RHR: High Cortisol and Brain Fog

Chronically high cortisol levels, which are associated with stress, have been shown to kill brain cells, cause premature aging in the brain, and decrease the rate at which new brain cells are made. In this podcast, you’ll learn how to diagnose high cortisol and how to protect your brain if you’re suffering from this problem.

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Cortisol is a steroid hormone released by the adrenals, which sit on top of the kidneys. I’m sure most people listening have heard of cortisol, so I’m not going to go into too much detail. Basically, it’s a stress hormone that gets released in order to manifest our fight-or-flight response in stressful conditions. Another thing that cortisol can do is raise blood sugar if it’s dropped below a safe level, through gluconeogenesis. Then finally, cortisol has the ability to suppress the immune system and act as an anti-inflammatory compound.

In this episode:

2:55  What Chris ate for lunch
4:59  What is cortisol?
10:02  Functional disorders vs. diseases
15:20  The effects of chronically high cortisol
21:20  Testing for cortisol and adrenal fatigue syndrome

Steve Wright: Chris, how are you doing? How is the new book launch going?

Chris Kresser: Hey, Steve. I’m doing pretty well. How are you doing?

Steve Wright: I’m feeling it right now, man.

Chris Kresser: Feeling it. All right. You’re on track. Glad to hear it.

Steve Wright: Yeah.

Chris Kresser: As I hope everybody knows, my book came out in paperback. It was rebranded as The Paleo Cure. It’s going well. Not much to report. To be honest, I’ve been pretty focused on a lot of other things at the same time, so it hasn’t occupied my full attention. I like the cover design that they did. Yeah. I’m happy with the way things are going. Now, I’m just kind of full steam ahead with preparing the clinician training program.

Steve Wright: Awesome. Before we get into today’s question, and if people aren’t familiar with RHR, this show is created by you and for you. So go to ChrisKresser.com/podcastquestion if you have a question that you’d like Chris to answer. Before we get into today’s question, people are dying to know what you’ve been eating all day.

What Chris Ate for Lunch

Chris Kresser: So intermittent fast day. I had coffee and cream this morning. I was busy. I had a lot of other things going on this morning and just didn’t feel super hungry. So that’s what I did. Then for lunch, I had leftover chicken thighs from last night, some steamed kale with a little bit of olive oil on it, and some sweet potato hash browns.

Steve Wright: Yummy. I’m in.

Chris Kresser: Yeah, it was good. And a little bit of kefir to wash it all down. We’ve got a good question today from Al in Melbourne, Australia. Let’s give it a listen.

Al: Hi, Chris. My name is Al. I’m contacting you from Melbourne, Australia. Thank you very much for your podcast and your website. They’ve been an incredible resource for me. They’ve built so much context into understanding my health concerns. My question relates to cortisol levels in general, and in particular, as they relate to fatigue and brain fog. My blood tests have shown that I have high cortisol levels at times during the day. However, they don’t fall outside or above the threshold for Cushing’s. Assuming that my high cortisol is not caused by some sort of benign or cancerous tumor, what avenues would you investigate and what contributing factors would you think affect cortisol levels negatively or positively, which might affect brain fog and fatigue? Thanks very much.

Chris Kresser: This is a great question and touches on some things that we’ve talked about before, but I’m not sure we’ve ever really discussed all in one place, so I’m looking forward to doing that. Before we dive in and answer Al’s question though, we have to go over a little bit of basic terminology, especially because there’s a little bit of a difference in how people talk about these things in different countries.

What Is Cortisol?

Al mentioned cortisone. Cortisol and cortisone are two very similar hormones. They’re both steroid hormones. Cortisol is also known as hydrocortisone, to make it even more confusing. We tend to measure cortisol more frequently here and talk about it more often here in the US. From what I gather, in other countries like the UK and Australia, I hear cortisone discussed more regularly. I’m not sure if that’s just the context that I’m hearing it in or if that’s actually the case.

