Welcome to human lab essentials, where we revisit past episodes for the most potent and actionable science-based schools for mental health and physical health and performance. I'm Andrew Hubernen, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. This podcast is separate from my teaching and research roles at Stanford. It is however part of my desire and effort to bring zero cost and information about science and science related tools to the general public.
Today we're going to focus on how particular hormones influence our energy levels and our immune system. We're going to talk about the hormones cortisol and epinephrine also called adrenaline. If you're somebody who has challenges with sleep, or somebody who has challenges getting your energy level up throughout the day and getting your energy level down when you want to sleep, today's episode is also for you. And we're going to talk about the immune system and how to enhance the function of your immune system.
We're going to say that most people like to have a lot of energy during the day, if you work during the day, and they like their energy to taper off at night. And I think it's very to say that most people don't enjoy being sick. It turns out that the two hormones that dominate those processes of having enough energy and having a healthy immune system are cortisol and epinephrine. I just want to talk a little bit about what cortisol and epinephrine are, where they are releasing the body and brain, because if you can understand that, you will understand better how to control them.
First of all, cortisol is a steroid hormone, much like estrogen and testosterone. In that, it is derived from cholesterol. So understand that cholesterol is a precursor molecule, meaning it's a substrate from which a lot of things like testosterone and estrogen are made. So understand that cholesterol can be made into estrogen, or testosterone, or cortisol.
And that cortisol is the competitive partner to estrogen and testosterone. What this means is, no matter how much cholesterol you're eating or you produce, whether it's low or high, if you are stressed, more of that cholesterol is going to be devoted toward creating cortisol, which is indeed a stress hormone. However, the word stress shouldn't stress you out because you need cortisol. Cortisol is vital.
You don't want your cortisol levels to be too low. It's very important for immune system function for memory. You're not getting depressed. You just don't want your cortisol levels to be too high, and you don't want them to be elevated even to normal levels at the wrong time of day.
Epinephrine or adrenaline has also been demonized a bit. The stress hormone, this thing that makes us anxious by your flight, the fact that matter is that Epinephrine is your best friend when it comes to your immunity, when it comes to protecting you from infection. And Epinephrine, adrenaline, is your best friend when it comes to remembering things and learning and activating neuroplasticity. We're going to talk about that as well.
Once again, it's a question of how much and how long and the specific timing of release of cortisol and Epinephrine, as opposed to cortisol and adrenaline being good or bad. They're terrific when they're regulated. They're terrible when they're misregulated, and we'll be lots of tools to regulate them better. I'd like to take a quick rate and acknowledge one of our sponsors, better help.
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Your brain makes what we call release in hormones. And in this case, there's quarter-trip and releasing hormones. Our H is made by neurons in your brain. It causes the pituitary.
This gland that sits about an inch in front of the roof of your mouth and the base of your brain to release ACTH. ACTH then goes and causes your adrenals which sit above your kidneys and your lower back to release cortisol. A so-called stress hormone, but I would like you to think about cortisol not as a stress hormone, but as a hormone of energy. This is a situation in the brain of body whereby you want to move and whereby you don't want to rest and whereby you don't want to eat at least at first.
Epinephrine, we're adrenaline 101 in less than two minutes. When you sense a stressor with your mind or your body senses a stressor excuse me from a wound or something of that sort. A signal is sent to neurons that are in the middle of your body. They call the sympathetic training ganglily.
They don't necessarily matter. They release an weapon very quickly. It's almost like a sprinkler system that just hoses your body with an effort. That will increase heart rate, increase breathing rate.
It will also increase the size of vessels and arteries that are giving blood flow to your vital organs. You also release adrenaline from your adrenals, again, sitting right on top of your kidneys. You release it from an area of your brain called locus, or release, and that creates a alertness in your brain. So we have cortisol and we have Epinephrine and their net effect is to increase energy.
So the first tool is to make sure that your highest levels of cortisol are first thing in the morning when you wake up. One way or another, every 24 hours you will get an increase in cortisol. It's to stimulate movement from being sleep, presumably horizontal, to getting up and starting to move about your day. The best way to stimulate that increase in cortisol at the appropriate time is that very soon after waking, within 30 minutes or so after waking, get outside, view some sunlight.
Even if it's overcast, get outside, view some sunlight, no sun glasses, do that. Because in the early part of the day, you have the opportunity to time that cortisol release. So early part of the day, it will improve your focus, improve your energy levels, and it will improve your learning throughout the day. So here's how it works.
