Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I’m Andrew Huberman, a professor of neurobiology and ophthalmology at Stanford School of Medicine. This podcast is separate from my teaching and research roles at Stanford, but is part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public.

In keeping with that theme, I’d like to thank the sponsors of today’s podcast. Our first sponsor is InsideTracker, a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and reach your health goals. I’ve long been a fan of doing blood tests and more recently as they’ve been developed also DNA tests, as so many of the factors that impact our immediate and longterm health and inform our health choices can only be analyzed by way of blood or DNA tests. The great thing about InsideTracker is they make getting the blood and DNA test extremely easy.

InsideTracker offers a convenient and comprehensive way to access your health information. With their services, they provide clear directives on how to use that information to optimize your health. They provide insights on exercise, nutrition, and supplements and their plans can be accessed at insidetracker.com/huberman with 25% off by entering Huberman at checkout. Today’s episode is also brought to us by Athletic Greens.

Athletic Greens is an all-in-one vitamin, mineral, and probiotic drink that I have been taking since 2012. I’m delighted that they are sponsoring the podcast. Taking Athletic Greens once or twice a day covers all of my nutritional, vitamin, mineral, and probiotic needs. It can be hard to get vitamins, minerals, and probiotics from food on a consistent basis, especially when I’m working a lot, when stress and sleep aren’t optimized, etc. With Athletic Greens, I make sure to get all of the things I need and then any other supplements I take or what I eat can be considered additional insurance. The great thing about Athletic Greens is that it tastes great. I like to mix mine with water and a little bit of lemon juice. I take it once early in the day and then sometimes again in the afternoon.

Headspace makes it easy to stay consistent with my practice.

The fact that Athletic Greens includes probiotics is really important to me. There are so many data now pointing to the fact that probiotics, gut-brain health, and gut health generally are very important for metabolism, hormone output, neurotransmitter production, and many other vital things related to our health. Athletic Greens makes it easy to make sure I’m getting everything I need in the vitamin, mineral, and probiotic department. If you’d like to try Athletic Greens, you can go to athleticgreens.com/huberman and claim a special offer. They’ll give you five free travel packs, plus a year supply of vitamin D3 and K2. There’s now a ton of data pointing to the fact that vitamin D3 and K2 are important for a huge number of health-related factors, including hormones and metabolic factors. So, they have the year supply of vitamin D3 completely free along with your Athletic Greens offer, and you get the five free travel packs.

Today’s episode is also brought to us by Headspace. Headspace is a meditation app that makes meditation easy. I started meditating many years ago, but I found it was difficult to stay consistent with my practice. Headspace makes it easy to stay consistent with my practice.

I learned about Headspace a few years ago on Jet Blue Flights when they had them included as an option of whether or not to watch a movie, or a television show, or do meditation. I tried the meditation and I really liked it. It was very easy to follow along with a Headspace meditation. The meditations that they include on the Headspace app are also backed by dozens of peer reviewed quality independent studies. And of course, there are now thousands of peer reviewed quality studies pointing to the fact that a meditation practice is beneficial for improved sleep, reducing stress, and a number of other health metrics, such as cardiovascular disease risk, et cetera.

When I was stressed or really busy, I tended to drop the meditation practice and run around doing other things. This was really a kind of catch 22, as that’s when I probably needed the meditation practice the most. The great thing about Headspace is that it has allowed me to stay really consistent with my meditation practice. They have meditations of different duration and type, so you never get bored.

I actually look forward to my meditation practice and it continues to benefit me. In fact, since starting Headspace, I’ve been consistent with meditation for much longer than I ever had previously. If you want to try Headspace, you can go to headspace.com/specialoffer and you’ll get a free one month trial with Headspace’s full library of meditations for every situation. That’s their best offer out there right now.

Today, we’re going to continue our discussion about hormones and we’re going to focus on how particular hormones influence our energy levels and our immune system. Last episode I mentioned at the end that we were concluding our month on hormones, but we decided to include this additional episode, so this would be the fifth episode in the sequence of episodes about hormones.

Because there are two hormones which are vitally important for a huge number of biological functions that we will talk about today, but that are particularly important for energy levels and your immune system. This is something that I get asked about a lot. So rather than skip to the next general topic, today we’re going to talk about the hormones cortisol and epinephrine (also called adrenaline).

Today’s podcast will cover the biology of cortisol and epinephrine. We’ll discuss the mechanisms and provide tools for those who struggle with stress and energy levels. We’ll also talk about how to enhance the function of the immune system, as well as topics related to learning and memory. We’ll discuss so-called nootropics, smart drugs and how they work, as they are related to the epinephrine system.

