 Up next, starting the afternoon, we have Nora Gagatis and her title is Re-Thinking Fatigued, the Adrenal Neck. From DC Berkeley, hey. So my name is Nora Gagatis and for those of you that don't know me, I'm the author of Final Body and Final Mind, hopefully you're familiar with that. But I'm also the author of a newly released book called Re-Thinking Fatigued, which her dream was really telling you what you can do about it. And this is currently available in all the e-book formats online, you know, Kindle Live Books, Nook and all of that. Unfortunately, due to the time constraints that we have today, we're not going to have much of a chance to talk about what you can actually do about it, but it's all in the book. So I'm hoping to broaden your thinking about this all to common issue and challenge you guys all to think about this in yourself in some new ways you maybe haven't thought of before. I really hope and expect that you're going to come away from what I'm about to present here with some very new and considerably updated and in a modernized appreciation of so-called adrenal issues, right, that lay the groundwork for actually being able to successfully address them. So with that much further ado. Oh, okay. Problems. There we go. So I don't need to tell any of you that we're living in a really profoundly stressful world now, something our ancestors could not have possibly even begun to fathom. And your stress management capacity can totally make or break your health and your quality of life. You can be doing virtually everything else right. And stress alone, especially if it's mismanaged and really chronic can totally unravel you. And I'm sure a lot of you already understand that. I do. But a typical stress reaction, you know, creates a cascade of roughly 1400 biochemical reactions in your body. And managing these reactions is essential toward optimizing your health process and brain function. So what stands between this whole modern day stress monolith that we're living in and our health is insignificant measure the health of our adrenal function. And unfortunately, the adrenal related issues are very poorly understood nowadays by by most health care providers, even natural health care providers. And they're often still based in very outdated sort of 1950s based information and 1950s based stress physiology. And this presentation really brings the whole issue of stress management and adrenal health into the 21st century. And it's going to provide you with a much broader and more practically useful perspective of the subject. You know, our drenals are our stress hormone factories and they're poised to respond to the stress to the stressors we face or the stress that we impose on them. So adrenal dysfunction is often perceived as one thing when in fact it may be many things. And what's commonly referred to as adrenal burnout, we hear everybody walking around talking about adrenal burnout. It's frequently something else entirely. And unless the source of the problem can be actually identified, it can't be effectively addressed. And I think that makes sense. So I plan to go through some of the more common adrenal issues here and offer a different way of thinking about your adrenal health. The big surprise here is that the problem may not be your adrenal glands at all. So, you know, stress basically, the way I like to define it is what it isn't. And stress isn't what actually happens to us in life. It's how we respond to what happens to us. And stress can be either physical, emotional or physiological, where the effect is always physiological. So another really important thing to keep in mind here is that our stress hormones are there to essentially keep us alive and particularly help us deal with emergencies. You know, we're actually not meant to live in a perpetual state of emergency. And our stress hormones are actually designed to work in a much more punctuated fashion. Mainly under particularly challenging or threatening circumstances, say for instance, you know, like being chased by a cantankerous woolly mammoth or running away from an ugly blind date or something. I don't know. But, you know, our adrenal reactions basically rapidly raise our blood sugar in order to, you know, increase our access to basically rocket fuel, right, that metabolic kindling, and give us that shot in the arm that we can use to outrun whatever it is that might be pursuing us or, you know, deal with that extreme exertion. So small amounts of hormones like cortisol are also necessary for other things. You know, it's not all bad. You know, we need it for good gut health. We need it again to manage our stress and for healthy moods and sleep cycles and things like that. Too much or too little can be really problematic. But our bodies and brains are really only designed to handle so much, you know. And we're not supposed to be marinated in cortisol 24-7 on an ongoing basis. So we're actually designed physiologically to be functioning in a calm, relaxed, parasympathetic state like 99.9% of the time. And then, you know, and then maybe 0.1% of the time, you know, when we shift into survival mode, that, you know, that's called for, what's called for then is sort of this need for emergency exertion. And cortisol basically gives us the boost and adrenaline, give us the boost that we need in order to deal with that. Unfortunately nowadays, this whole thing is really flip-flopped. And so many people are being chased around by cantankerous wooly mammoths and saber-two tigers and whatever, pretty well 24-7, 99.99% of the time. And then the other 0.01% of the time, if you're fortunate enough to have the luxury to take what some people actually call a, this mythical thing