On a sunny day, so no cloud cover provided that the sun is not yet overhead. It's somewhere low in the sky, but it just costs the rise and if you wake up a little bit later, it could be somewhat low in the sky. Basically, the intensity of light, the brightness is somewhere around 100,000 locus. It's just a measurement of brightness.
On a cloudy day, it's about 10,000 locs. So 10 fold reduction. But bright artificial light, very bright artificial light, is somewhere around 1,000 locs. So even though you have a very bright ball, so you're right next to you, that's not going to do the job.
Your phone will not do the job. Not early in the day. To get the cortisol released at the appropriate time, you need to get outside. So let's just set a couple of general parameters.
If it's bright outside and no cloud cover, get outside for 10 minutes. If it's a cloudy day, dense overcast, you're probably only about 30 minutes. If it's light cloud broken cloud cover, it's probably going to be somewhere between 10 and 20 minutes. This is why it's vital to get this light on a regular basis.
To get that cortisol release early in the day. That sets you up for optimal levels of energy. Now throughout the day, you're going to experience different things. Most of you are not spending your entire day trying to optimize your health.
Some of you might be, but most of you have jobs, families, and commitments, life enters the picture and provides you stressors. Those will cause increases in cortisol and have an effort. The key is, these blitzing cortisol and epinephrine need to be brief. You can't have them so often or lasting so long that you're in a state of chronic cortisol elevation or chronic epinephrine elevation.
This system of stress was designed to increase your alertness and mobilize you towards things, get you frustrated and provide the opportunity to change behavior. And the reason it works is that cortisol, when it's released into the bloodstream, it actually combines receptors in the brain. It's also important to understand the amygdala, the neuroficity of brain ability changes off and responds to experience. First stimulated by attention and focus, and often at a level of state of agitation.
So understand that and you won't be quite troubled about the stress increases that you experience throughout the day. There are ways to leverage stress, epinephrine, cortisol, and ways that serve you and do it in a deliberate way. There are also ways to do that that increase your level of stress threshold, meaning they make it less likely that epinephrine and cortisol will be released. So I want to talk about the science of those practices.
I can ask about these practices a lot. I can also call two more breathing, things like ice baths, things like high intensity interval training. All of those things have utility. The question is how you use them and how often you use them.
Those tools, just like stress from a life event, can either enhance your immunity or deplete it. That's right. Those same practices of ice baths, two more breathing, high intensity interval training or training of any kind can deplete your immune system or it can improve them. Excuse me, they can improve it, meaning they can improve your immune system.
The key is how often you use them and when. And so I want to review that now in light of the scientific literature, because in doing that you can build practices into your daily or any other day routine that can really help buffer you against unhealthy levels of cortisol and epinephrine. In every single level of cortisol and epinephrine, cortisol increases at a much too great or that lasts too long. Epinephrine increases at a much too great or that lasts too long.
Let's say somebody tells you something very troubling, or you look at your phone and you see a text message that's really upsetting to you. That will cause an immediate increase in epinephrine adrenaline in your brain and body. And chances are it's going to increase your levels of cortisol as well. Let's say you get into an ice bath or cold shower.
That will cause an equivalent increase in epinephrine and cortisol. Let's say you go out for high intensity interval training. You decide you're going to run some sprints, if you use them repeats, or you're going to do some weightlifting in the gym or you decide you want to do some hot yoga, you're going to increase your epinephrine and cortisol levels. And guess what?
They increase your levels of energy and alertness. It can be beneficial for how you get clearance from your doctor to have some sort of protocol built in your day where you deliberately increase your levels of epinephrine and your levels of cortisol. So it's really important to understand that the body doesn't distinguish between a troubling text message, ice, tumor breathing, or high intensity interval training or any other kind of exercise. It's all stress.
Cognitively refraining that and telling yourself I like to say, I enjoy it. It's not going to change the way that that molecule impacts your body and brain. I sort of chuckle because people would love to tell you that all you have to do is say, oh, this is good for me. No.
What it does to tell yourself that it's good for you or that you enjoy it is that it liberates other molecules like dopamine and serotonin that help buffer the epinephrine response. Now, the way that does that I talked about previous episode about this mention that dopamine is the precursor to epinephrine. Epinephrine is made for dopamine. And that's why if you tell yourself you're enjoying something and because dopamine is subjective that you can in some ways, it's not completely line yourself, you can get more epinephrine, you get more mileage or more ability to push through something and you can sort of reframe it, but it's not really cognitive reframing.
