Reset Your Stress Response: Get the HPA-Axis Back in Balance

In this webinar, Director of Clinical Education for Precision Analytical, Dr. Debbie Rice, walked through the nuances of assessing cortisol health and the HPA-Axis.  Where does Cortisol come from? How does it affect inflammation and autoimmunity? How can patients change their lifestyles to improve their stress response? All of those questions and more are answered in this informative webinar from January 2022.


Please Note: The contents of this video are for educational and informational purposes only. The information is not to be interpreted as, or mistaken for, clinical advice. Please consult a medical professional or healthcare provider for medical advice, diagnoses, or treatment.

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Full Transcript and Time Stamps

00:00 Webinar Begins

03:26 Stress Response – Cortisol Response

14:28 Stress Response – Cortisol Highs and Lows

21:15 How it works

30:04 DHEA

33:29 Diurnal Pattern

36:26 How to evaluate

43:15 Testing for stress response

48:09 Treatment and Evaluation

53:45 Q&A





0:00 Webinar Begins

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Thank you, Mark. I am so excited to be here. And thank you all for joining us on this journey. So, today, we're going to talk about stress, how to reset your stress response. It’s January, people have a lot of new goals. So, why not have that part of our goal be: evaluate stress, look at how stress works, and what we can do about it?


Um, alright, so, stress response. When we think about stress, I hear a lot of people throw around stress, pretty easy. Like, oh, it's just stress, like, oh, it's just, you know, like, it’s nothing. But stress is actually a really big thing. So much so, that there's a big part of our whole anatomy and physiology that is dedicated to dealing with stress. So, when we think about stress, we want to know what is stress, and stress is anything that creates an imbalance in your system. What balances my system is probably very different than what balances your system. So, we need to think about homeostasis, maintaining a steady state or optimal stability. We think about that, think about like your temperature, right? Like your body temperature stays within a very small window. We want to make sure that that doesn't go super wonky.


Same thing with fluid balance: mood, energy, blood sugar.


We also think about stress, we want to think about, what does that stress look like? Is it a real stress or is it a perceived stress? We're talking about real stress.


We're talking about things like not sleeping or blood sugar regulation, injury, right? Like you fall and you hurt yourself? You're in a car accident, those are real stressors, dehydration.


Real stressor. Perceived stress. Right, like, those are things that you think about, work, demands of work, family, relationships, anticipated stressors, things that have happened in the past, that you think about, that you perceive as stressful.


Your body has the same response, whether it is real, or perceived. Your body does not have a good idea of like, oh, this is the good stress, right? Like, oh, this is, you know, I have my calendar packed, because I have to hang out with this person, because I'm thinking of that as self-care. So, that's the good stress, no, your body does not categorize stress as good or bad. It's just a meter of it is. Right?


And we have to remember that with that meter of it is, and even just as buckets get full and overflow, your body's capacity to handle that good and bad stress can also overflow.


So, we want to be aware of where are that stress comes from and what that means for your body.


So, when we're talking about stress, we also want to understand what, what does the body do with this, right? So, in the stress response, let's talk about the hormones that are involved. So, we have adrenal glands. We have two of them, generally, and these sit atop your kidneys. So, you have two kidneys and on top of your kidney there's a little, like, triangle gland. That is your adrenal gland. two of them. There's an outer portion of the adrenal gland that is called the adrenal cortex, and then the inside is called the adrenal medulla.


So, things that we generally test for, when we're looking at hormones, for testing for stress response, our cortisol, and DHEA, those are the big ones, that we look at testing and being able to measure and evaluate. Where do these come from?



3:26 – Stress Response – Cortisol Response

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Your cortisol actually comes from the adrenal cortex. And when we look at this little picture on the side, the big part that's all pink and has little white polka dots there, that is the Zona Fasciculata, that, it's big because the body works really hard at making cortisol for you. That's where cortisol comes from. The DHEA and DHEA-S also come from the adrenal cortex.


They come from the Zona Reticularis, which is on the further bottom part of that diagram. And then we also have Aldosterone. We don't really think about when we're thinking about stress hormones, but aldosterone is important. It comes from the Zona Glomerulosa, and this can influence your salt, potassium, can influence your blood pressure. Which is important when we're thinking about stress and stress response. And we also have catecholamines, and so we think about catecholamines, these are amines structures that come from the adrenal medulla.


This is your epinephrine, and norepinephrine. So, these are the different hormones that are going to be involved when we're looking at evaluating stress and that stress response.


When we think about stress response, and you'll hear this also probably thrown around a lot, is the HPA axis. This is the hypothalamic pituitary adrenal axis. And when we're talking about cortisol reaction, we're talking about the HPA axis and cortisol response. So that hypothalamic pituitary adrenal axis has a signaling mechanism that starts with any kind of stressor. Again, real or perceived. Right? So, when we get that stressor signal this starts out in the hypothalamus and the hypothalamus sends out a hormone called the corticotropin releasing hormone or factor. This happens in the periventricular nucleus of the hypothalamus.


The CRH then hits to the pituitary gland, pituitary gland gets the handoff and says, all right, there's been a stressor, we need to finish out.


The signaling, sends ACTH, from the anterior pituitary down through the portal vein to the adrenal glands. The adrenal glands get hit with this ACTH,


they're like, all right, we're on, this is where we get to release cortisol, and this is where we start to have that cortisol release and stress response. So, that is your HPA or hypothalamic pituitary adrenal axis response. We want to remember that this happens in the brain. The cortisol response starts in the brain. It doesn't start in the adrenal glands. It starts in the brain.


So, we have to remember that the signaling for your stress response involves brain, brain action, and brain signaling.


With the HPA axis, we want to remember, there's a difference between a cortisol response, and they catecholomine response. So, remember, in this last slide, the catecholamines are going to your epinephrine and your norepinephrine. So, there's a difference in how these work and how your body responds to stress.


So, your cortisol, which is released by the adrenal cortex. When the body makes cortisol, it does this on demand, as needed, when signaled, it is not made and then stored to be available to deal with stress, so, your body gets a signal, then produces cortisol.