Cortisol, as I said, is a steroid hormone. It’s released by the adrenals, which sit on top of the kidneys. I’m sure most people listening have heard of cortisol, so I’m not going to go into too much detail. Basically, it’s a stress hormone that gets released in order to manifest our fight-or-flight response in stressful conditions. Another thing that cortisol can do is raise blood sugar if it’s dropped below a safe level, through gluconeogenesis. Then finally, cortisol has the ability to suppress the immune system and act as an anti-inflammatory compound. Now, cortisone is another steroid hormone. It’s also released by the adrenal glands and it has very similar properties to cortisol. It acts as an anti-inflammatory compound. It can act as an antidiuretic hormone. Like cortisol, it has the ability to elevate blood pressure in stressful conditions. So cortisol, cortisone, they’re both steroid hormones. The difference is cortisol is the more active form when it comes to glucocorticoid activity. Cortisone is a precursor that can be converted to cortisol, in a process that I’m not going to go into. It gets complex.

But the real gist here and the thing to be aware of is these are stress hormones that are produced in a stress response. That stress response can be anything from what most people typically think of as stress, which would be driving in a traffic jam, getting in an argument with your spouse, financial stress or working too much; all of that sort of thing. But physiological conditions can also cause a stress response. I’ve often said to some of my patients who say, “Oh, I don’t have any stress in my life,” you know, if you’re independently wealthy, laying on the beach in Thailand somewhere, and you have a gut disorder, parasite, leaky gut, autoimmune disease or something like that, you are under stress. That’s a disturbance of homeostasis in the body, and you’re experiencing a physiological stressor. So all of these things can cause an elevation in cortisol, produce cortisol. The problem, of course, is that these days, in our hectic modern lifestyle, even though we might not experience life-threatening events very often, we are under a constant background of low-level or even sometimes high-level stress, which causes the chronic overproduction of cortisol.

Steve Wright: I think that it’s really important what you were kind of saying there, which I’m not sure if it was going to be picked up by everybody, but it’s also my sort of view, is that stress isn’t always necessarily a negative thing.

Chris Kresser: Mm-hmm.

Steve Wright: And also, cortisol. Because cortisol, as you mentioned, just in the fact of how we discuss it, it’s always coming from a stress response. It doesn’t mean cortisol is a bad thing. Like, cortisol is so important for the body. It’s just important in the right amounts at the right times.

Chris Kresser: That’s right.

Steve Wright: I think unfortunately, there’s been a lot of unfortunate backlash. I’m just feeling for my buddy cortisol there. I think he’s been getting beat up too much lately.

Chris Kresser: Yeah. Like everything else, too much is a bad thing, too little is a bad thing. You know, the stress response is something that keeps us alive and kept us alive throughout our evolutionary history. If it wasn’t there, we couldn’t survive and adapt in an ever-changing world. So it’s absolutely essential to our survival. There’s no doubt about that. The problem is the way that the stress response system was designed—or the way that it evolved over time was in a completely different environment than the environment that we’re living in now. So it’s not really set up for the kind of chronic, persistent stressors that we’re experiencing today.

Functional Disorders vs. Diseases

Now back to Al’s question. He mentioned Cushing’s disease. This is a big area of confusion, the difference between what is often referred to as adrenal stress, adrenal fatigue or adrenal fatigue syndrome, which is a functional disorder—and I’m going to define that a little more clearly in a second here—and a disease like Cushing’s disease. Because if you go to a conventional doctor and you say, “I think I have a problem with my adrenals,” the first thing they’re going to do is roll their eyes and say you’ve been reading too much on the Internet and to stop doing that. Then if you press them, they might say, “Okay. Well, we’ll test you for Cushing’s disease.” You know, it’s a disease. It’s a clear, distinct pathology. It’s characterized by increased secretion of ACTH in the anterior pituitary gland, which in turn, causes excess cortisol production. It’s most commonly caused by a pituitary adenoma, which causes the increased secretion of ACTH or excess production of corticotropin-releasing hormone (CRH) in the hypothalamus. So this is a structural disease. It’s a problem with the hormone-producing gland—in this case, the hypothalamus or the pituitary—that then causes the excess cortisol production at a very high level, and it leads to a condition called Cushing’s syndrome, which is also a pretty distinct disease entity.

