Welcome to the Evolution of Medicine podcast! This episode is the second installment in our series with Carrie Jones, ND, MPH and DUTCH Test. Dr. Carrie Jones is a force in the functional medicine community, a modern doc with a holistic approach who can appreciate the best of both medical practices. In her own words, she “helps hormonally challenged people feel less crazy” by using testing and her own extensive knowledge to help people understand their hormones so they can feel empowered to take control of their health.

In this episode, we take a deeper look at stress resilience and share concrete ways you can use the cortisol awakening response with your patients. We also discuss autoimmune patients, some of the most challenging cases to tackle, and how the CAR influences immunity. It was a fascinating 30 minutes, and I think you’ll really enjoy it. Highlights include:

  • What the cortisol awakening response can reveal about health, and how to dial in that information for patients
  • The impact of the cortisol awakening response on energy levels, resiliency, mood, blood sugar management and autoimmune recall
  • How the cortisol awakening response can be an early indicator of autoimmune disease and testing can help you recognize and address it earlier in your patients
  • And so much more!

Resources mentioned in this podcast:

James Maskell: Hello, and welcome to the podcast. This is the second in the series with Dr. Carrie Jones. She’s the chief medical officer for DUTCH Test. We will be talking about the cortisol awakening response. Today, we went a little bit deeper on resilience and specifically how you could use the cortisol awakening response with patients. There was a really incredible moment where we were talking about autoimmune disease and the CAR, that if you’re working with patients in autoimmune, I highly suggest you stick around for really, really interesting half an hour. Enjoy. A warm welcome back to the podcast, Dr. Carrie Jones. Welcome, Doc.

Carrie Jones: Thanks so much, James. This is going to be great. Number two.

James Maskell: Really excited to go a little bit deeper into the conversation that we started last month. I know we were speaking initially just about how the cortisol awakening response became a pretty default tool for testing stress in our community, and I’d love to go a little bit deeper into what these tests reveal about health more specifically and how we can dial it in for our patients.

Carrie Jones: Yeah, this is definitely the meat of it. This part of the podcast, I think is what’s going to get people really excited, because on the last podcast, as a reminder for those maybe who listened last time, maybe you had this is…you’re just catching the second one, we’re talking about the cortisol awakening response or the CAR. It occurs on wakening in the absence of any apparent stressful situation or imminent danger, as research likes to say. I think that’s really cool because it’s not a stress response that sets it off. The body’s natural way is to get you ready, push you into alertness, handle your blood sugar, handle your inflammation, gets you going and ready for the day.

It’s really hugely impacted by your health status, your sleep the night before, lifestyle things you’ve chosen, your stress perception for the day, or what’s going on in your week or your life or your month or, geez, your whole year for some people. Right? This is why I really like to test the cortisol awakening response. Some of the things I want to really touch on this podcast is for people to understand energy levels, resiliency, mood, blood sugar management, autoimmune recall. These are huge aspects of people’s life that they’re struggling with.

They’re coming in and saying, “My blood sugar is a mess. It’s all over the place. I can’t recall things like I used to. I think I might be getting dementia, and that’s scary. I have autoimmune, I have Hashimoto’s, I have MS, I have Addison’s and it’s worsening. My symptoms were under control and they’re not under control anymore. Oh, by the way, my stress is a 10 out of 10. Can you help me? Can you figure it out?” This is where the CAR really comes in, because it gives us so much information.

Let’s first talk about resiliency. There are these two authors, Martin and Marsh, and in 2006, they proposed five points to academic resiliency. Now, I know we’re in medical, I know we’re in health resiliency, but I really liked it because they were talking about if you take a test…in one of the studies I was also reading, it was about swimmers. Professional swimmers who are going to do a swim competition and how they handled resiliency. First is confidence, second coordination or planning, third is control, fourth is composure, how anxious are you, and fifth is commitment, which is your persistence.

If you take into account your confidence, your coordination, your control, your composure, your commitment, then they found the better those were the more resilient you were. When I talk about this with patients, it’s amazing how they can point out, “I am not composed. I go from zero to 10, I have massive mood swings, I get anxious or I get angry or I cry at the drop of the hat.” Other people are like, “I don’t have the commitment. I’m too tired, I hurt, I don’t have the family support, I don’t have the financial support.” People can pick out in here what is getting in the way of the resiliency.

But if we take it one step further, they say that there are two characteristics of resilience. One, that there’s some significant level of adversity and pressure that’s experienced, but two, the individual is still able to experience positive outcomes. In the study, that I’m quoting, it’s the same one as from before, it was a successful for performance. It’s either, again, a successful swimming, you won, you passed the test, what have you. What I find, when it comes to resilience, is that everybody has adversity, right? We all have adversity. Life is stressful, but it’s how we handle it, how we prepare for it, how we plan for it, our mood about it, and positive outcomes.