called a vacation, you know, where you actually get to sit on a white sandy beach with an umbrella drink, you're basically there probably not doing much more than stressing out the natives. And then you go back to, you know, your state of, the state of chaos you call your life and go back to the chronic self, state of self abuse again. Well our ancestors would never have comprehended doing things this way. And our bodies and brains were never ever designed for it. It's a very, very real problem, real problem designed or associated with modern life. So this is the man often referred to as the father of the study of stress physiology. His name is Dr. Hans Sellier. And he was a brilliant Canadian, Canadian, hey, endocrinologist and researcher. And he was nominated more than once, actually close to 10 times for the Nobel Prize. So, you know, the guy was no slouch. And he had some brilliant ideas. And his model of stress involving these progressive stages of adrenal exhaustion were accepted for many years, in natural health circles, as sort of kind of being the gold standard. And this stuff is still being taught today in fact. And I learned it too in the beginning. But it's really no longer accepted by the current science of stress physiology. And, you know, we have these new advancements in our understanding of stress physiology and what actually constitutes adrenal compromise. And it just really isn't what Sellier proposed. And stress and adrenal, quote unquote, exhaustion does not necessarily progress in predictable stages as, you know, as they used to think. In other words, most of natural medicine is still unfortunately in the 1950s when it comes to adrenal issues. Of course, that said, this means, you know, conventional medicine is probably still pretty much in the dark ages when it comes to this whole issue. But this is the basic model of what Sellier proposed. It all seems logical enough at first. He originally proposed in 1956 that the stress response had certain progressive stages. There's an alarm stage where cortisol significantly elevated or high. There's a resistance stage where it could either be high or low. And ultimately there's an exhaustion stage where cortisol becomes chronically depressed. And then you have this further broken down into seven different subset, you know, progressive stages of adrenal exhaustion. Stage seven is basically the last nail in the coffin where your adrenals are just too little smoldering nuggets sitting on top of your kidneys and, you know, and that's that end of story. And in fact, as it turns out, now that we have some better and more affordable testing to show it, a person can go into elevated states or depressed cortisol patterns almost literally overnight. There are some people that can be exposed to chronic even severe levels of stress over years or even decades, and the pattern never really changes. So there's a lot more to the story than meets the eye. But Sellier's model is basically a glandular model of adrenal dysregulation. And the glandular model is largely, it turns out, just inaccurate most of the time. And that's why you can take adrenal supplements till they're coming out of your ears and they just simply never do a thing. Now, this part of Sellier's understanding really is true. That cortisol is in fact released as part of a generally predictable daily circadian rhythm where it is highest in the morning and it's at its lowest level at night. Now, this is an overview of our primary stress response system. Most of what's thought of as adrenal dysregulation is not glandular at all, and that's part of the myth. But it's instead due to brain-based mechanisms and dysregulation resulting in faulty signaling to the adrenal glands and poor integration of your cortisol rhythms. In other words, your adrenal glands are just two little hormone factories sitting on top of your kidneys. They basically just do what they're told to do by your brain. Now, this particular study by Bruce Sherman McEwen in physiology reviews back in 2007 titled Physiology and Neurobiology of Stress and Adaptation, The Central Role of the Brain. And in it he says, quote, the brain is the key organ of the response to stress because it determines what is threatening and therefore potentially stressful as well as the physiological and behavioral responses which can be either adaptive or damaging. You know, plain and simple. There's a lot of research happening in this area right now. So basically there are four areas of the brain involved in regulating your adrenal function. You have the hypothalamic pituitary adrenal axis. And this basically controls the amount of cortisol you're producing at any given time. You also have the hippocampus, part of your temporal lobes deep in the limbic part of your brain. And this particular area of your brain is involved with regulating your cortisol circadian rhythm, okay? Then you have your mesothencephalic midbrain. And this particular part of your brain is involved with eliciting the amplitude of your adrenal or your stress response. And then finally you have the pineal gland which is responsible for obviously the production of melatonin and in so doing involved with cortisol melatonin balance which is the basic circadian rhythm. So here we just sort of have another way of looking at this in more detail. The brain sends messages to the adrenals from the HPA axis where the messaging is sent through these little areas of nuclei from the brain. And these nuclei activate the adrenal glands and they cause them to release glucocorticoids. Mainly cortisol but also the catecholamine neurotransmitters like epinephrine and norepinephrine and that sort of thing. Now basically inputs from