The reason why I say that this is a slow response is because, that, the signals have to hit the brain and the brain hasn't sent, you know, all of those signals and key movements down to the adrenal gland to release cortisol. The lag time in this is usually about 10 minutes. And this is 10 minutes after epinephrine and norepinephrine have been released. What happens is as catecholamines that are produced out of the adrenal medulla. This is a fast response.


So, think about when you, we're talking about the nervous system response to stress, the spinal cord is also involved in the nervous system. When you touch a hot stove, a lot of times you don't even think about it.


Your hand reacts, right, like your hand goes away. It's not because your hand has sent signals all the way up to your brain, and then your brain decided, oh, I should move my hand.


No, your hand sent a signal to your spinal cord.


Your spinal cord was like, nope, and take your hand off. That is the same type of communication that happens with your catecholamines and epinephrine and norepinephrine. It's an immediate release. Your body gets a stressor signal, catecholamines release epinephrine, and norepinephrine,


and then cortisol comes in about 10 minutes later to continue to support you in that stress response. So, that's where we have that slow versus fast stress response and hormone signaling release or reaction.


So, with the cortisol response we've discussed, it is produced in the zona fasciculata in the adrenal cortex. The adrenal glands, Cortisol is a glucocorticoid. What that means is it's a steroid hormone.


It utilizes sugars and fats to mediate our response. This can be anti-inflammatory. This can influence immune response. But it utilizes sugar and fats to help maintain that stress or cortisol response. So, cortisol’s released in response to a stress, we talked about what stress could be. It is also released in the presence of low blood sugar, that's technically a stressor, lik,e when we, in an easy to think of way, right? Like our body gets energy from two sources: from cortisol and from food. And if we don't have food, your adrenal glands have to make up for that lack of blood sugar or food support.


When cortisol is released, the reason why it does this, when our bodies sense that acute stress,s we have to be ready to run from that saber tooth tiger, cite that, scary, whatever is happening. In order to do that your body needs to have glucose available for energy. And so, cortisol blocks insulin, right? So, insulin's job is to, you know, send these little signals to, though in glucose, comes through your blood vessels. It signals the cell to grab glucose, put it in the cells, and be ready, so that it can have energy to do what it needs to do when you are running from a sabretooth tiger your insulin gets shut down so that glucose can be ready and available in the bloodstream. So, it can go to your muscles, it can go whatever organs need to get you out of that stress situation.


Cortisol also induces gluconeogenesis. That means the breakdown of glucose or sugar from your fat cells in the liver.


It also reduces protein uptake, right? Because the whole point of this is to give your body energy from sugar and glucose so that you can keep glucose in circulation, helps your brain stay in focus as well. And cortisol can also, will also suppress your immune system. Why? Because if you need to run from a saber-toothed tiger, you should not be laying down coughing, right? So, your body needs to be able to run or fight that stress. It also increases blood pressure. This is where that aldosterone can also come into play.


It vasoconstricts your blood vessels, so you can get more blood going to where it needs to go.


It also improves focus, mental and physical. It can improve your eyesight. So, all of these things happen when cortisol gets that signaling, it's released from the adrenal cortex. Your body is ready to fight. It is ready to run, it, is ready to save you from whatever is happening.


So, when we have the stress response, that short-term effect or acute response to stress when cortisol is released, generally anti-inflammatory, and have the ability to, and energy, ability and energy to fight or deal with stress, increase focus, increased blood pressure. This means increased heart rate and blood flow to your muscles. This also means decrease digestive effort, right? Like your body is not going to be digesting food, like Thanksgiving Day when you are running. Like, we've all tried that right, like you eat and try to run, it's pretty miserable. Your body needs to divert its blood flow away from digestion to muscles, so you can deal with the fight.


It decreases your sex hormone response because your body's not worried about making babies.


It's worried about running from the saber tooth tiger, and again, it decreases your immune response. The long-term effect of cortisol. So, this is where our body's evolutionarily, you know, we were we were set to respond and run from acute stressors.


We're, we're not well adapted to long term effects of cortisol release, because when you have all of those acute things that are happening to help save you, but it never stops. This is where you start to have disease states, right? So, this is where you start to have insulin dysregulation. Why?


Because insulin has been turned off, it's not supposed to do its job.


So, in a long-term state, it's still not doing its job, because it's still trying to help you fight that stress. This can lead to blood sugar irregularities, dysglycemia, diabetes, weight gain, because your body is not having a metabolic balance. Your, this is where you can also get like weight gain around the middle.


Right, like you have that release of cortisol, I call it little cortisol tire, immune suppression and immune dysregulation, chronic fatigue. And this is usually longer and longer term of cortisol, right, like your body's burning through cortisol and your gas tank is getting empty, you don't have enough cortisol to continue to support that long term response to stress. Gastrointestinal issues, things have been shut down, right?


So, when we think about GI function and digestion, this is part of the parasympathetic nervous system, so our nervous system has this sympathetic and the parasympathetic, you're sympathetic is the drive run, do, parasympathetic is calm, rest, relax, digest. When we shut down your gastrointestinal function, we also shut down that parasympathetic nervous suppression. So, you have nothing to counter-balance, that sympathetic drive. That cortisol rush, run, go, do.


Cardiovascular concerns without blood vessel constriction. You can have increased blood pressure and overcompensation of the cardiovascular system. It's working hard, right? Like, your heart rate is still trying to manage that stress. Just think about, like, when you are initially stressed, say that you're in a car, and you're driving, and somebody cuts you off, right? Like your initial response to that stress, eventually your body gets used to it, but there's still this higher demand that should not be there consistently. And then sex hormone imbalances.


And again, your body's not worried about making babies, it’s worried about getting you safe, running from, running from things. And we think of this. We think like infertility, irregular periods, low libido and sex drive, heavy periods. Things that can alter normal reproductive balance.



14:28 Stress Response – Cortisol Highs and Lows

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And with the stress response, so cortisol can definitely have its high highs and low lows. And we're talking about pathologic issues.