The cognitive part is the trigger, but it's a chemical substance that's actually occurring there. It's dopamine giving you more epinephrine, a bigger amplitude of epinephrine release, and it gives you some sense of control. So here's a protocol that anyone can use if you want to increase levels of energy to suffer from low energy during the daytime, or whenever it is that you like to be alert. Pick a practice that you can do fairly consistently, maybe every day, but maybe every third day or every fourth day, maybe it's a nice bath or a cold bath, maybe it's a cold shower, maybe it's the sick like inhale exhale breathing protocol.
It's right. It wasn't clear and people are just, I'm not going to do the whole thing right now, but I'm only going to do a few rounds of this or a few cycles I should say. So it's inhale. I would do that more deeply more like you do that 25, 30 times repeatedly.
You will start to feel warm. People in the go get communicate that you're generating. You're not generating heat releasing adrenaline. Inhale exhale, inhale exhale 25, if you feel agitated and stressed, that's because you're releasing adrenaline in your body and that's because you're releasing an or epinephrine in your brain and you'll be more alert.
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Again, that's drink AG1.com slash humorman to claim that special offer. So if all these protocols, all these activities are just equivalent, they're just stressed, then how do we make them good for us? How do we actually benefit from them? Now of course, the cold itself can have some health-promoting effects that can increase brown fat.
They're mechanisms of metabolism, high-intensity interval training or other forms of exercise. Of course, has cardiovascular effects that can be good for us. That's great training, etc. But what we're talking about here are ways to increase energy and to teach our brain and body to teach ourselves how to regulate the stress response.
So in addition to the benefits of the actual practices, what we're talking about is building a system so that when you experience increases in epinephrine and cortisol from life events, you're able to better buffer those. And we are also talking about ways that you can increase energy overall because that's what today's episode is all about energy and immune system. There's a biological mechanism that's very important if you want to do those things, increase energy and your immune system on demand, learns about for stress on demand in real time. And it means taking these protocols, these practices, whether or not it's cold water or ice bath or exercise or any of those and making one small but very powerful adjustment in how you perform them.
But in order to make that adjustment, I can't just tell you the adjustment. I have to tell you the mechanism so that you know if you're doing it correctly or not. This is really case where if you understand a little bit of mechanism, you will be far better off than just adopting protocols. Cortisol, as I mentioned, is released from the adrenals.
It can have action both in the body and in the brain. Cortisol can cross the blood brain barrier. Epinephrine cannot. That's one of the reasons why it's released both from the adrenals in your body and release from this brain stem area that looks to release in your brain.
That's a powerful thing because what it means is that the body can enter states of readiness and alertness while the mind remains calm. So I'm presuming at this point that you're getting a morning light at the time your cortisol entries. I'm presuming that you want more energy or that you want to increase your immune system. It's function and it's ability to combat infections of various kinds.
Now, the simplest way to describe how to do that would be in the context of cold water or breathing protocol. Let's presume cold water. So let's say you decide to take a cold shower. You get into the cold shower and if it's cold enough, that will be stressful.
You will experience an increase in epinephrine. You will increase your alertness. Now, using this as a practice as a tool to build, you could call it resilience with the ability to stay calm in the mind while being stressed in the body. Epinephrine's in the body.
And you do that by subjectively trying to calm yourself. You can do that by telling yourself it's good for you by emphasizing your exhales. Anything that you can do to try and stay calm despite the fact that you're in a heightened state of alertness. You do this with exercise, you do this with music.
Pretty much anything that will give you a really heightened state of alertness offers you the opportunity to try and stay calm in the mind. What you do at a mechanistic level is to have adrenaline released from the adrenals, but not have adrenaline epinephrine released on the brain stem to the same degree. So you're not just trying to buffer this. You're not trying to go from being able to grind this out.
You're not trying to grind it out. You're trying to move through this calmly while maintaining the alertness. In the immediate period, following that practice, your system, your entire brain and body are different. Your body is actually primed to resist infection when you have high levels of epinephrine in it for short periods of time.
So the scientific study that explored how increasing adrenaline in the body can improve immune resistance is grounded in a well-known phenomenon that increases in stress actually protect you against infection in the short term. So I want to look at the classic day of first, describe what was done, and then I want to talk about the more recent study, which is immediately actionable. There are classic set of studies that are really based mainly on the work of somebody named Bruce McEwen who was at Rockefeller University of New York. I'm not going to go through all the details of the study, but essentially what they were doing was exposing subjects to some sort of infection, either bacterial or viral infection, and inducing stress.