So when we talk about adrenal stress, adrenal fatigue syndrome, high cortisol or cortisol dysregulation, we are not talking about Cushing’s disease. We’re not talking about these clearly-defined disease entities. We’re talking about a more functional disorder. What I mean by that is it’s a condition that is measurable using objective lab findings, but it’s not a clearly-defined disease entity. It’s more of a syndrome.

There are lots of syndromes in medicine that are discussed and recognized by conventional doctors. One example would be irritable bowel syndrome (IBS), which is really nonsensical in a way when you look at it. If you really understand the diagnosis of IBS, it’s a diagnosis of exclusion. You basically rule out a bunch of other potential conditions, like inflammatory bowel disease. Then if you rule all those other conditions out, the person gets this label of irritable bowel syndrome. It doesn’t mean that irritable bowel syndrome is made up or it doesn’t mean that the symptoms aren’t real. It doesn’t mean that there aren’t real, actual, measurable things that you can detect in terms of people who have it. It just means that it’s not a clearly-defined disease entity with a single etiology/cause and a single treatment. Another syndrome is premenstrual syndrome (PMS). That’s a collection of signs and symptoms that are very real for women who experience it, but it’s not a clearly-defined disease like type 2 diabetes, for example.

So adrenal fatigue syndrome I think is another syndrome. It’s a collection of signs and symptoms which are measurable. We can look at a diurnal cortisol profile, which I’ll talk about a little bit later, and we can see that cortisol is dysregulated. The production of it throughout the day might be too low in the morning and too high at night, or it might be a little bit high throughout the day or a little bit low throughout the day, but it’s not high or low enough that it suggests Cushing’s disease or one of these more clearly-defined disease entities. We’re talking about things at a more functional level, at a level that hasn’t evolved or may never evolve into a frank disease, but is nevertheless still very potentially debilitating. I mean, I have patients with severe adrenal fatigue syndrome, who can hardly get out of bed. You know, they’re still told by their doctor that there’s nothing wrong with them and they should probably just take an antidepressant. So I just want to be really clear about that right off the top, because there’s so much confusion about what adrenal fatigue syndrome is and what it isn’t. When we’re talking here about high cortisol, we’re not talking—I’m not talking about, at least—a situation where there’s a structural problem. We’re talking about a more functional disorder.

Steve Wright: That’s a really important clarification.  I’m glad you mentioned that. Also, I just want to take a minute to say that if people aren’t watching this on YouTube, you should totally check it out, because Chris and I didn’t even send each other a text message, but we decided to wear basically the same shirt today.

Chris Kresser: We did coordinate it, Steve. Don’t lie.

The Effects of Chronically High Cortisol

Now that we’ve talked a little bit about what cortisol and cortisone is and kind of laid out the context for this whole discussion, I’d like to talk a little bit more about the effects of chronically high cortisol or dysregulated cortisol, whether that’s from physical, emotional or mental factors.