Caffeine has the potential to rewire our brains for better or worse. We’re going to explore the biology of comfort foods and how they affect our energy levels in the short and long term. We time-stamp every episode and caption them in English and Spanish. It may take a couple days for the captions to appear on YouTube, so please be patient. If you have any questions during the episode, please put them in the comment section.

Subscribing to the channel is a great way to stay up-to-date on the latest tips and tricks for increasing energy and improving immunity. In this episode, I’ll cover three topics that I promised to mention in previous episodes: intermittent fasting, why your stomach grumbles, and a powerful way to increase growth hormone.

First, let’s talk about intermittent fasting. Last episode, I discussed how growth hormone and thyroid hormone can be increased through sauna, exercise, sleep, and other activities. Increasing growth hormone can be beneficial for burning off body fat, improving muscle and tissue health, and improving cartilage health.

Next, let’s talk about why your stomach grumbles. I forgot to mention the biology of this last time, so I’ll cover it now.

Finally, I’ll discuss a powerful way to increase growth hormone without using a sauna or wrapping yourself in plastic bags and going for a jog. This can help with increasing metabolism, fat burning, and tissue repair.

Fasting increases growth hormone levels due to the release of the hormone ghrelin. This was discovered through a study which we will link to. It was previously discussed in a podcast about hunger and timing of meals and hunger, that when you’re hungry, ghrelin is released in the body. Ghrelin is sometimes referred to as the hunger hormone. Despite many claims online that intermittent fasting leads to increases in growth hormone, very few studies were found to back this up.

Ghrelin is a hormone that makes you hungry when your blood glucose, or blood sugar, is low. It binds to the receptor in the brain that usually binds growth hormone releasing hormone, which in turn stimulates growth hormone. Studies have shown that fasting can increase growth hormone levels by up to double in the waking state. It is not as effective as taking growth hormone or using a sauna, but it does have an effect. Later in the episode, we will discuss different patterns of fasting and eating that can control epinephrine, such as how long to fast for and how many days.

Fortunately for people like me who love to eat, that’s not the case. We also said we’re going to talk about tummy grumble – when your stomach growls it is not because of fluid sifting around in there. A lot of people think, “Oh, you know it’s fluid sifting around.” Turns out that your stomach has smooth muscle that lines its sides and when you eat something or you don’t, every once in a while your stomach cinches off at the two ends like a bag with a hose on either end, ‘cause that’s essentially what your digestive system is. And if there’s nothing in there, what happens is the muscles that line the sides of your stomach they kind of extend around the stomach and these cables, those are always there and if you have food in your stomach, what they do is they churn your stomach. They literally turn the muscles of your stomach like a tumbler to help break up the food that presumably you didn’t chew well enough ‘cause you were eating too fast. When you don’t have any food in your stomach, that churning continues. And that contraction of the muscle, the turning, literally turning over of your muscles, they don’t flip over completely, but the turning over of the muscles, that’s what causes the stomach growling. If you don’t want to be the person in the meeting, or sitting there at a quiet theater whose stomach is growling, chew your food better. We’ll talk specific fasting protocols later in the episode.

Sauna is the simple solution for increasing growth hormone release. Last episode, I talked about how controlled, safe hyperthermia can cause huge increases – anywhere from 300 to 500, and even 1600% increases. I also pointed out that many people don’t have saunas in their homes, and would have to find other ways to safely increase their body heat, such as creating a steam room in their bathroom or jogging with extra sweats.

Many of you asked about hot baths and whether they increase growth hormone. Hot baths will increase growth hormone, however the temperatures that are needed for this are high enough that there is a risk of burns. I cannot make any recommendations about hot baths, but if you can tolerate a nice hot bath, you will get some growth hormone release.

The sauna has the advantage of allowing you to enter a 175 degree or 200 degree environment safely, provided you are not pregnant or a young child. This will lead to big increases in growth hormone.

Hot baths can lead to lesser increases in growth hormone. Temperature regulation is an important topic that will be discussed in a future episode, but caution should be taken when playing with hyperthermia or hypothermia. Cold baths, ice baths, hot showers, and hot baths beyond what is comfortable should be done with the advice of a doctor.

Most people want to have energy during the day and have it taper off at night, as well as a healthy immune system to ward off infections. The two hormones that dominate these processes are cortisol and epinephrine (also known as adrenaline). In the body, adrenaline is called adrenaline and in the brain, it is called epinephrine.