neurochemicals like neurotransmitters or cytokines, inflammatory compounds, to what are called the paraventricular nuclear cells or PVN cells of the hypothalamus, determine the cortisol output that your adrenals produce, the amount of cortisol that your adrenals produce. So if there is excessive input, say too many excitatory neurotransmitters and that exceeds the inhibitory input, then the result will be excitatory or stimulating, you know, makes sense. So in other words, too many stimulants, too much stress in your life, too much exercise, too much burning, the candle at both ends can all potentially lead to something like that. And if the input is more inhibitory instead, then cortisol output is going to be inhibited for better or worse. So it turns out, though, that infections in certain types of inflammatory compounds or cytokines, in other words, have a huge dampening effect or can have a huge dampening effect. The amount of cortisol produced, along with your neurotransmitter activity, by the way, is controlled by what is called the central integrative state of the paraventricular nucleus of your hypothalamus. I know you knew that but I'm just reminding you. So there are basically two ways in which the hypothalamic sort of interference can result in adrenal dysregulation, you know, creating the effect of too much cortisol or not enough. So what effect would most adrenal supplements out there have on this, do you think? None. No effect at all. You know, surprise. So this diagram is taken from what's called an ASI, Adrenal Stress Index. Many of you are probably familiar with it. And it's a salivary hormone panel basically designed to measure your overall cortisol burden and also your basic cortisol rhythms. To me, that's the most important part of this thing. There are, you know, pages of other things that they like to measure in there, too. But, you know, the primary purpose is to really get a clear snapshot of how your adrenals are functioning in general, and particularly within the context of cortisol. So I'm kind of biased in my preference for diagnostics lab, you know, for this when it comes to that. But there are probably a lot of other labs that are doing a good job, too. That said, I know I'm going to warn you right now to ignore their marker for IgA sensitivity for alpha gliadin, you know, that salivary would ever test. If by some miracle you test positive, you can pretty well take that to the bank. But it's mostly about, you know, showing false negatives. I only use Cyrex labs for that type of testing. But, you know, they try to add bells and whistles. But nearly everything I want to know is right on the front page of the test. The overall cortisol burden and the graphic representation of the cortisol circadian rhythm here. And this particular diagram in the slide basically shows what's supposed to be generally optimized cortisol circadian rhythm. Here's, you know, the dotted lines here represent the normative range. You know, it's all supposed to be taking place in here somehow. And this is just kind of as the semi-solid line depicts just a perfectly normal cortisol rhythm where it is highest in the morning when you first wake up and then it kind of levels off during the day and begins to decline. And then by, you know, by midnight, hopefully it's down at its lowest step, which makes sense. That's when you need the least stimulation. So, but an aside here is that the current normative range is really standardized for the automatic assumption that a person's obviously dependent on glucose as a primary source of fuel because the reason it's highest in the morning is to bring your blood sugar up so that you can feel activated and energized and start your day. And there really isn't any standardization for anyone operating with a primarily fat burning well, you know, adaptive ketogenic metabolism. So you're kind of left, you know, having to sort of use a judgment, make a judgment call when it comes to evaluating this in people you know have adopted this other way of eating. So sometimes what we'll see may look like low morning cortisol in a person who's ketogenically well adapted. You know, I'll typically ask them whether or not they have trouble waking up in the morning, trouble getting going, you know, and if they don't then I don't worry about that particular variation. So in general ketogenically well adapted individuals tend to need less cortisol in, you know, overall. And especially early in the day to get going, although we still use a little cortisol in order to mobilize and increase fatty acids, you know, in the bloodstream from our fat cells to be used as fuel for energy production. So it still has a role to play. But this happens to be the ASI of a person with chronically elevated cortisol levels. They also have an elevated fasting glucose and a really high prediabetic hemoglobin A1C. And in this person's case their diet is actually pretty good. It's not that bad at all with respect to carb intake and that sort of thing. But they've also, you know, they also happen to be gluten intolerant, which of course is a stress and something that can elicit inflammation and stimuli, you know, and all of that sort of thing. And they also happen to be malabsorptive. And they've been experiencing muscle wasting, surprise, surprise. One of the things about cortisol is that it is a catabolic hormone. As opposed to anabolic, which builds things up. Cortisol is catabolic, which means it breaks things down. So when you have over-elevated cortisol levels, it's very hard to make gains with your fitness regimens. You also, very often, when somebody says they have a lot of trouble gaining weight, I'm interested in, number one, are they