And these are significant considerations when looking at cortisol function and how the bodies releasing cortisol. When you have too much cortisol, this is called Cushing's, this is usually a pathologic state of consistently high levels of cortisol. So, cortisol has a diurnal rhythm, it goes up and down throughout the day, with Cushing’s, you don't see a pattern. And this is usually from a tumor that encourages improper inconstant, signaling to release cortisol.


Low cortisol, is called Addison’s. And this is when the body doesn't have enough cortisol or aldosterone to keep that cortisol diurnal pattern going, this can be life-threatening and needs appropriate treatment. When we're talking about HPA or hypothalamic pituitary adrenal axis function,


Cushing's and Addison's are significant disease states. A lot of times we fall in what I call this gray area of inappropriate or improper stress response. Now, does that mean that you can still not feel great and still have certain components of high cortisol or certain components of low cortisol? Absolutely.


But it's not a true disease state in conventional medicine, you can still be highly symptomatic with this, though.


In addressing that, I also want to talk about adrenal fatigue. So, the old-school thought for adrenal function was adrenal fatigue. We had a phase one, phase two, and phase three.


I want to make sure that we are on the same page when it comes to describing what that means, when we're talking about adrenal fatigue,


this implies that the adrenal glands are not able to respond and that's not necessarily the case where we have talked about adrenal fatigue in functional medicine. More appropriately, this is categorized as HPA axis dysfunction or HPA axis inbalance. This points were specifically and accurately to poor functioning of the brain to adrenal communication. Because of the way that this signaling happens when you get that stressor response, and it sends out a signal to the brain, and the brain is pushing out all of these signals to get that cortisol made. When you have sufficient cortisol, there's a negative feedback loop that happens to go back to the brain to say, OK, we have enough cortisol. We don't need any more of that.


But if you are continually stressed, right? Your, your body keeps score of this. If you are continuously stressed, you're not going to get that negative feedback loop. So, what happens is the brain gets a little confused because it's still getting this stress signal, and it's still sending that signaling to the adrenal glands, the adrenal glands are still getting signaled. It's just that the signaling pattern is not where it should be.


You're getting too much too often without enough of a break, right, like, our body doesn't have that ability to have, what I call that, resiliency, where your body can stop that stress response, and re center itself, right?


Like, restore it's normal capacity and function.


So, when we're talking about adrenal fatigue, that is, that is not the right term or description that we want to use. And we're talking about adrenal gland function or cortisol response to ongoing stressors. That's going to be more appropriate as HPA axis dysfunction or HPA axis imbalance.


The other thing that I want to talk about is, when we talk about stress and stress response, a lot of times, people will bring up the pregnenolone steal. So, pregnenolone is seen as a precursor


to cortisol, to progesterone, to estrogen.


And that is very true. Pregnenolone is still the precursor to make DHEA ,to make all of these different hormones.


But it doesn't, it's not like there's just this big pool of pregnenolone that's available. And then when you get stressed out and the cortisol steals that all for itself, right, that's not what happens. That's not why there is sex hormone imbalance. That is not why that there's immune system imbalance.


It's because the signaling of stress ends up creating a whole other cascade of events that sets the body up, hopefully, for success in an acute stress response, but not in a long-term stress response.


So, in looking at physiology, the pregnenolone steal is not real.


What we need to understand is that cholesterol is the backbone for hormone production.


Cholesterol turns into pregnenolone.


And when we're looking at this signaling for the stress response, different cells have different responsibilities with different enzymes to do their job.


So, we know that the zona fasiculata makes cortisol.


And this has to have a specific enzyme to do this from cortisol, right? For example, to the ovaries. Have a specific job to make progesterone but they have a particular cell with specific enzymes to help make that progesterone once that specific cell pulls the cholesterol into it. So, do you have a pool of cholesterol? Absolutely. Does that mean that cholesterol influences your ability to make hormones?


Absolutely, but it's not based on pregnenolone, and it's not based on and pregnenolone steal.


To show this, Tom Williams did a diagram where we're looking at the different zones of the adrenal glands. We had the Zone glomerulosa, this is what makes the aldosterone. We have the zona fasciculata, this is what makes your cortisol and the zona reticulata, that’s nicer DHEA.


When we look at this, we can see each of the zones or cell types pulls the cholesterol in and yes, it does through the star protein through the mitochondria make pregnenolone, but from pregnenolone has the, each have different enzymes that help break down that pregnenolone into different


metabolites that give us eventually the aldosterone, eventually the cortisol, eventually the DHEA.


So, it's not a pregnenolone based dependency, and it doesn't become a steal.


Every cell line has its own capacity to pull cholesterol, and then get the signaling to then make pregnenolone, to make the hormone that it needs.



21:15 How it works

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So, in the stress response, how it works.


So, cortisol, being a glucocorticoid, has to be transported into the cell.


The cool thing about cortisol is it does not need a transporter. So, I would say, a lot of times, most of the hormones in the body need what I call a babysitter, or some kind of transport protein or binding globulin to get where they're supposed to be. They should not be left unsupervised. They are all like naughty children and need to be escorted, generally, where they need to go.


The cool thing about cortisol is it does not need a transporter to get inside the cell, but once it gets into the cell, there's a glucocorticoid receptor. And when we're talking about cortisol signaling, cortisol has to get into the cell to create that stress response, right?


Once the cell binds to the glucocorticoid receptor, there is what we call chaperone protein.


This is called heat shock protein 90, and what this means is the heat shock protein 90 acts as a carrier to pull cortisol from the glucocorticoid receptor into the cytoplasm of the cell, pulls that into the mitochondria.


When the glucocorticoid or cortisol is kind of hanging out, the glucocorticoid receptor is kind of waiting for cortisol to come over.


The heat shock protein 90 hangs out on top of the glucocorticoid receptor, waiting for cortisol to come over and do its job, and then the heat shock protein 90 can make, you know, escort it over to the mitochondria to do what it's supposed to do.


Once that happens, you can have the cortisol response in the cell. So, when we're looking at this, we can see the glucocorticoid receptors and the communication, a lot of times, rely on mitochondrial function to be able to get that cortisol development, right? Like when we're looking at hormone or steroid genesis, that happens in the mitochondria. We have to have communication from the glucocorticoid to mitochondrial development. Sometimes this also gets transferred into the nucleus.