We know that high cortisol is associated with suppressed immune function, hypertension, high blood sugar, insulin resistance, carbohydrate cravings, metabolic syndrome, type 2 diabetes, fat deposits on the face and the neck and the belly, increased accumulation of visceral fat around the organs, reduced libido, and bone loss. And that’s just for starters. So it’s definitely a major issue. It can wreak havoc all throughout the body. But it doesn’t have specific effects on the brain. Animal studies have shown that giving rats daily injections of cortisone can kill brain cells. Cortisol has been shown to damage and kill cells in the hippocampus, which is the area of the brain responsible for episodic memory. Chronic stress has been shown to cause premature brain aging. Cortisol binds receptors inside of brain cells and causes them to admit more calcium through the channels and their membrane. This has the effect of essentially exciting brain cells, which helps us to cope in a life-threatening situation. But if that cortisol release becomes chronic and you have this ongoing excitation of the brain cells, then they become overloaded with calcium and they die. They’re literally excited to death. Lastly, we also have studies that have shown that cortisol decreases the rate at which new brain cells are made. So I think it’s pretty safe to say that chronically high cortisol has a number of adverse effects on the brain. It has a neurodegenerative effect, so it can actually degenerate the brain over time. That could certainly cause brain fog, difficulties with cognition, difficulties with word recall and memory, anxiety, depression, and all kinds of other neurodegenerative disorders.

Steve Wright: So Chris, when it comes to low cortisol, in my opinion, it seems to be way understudied compared to high cortisol. In the research it seems, for instance, that 90% of the research is on high cortisol and 10% on low cortisol. I’m curious, when it comes to the fact that high cortisol can over-excite the brain, and we want an optimal amount of cortisol, can we also then begin to understand that low cortisol might not excite the brain enough and therefore we might end up with brain fog at the high and the low end? Or is that not something we can infer at this point?

Chris Kresser: I don’t know that cortisol plays an important role in maintaining a certain tone in the brain. I see where you’re going. But I certainly agree that there’s a huge lack of research in terms of the effects of low cortisol. You’re right that it probably is at least 90/10, if not 95/5, in terms of what’s out there right now. But there’s no doubt that low cortisol has a number of negative effects as well. Some of them are similar to the effects of high cortisol and others are different.

One of the main impacts of low cortisol is kind of runaway inflammation. As I mentioned, cortisol plays an important role in resolving the inflammatory response. So if you have really low cortisol over time, then you can get stuck in this kind of chronic inflammatory state, because cortisol isn’t able to play that role of turning off the inflammatory response. It’s interesting too, because I’ve talked to other—I think it really depends on the patient population. Because I work with people who are sick and have been really quite sick generally and have been quite sick for a long time, I tend to see a lot more people with low cortisol. But the classic sort of type A personality and high-functioning but really stressed-out person who will tend to have more high cortisol—and I have other colleagues that work with a different population that frequently see high cortisol and less commonly see low cortisol. Whereas for me, I would say it’s way, way more common to see low cortisol. We treat a lot of people with gut issues. I think having a gut problem for a long period of time eventually just really compromises cortisol production.

Steve Wright: Yeah. It’s also I think one of the crux of why this talk is so important, is that whether it’s an actual disease with Cushing’s or if it’s a syndrome, the symptoms are kind of the same almost. Then whether it’s high or low cortisol, you can get so confused if you just look at symptoms.

Chris Kresser: Yeah. I mean, symptoms—this is why in functional medicine, we’re always saying, “Test. Don’t guess.” Because symptoms are not reliable as the sole method of diagnosis, because there are so many symptoms that are nonspecific, which means they can apply to any number of different things. Something even like cold hands and feet, which almost everyone would think thyroid in that situation, but in my experience, as often as not, that’s related to adrenal fatigue because of the autonomic nervous system dysregulation that happens. I mean, symptoms are important clues in terms of directing us toward the right test to do, but just making a diagnosis based on symptoms alone with these things is not really reliable.

Testing for Cortisol and Adrenal Fatigue Syndrome

Let’s talk more about testing for cortisol and adrenal fatigue syndrome, if we want to use that broad level. There are several different ways to test cortisol. One is in the serum, which I think Al referred to in his original question. Serum cortisol testing is accurate. The downside is that cortisol is a diurnal hormone, which means that it’s produced in different amounts throughout the day. Normally, in the morning, cortisol should be high. Early in the morning, it reaches the highest point, before you wake up, depending on when you wake up, and then it starts to decrease slowly throughout the day. Cortisone and melatonin oppose each other. As cortisol is going down throughout the day and into the evening, melatonin, which is the hormone that helps with sleep, helps us to fall asleep and stay asleep, that’s going up. So if you just do a blood test of your cortisol level at some point during the day, the only thing it’s going to tell you is what your cortisol was at that time during the day. Since it’s a diurnal hormone, that single reading, yeah, it’ll tell you something, but it won’t tell you what you really need to know.