malabsorptive? And number two, you know, what's going on with their cortisol rhythms? They also may, this particular person also was showing some signs of early neurodegeneration. Because again, the richest repository of cortisol receptors in the brain is the hippocampus. And that's the first part of the brain to deteriorate in things like dementias and Alzheimer's. One very common source of excess cortisol production is also overtraining by athletes. It's a surefire recipe for crashing later on. And more is not better. And there was a former elite trainer, his name was Mike Menser, way back when. And he once said that overtraining is not just a bad mistake. It is literally the worst mistake you can make as an athlete. It's also a very good way of suppressing your immune function and making you vulnerable to a lot of unpleasant things long-term. So here are the common symptoms of chronically elevated cortisol. Basically, not feeling rested after sleep, finding it hard to recover from physical activity, abnormal weight loss, or abnormal weight gain. There are different reasons for both. Being more fatigued after meals, chronically elevated fasting glucose and hemoglobin A1C, even if you're on a low-carb high-fat diet. Having a lot of nervous energy, poor sleep, possible GI symptoms. You know, through a process of the suppression of secretory IgA, excessive cortisol tends to suppress secretory IgA, and that can lead to things like dysbiosis and leaky gut and things like that. It can lead to neurodegenerative changes. In other words, learning and memory issues. Where do I leave my car keys again? You know, stuff like that. Elevated cortisol can also lower your T3 thyroid hormone by suppressing an enzyme called 5D-idonase, which is responsible for the conversion of thyroid hormone T4 into active T3. So that could show up in your blood cams, too. It's like, you know, if you're constantly driving with your pedal to the metal and running your engine too hot, doesn't it make sense that the central computer in your car might try to adjust the aisle by dialing it down a little bit so that you don't blow a gasket? That's kind of the idea. But in these cases, what you often see in blood chemistries is a functionally or clinically depressed TSH, coupled with T3 and T4, you know, depressed T3 and T4 hormones. This is what I often refer to as depressed thyroid function, secondary to pituitary hypofunction related to chronic stress. Excess cortisol also increases your protein breakdown that can lead to muscle wasting. And remember, your heart is also a muscle. And that's one reason why marathon runners are notorious for dropping dead, you know, due to heart failure, because they're constantly stressing themselves in an unreasonable way for prolonged periods of time. It's also invariably leads to neurodegenerative changes in the brain, and this can also lead to bone loss that may result in things like osteoporosis over time. Excess cortisol also suppresses your immune function and interferes with healing and regeneration. And that can cause shrinking of your lymphatic tissue over time and also diminish your lymphocyte numbers and your lymphocyte functioning. Again, as I mentioned, you can depress in a secretory IGA production, which is, of course, your first line of defense of your immune system in both your gut and lung tissue, which is in short not a good thing. So this is what depressed cortisol looks like on an ASI. And this is also an example of what, you know, what's typically referred to in mainstream natural medicine is stage 7 adrenal exhaustion, right? The last nail pounding into the coffin, the burned out adrenals. This person happens to experience depression and fatigue, chronic fatigue, some anxiety, and they regularly crave caffeine and alcohol. And this person also had a lot of food sensitivities, and that may be one likely cause as well as a known parasitic and also a chronic viral infection. Things were going really well for them. They had a lot of chronic personal stress and they were also drinking too much and had not enough rest. So if we're looking at this from a brain-based perspective, just the brain-based perspective, you know, inflammatory cytokines generated through the food sensitivities and infections can adversely alter the paraventricular nuclear cells of the hypothalamus and dampen their output. And this really needs to be addressed on that level and not with a bunch of adrenal supplements. So what are the common symptoms of chronically low cortisol? Well, basically, you know, chronic fatigue and decreased tolerance to cold or stress, poor circulation, low blood sugar symptoms, which by the way, in other words hypoglycemia, in other words, this is not a dietary sugar or starch deficiency. There is no such thing. You may feel a little better eating sugar starch, but what you're doing is putting a band-aid on the problem and what you need to do is dig deeper to find out what the root of the situation is. You really do need to find out. You may be experiencing excessively low blood pressure, apathy or depression, poor stamina, joint aches and pains, muscle weakness, a need for excessive amounts of sleep, lowered resistance to infection. You get sick more often maybe than a lot of people, and also having a sort of a subnormal body temperature. It may not be thyroid related at all, primarily. So what are some of the potential causes of what looks like adrenal burnout? Well, again, you know, infection or inflammation, you know, leading to decreased hypothalamic output, we already talked about that. That's a possibility. But also free radical processes and cancers, right, can lead to a state of chronic fatigue. Pituitary