Because if we routinely get positive outcomes, then we’re going to feel better about it and we’re going to be able to overcome it. What’s great is that the resilience ability affects not only your physiological, can you get out of bed in the morning, do your joints hurt, are you inflamed, do you have headaches, how’s your digestion, but it also affects your cognitive and your behavior. Because if you’re don’t feel very resilient, you’re probably going to be more depressed, less motivated, not as happy, and you’re not going to contribute as much maybe as you would like to your life or your family or significant other or your friends or what have you. It’s really important that we have resiliency as humans.

Then to tie it back, how does resiliency tie into this cortisol awakening response that we’ve been talking about over and over? It turns out that research says a too low or too high cortisol awakening response, 100 percent affects your resiliency. If you test and you know what your CAR is and we know how to address it, then imagine all those resilience points that we talked about getting better, and now your moods better, and now your inflammation is better, and now your energy’s better, and now the way you interact with the world is better, and your production is better. All these things are so much better, and we just have to look at this marker, this cortisol awakening response.

What I find super cool is the ability of resilience. Just as an example, and this is…I’ll give you this as an example of me because I’m super proud of my little resilient body in this example. But I did the five-day fasting mimicking diet and I took CAR test the day before the day…all five days, and then two days after. I did a lot of saliva tubes. That’s for sure.

James Maskell: That’s a lot of spitting and a lot of tubes.

Carrie Jones: And a lot of collection, but I did it in the name of science so I can talk about it. My personal cortisol awakening response, the day before testing, was pretty good. I go up, within 30 minutes normal, and then I go down, down, down through the rest of the day. That’s about how I feel. I don’t rely…I don’t drink coffee, I do like green tea, but more for the health benefits, less for the caffeine. I’m more of a morning person. My husband and friends tend to describe me that way.

Now, when I got into the fasting mimicking diet, on day two, my cortisol awakening response shot up and stayed up. It’s like my body was going, “What are you doing? What is this? You normally eat? Where are you not eating? We have to shift everything to deal with the fact that you’ve made changes.” Right? A stressor happened in my body, even though the fasting mimicking diet has a lot of beneficial things and I’m still really restricting my calories and it was different than my norm. So my body reacted by raising my cortisol to address the fact that I was lower energy, I was lower calorie, therefore I was lower glucose.

But the really super-cool thing is two days after stopping the fasting mimicking diet. Within two days, I bounced back. Within two days, my cortisol awakening response was almost basically back to normal and I felt pretty good. I felt back to normal, and that’s normal. That’s a normal healthy response. When people do something out of the ordinary or something happens to them, they should be able to adjust and then get back to homeostasis. Their CAR and their cortisol release should address whatever is happening and then go back.

The way I describe it to people is like a trampoline. When you are going through life bouncing on your trampoline, you should be able to bounce down and go back up over and over and over again. But what happens is people don’t take care of themselves and they just keep putting more and more and more on their trampoline, and now when they bounce, it’s become threadbare or maybe there’s holes. So, you bounce and you don’t have the snap back up like you used to, or you bounce and you actually…your foot falls through. Now you hit the ground and then that’s how people feel, that’s what they say when they come in to see you.

They’re like, “Yeah, I don’t have the bounce like I used to. I don’t know what’s going on. You’ve got to help fix me.” We can see it in the CAR and the cortisol awakening response. But what’s even cooler than that is that it’s completely malleable, it’s completely changeable, and I think people…I want people to know that when they run these biomarkers, when they run these tests, that, again, it’s not set in stone. There was another study where they took 38 subjects, and I would have loved to be on this study. Thirty-eight subjects for three months. They sent them to a meditation and yoga retreat center. They did an all-vegetarian diet and they did no regular work for three months.

For three months, no regular work. I mean, that would stress me out to know what work I was coming back to. But for three months, yoga meditation and what they said was, “The increased CAR we report is likely related to increases in morning wakefulness and stress resilience.” These results are consistent with others who have reported increases in the CAR after mindfulness-based practices. It is also possible that this intervention improves sleep quality, and this in turn impacted a more dynamic and robust CAR. It just goes to show. Now I know not everyone…I certainly can’t go to a three-month, all-inclusive, no-work yoga and meditation retreat. But—

James Maskell: Yeah, where does one sign up for one of those scientific studies?

Carrie Jones: Right, exactly. Right? I’ve got the slides, so we’ll write the authors and see how we get involved in that. But just using the consistent mindfulness-based practice and better sleep, their CAR became more dynamic, more robust, and they said they had increased stress resiliency. My personal takeaway from that is that, one, obviously what we’ve been preaching, your CAR is a good indicator of stress resiliency, but your CAR is malleable and it is responsive to inside and outside forces.