Sounds like a double whammy, right? You think that maybe getting a little electric-foot shock or cold water exposure, or something to increase your levels of stress in adrenaline would just make the effects of infection worse, but no, quite the opposite. Brief bouts of stress, which now you should be thinking about in terms of cortisol and epinephrine release, were actually able to increase immune system function. The duration here is really important because of stress day too high for too long, then yes, indeed stress can hinder the immune response.
But for a period of about one to four days it actually can protect you by way of increasing the immune response. There's a human study that I definitely want to point out to you because it was published more recently than the McEwen work. The title of the paper is voluntary activation of the sympathetic nervous system. That's the system that causes fight or flight and AKA stress.
This is Cox K-O-X at all, P-N-A-S, Bruce's National Academy of Sciences 2014, and they incorporated the ever famous Wim Hof breathing. Here's what they did. They injected people with E. Coli, and they had groups that either did the sorts of breathing out of the striving that increased adrenaline release.
Although I should say, I don't think you need that breathing to get adrenaline release. You could do what Coli exposure you could do with other things, high-density energy as well. And what they found was that the response to the E. Coli was quite different in the people that had a protocol, and this is breathing, to increase adrenaline.
So this is a remarkable study because what they found was that the fever, the vomiting, all the negative effects of E. Coli, many of them, and some cases, all of them were greatly attenuated by way of engaging the adrenaline system. The point is you can control your immune system by finding a way that you can increase adrenaline. And this runs counter to what we always hear, which is don't get too stressed or you will get sick.
Learn to control adrenaline, turn it on and turn it off. Learn to control cortisol, turn it on with light in the morning, turn it off, and then when it spikes, because of light events, learn to turn it off. Learning to turn it on and off adrenaline, aka epinephrine, and learning to turn on and off cortisol, affords you the ability to turn on energy and focus in your immune system. That's the most important point for today's podcast.
And understanding that it doesn't matter what protocol you use. Maybe it's a coffee and running up a hill five or six times. That will improve your immune system function if you get adrenaline in your system. You can use a high-spat.
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I'm talking about increasing energy and increasing immune system by way of cortisol and epinephrine, but I'd be totally remiss if I didn't cover how cortisol and epinephrine, if chronically elevated, or elevated too high, can have a lot of detrimental effects. Your immune system over time will get battered and you won't be able to fight infection off as well. You can start laying down this over a classic pattern. Of course, I'll induce body fat.
Why do we seek high fat and or high sugar foods when we are stressed for a while? Why would that be? And the reason is that the cyclic luke of corticoids, of which cortisol is a glucocorticoid. It's caused as we mentioned before by leasing hormones from the brain and ACTH from the pituitary, etc.
But, normally high levels of glucocorticoid shut off the releasing hormones in the brain and the pituitary. They shut down in an so-called negative feedback loop. Chronic stress, however, stress that lasts more than four to seven days. Causes changes in the feedback loop between the adrenals and the brain and the pituitary, such that now the brain and the pituitary respond to high levels of glucocorticoid cortisol by releasing more of them.
It becomes a positive feedback loop. And that's bad. It's a cascade of stress equals more stress equals more stress. So it's very important to learn to turn off this response.
So there's one study that Dominar colleagues did where they stimulate chronic stress by increasing cortisol and cortisol. And they found that subjects would increase their consumption of sugar and fat. So it would even be ignored. And that led to all sorts of things like type 2 diabetes, this function in the adrenal output, etc.
And so the real key is to learn to shut off the stress response. And you should watch yourself next time you experience stress. It's a short term bad as stress. Typically it blocks hunger.
If it's a longer bad as stress typically it triggers hunger, impritulively, so-called comfort food, sugar and fatty foods. Other bad effects of stress is that yes indeed stress can make you go gray. Pigmentation of hair, just like the mutation of skin, is controlled by melanocytes. Well, it turns out that activation of the so-called sympathetic nervous system, which is really just another name for the system that liberates adrenaline from the adrenals and epinephrine in the brain, drives the patient of melanocytes in hair stem cells.
So indeed there's a rate of aging that we will undergo based on our genetics. But stress will make us go gray. How do I know difference between chronic acute stress and how do I keep chronic stress at bay? Once again getting your light and your feeding and your exercise and your sleep on a consistent schedule or consistent ish is going to be the most powerful thing you can do in order to buffer yourself against negative effects on mental health and physical health for that matter.