hyperfunction, you know, low adrenocortic atropin hormone. Having abrupt withdrawal from long-term steroid use, probably not too big a going concern for most people, but you know, you see that sometimes in athletes. Iron deficiencies and also B6 and B12 types of anemias. Also insufficient cholesterol. You know, anything that lowers cholesterol is not good for this, right? Because adrenaline, cortisol, you know, these hormones are steroidal hormones. They're basically cholesterol-based hormones. So statin use is not friendly to something like this. You know, nutritional deficiencies like B vitamins, minerals, EFAs, there's certain raw materials needed in order to manufacture these substances needed. Malabsorption, you know, digestive disorders, leaky gut, that sort of a thing. Autoimmune disorders, which we'll get to. And also things like that can trigger or exacerbate hypoglycemia. Things like, oh, I don't know, diets high in sugar and starch. And poor or irregular eating habits, too, that can lead to this roller coaster ride and not a fun one. That where you're constantly using your adrenals to manage your blood sugar, which they were never designed to be managing your blood sugar all day long like that. Not like that. In my view, it's better to get away from having to deal with blood sugar altogether by adopting a more fat-based ketogenic approach to eating, but, you know, that's just me, hey, maybe not just me, but I'm biased. But blood sugar surges are the surest way of screwing up your adrenal function or pretty much just about anything. It has a huge, massive endocrine effect. Also constant stimulants seeking, either through substances like caffeine or nicotine or whatever, or excessive exercise or, you know, seeking external stimuluses all the time. You know, there's always these sort of thrill seekers out there looking for that adrenaline rush. These are the people you see bungee jumping out of airplanes and Mount Dew commercials, right? If you have a red bull habit, you might need to rethink that. But also, this is an increasingly common issue in our society today, something our caveman ancestors really knew absolutely nothing about. I certainly don't know anything about. But this can also be some combination of the above and also perhaps a few other things that we'll get to. We're always tempted to look for one thing, but it's oftentimes layers of things. But an important thing to remember is that our adrenal hormones are all about survival. Some things bear repeating. And that need for survival basically takes precedence over absolutely everything else, including the production of your sex hormones and immune enhancing DHEA and a whole lot of other things. If you're being chased by a Saber-Toothed Tiger, how much priority is your sex hormone production or your DHEA production going to be? You know, not particularly important. And if you're metaphorically being chased by Saber-Toothed Tigers 24-7, how's the health of your sex hormones or DHEA going to look like after a while? Not really that good for date night. You know, there's this phenomenon referred to as the pregnenolone steel. As you can see, where steroidal hormone production ends up getting diverted away from sex hormone production, straight to the survival hormones. And, you know, this can lead to really big problems and uncomfortable symptoms in women going through menopause, but also it can be a common cause of depressed testosterone in men, although the most common cause of depressed testosterone in men is something called aromatization, which is basically related to metabolic disorder. And my friend Dr. Janet Lang is fond of referring to the closely related sort of steroidal hormones here in terms of being a family, right? They function together and they dysfunction together. And anything you do to one of them is going to impact all of them. So think before you start slathering on these hormone creams, whether they're bio-identical or not, it doesn't matter. You're basically, you're shutting down feedback loops, you're screwing up communication in the system, and you're not just affecting that one hormone, you're affecting a whole bunch of things. This is actually in somewhat the sort of disturbingly the most common form of adrenal dysregulation that I see in my practice. The part of your brain's temporal lobes called the hippocampus is responsible, among other things, for mitigating your stress response. That's the primary place your brain mitigates stress response. And it has the richest repository of cortisol receptors of any other part of the brain. And this part of the brain is also responsible for the integration and conversion of short-term to long-term memory, and it's also learning. So this is where acetylcholine is produced, which of course you need for normal cognitive functioning and memory. And it's the part of the brain that's incredibly important too for supporting neurological stability. This is the first part of the brain to deteriorate in Alzheimer's disease and dementias, and it's the very first part of the brain to suffer under chronic stress. So the symptoms of dysregulation here, something you need to take very seriously and take inventory of as I go through this, include things like problems falling asleep, problems staying asleep, energy crashes in the late afternoon, real difficulty getting going in the morning, often coupled with problems winding down at night. There's kind of an up and down kind of a thing to it. Memory problems, difficulty learning, new information, forgetfulness. Ongoing issues here can increase your risk for cardiovascular disease. It can also lead to GI problems because these cortisol rhythms also help coordinate gut