My second takeaway is that people who downplay mindful-based practices are wrong, because regular mindfulness-based practices, meditating, journaling, taking care of yourself, self-care, grounding, that kind of things, coupled with good sleep, it does wonders for your cortisol awakening response. It’s like an adaptogen. It’s like an adaptogenic herbs for your cortisol awakening response. Don’t rush it aside, don’t downplay it. Those of you who are listening to this going, “I don’t have very good resiliency,” you can change it, which is so fantastic.

But what I want to move into next is, what else does the CAR affect? The big one is recall. So many people worried about Alzheimer’s dementia with good reason, and they’re struggling for recall when trying to remember things the day before. The CAR is controlled by the hippocampus, so any kind of hippocampus damage or atrophy will affect your cortisol awakening response. That normal rise in cortisol helps to improve your recall for the next day. If you are under a lot of stress, you’ve got a flatline CAR, and the next day you’re like, “What did I read? What did he say? What was that thing I was trying to remember? What did I need at the store that I said yesterday?” It gets tied hand in hand. If you can get your CAR up and your stress under control, then your memory greatly improves.

However, as many people know, cortisol can be quite damaging to the hippocampus, which again, memory. If you have too high of a cortisol awakening response, you wake up hypervigilant, you wake up anxious, you wake up zero to 10, that can actually be problematic for the hippocampus. It’s like Goldilocks. Like anything, it’s not too much, not too little, and then you will have the perfect recall. If those listening are having problems with recall, let’s test your CAR and let’s try to help you out.

What about inflammation? I get asked this a lot. “Carrie, I wake up in pain, I wake up, my joints hurt, I wake up stiff. Could that have to do with cortisol?” Absolutely. There’s a quote here in the Journal of Psychiatry and Psychiatric Disorders in 2018, and they said, “Chronic circadian misalignment,” so if your circadian rhythm’s all messed up, “significantly reduces cortisol levels and it increase the release of inflammatory factors, including tumor necrosis factor, interleukin, and C-reactive protein.” Those of you with chronic circadian misalignment and low cortisol levels, you’re going to have higher inflammatory factors.

You’re probably going to be the people who wake up in pain. Joint pain, inflamed, puffy, those sorts of things, because that misalignment and your cortisol is being affected. As we know, cortisol’s anti-inflammatory to a point, and we need that inflammation…excuse me, not the inflammation, that cortisol to drive the inflammation up to a normal level. Now, we also know if you get too much, if you have too much inflammation, obviously it’s a problem. But what happens is there’s a feedback mechanism.

People will say, “Well, I don’t understand how this works.” It’s a feedback mechanism. Cortisol goes up and then it shuts down the loop for further inflammatory cytokine production. If you don’t get that healthy rise in cortisol, you don’t get that feedback loop, so the body just keeps making, making, making more inflammatory cytokines, and that’s why you hurt, that’s why your inflammation keeps going and you can’t heal. It’s really important that we focus on that CAR.

Then, if we talk about inflammation, we have to talk about autoimmune, because this is the big one. This was the huge aha moment for me that I had a couple of years ago. I was at an autoimmune conference, and a PhD in immunology, Dr. Heather Zwickey said, “Well, don’t you know the cortisol awakening response is what helps kill the autoimmune cells made in the thymus gland?” I was like, “What? Are you serious?”

What happens is, for people who don’t know what I’m talking about, your thymus gland, and not your thyroid, but thymus gland makes immune cells, and the T-cells in your thymus gland go through a process where they go from immature, then they differentiate, and then they keep going through this kind of a factory, through these different steps. At one of the very last steps, the body goes, “Okay, little T-cell, I can’t release you if you’re autoimmune. If you are accidentally created to be autoimmune, then I have to kill you.”

What the thymus gland does is it runs it through something called central tolerance, which is where it takes the T-cell, and it runs it basically through every tissue in your body. It’s very smart, thymus gland, and it runs it through every tissue in your body, and if you pop positive, which means you fail central tolerance, in my head the analogy is you get pulled to the side and you’re going to be killed, because you can’t have a T-cell that’s reactive to yourself. That’s a fail.

But in order to kill it, you have to have the cortisol awakening response. What stimulates the apoptosis or the killing of those cells that fail central tolerance is your CAR. Now, if you don’t have a CAR, if you don’t get the cortisol awakening response, then those sneaky little bastards, those T-cells that are reactive to things like your thyroid or your adrenal glands or whatever, your brain, your joints, they sneak out into circulation and they can increase your risk for autoimmune or increase your symptoms if you already have that autoimmune.