Now, it sounds like Al had maybe several blood tests throughout the day. That’s unusual. I rarely see that happening in the US here. In fact, I can’t think of a single patient that I’ve ever heard of—I mean, we don’t do that kind of testing, and I’ve never even seen someone who’s done that. To get that diurnal rhythm, saliva testing is what’s most often used. That’s because it’s a lot easier to just spit into something four times a day than it is to get your blood drawn four times a day. Saliva testing for cortisol has been shown to be quite accurate too, despite a lot of conventional doctors that tend to kind of poo-poo saliva cortisol testing. But if you look in the scientific literature, you’ll see that it’s being used to make prognosis for Alzheimer’s and other neurodegenerative conditions. The extent to which the cortisol rhythm is dysregulated—you know, the more dysregulated the cortisol rhythm is, the worse the prognosis in those conditions. So it is being used in peer-reviewed clinical research, and it is a valid way to test for your cortisol levels throughout the day. Then they’ll estimate what your total cortisol levels are, based on those four samples throughout the day.

Another method for testing cortisol is 24-hour urine testing. This is where you walk around with a jug and collect your urine over a 24-hour period. That’s I think the most accurate way of measuring your total cortisol output. That’s because the saliva test is testing free cortisol, which is about 1% of the total amount of cortisol that’s in your body. Whereas in urine, you can test all of the metabolized cortisol, like tetrahydrocortisol and tetrahydrocortisone, and that is the rest of the 99% of cortisol. That will give you, when you do the total metabolized amount of cortisol in the urine, that gives you I think a more accurate indicator of how much cortisol is being produced.

And there are situations where you can have normal or even high free cortisol, but low metabolized cortisol. One example of that is in hypothyroidism, where there’s poor clearance of free cortisol into metabolized cortisol. The other advantage, which I kind of just referred to with the 24-hour urine cortisol, is you get to see the levels of the other cortisol metabolites, like the downstream cortisol metabolites, and that can give you a little bit more information.

Then there’s a new method that’s kind of a combination of the best of saliva testing and urine testing. The downside of the 24-hour urine testing is you don’t get that diurnal rhythm just like with saliva. You don’t get the morning value. There’s no indication of how it changes over time, because all of the urine is just going into the same container. There’s no way of telling when each sample was taken. But there’s a new lab called Precision Analytical in the US. It was started by I think a former VP of testing at ZRT Laboratory, a guy named Mark Newman. They’re doing what they call DUTCH testing. I think it stands for dried urine testing for comprehensive hormones. What they do is they have the patient do four urine samples at the same time that the four saliva samples would have been done, and they just saturate an absorbent cloth with urine. Then you get all of the metabolites that you would get from 24-hour urine testing, including the total amount of cortisol, et cetera, but you also get the benefit of the four different time readings of saliva testing. That’s what we’re using now in the clinic. I really like the test a lot. It’s really helpful. So those are all the different ways of testing your cortisol levels.

What you’re looking for is you want to find out if the cortisol levels are high overall. Like, is the total amount of cortisol produced high? Is the total amount of cortisol produced low? Or maybe the total cortisol is normal, but it’s too low in the morning and too high in the evening. That can cause problems, even though the total amount isn’t above or below a range. So that’s the first thing to figure out.