So, cortisol can go to a couple of different places, but the, the main worker of the cell is going to be the mitochondria. We know the mitochondria is like the powerhouse of the cell, right. Like it does all of the things.


So, we rely on mitochondrial health to grab that transport of cortisol, and get that cell signaling going, so that we can have appropriate cellular response.


The glucocorticoid receptor can bind to multiple steroid hormones, including estrogen, or estradiol, androgens, like testosterone, aldosterone, and progesterone, here, the focus is just on cortisol.


We also have that heat shock protein 90, there are a couple of heat shock proteins, heat, shock protein, 90 and 70 are the big ones and we're talking about cortisol and cortisol transport. But the reason why we have heat shock protein 90 is this helps,


in general, the heat shock protein 90 protects cells from heat shock.


Which seems weird, but there, when we're talking about cellular function, you have to remember just even as a person, right? Like, you can be clumsy, you can hit things, you can do things like, things may not always be perfectly aligned. Same thing happens with our cells, right? Like, cells are small, and there's a lot of stuff inside those cells, like if we look back at what all is in those cells, we have an asthma in particular. We have a nucleus. We have mitochondria of all sorts of things going on in there. And these can also bump into each other. Sometimes what happens is the heat shock protein, if there are any misalignments in the cells or any proteins that are not staying stable in their form, the heat shock protein 90 helps keep it stable, keep it in a good form. The heat shock protein is also, or can also be known as a stress protein. So, you can have a heat shock protein 90 or a stress protein 90 more commonly are more familiarl. It is the heat shock protein 90.


So, what are heat shock proteins and why are they helpful? They are responsible for appropriate presentation and folding of proteins. So, we think about, like, what does that mean. Think of how a DNA helix is organized, right. If this is not organized in an appropriate manner, the DNA doesn't work the way it's supposed to, just work appropriately. This is the same for other proteins that are found in the cells on the cell’s receptors. And so, the heat shock protein is responsible for watching over and ensuring all of these proteins have the appropriate structure to do their job or jobs.


Heat shock protein 90, specifically, helps with appropriate protein folding. It maintains an open site for the glucocorticoid receptor binding. It assists in transport of glucocorticoids, cortisol, and other hormones.


It can assist in self signaling, and it supports angiogenesis. Angiogenesis is blood vessel development so, that can work to the betterment or not of certain cells. We also have a heat shock protein 70, this one that protects cells from oxidative stress ,when we think of oxidative stress think of DNA damage, think of cellular destruction. Those are never a good thing, right? So oxidative stress is stres, on the cell that makes it not perform as well as it can. Heat shock protein 70 disposes of damage proteins. So, if they're so messed up that they can't be, you know, folded back and put back to appropriate form, it damages then. It also inhibits apoptosis, apoptosis is where the cell, you know, cell death, right? Like that. So, your dad, we're going to get rid of you. And this can also work to its favor or not, depending on what is happening in the cell.


Heat shock protein 90 and Heat Shock protein 70 can work together to transfer proteins, and they can work together with glucocorticoid transfer and signaling.


So, how the heat shock protein works, right? Like, it organizes things so thinking, you know, when we have this visual here, think of all of that stuff just being a mess all over the place.


Heat shock protein comes in. Folds everything nicely puts it in its place. It protects it, it transports it, it organizes it, it realigns it. So, puts everything back in place to make sure that everything is working the way that it should.


So, when we're looking at stress response and how it works, we have cortisol production. So, we think of cortisol. There is active cortisol, but there is also inactive cortisone.


So, our body has, when it makes all of this cortisol, about 5% of cortisol is free and available. So, our body makes this cortisol, but then has to activate it into its free form. In the free forms of cortisol, we have cortisone and cortisol, there is a, an enzyme


that is called the 11 beta HSD enzyme, and this enzyme helps to either activate to the active form of cortisol, or deactivate to the inactive form of Cortisone. So, the 11 beta HSD 1 enzyme activates to cortisol.


Where they 11 beta HSD 2 enzyme deactivates to cortisone.


And when we're looking at this, cortisone, as a metabolite, ends up being THE and cortisol, as a metabolite, ends up being THF, so when we're looking at metabolites this is like that


overall production of that free cortisol and we're looking at what's active, what is inactive? Here we can also see that the five alpha enzyme influences cortisol and cortisone metabolism. We have five alpha enzyme effect with androgens. We have five alpha that can also influence progesterone, so the five alpha enzyme inserts itself in a lot of different places. So, when we think of the five alpha enzyme, don't think of just androgens. A lot of times, we think of five alpha for PCOS, or higher androgen symptoms, We also want to consider that in cortisol and cortisol function.


With regard to cortisol being active and cortisone and being inactive, the deactivation of cortisol happens in the kidney and reactivation usually occurs and fat cells and or the liver.


So, there are multiple things that are happening in multiple places. The body, it's a pretty complex system.


Which is why when people say, oh, it's just stress, it's not just stress. It's a big, big part of your day-to-day and how your body can actually respond. What it's supposed to do, how it's supposed to do and how it's supposed to balance that.



30:04 DHEA

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So, part of this stress response is DHEA as well, so this is one of the other stress hormones that we think of that we can also measure and want to evaluate. So, DHEA is produced in the adrenal glands in the adrenal cortex.


It's also made in the gonads and the brain. DHEA is also seen as a parent hormone. Some people will say it's very similar to pregnenolone, it is considered a major precursor to other steroid hormones like testosterone and estrogen. I say that DHEA plays in both the sex hormones and the adrenal hormone worlds because it can influence sex hormone function, but it's a big player in adrenal stress response as well.


DHEA supplies about 75% of estrogen to pre-menopausal women and in menopause, the androgens, DHEA falls in the androgen supply 100% of our estrogens.


DHEA sulfate does not cross the blood brain barrier, but DHEA can.


DHEA sulfate does not follow a diurnal pattern throughout the day. It is constant and most abundant, a lot of people because of that use that as a better measurement of adrenal or stress reserve.