motility and also your immune function because the rhythms also coordinate and modulate your immune function. In addition to leading to things like cognitive deterioration, dementia, you might also see signs of neurological instability. And this can be things like mood-lability, in other words, mood swings, emotional reactivity, panic attacks, neuralges, migraines, increased seizure potential, not good stuff. The thing is that a lot of mood disturbances do have a circadian rhythm component and it's something to rule out and to look at. So this is what it looks like on an ASI. And this person basically experiences extreme fatigue in the morning. Is there any wonder why? And then they crave caffeine, drink a whole pot of coffee or whatever it takes to get themselves going. They're chronically irritable. They're chronically agitated. They have a lot of emotional reactivity and a lot of problems with restless sleep and winding down at night because of course when they're supposed to be sleeping, look at where their adrenal hormones are doing. I had this one right in my book, Primal Body, Primal Mind, when I called it a brain-based adrenal pattern. But it was wrong, although I was using the best and most accurate information I had at the time. When I called this pattern an HPA-axis issue, it isn't. It's most likely a hippocampal issue and it is not a good problem to have. This type of adrenal issue needs to be taken very seriously, needs to be addressed very aggressively with diet and nutritional support. And I talk about what to do with this in the book. I'd be recommending a fat-base ketogenic diet for this person so fast it'd make your head spin because a person like this has literally zero room for error. And this person is for sure going to have all kinds of serious blood sugar issues and it has to be gotten under permanent control. So temporal lobe degeneration as a result of this is no joke at all. We joke about senior moments. It's not funny. It's all too common nowadays and a lot of younger people are having these senior moments, you know, showing up in younger and younger individuals. Radiologists are seeing this sort of thing even in relatively young individuals nowadays and calling this a normal variant of aging. There is nothing normal about this simply because it is becoming commonplace because of the crazy life that we lead and because of the way we eat. So causes of hippocampal degeneration include things like chronic stress, basically leading to chronic cortisol marinate of the delicate hippocampal tissue, excess dietary sugar and starch and chronic dysglycemia leading to cortisol surges and insulin surges and free radical activity and neuro-inflammation. Also other chronic neuro-inflammation due to dietary antigen exposure, like gluten and other types of food sensitivity issues and also exposure to haptans, environmental compounds and things like that. Methylation defects are also oftentimes a problem with this as well because methylation is incredibly important for the integrity of the hippocampus. Also poor digestion and diet can lead to key methyl donor deficiencies, especially B12-infolic acid and then lead to elevated homocysteine levels, which by itself is neuro-inflammatory neurodegenerative. And also there's also deficiencies of elongated omega-3s, especially particularly DHA, which is of course needed to help modulate cortisol in the brain and as possible autoimmunity as well. And then excess dietary and sugar and starch and chronic dysglycemia. And I just kind of want to make this point. And the title of the study pretty much says it all. Quote, higher glucose levels are associated with lower memory and reduced hippocampal microstructure. That's the title. It kind of says everything. And the conclusions of the study, where's follows. They said, our results indicate that even in the absence of manifest type 2 diabetes, mellitus, or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning relevant brain areas, such as, oh, I don't know, the hippocampus. So, you know, in the face of the things we can't control, we need to control the things we can. And what we put in our mouths is something we still have some control over. So moving right along, we also have the pineal gland and melatonin and pineal activation. And melatonin and cortisol are always in direct opposition to one another. When melatonin is up, cortisol is down. When cortisol is up, melatonin is down. And this is the cortisol melatonin circadian rhythm, okay? And the pineal gland, which produces melatonin from serotonin, is influenced by light input through something called the suprachiasmatic nucleus, which is, again, sensitive to the time of year and how much light we're getting exposed to during the day and all of that. That's what typically governs the melatonin circadian rhythm. But the most common thing to disrupt melatonin is actually a cortisol issue. But, of course, when you live in modern, you know, day 24-hour sunlight in the form of electricity, that doesn't help either. But other things can disrupt healthy melatonin production in circadian rhythms, too. Inadequate sleep disrupts this, which in turn dampens your immune response. The dysregulation can also be seasonal for some people, or for people who don't get enough time outdoors during the day or enough exposure to normal, you know, normal daylight. Pineal disturbances can influence metabolic syndrome and weight problems, you know, pretty substantially, actually, which is one reason why sleep is so important when it comes to weight issues. If your melatonin levels are too low, then your sleep is going to suck, basically. And you're also probably not going to dream very much, which can also be