Then if you determine that you’ve got this issue, then there are—you know, the treatment of adrenal fatigue syndrome is beyond what we can cover right now, especially because we’re at the end of the episode. But if you have my book, there’s a bonus chapter on adrenal fatigue syndrome, which talks more about it and talks about diet, lifestyle, and supplementation strategies that can be really helpful. I’ve put together a pack of supplements that I have found to be really helpful for treating adrenal fatigue syndrome. They’re in my store, store.ChrisKresser.com. If you just look in the collections there, you’ll see the “Adrenal” collection there.

Essentially, the focus is, from a dietary perspective, you want to make sure you’re getting plenty of protein, because it has a stabilizing effect on blood sugar and the adrenals. You want to make sure you’re not too low carb or too high carb. Moderate carb tends to work best for adrenal fatigue. You want to make sure you don’t go too long without eating. Intermittent fasting has a lot of benefits and is great, but it doesn’t tend to work very well for people with adrenal fatigue issues.

From a lifestyle perspective, stress management, of course, is just absolutely crucial. That’s why we’re always beating this drum. I think people sometimes feel like stress management is optional or just this thing that you might do if you get to it and you have time, which is unfortunate, because it’s so critical and there are so many studies now that show that things like meditation and mindfulness-based stress reduction (MBSR) can have a more potent effect than drugs, in some cases, in terms of disease prevention and reversal. And with adrenal fatigue, I’ll say this—I’ve never seen a patient recover from it just by taking supplements and making diet changes. You absolutely have to do stress management stuff. I’d say if you could only do one thing, it would be the stress management thing, not the supplements or the diet changes. Of course, the best approach is to do all of them, but that’s how important the stress management stuff is. In 14Four, which Steve mentioned in the beginning of the show, I walk people through a stress management routine. We have video and audio demos of things like a qigong routine, guided mindfulness-based stress reduction practice, and guided meditation practice. So if you’re new to this stuff and you really want to get started and have some support in doing it, 14Four is a good option for doing that.

Steve Wright: Yeah. I’ve actually seen the exact same thing with clients, back when I was working one-on-one with a lot of people. I just had to start telling some people, like, “Look, you can’t out-supplement or out-drug a stress problem. You just can’t.”

Chris Kresser: You just can’t. No. No way. We’ve talked about this before, Steve, that it’s tricky because it’s a lot easier to just take a pill. And changing your diet is not easy, but in a relative way, it’s easier than changing how you relate to the world, which is often what is really at the core of stress management. Like, learning to say no, valuing your rest and leisure time, taking time out to just do nothing for a short period of the day. Those are things that aren’t really valued in our culture. You’re kind of swimming upstream when you make the choice to do that. But I can say from my own experience and also from my work with a lot of patients that that’s really the best choice you can make for supporting yourself through this. Last year, we did a stress management month. I think we should probably do another one this year, because it’s just so important and so many people struggle with it. It’s really hard for people to stick with, including myself. I mean, I know more than anyone probably how important it is, and I do have a daily meditation practice that I’m pretty good at sticking with because I’ve been doing it for almost 25 years now, but it’s still hard. Even after all that, it’s still challenging, with everything else that’s going on, to stick with. So it’s not like I’m perfect in that regard, but it’s something that I really know on a deep level is crucial for health. Hopefully, this was helpful and I answered your question, Al and everybody else who is listening. As Steve said, keep your questions coming. I look forward to talking with you next week.

Steve Wright: Thanks, Chris, for all that new info. If you want to submit your question, please go to ChrisKresser.com/podcastquestion. In the meantime, between these episodes, between the emails you’re going to be getting from Chris, he’s always posting new and relevant studies, data, and things like that on social media. Go to Facebook.com/KresserInstitute if you participate on Facebook. If you participate on Twitter, go to Twitter.com/ChrisKresser. You’ll get the latest updates about things that don’t necessarily always make the podcast or make his blog. It’s a great way to just kind of stay in contact and find out what he’s thinking about. Thanks.

Chris Kresser: All right. Thanks, Steve. Thanks, everyone. See you next time.

Steve Wright: Thanks, everyone.