They’re, well, DHEA and DHEA-S have been found to heavily influence brain and nervous system function, specifically mood, neurotransmitter regulation and production more specifically with dopamine. It can influence immune function and endothelial function, endothelial being those blood vessels, right? So, when we're looking at elasticity, responsivity of your endothelial cells, how your blood vessels work on pump blood.


I will say DHEA is not greatly understood yet.


We know a lot about it, but we still have so much more new information that is coming up that like ,there's a lot more research and information that should be done on DHEA because it has many areas that it can influence.


When we're looking at DHEA versus DHEA-S. So, DHEA is the active form, DHEA-S is the inactive form.


DHEA converts to DHEA-S,


through the sult to a one enzyme, and the DHEA-S can convert back to the active form of DHEA through the sulfur transferees enzyme. And this enzyme requires this team. DHEA to DHEA-S needs a sulfur donor where DHEA-S to DHEA requires cysteine. So, when you're evaluating DHEA and DHEA-S, I think it's important to look at where the DHEA levels are, where the DHEA-S levels are. Is there a balance? What does that look like, and how does that progression look, like when you're testing, are there changes, are they consistent, do you need support for sulfur donors? Do you need support for cysteine to help clear out some of that DHEA-S. As I said before, DHEA has a diurnal rhythm. It generally follows that cortisol pattern of the rise and fall, DHEA-S does not have a diurnal rhythm.


So, a lot of times when people are doing blood work, they will test DHEA-S to see what that adrenal reserve It looks like.



33:29 Diurnal Pattern

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In the stress response, we also want to think about the diurnal pattern, and what we mean by diurnal pattern’s that up and down pattern of cortisol. So, DHEA has a diurnal pattern similar to cortisol.


And cortisol should follow a diurnal or circadian pattern. What that means that we're talking about circadian, right, is the sun rise and fall, that's what we're talking about circadian.


So, when we think about the sun rises, and then falls, rises early in the morning, falls later in the afternoon, we want cortisol to also rise in the morning and fall in the afternoon. So, cortisol is the daytime hormone. Melatonin is the nighttime hormone. Cortisol has to have this rise throughout the day, and then fall to pass the baton to melatonin. If you don't have an appropriate rise and fall throughout the day, melatonin does not get the signal.


Doesn't know what to do.


Cortisol should start signaling, so are old brain, which is really insane to me. Even when you are in a closed off room, you have curtains shut off like your old brain knows when the sun is starting to rise, and it starts to send that signal to cortisol to start to rise. Just before you're waking so that you can get up, get ready for your day. Cortisol peaks as the sun peeks and then wanes into the evening. Melatonin takes over at night when cortisol levels should be low.


When we're talking about cortisol and stress response, I know we've talked about this a little bit. We also want to look at that sympathetic versus parasympathetic nervous system response. So, as we discussed a little bit before, the sympathetic nervous system is more of that run, fight, flight, action, go, do, the parasympathetic nervous system as that rest, digest, calm.


And we have this big push of cortisol because we are running from our saber-toothed tiger or we are fighting our saber tooth tiger or we're doing whatever with a saber toothed tiger that is stressful.


Our body doesn't get the chance to again have that negative feedback loop to calm things down so you can reset that nervous system response, and this is very similar, right?


If you have a huge cortisol response that turns into a chronic cortisol response, you're going to have a chronic sympathetic increase or simply what we call sympathetic nervous tone. Meaning that your body is always on this high level, right? And you don't get the balance of a parasympathetic calm to reset everything.


And when your body, again, overflows like a bucket because you're sympathetic, sympathetic, sympathetic, cortisol, cortisol, cortisol, cortisol, you don't have a stopping point, or you don't have a turn off points so that that parasympathetic can come in and balance everything. This puts your system out of balance.



36:26 How to Evaluate

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So, when we're looking at the stress response, we want to understand how to evaluate, right? So, we want to understand the physiology and function of stress, stress response, cortisol, that's going to be the how and the what, so what the hormones do, and how they do it.


We want to understand the players in the game.


So, the enzymes, the protein carriers, the signalers, right? Like, how does the stress response influence brain function to signal your adrenal glands? How, what are the other hormones that are involved in that stress response? What are the other things that are going to influence how well that cortisol gets signaled through the cells, through your liver? Right.


Understanding the influencers of your stress response.


So, these are the contributing factors to the situation, right?


Like, how did you get here and understand how and what to test. So, we want to know what hormones we're looking at we want to what the best methods are to measure this function.


How to evaluate influencers when we're talking about influencers of your stress response. We're thinking about lifestyle. So, what do you do on a day-to-day basis? What are you exposed to every day? What if you work in a nail salon? Right? You do nails all day? What are the chemicals you’re exposed to? What if you do construction, what are the things you're exposed to? What if you’re a painter? What if you're an artist? But what if you go to an office and you sit all day, right? These are day-to-day things, and we consider what those influences are for your lifestyle. What are the different stressors that you are exposed to? What are the foods you're exposed to? What are the chemicals we're exposed to? What are the things that you wash your hair with, right? Like all of those things. How is your sleep pattern? We know that circadian rhythm is really important to cortisol function. We want to know what you're doing for your sleep pattern. What time do you go to bed? What time do you wake up? When I talk about sleep pattern and adrenal function, I always compare this to our adrenal glands are like a puppy.


The reason I say that is because puppies are very, they do very well with routine. Right? Same thing with our adrenal glands. They want to know when it's time to go to bed. They want to know when it's they will actually, they know they know when it's time to go to bed. They know when it's time to wake up. They know when they're hungry. They know when it's time to go for a walk, they know when they need to drink water, right? It's all about routine, that circadian rhythm creates a routine and the adrenal glands you so much better with their routine.


Same thing with blood sugar regulation. So, when we're looking at blood sugar regulation, it's not only what you put in your mouth but the timing of when you put things in your mouth.


So, blood sugar regulation can really add a lot more stress to the adrenal glands or not, and I think that that can be an active choice. Inflammatory triggers again, what are you exposed to? What are the stressors that you're exposed to? Is it a relationship? Is it a chemical?