related to be six deficiency. And you're not going to have enough appropriate REM sleep. But also your immune system is going to be weakened and there's going to be a pronus to getting sick a lot more frequently. A lot of people notice themselves getting sick a day or two after pulling an all-nighter or flying through multiple time zones. Dear God, I know that one. I just got back from a tour through Australia and there were time zones within Australia too. It was crazy. But anyway, melatonin actually primes and stimulates your immune function and inflammation while cortisol dampens it and reduces inflammation. That's essentially a modulatory pattern or dance. No good or bad guys, but it all needs to be in some form of appropriate balance. So you need to get these melatonin cycles under control. And I talk about ways of doing this in the book. And by the way, you don't do it by taking melatonin supplements. The worst possible thing you can do. You want to screw up your melatonin cortisol rhythm, take that melatonin at night. You'll do it every time. So the other aspect of this is your mesolympic and mesencephalic midbrain. It's right at the top of your brainstem and it's the part of your brain that is all about survival, right? It's where our brains epinephrine and norepinephrine are produced, your brain's version of adrenaline. And the midbrain basically controls what you can think of as the amplitude of your adrenal or your immune response. This region of the brain is also really sensitive to inflammation, particularly interleukin-6, the richest repository of interleukin-6 receptors, very nasty type of cytokine. And it basically generates hyperfunction by overstimulating the mesencephalic reticular formation, which is the part of the brain that produces norepinephrine. So strong emotional reactions and events can really plasticize activity here. In other words, things get stuck. There's kind of a feedback loop. And it can kindle really long-term issues in people, especially like traumatizing events and things like that can lead to a more chronically exaggerated stress response. And, you know, you can have a tendency toward hypervigilance and big startle responses, OCD type stuff, the overactive mind that won't shut off and post-traumatic stress disorder sorts of symptoms. People with this type of brain dysregulation, you see them wearing like sunglasses all the time. Even indoors, even on cloudy days, even early in the morning or in the evenings, they're really sensitive to bright light. They're also really sensitive to loud noises. They don't like that. They cannot stand crowds for love or money. And movement close to them tends to be over-activating of this part of the brain. Many people, these issues also have elevated, you know, GAD antibodies. You run into that pretty often. Can't really get into that. You know, the part of the... What helps wind this part of the brain down is, of course, our GAVA-nergic system. And so you kind of have to look, too, at... You got to look at GI infections and severe dysbiosis also, because that tends to depress GAVA. So that's one of the things to look for in this sort of instance. This part of the brain is directly connected to the gut through the vagus nerve. And they actually emerge from the same tissue at one time and remain connected throughout our lives. And so certain types of lactobacillus rhamnosis is something that sometimes can enhance GAVA activity in this part of the brain. But the brain and the gut are always connected. So what are the potential sources of chronic fatigue? Again, we talked about chronic infections of all kinds, free radical processes, mitochondrial dysfunction, inflammation, depressed thyroid function. And again, you know, especially the type associated with deprespituitary function. Diagnosed or subclinical anemia, or also excess iron and ferritin, can also lead to extreme fatigue and almost thyroid-like symptoms. These are things to rule out. Now, this is an artistic rendition of our intracellular ATP-producing energy factories, our mitochondria. And if this organelle isn't working well, then you don't either. And these energy-intensive organs, energy-intensive organs like the heart and the brain have really, really high level of mitochondria. And they're really vulnerable to mitochondrial health compromise. So mitochondrial respiration basically produces ATP, but at the same time, this process also generates a lot of free radical activity in the process. And so a well-adapted ketogenic state seems to regulate mitochondrial uncoupling that has the effect of dampening free radical activity. A well-adapted ketogenic state is also known to enhance the generation of antioxidant activity, including increasing glutathione in the brain's hippocampus. Hello. And that seems to also be able to protect vulnerable mitochondrial DNA from being damaged. And this is a study related to that I don't have time to share with you. I've still got a couple of minutes. All right. So there's one more adrenal issue to consider here, and that's adrenal autoimmunity. And this is our nation's most famous sufferer of a form of adrenal autoimmunity called Addison's Disease. Extremely common today, but it's only rarely ever diagnosed. And the reason for this is that you're not diagnosable with Addison's Disease until a minimum of 90% tissue destruction has already occurred. That is the standard of medical diagnosis. So if you're only halfway there, you're only at 45%, I promise you will notice this in every part of the way you feel and function, but you won't have any answers. You're going to think that you've got some form of adrenal fatigue or adrenal burnout. But is this really a glandular