James Maskell: Yeah. This is super fascinating. I’m glad you brought this up because ultimately the journey from health to autoimmune disease is something that I think functional medicine has a much better grasp on than conventional medicine. But, typically, it’s talked of in terms of environmental factors like toxins or leaky gut kind of stuff. How new is this research into this part of the mechanism?

For all of the doctors that I know that have maybe come to functional medicine because of something like Hashimoto’s, right? I think we all know quite a few doctors who have arrived here from reversing their own autoimmunity. It seems like this might be an early indicator that you’re heading in this direction and we can catch it earlier.

Carrie Jones: Yep, I would agree. I think because…well, the biochemistry has been there forever, right? The biochemistry is what it is. The cortisol awakening response is what helps trigger the killing of those cells in the thymus gland. People learned it in physiology, they’ve learned it going through an anatomy class and what have you, but it doesn’t…it never…it hasn’t gotten highlighted until very recently. I think people are like, “Okay, yeah, yeah, yeah. That’s how cells can fail central tolerance.”

But they look to the outside. Just like you said, they look at leaky gut, they’re looking at environmental toxins, they’re looking at genetic risk, they’re looking at whatever, and they’re not…they didn’t go back and look at when you have autoimmune just right there in your thymus gland. By highlighting the fact that, “Oh, these cells will get killed if you have a normal CAR, let’s focus on that. Let’s get your cortisol awakening response up in the morning.” Now, having said that, is there a lot of good…are there billions of dollars to be made increasing the cortisol awakening response?

No, but there are billions of dollars to be made in treating, like MS, right? Or Addison’s disease, or some of these other rheumatoid arthritis. That’s where the money goes, and so the CAR fell to the wayside. That’s why I’m so excited that it’s found its shiny moment again, because if you have a low CAR and you have autoimmune or you have a strong family history of autoimmune or you have all the risk factors for autoimmune, you want to address that CAR. You might as well address what you can address from the inside. Right? Because that’s usually relatively easy. We can work on getting the CAR up.

James Maskell: Even though it could be classified as an environmental issue, ultimately a lot of the CAR is being response to full patterns and other things that aren’t related to your environment.

Carrie Jones: Right, exactly. Exactly, and in, yeah, choices. You choose to stay up late, you choose to be on your phone, therefore you have terrible sleep and now you have CAR issues, and you do it night after night after night, then you’re going to have problems. Your trampoline is going to wear thinner and thinner and thinner, and then you’re going to show up at a functional medicine practitioner’s office because nobody knows how to address, as you’ve moved through this progression of a threadbare trampoline when we can address all these things.

We can test for it for one, and get a really good picture, and then address it. This is why I love it. For those looking at the slides, when I was talking earlier about the breast cancer, this is one of the research studies. This is from 2000 in the Journal of National Cancer Institute, where they said patients with metastatic breast cancer whose diurnal cortisol rhythms were flattened or abnormal had earlier mortality. So breast and actually prostate. I don’t have the prostate studies listed, but prostate is in there as well.

Those with the breast and prostate cancer active, they’re actively working with breast and prostate cancer. Unlike, “test your CAR, you have to test your CAR, if you don’t, research says you’ve earlier mortality” and we can’t have that. The CAR is modifiable, so let’s modify it and help improve outcomes. To sum up, testing the cortisol awakening response really gives you valuable health insight related to both resiliency but longevity, right?

Autoimmune longevity, cancer longevity, all these longevity things that are so important. That’s why I think this podcast is the meat of it, where people can really relate to those symptoms. People really are like, “That’s what I went to my doctor for, that’s what I went to my practitioner for.” For the practitioners listening, they’re going to look at this like, “Oh my gosh, I can do so much with that. That gives me so much insight onto so many things by one easy test.” It’s modifiable, so let’s work on it.

James Maskell: Yeah, super interesting. Well, look, thank you so much for coming to share about it, and I really think that there’s some pieces in here that may be new to a lot of practitioners. Ultimately, we’re in the process of shifting from a disease-centric system to a health-centric system. What I’m super-excited about is just seeing how very easy to quantify and easy to collect markers, in a certain way, could help us get ahead of the curve, but not have a slip into some of these really costly chronic illnesses.
Ultimately, I’m excited also for the third in our series that’s going to be coming up next month, where are we going to go deeper into really chronic patients, because that’s typically who are coming into a lot of the clinics that we work with. Yeah, I appreciate today, and I think we covered some ground that will be new and innovative to a lot of practitioners listening. Thank you so much for being part of it. Dr. Carrie Jones is the chief medical officer for DUTCH Test. Check out dutchtest.com. They’ve got some great support for practitioners who want to start implementing the DUTCH Test, and we’ll see you next month, we’ll go into more about super-chronic patients, and we’ll see you then.


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