Is it something different, oxidative stress? So those are going to be chemicals, nutrients, and mitochondrial health. How well is that powerhouse that helps with the signaling and development of cortisol? What does that look like for you? Right. Like if that, if your mitochondria can't handle your cortisol response, it can't give the right signaling, then that's also going to be a problem for how well you can deal with stress.


Mitochondrial health is your cellular health, you need to manage your mitochondrial house, this is your powerhouse. If you have weak mitochondria, you have weak cellular function, that also means weak metabolism of hormones and execution of overall function.


Like just weak, and these are those individual components that we talk about, like the heat shock proteins, right? We want less damage to cells, less shock to cells, improve cellular function. We want to make sure all of our proteins are where they're supposed to be, how they're supposed to be.


We want to have that nice little organized closet, those heat shock proteins and mitochondria can help improve how well organized your cells are, how well those proteins can respond.


So, we want to support cellular and mitochondrial health. We also want to look at diet, and this is where everyone is individual. This is not going to be a lecture on, you should be carnivore. You should be vegan, you should be Mediterranean. I don't know who you are. I don't know what your body does best.


What you need to talk to your provider about that, maybe, you do better with a, you know, paleo style eating, or I don't know. Every person is different, and every person needs to be individually evaluated to understand what is inflammatory for them and what isn't. Sleep and circadian hygiene. Making sure that you are getting to bed around the same time, every night, within an hour, making sure you are waking up, around the same time, every morning, within an hour. Making sure that in that circadian rhythm, you have good blood sugar stability. You have good movement, optimal immune function, right? Well, we have immune stress that's also a stressor to our system, so we want to make sure their immune system can respond appropriately. Optimal, glycemic regulation, blood sugar.


Supportive nutrients and supplements. So, when we look at supportive nutrients and supplements, we have to remember, right. These are supplemental to everything that you are doing. So, things that can support mitochondria on cellular health, CoQ10.


Suflorophane, quercetin,


alpha lipoic acid, glutathione, very strong antioxidant support, NAC or N-Acetyle-Cysteine,


Resveratrol, Vitamin E, B vitamins, lots of different B vitamins, B one, B six, B three, PQQ. Melatonin is actually a very potent antioxidant.


We think of this, we want to think of co factors for mitochondrial function in general, NAD, FAD, carnitine, magnesium, iron, oxygen, right? Our bodies need oxygen.


We need oxygen to transport everything off, everything in our, everything in our body needs oxygen. We have an electron transport system in the cell, relies on oxygen. If we don't have oxygen. We can't have appropriate cellular function.


Strength training and movement, right? Like, we need to strength training and improves blood flow, improves oxygenation, of cells, muscles, anti-inflammatory foods for whatever that looks like for you, routine sleep.


Think you guys are seeing a little bit of a routine or a theme here. Detoxed support right, sauna, infrared, hot, cold, or Hydrotherapy treatment. Cold baths that can be really good at helping to activate certain immune factors and even metabolic support, intermittent fasting can also help with that, rather give you, give your body a break. It can actually focus on detox instead of having like being overwhelmed with certain foods and nutrients. When it has a little bit of a break, it can focus a little bit better on some detox, now, all within moderation. And everybody has a different metabolism. They need to evaluate monitor and support.



43:15 Testing for Stress Response

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Testing for stress response. So, what we want to see in testing, we want to see your cortisol production capacity. So, in that 12-to-24-hour period, we want to see how much cortisol can your body make?


Is there a problem with how your body is making cortisol, is it making too much, is it making too little? What does that capacity look like?


We want to see the amount of free cortisol that's available and we want to see how that free cortisol is used throughout the day or that daily pattern.


So, this is going to be a big component of overall cortisol and adrenal response.


The DUTCH test, we have a DUTCH Complete test, this is all dried urine only.


And what this looks at is a diurnal record or a diurnal pattern of that free cortisol throughout the day.


You do the collection samples at dinnertime, at bedtime, you can do it in the middle of the night if you have that person that's not like you know, I wake up every, every night at 3:30 in the morning. Do an overnight sample.


First thing when you wake up or when the alarm goes off, and then two hours after waking. This is going to give the reason why we're doing that tiny is because we want to see what that cortisol is doing. Want to know what that cortisol pattern looks like, of what is free and available for your body to use throughout the day.


You can also do DUTCH Plus. This is urine testing, plus saliva for the cortisol awakening response.


So, this is all the urine testing plus the added part of salivary testing, so the saliva tubes have a little salivette, which looks like almost take a little cigarette filter, that you can just pop in your mouth and leave it on. For about 30 seconds, it absorbs the saliva and hormones pop it back out. The reason why we do saliva is because this is the best way to measure the cortisol awakening response, when we're looking at the cortisol awakening response, this is a very specific to timing, which is why urine is not optimal. That's not to say that urine is not an accurate representation of cortisol, but because timing is so important, saliva is preferred.


And so, this cortisol awakening response has to be tested and measured, right


when you wake up, 30 minutes later, and 60 minutes later, what we're looking for is that diurnal rise, or expect a diurnal rise of that cortisol profit. If you want to see what your cortisol's doing and then the dried urine collection for the metabolite. So that's what we can see your metabolized cortisol. Are you doing active cortisol, inactive cortisone and we also get to see sex hormone metabolites with that as well?


The cortisol awakening response is going to be again, that very specific part of that waking to 30 minutes, and then the 30-minute to 60-minute reaction. The cortisol Awakening response is like a mini stress test for HPA axis dysfunction, like how does your body really respond to stress?


So, as an example, a couple of years ago, Mark challenged me to do cortisol awakening response test, but not, I'm waking to an actual stressful response. So, we were at a conference that had a slide that dropped, like, you go all the way up the stairs and then it dropped out from underneath you. And then you went careening down this tunnel and he was like, hey, let's check your cortisol awakening response.


And I was like, great, I'm going to die, so have all these tubes, right, and so we're checking how, you know, my anticipated stress, right, leading up to this stressful response.


And when we did this, you know, testing before, not during the slide but right after, and then how my stress response responded in kind right like that 10 minutes, 30 minutes, 60 minutes. What that looked like.


