Ok, so this is talking about cortisol in the sense of the body becoming resistant to it, but I think there are interesting correlations. If the body's inability to use cortisol leads to inflammation then perhaps too low levels of cortisol could have a similar response. In other words, perhaps I need to up my medication when I'm injured after all.
Original post and podcast here.
Concrete evidence linking chronic stress to inflammation and modern disease
Chris Kresser: All right, so the first study is right in line with the April Best Your Stress Challenge, and if you haven’t heard of this, go check out my blog, ChrisKresser.com. You now, there are a lot of 30-day diet challenges. There’s the Whole30, and there’s the Personal Paleo Code, my program where we ask people to give the Paleo diet a try for 30 days and give it that chance to change their lives and make a big difference in their health. But I’ve talked a lot about the importance of stress management and improving stress tolerance and mitigating the impacts of the stress that we can’t get rid of on our life, so I thought it would be a good idea to spend April doing a 30-day Best Your Stress Challenge. So, the idea is to apply that same concept of a 30-day diet challenge to stress management, and I wrote a post about this a little while back, I think, on March 30 and offered some ideas for what people can do to manage their stress throughout the month of April and just to make a commitment and preferably a small, fairly manageable one because oftentimes we have a tendency to commit to more than we can do and then we don’t follow through, so just setting a small goal, like meditating for 10 minutes in the morning or doing a deep relaxation exercise every afternoon or taking a walk in the woods or on the beach — whatever it is that helps you manage your stress — and doing that throughout the whole month of April and seeing how that improves your health overall.
So, the other day, I saw a new study with the title Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk, and since I’ve been thinking a lot about stress and the effects of stress on disease, I thought it would be a good idea to talk a little bit about this study because it’s really interesting, and it takes our traditional concept of how stress contributes to disease and kinda turns it on its head. It’s some relatively new information. I’ve seen a few other studies with a similar theme, and if anything, it just reinforces what we’ve been talking about in terms of the connection between stress and disease and the importance of managing stress and either reducing the symptoms of a disease that we already have or helping to cure it entirely or preventing the risk of acquiring a new disease. So, stress is associated with just about every modern disease that you can name, from depression to cardiovascular disease to type 2 diabetes to autoimmune conditions like rheumatoid arthritis and Crohn’s disease and multiple sclerosis to upper respiratory infections and even the common cold. And up until pretty recently and still now, I think, most people think that stress causes disease by dysregulating the hypothalamic-pituitary-adrenal axis, but this notion that stress acts simply by elevating cortisol levels is becoming less and less likely, at least in the current scientific literature. So, what this new paper and other recent papers suggest is that it’s actually the sensitivity of cells or the target tissue to cortisol, not absolute levels of cortisol that’s most important. So, glucocorticoid resistance, which is a decrease in sensitivity of immune cells to glucocorticoid hormones like cortisol, makes it more difficult to shut off the inflammatory response. So, let me break that down. When you’re insulin resistant, you’re producing enough insulin, but your cells are resistant to the effects of insulin, so it’s like insulin’s knocking on the door, but nobody’s inside or whoever’s inside isn’t listening, so the door doesn’t get open, and insulin can’t perform its function. The same is true with leptin resistance, and there’s even thyroid hormone resistance where thyroid hormone can’t activate the cellular receptors for thyroid hormone, so even though there’s plenty of thyroid hormone circulating around, you experience all the signs and symptoms of hypothyroidism because thyroid hormone isn’t affecting the receptor.
So, this study and others like it suggest that there’s a similar phenomenon with cortisol resistance. So, it’s not high levels of cortisol, per se, that are contributing to an increased susceptibility of disease, but it’s instead the insensitivity of cellular receptors to cortisol that’s the problem, because one of cortisol’s jobs is to turn off the inflammatory response once it gets started. So, let’s say you catch a cold or you get a cut or you have some kind of injury or illness, and inflammation is the natural response to that. Inflammation is not all bad. In an acute setting, inflammation is what helps us to heal. The problem happens when inflammation doesn’t get turned off appropriately, and then it just kinda runs wild and you get chronic inflammation, and it’s that chronic inflammation that is a risk factor for disease, not the acute inflammation that helps us to heal. So, in a normal functioning person, what would happen is that you’d get a cold or you’d get some kind of injury or acute condition that causes inflammation, and then the glucocorticoids, like cortisol, are produced and they turn off the inflammatory response by activating the glucocorticoid receptors. So, what these researchers have found is that people who are under chronic stress, that doesn’t work right. The cortisol gets secreted, but it doesn’t activate the receptors, and then you get a runaway inflammatory response. And this has been shown in other studies. They’ve found that cortisol resistance is present in spouses of brain cancer patients, in parents of children with cancer, and in people that are very lonely, and all of those populations are known to be experiencing significant stress.