issue? No, it's an immune issue, and it needs to be addressed on that level, regardless of whatever tissues are involved. And again, it may be responsive to taking supplemental adrenal glandulars, one of the few things that adrenal glandulars may be helpful for, but in tandem with a lot of immunomodulatory steps, whole other subject, and again, this basically speaks to the commonality of this problem. Common symptoms, basically the same symptoms as adrenal fatigue. There was a really interesting case study. There was a woman who came into my office in her summer. She was suffering a very wide range of debilitating symptoms for a number of years and prior to showing up, and she did a bunch of Cyrex testing, found that she had a ton of food sensitivities. She had a leaky gut, all kinds of antibody production against a variety of tissues, including her adrenals. Her fatigue levels were totally extreme. She also had Hashimoto's and a few other associated tissue antibodies that she discovered, and that all made sense. So this person was sensitive to absolutely everything. She was struggling for answers, couldn't find them, but all this kind of made sense. We addressed food sensitivity issues, did some work on her gut, and then she adopted some nutritional strategies, basically, that I talk about in my book. And, you know, recently we did this ASI as a way of checking up on her adrenal function, and you can see her morning cortisol levels are kind of depressed, and they're actually pretty low pretty much throughout the day. But it turns out she doesn't have any depressed energy problems at all. Her energy levels are excellent. She's never felt more vitality in her entire life. And she also, usually with low cortisol, it's very hard to heal your gut, but she doesn't show any signs of leaky gut anymore either. Her numbers look great. She's lost all the weight she's needed to lose. Basically, she's become a fat burner, and so she's not really relying on glucose as a primary source of fuel, so the need for cortisol is a lot less, so she's being able to make much more efficient use of the cortisol that she's able to produce, which is really awesome. You know, Hans Selyed basically said, and he got a few things right, it's not stress that kills us, it's our reaction to it. Also Ralph Waldo Emerson basically said the world belongs to the energetic. And don't make the mistake, though, of confusing real natural energy with nervous energy or the effects of stimulant use. Neurosis and de-stimulation are just simply not the same thing. So what's thought of as adrenal fatigue or adrenal burnout is all too commonplace in this truly sort of non-paleo modern phenomena, even among many modern-day paleophiles, right? So sometimes the symptoms are related to chronic infections and also very commonly things like mitochondrial dysfunction or brain-based issues that need addressing. And increasingly commonly, there may be autoimmune involvement or it may be some combination of these things. It can take a lot of testing to figure out what's going on, but it's no longer as simple as any sort of progressive model of adrenal exhaustion that was proposed by Selyed in the 50s. So even though we have zero time here to go into specifics, here's the general advice to consider. Please resist hormone therapy approaches unless there is absolutely no other choice. And yes, this means bioidentical hormones too. Be leery of any adrenal approach that involves the use of things like isocort or whatever it is they're using nowadays. Always get to the root of the adrenal dysregulation first and then restore healthy function rather than treating the adrenals as though they don't know what the hell they're doing, all right? The body will always have its way. So you might as well play by your body's rules. And again, in the face of all the potential stressors in your life that you have, it's just critical to take control of what you can, but it's also critical to be good to your brain. Supply it with nutrients and healthy natural dietary fat, preferably in the absence of dietary starch and carbohydrates or sugars. Get the blood sugar under control or better yet eliminate the issue by adopting a fat-based ketogenic diet, I'm just saying. Learn to take some time out, neurofeedback, biofeedback, meditation, massage, infrared, saunas, vacations, adequate sleep, whatever it takes to relax you. Or you can always do this. And then detoxification has to be part of the equation nowadays. You have to compensate as much as possible for the toxic bombardment and oxidative onslaught from our environment. It's more than just a matter of avoiding toxins in the first place, that's not enough. And you also have to detox your mind too, focus on appreciation and gratitude. Try to avoid self-medicating. And remember, cut yourself some slack, try not to take life in all its little dramas too seriously, turn off the news, get outdoors, practice a little earthing maybe, learn to laugh more, and give time for the really important things and the people in your life. So for more information, there is my book, Primal Body, Primal Mind, which some of you are familiar with. There will be a book signing tomorrow at 4 o'clock. I have a tiny little handful of my book there. And then there is also my new book available in all the e-book formats called Rethinking Fatigue, which your adrenals are really telling you and what you can do about it. And please remember to sign up for my free newsletter. So thank you very much for your time. We don't have any time for questions, nor do you mind taking them in the hallway? Yeah, I mean, come find me during the book signing tomorrow. Or just grab me in the street or something.