My cortisol awakening response was very similar to my actual response to this stress doing the slide.


And so, when we're looking at that cortisol awakening response, it really is a nice way to say, are you responding appropriately to stress? If that saber toothed tiger, if that slide is going to drop out from underneath my feet, do I have the appropriate stress response? And that's what we're looking for with the cortisol awakening response, we want to know if you have the appropriate signaling, you have the appropriate amplitude. You have the appropriate response of cortisol when it matters, right, when that stress hits you.

47:41 Long-term effects of cortisol

So, remember, the long-term effect of cortisol. We don't want this to be a chronic issue. Because if your body has not been able to rebound, it hasn't had that negative feedback loop. It hasn't been able to calm itself down. These are all the things you're going to be dealing with because your body hasn't been able to shut down that cortisol response. And this is why cortisol, cortisol management, stress management, is a big thing. And it's not just stress.



48:09 Treatment and Evaluation

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In treatment and evaluation, again, by cells, the major contributing factor, genetics can also strongly influence this, right?


But we can also influence the certain genes that may or may not be turned on by stress factors, right, by certain foods, by certain oxidative stress.


One of the questions that we always want to ask when we're evaluating stress in a stress response, how did we get here?


How are we here? How are you managing your day to day? Are you sleeping? What is your day, how did we get here? And remember, you can never out supplement a poor lifestyle. I've had patients come back to me and say, my supplements aren't working.


OK, well, what things have changed since the last time we spoke?


Well, I'm still going to bed at 3:00 AM and working 15 hours a day. I'm sitting on my butt, I'm not eating maybe, maybe twice a day I might eat when I get home at like nine o'clock.


And I don't have any physical activity.


I bet the supplements aren't working.


You're, you have to initiate those changes to that stress response. How did you get there?


The supplements are meant to support those changes in your lifestyle.


Stress management, the way you interpret stress is likely different than the way I interpret stress, right? Like, there are some people that have these schedules that I'm like, what?


But they have great stress management, and it's not affecting them as much as it could affect me. So, everybody is a little bit different in what their stress


point of craziness feels like, there are some people that can just roll with the punches, and they're totally fine with it, there are some people that are much more reactive. This all depends on how many stresses you've had, how your body has managed stress. Even leading up to this, remember, your body always keeps count. There is a cumulative effect of stress, so even when somebody says, well, it's not a big deal. I’ve been doing this for 20 years.


OK, that might seem routine to you, but your body now has, like, where you started here with your stress is now up to here, and your bucket is going to overflow, and you don't have the capacity to keep doing this any longer.


Sleep hygiene is also going to be important. You need to make sure you, you need to prioritize sleep.


Sleep is super important. And there is research that suggests there are certain times for sleep hygiene to be better than other times, right?


Even if you're sleeping nine hours from 2:00 AM to 11:00 AM, that's going to be a different quality of sleep than if you go to bed from 11:00 PM until 8:00 AM. So, remember that with the circadian rhythm and how your body responds to that. Blood sugar regulation, body movement, this is an individual assessment individual response you have to customize how you move forward with stress management.


Other considerations for stress and stress management. Breath work. There is wonderful


research on breath work, and how actual breath work and meditation. So, there's a difference between prayerful meditation versus, like, breath work meditation.


If your mind is consistently going in a meditative state, that's going to be different than if you're quieting the mind in a meditative state, right?


But there's research that shows breath work,


there are magic numbers to reach with regard to breath work that helped to reset that stress response in your brain, because that's where the signaling begins. Meditation, or meditative activity can also hel,p HPA axis support can also include herbs and nutrients. We think of herbs that can support HPA function. We're looking at like Gingko, ashwagandha, holy basil, rhodiola, nutrients, such as magnesium, like magnesium is involved in every enzymatic action in your body.


Different trace minerals, zinc, sunshine and circadian balance. Re-assess and re-evaluate your priorities. You need to look at what is important to you, and your health should be in the top tier.


Building muscle mass. That also helps with stress response.


Not only are you moving your body but you're increasing your blood movement. You're increasing oxygen delivery to organs, cells, and muscles. Hugs and oxytocin release, right, pets, partners, family, friends. You want to have connection whether it, I mean whether you're the kind of person that can get that oxytocin release and doing a FaceTime call. Or if you're a toucher, right? Like you need to have the hug. You need to have the touch. You need to have the in person. Do what you need to do to get that oxytocin release because that also helps to, you know, improve that dopamine response, reduce that stress response, and then grounding is also really important.


Feed on the grass, like literally grounding, feet on the grass, feet on the sand, ocean, salt water, air, like in nature, touch a tree, you know, step on some grass, that will also help connection with nature, actually does a lot to get your body to reevaluate its stress response or reset its stress response.


And that includes our talk.


Um, I'm going to also put on here, as Noah had said at the beginning of the webinar, we do have some options for new providers in doing any kind of testing. We are here. We've got your back. We have lots of great tools, not only for the testing, but also in helping to evaluate the testing, where to go from there.



53:45 Q&A

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Thank you very much, doctor Rice. We do have a few good questions in the chat. Sadly, I don't think we'll be able to get to all of them in the time we have left. But let's dive into what we can before we get started to remember. Doctor Rice is a doctor, but she's not your doctor. Please consult with your doctor before changing your treatment plan.


This webinar is intended to be used for educational purposes only and not intended to be advice for medical treatment.


So, doctor Rice, does the diurnal pattern of cortisol work around the sunrise and sunset, or do we each have our own unique diurnal internal rhythm?


It's a great question. Generally, research supports that it is involved with Sunrise and sunset. There have been some off studies where people have been put in a cave and kind of seeing like what the normal body rhythm ends up being, but in general, it is relative to sunrise and sunset.


Should the cortisol metabolites be considered when developing a treatment plan? And if so, how so?


100%. I think they should be because it's all part of the picture. It lets us know how your body is signaling to activate or deactivate cortisol.


Some of these may be tricky to say in general because it can be influenced by thyroid function, it could be influenced by overall evaluation of your stress response. Things that can, in general, activate cortisol, cortisol activated or things like licorice, but you have to be careful with something like licorice. right, it can affect blood pressure. It can affect electrolytes.