There are things that one can take supplement prescription drugs, etc. All supplements of course have to be checked out for their safety margins for you because they get a different person person you're responsible for making sure they're safe for you if you decide to use them. One of the most common ones is ashwaganda. It has a very strong effect on cortisol itself.
The decrease in cortisol in humans is 14.5 to 27.9% reduction in otherwise healthy but stress humans. The other compound that I think deserves attention is apigenin, api, g-e-e-n-i-n-appigenin which is what's found in kimamile. I take it before bedtime, 50 milligrams. The major source of action is to calm the nervous system and it does that primarily by adjusting things like that.
But in chloration it also has a mild effect in reducing cortisol. So ashwaganda and apigenin together I would consider the most potent commercial compounds that are in supplement non-prescription form that one could use if they were interested in reducing chronic stress especially late in the day by way of reducing cortisol late in the day. So if you're getting the impression that cortisol and apinephrine are a bit of a double-edged sword you want them elevated but not for too long or too much. You don't want them for days and days and days but you do want to have a practice in order to increase them in the short term.
So we should talk about protocols that can set a foundation of cortisol and apinephrine that is heading towards optimal. Optimization is always going to be a series of regular practices that you do every day. So sleeping at certain times, light at specific times, food at specific times, certain foods etc. And that's how you individual with there are some universals and we cover a number of those in the discussion today.
Meal timing. Meal schedules has a profound effect on energy levels. And as I mentioned before the energy I'm referring to is not glucose energy. So what I'm talking about is neural energy, apinephrine and cortisol.
So fasting and timing, eating are two sides of the same coin. When our blood glucose is low cortisol and apinephrine are going to go up. Anytime we have an eaten for four to six hours, levels of apinephrine cortisol are going to go up resubentially. One thing that many people do to great benefit is they follow a so-called circadian eating schedule.
The eat only when the sun is up, they stop when the sun is down. More or less. The other way to think about this is they stop eating a couple hours before sleep and they eat more less upon waking us when they're waking up more or less around the sun rises and then plus or minus two hours. Now let's say you decide to do what I do which is I skip breakfast.
I drink water, I drink water, I drink coffee and I drink for 90 minutes or two hours and then I drink my caffeine. And then my first meal is typically around lunch, 11, 30 or 12. So cortisol increase, I got something in the morning, so I'm getting a big pulse and energy early in the day. And yes, there's a little bit of agitation.
I am hungry sometimes early in the day, sometimes no. But my adrenaline system is used to kicking in right around noon. At the point where I eat, as long as I don't eat carbohydrate, in my case, I know that my apinephrine levels are going to stay for you high. So for me, it's usually meat and salad or something of that sort of fish and salad.
So fasting is a tool for many reasons. It increases growth hormone, et cetera. But today, I'm talking about fasting as a tool to buy a seer system toward more apinephrine adrenaline release and toward more cortisol release. But still low enough that it's not chronic stress, that it's not causing negative health effects.
So I'm going to learn how to regulate these hormones with behavior with nutrition, perhaps with supplementation. I also want to mention again that I think there's great benefit to having a practice that perhaps you do every other day, but if you can't maybe ever read third day or every other day, of deliberately increasing your adrenaline in your body while learning to stay calm in the mind so that you learn to separate the brain body experience. The idea is to stay calm in your mind so that you can regulate your action. So once again, we covered autonomic material.
I hope right now you're thinking, okay, am I in a state of chronic stress? Am I under activated? Or could I afford to increase my levels of adrenaline cortisol to improve my relationship to my immune system and to energy, neural energy. And I hope that you'll think about some of the ways in which cortisol and adrenaline are not good or bad.
It stresses and good or bad, but short-term stress is healthy. Alertness and energy is healthy even if it puts you at the edge of agitation. That's an opportunity to learn how to control these hormones better. And I hope that if you're in a state of chronic stress that you'll do things to start tamping down some of that stress.
And that you realize that your nervous system and your hormones system are linked, but there are linked in ways that you can control. We don't have to be slaves to our hormones. And certainly not the hormones that cause a stress. We can learn to control those both at the benefit of our body and benefit of mind.
Thank you for joining me for what I hope was an informative discussion and an actionable discussion about how to increase energy and immune system by way of cortisol and adrenaline. I really appreciate your willingness to learn new topics as well as to embrace and think about new tools and whether or not they're right for you. And as always, thank you for your attention.