So, in this study, the researchers used, I think, a pretty ingenious model to demonstrate this effect. I mean, it’s well established that chronic stress increases the susceptibility to the common cold and upper respiratory infections, as I mentioned earlier. So, the researchers actually did two studies in one. The first one was meant to determine whether stress causes cortisol resistance and whether people with cortisol resistance are more likely to develop a common cold in the first place. And then the second one was meant to determine whether cortisol resistance could predict the amount of local inflammation in the nose, for example, in response to a viral infection. So what they did is they actually purposely infected people with a virus, a rhinovirus that causes the common cold and respiratory infection, and as expected in the first study, the results did show that exposure to stress increased cortisol resistance, and in the control group they found that exposure to an acute stressor was associated with white blood cell count, but in the group that was under chronic stress there was no association. So, in other words, what should happen is that when you’re exposed to a stressor, as I mentioned, cortisol should turn off the inflammatory response and reduce the white blood cell count, but that didn’t happen in people that were under chronic stress and had cortisol resistance.
In the second study, they found a correlation between cortisol resistance and the levels of various proinflammatory cytokines locally, like interleukin-6 and TNF-alpha. And then they also saw a decreased sensitivity of white blood cells to the inhibitory effects of cortisol, like we’ve been talking about. So, in other words, when you’re stressed out, the immune system cannot turn off the inflammatory response like it’s supposed to, and then you’re more likely not only to get sick in the first place, but you’re more likely to stay sick for longer because that inflammatory process doesn’t get inhibited. So, the interesting thing also about this study is that there was no correlation between actual cortisol levels, like circulating cortisol levels, and disease risk or inflammation. So, it seems like it’s the cellular receptivity to cortisol, the sensitivity of the receptors to the actions of cortisol, that’s the most important, rather than the circulating levels of cortisol themselves. So, I thought that was pretty interesting, and it may not change things from from an end-user perspective too much because the idea is still that you want to take steps to manage your stress, but for me, every study I see like this is just another affirmation of the importance of stress management, and I see it in my work with my patients, I see it in my own life and my own experience, and people might be getting tired of hearing me talk about it, but I’m gonna keep talking about it because I thinks it’s kinda the elephant in the room in a lot of cases. In my patient population, I think I can pretty safely say that people who are taking active steps to manage their stress have significantly better clinical outcomes than people who don’t, and I just think it’s a much bigger contributor to the whole disease process than most of us really realize.
Steve Wright: That’s pretty insightful, man. And I thinks it’s awesome that we’re getting more data on what the problem is because you do hear a lot about, well, you’re not totally stressed out or you can go do another CrossFit workout as long as your cortisol isn’t over 20 or something like that.
Chris Kresser: Yeah.
Steve Wright: So, this is cool to have a new model. Now, do you know if, for instance, because we’re a little bit better at measuring insulin resistance and leptin resistance, are the three correlated? So, if I’m insulin resistant, I’m likely leptin resistant or I am leptin resistant. Am I also cortisol resistant then?
Chris Kresser: I don’t know what the exact relationship between all of those would be, but I certainly think that HPA axis dysregulation can contribute in some way to leptin and insulin resistance and probably vice versa. I wish there was a way of testing for cortisol resistance in the commercial setting. I don’t think there is. I think it’s only available in research settings. But what’s interesting about this study is that I think, like you said, the idea that we can just run an adrenal stress index or any kind of hormone profile where we measure cortisol, and if the person has normal cortisol we say: OK, you’re clear to do, you know, five CrossFit workouts a week. We can’t really make that assumption because that test is not gonna show cortisol resistance in the white blood cells. I think ultimately just paying attention to symptoms is a pretty good guide because if you have this cortisol resistance pattern, you’re gonna have more difficulty recovering from workouts because that inflammatory response won’t get turned off. I mean, working out, especially lifting weights, but doing any kind of intense workout is basically like a controlled stimulation of inflammation. You’re breaking down tissue when you lift weights. You’re breaking down your muscle tissue, and the idea is that when it builds back, it builds back bigger and more able to deal with the next stressor, in that case, lifting weights. So, that works well if you give the body long enough to recover, if you give the body long enough to turn off that inflammation and then to start the anabolic process rather than the catabolic process of building the tissue back up. And if you’re a healthy person with no significant stress levels and you’re not dealing with any chronic inflammatory condition, that should happen fairly quickly and commensurately with the amount of exercise that you did. But if you’re dealing with chronic stress and you have cortisol resistance, here’s what’s gonna happen: You’ll do the intense workout, you break your tissue down, which is what happens and is the whole point, but the recovery process will be very, very slow, and the inflammation will persist. So, instead of taking one day or maybe two days to get back to baseline and then start building new tissue, stronger tissue, you’ll take several days to get back to baseline, or maybe you really never fully do get back to baseline. And then you do another intense workout, so then you break down more tissue and cause more inflammation, and then it’s a downhill slide from there. And I see this a lot in the CrossFit community, people who come to me who have been doing CrossFit. And this is not all people who do CrossFit. I’m talking about people who are under significant stress and who may be dealing with a chronic health challenge. But the fact is most of us in this modern world are under stress, and some of us are better at managing it than others, and some of us pay more attention to that than others, but I think this is a very real phenomenon and it’s not just affecting people who have kids with cancer or spouses with cancer or people who are socially isolated. It’s affecting all of us to some degree or another.
Steve Wright: Way to wrap that up. I think it’s important to keep learning about it.