So, I do think it should be part of the treatment plan.


I think it could be very difficult to use as a general statement without looking at other components. To dig in that a little bit we have this question asked a couple of times in different ways. So, I'll try to condense it into one question.


How should we treat someone with a low free cortisol but with a high metabolized cortisol?


Great question. And it's not an uncommon pattern to see on the DUTCH test, whenever I see a high metabolized cortisol that tells us, your body is getting the signal to make lots of cortisol, right? But low free cortisol, meaning it's not using that cortisol, there's a dysfunction or imbalance, and how the body is trying to perceive its use of cortisol. A lot of times, we see this pattern with inflammation.


Because we have cortisol to try to be anti-inflammatory.


We can see this with obesity or blood sugar dysregulation, this, in this creates imbalances, or, imbalances in insulin, and blood sugar can also increase cortisol. Long term stress. You're still getting that drive to produce cortisol, but your body is unable to use it or signal appropriately anymore. And sometimes that can happen with too much thyroid medication.


But a lot of times it falls into the long-term stress, inflammation, blood sugar, and slow dysregulation there. To follow up a little bit on what you just said,


and to answer your question at the same time, how is cortisol, both an anti-inflammatory and suppress the immune system at the same time?


So, the acute response with cortisol is to be anti-inflammatory and the acute response is to prioritize running from a saber-toothed tiger and not manage other immune issues.


So, depending on where the person is at in their stress response, if it's more acute, you're going to have more of an anti-inflammatory effect of cortisol while still reducing the immune response. Now, if this is kind of going from acute to chronic, you're going to have some imbalances in, is cortisol really anti-inflammatory right now? Or is it being more pro inflammatory?


Yes, I will say that. Is that why I feel normal in the morning when I have a cold and worse at night? When I'm going to bed because I'm losing the cortisol throughout the day? You have less cortisol, I mean, if you think about it, right, like inflammatory issues,


people will get Cortisone injections, because Cortisone is the, you know, injected form of cortisol, because it's anti-inflammatory.


Thank you, very much.


Here's another great question. I think, do the levels of cortisol and melatonin, or the pattern of these levels change with age and in response to changes in the levels of other hormones?




Yes, they can.


So, just by aging in general, right, like, depending on how well we are up keeping with our cellular health, our body gets kind of dragged through the mud, right? So, in that, the signaling for cortisol is not as good as it could be, which means the signaling for melatonin, it's likely not as good as it could be, which is why you start to have sleep issues. You start to have energy issues, right.


That, that's where you have those imbalances that can happen.


There are definitely other hormones that can influence that cortisol and melatonin response, as well, but that's probably a whole other webinar, probably, yeah.


We had a couple different questions around intermittent fasting in cortisol, so I'll ask, and try to ask this in the way that addresses multiple of those questions.


Can you please give us your thoughts around intermittent fasting and stress for those with moderate stress? Like, should they be doing intermittent fasting? How heavy must the stress burden be if it is counter-productive? And for those with general well-balanced blood sugar, how soon into fasting is cortisol produced?


So, there, and this would be hard to say as a general statement because everybody is a little bit different, I mean, I've tested some people and they are metabolized cortisol is in the tank, but they're free, cortisol's OK, and they feel great.


Other people have a completely different stress response to that.


So, there is value in testing where that court like how you're, how you perceive your cortisol versus, you know, after so many years how your cortisol looks.


Intermittent fasting.


If you are not able to stabilize your blood sugar with intermittent fasting, then it's likely too stressful on your body.


And I know the intermittent fasting can be a really great thing but not everybody is metabolically set up to do intermittent fasting.


And that needs to be an individual assessment when we're looking at, you know, tracking blood sugar and tracking mealtime and when you're eating window is.


You had also asked something about cortisol rise in intermittent fasting. Yes, when, when it rises in, in the well bound sugar, how soon into fasting is cortisol produced?


You should still have an appropriate circadian response to cortisol. Right? Whether you are intermittent fasting or not, you should still have that rise of cortisol first thing in the morning.


Is there any correlation between high or low cholesterol,


in cortisol values?


It's a great question.


We do know that cholesterol can influence availability for hormone production.


I don't know that we have enough consistent research to say this much cholesterol means this much cortisol.


It's a great question, though.


When is the difference between using dried urine to test cortisol and the cortisol awakening response, as far as the, the availability for patients and how they can use it? When should we do which test?


Yeah, I would say the dried urine. The DUTCH complete is still a wonderful test, it still gives you really great information, where I would press on a cortisol awakening response,


we see cortisol awakening response negatively affected by autoimmune conditions, inflammatory conditions,


mood changes, so we think of like anxiety and depression, and significant mood changes, and historically, chronic fatigue, that's where I would really kind of push more for the cortisol awakening response.


Is there a correlation between thyroid function specifically T3 and T4 and cortisol, and what would those correlations be?




So, the thyroid is the main metabolizer of the body.


So, the thyroid kind of runs the ship in letting cortisol know like, hey, we have enough gas in the tank to do what you need to do. If you don't have enough thyroid, we can't do what you need to do with cortisol function.


So, low thyroid function can also lead to low cortisol signaling and low cortisol function. To unpack your gas in the tank analogy, someone did ask specifically about the long-term effect of cortisol and how do we have a gas tank if cortisol is not stored? Where does that gas tank come from?


Hm. Hm. That you, that, you talk about.


That's a good question.


So, we literally don't have a gas tank. But it's more about this signaling of cortisol. So, if you continuously have the signaling going, the body never gets a chance to rebound.


And that's where the gas tank is too full, right. Like your overflowing, the tank, overflowing the bucket.


All right. Well thank you. Those are some of the questions that we had, that we were able to get to today. Thank you again for all joining us on our monthly webinar. And we look forward to having you join us again next month. We have some exciting webinars coming to you in the month of February. If you do have any additional questions about today's content, or for general questions about the DUTCH test, please e-mail our customer support team at info@dutchtest.com, or call us at (503) 687-2050. I hope you guys have a great rest of your day, and we'll see you next month.


Thank you.


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