things that we’re rebuilding create a buffer and a resilience against, we’re talking about stress now, but it really is a defense against all chronic diseases, which flow together in their depletion of metabolic reserves. So I want to bring that in because that’s something that I think is fundamental to a functional medicine approach.

James Maskell: That’s true, yeah. I think that’s really important to think through. And that’s really, our year of resilience is coming to an end. And I’m glad we’re talking about this because that’s what we’re talking about there. What are some of the supplementation, Dr. Mote, that you’re a fan of when it comes to these type of topics? What kind of things are you recommending for your colleagues that are coming to you, suffering from some degree of burnout or moral injury?

Christopher Mote: Yeah. So when we get our cortisol awakening response back, there’s one of two approaches that we take. One, when it’s a flattened CAR, there’s a lack of responsiveness to the brain. The assumption, and I believe rightly so, is that this patient then is suffering from the depletion of neuro-transmitters, be it dopamine, GABA, glutamate, norepinephrine, et cetera. And so they’re going to need help to support those. And so we’ll use nutraceuticals that support the body’s ability to make its own neuro-transmitters. I don’t know, can I give names or just talk ingredients?

James Maskell: Well, you can say whatever you want.

Christopher Mote: I use the CereVive. It’s the most useful product that I had in my practice for mood and concentration, and it is the go-to supplement. Two capsules at breakfast and two at lunch for everybody with a flattened CAR. And then when we have a heightened CAR, the support that we’re going to now is a liquid supplement that uses Huperzine, GABA, and L-theanine to really help provide a sense of calm to the brain when we have a heightened cortisol awakening response. And we’ll use that liquid, one or two droppers full, held in the mouth for as much as a minute and then swallowed, in the morning to really help patients who get up and are dealing with anxiety, brain fog, and have this heightened CAR. Beyond the actual mechanisms of action of these various supplements, Dr. Guilliams was involved in the formulation of these, and so he may be able to speak to those better if that’s important.

James Maskell: Yeah. I think that’s really great information that we want to make it as practical as possible for everyone out there who’s learning about this. And look, our goal has always been just to up level the quality of physicians and quality of functional medicine across the country. And it definitely feels that this particular topic, there’s so many topics that I say this about, but this specific topic just seems like a topic that is ready for functional medicine to break out into conventional medicine. Given one, how stressful the world is and is becoming. And secondly, that this pharmaceutical based approaches for diseases that are born of stress are destined to fail because of their ill attendance to the mechanisms involved.

Christopher Mote: Agreed. James, there’s actually a way that for doctors who are interested to pursue this in their own practice and for their own health can get started. And the Lifestyle Matrix Resource Center has got an entire clinical practice guide that goes through cases and answers questions and has protocols. And I was involved in the writing of that, together with the people at the Lifestyle Matrix Resource Center. And it’s a turnkey approach that not only helps empowers the clinician to get started with the testing and the treatment protocols, but even to market within and without their own practice. And so you don’t have to recreate the wheel. It was something I had to do 20 ago. It’s done for you. And all you have to do is reach out to the Lifestyle Matrix Resource Center.

James Maskell: Wonderful. Well, we’ll put all the details of that into the show notes below. Dr. Guilliams, Dr. Mote, thank you so much for being part of the Evolution of Medicine podcast. Really appreciate both of you coming on and sharing your wisdom today. I think on the clinical side, and then also on the practice management, practical application side, so much for us to learn. And appreciate you guys leading the charge to up level the quality of care delivery across the industry. So thank you for your participation today.

Christopher Mote: It’s exciting. Thanks, James.

James Maskell: So this has been the Evolution of Medicine podcast. We’ve been here with Dr. Christopher Mote and with Dr. Tom Guilliams. We’ve been talking about all aspects of stress, and we’ll have all the details in the show notes. If you want to find out more about what Dr. Mote was just talking about with regards to the stress program from LMRC, and if you want to find out more about the second edition of Dr. Guilliams’s book, we’ll have all the details there. But in the meantime, thanks so much for being part of the Evolution of Medicine podcast, and we’ll see you next time.

James Maskell: Thanks for listening to the evolution of medicine podcast. Please share this with colleagues who need to hear it. Thanks so much to our sponsors, the Lifestyle Matrix Resource Center. This podcast is really possible because of them. Please visit goevomed.com/lmrc to find out more about their clinical tools like the group visit toolkit. That’s goevomed.com/lmrc. Thanks so much for listening and we’ll see you next time.


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