I’m sorry for that. I didn’t create this naming system and the story behind it is uninteresting and not worth our time. I will use the words adrenaline and epinephrine interchangeably today and cortisol is cortisol.

I just want to cover a little bit about what cortisol and epinephrine are, where they are released in the body and brain. If you can understand that, you will understand better how to control them.

Cortisol is a steroid hormone, much like estrogen and testosterone, in that it is derived from cholesterol. This cholesterol could be dietary cholesterol, the fats that you eat, or it could be cholesterol produced by the liver. The relationship between dietary cholesterol, the fats that you eat, and blood cholesterol and liver cholesterol is a very controversial one.

Dietary cholesterol is a barbed wire topic, with people claiming it has zero impact on circulating cholesterol from the liver, and others arguing the exact opposite. There are some issues with the idea that all cholesterol levels are determined by dietary intake. For example, anorexics often have very high levels of cholesterol that their liver produces, even when they are eating very little or nothing at all. Cholesterol is a precursor molecule, meaning it is the substrate from which testosterone, estrogen, and cortisol are made. Cortisol is a competitive partner to estrogen and testosterone, so when a person is stressed more of the cholesterol is devoted to creating cortisol. It is important to note that cortisol is vital and that low cortisol levels can be problematic.

It is very important for immune system function, memory, and mental health to keep cortisol levels in check. We will discuss how to control the timing and levels of cortisol. Epinephrine, or adrenaline, has been demonized as the stress hormone, but it is actually your best friend when it comes to immunity, remembering things, and activating neuroplasticity. We will explore why this is the case.

Cortisol and epinephrine (also known as adrenaline) are essential hormones that can be both beneficial and detrimental depending on how much and how long they are released for. We can provide tools to help regulate them better. Cortisol is made by the brain when it releases corticotropin releasing hormone (CRH). This then causes the pituitary gland to release ACTH, which in turn causes the adrenals to release cortisol. Rather than thinking of cortisol as a stress hormone, it is better to think of it as a hormone of energy. Epinephrine is also produced by the brain, and is important for providing energy, as well as increasing heart rate and blood pressure.

When we sense a stressor, neurons in the sympathetic chain ganglia quickly release norepinephrine. This is like a sprinkler system that hoses our body with epinephrine, increasing heart rate, breathing rate, and constricting our blood vessels. At the same time, it will also increase the size of vessels and arteries that are giving blood flow to our vital organs. This is why our extremities get cold when we’re stressed and our heart is beating faster, as more energy is devoted to our core.

Adrenaline is released from the adrenals, located on top of the kidneys. This creates alertness in the brain from an area called the locus coeruleus. If the listener would like to learn more about the stress response and how to regulate it, they can listen to the episode about stress. The episode will touch on some of the same themes, but it is focused on energy and the immune system. Cortisol and epinephrine have the net effect of increasing energy.

I want to give you a tool that will help you regulate cortisol and can also help stave off certain patterns of mental illness. Of course, it is not going to cure mental illness on its own, but it can support a healthy state of mind and can help reduce unhealthy states of mind, including depression. The first tool is to make sure that your highest levels of cortisol are first thing in the morning when you wake up. Every 24 hours, you will get an increase in cortisol, which is non-negotiable and written into your genome. This increase in cortisol is there to wake you up and to make you alert, and to stimulate movement from being asleep to getting up and starting to move about your day. To stimulate this increase in cortisol at the appropriate time, soon after waking within 30 minutes or so, get outside and view some sunlight, even if it’s overcast. Do this for two to 10 minutes, depending on how bright it is. This has been backed by peer reviewed studies, and will improve your focus, energy levels, and learning throughout the day.

Getting sunlight on even cloudy days is vital to prevent a late shift in cortisol increase, which is a signature feature of many depressive disorders, including major depression, anxiety and insomnia. I mentioned in the episodes on sleep that brightness of light in regulating cortisol and sleep can be measured using lux, but I was not specific enough. Going outside and getting some sunlight requires that I also tell you how long and under what conditions. It takes 50 times longer to get as much light when looking through a window than going outside.

On a sunny day, provided that the sun is not yet overhead, it’s somewhere low in the sky. It could have just crossed the horizon, or if you wake up a little bit later it could be somewhat low in the sky. The intensity of light, the brightness, is somewhere around 100,000 Lux. Lux is a measurement of brightness. If you want to measure the brightness, you can download the app Light Meter which is a free app that will allow you to do that. It is not perfect, but it is pretty good and it is zero cost. I have no relationship to Light Meter the company.

On a cloudy day, it’s about 10,000 Lux. Very bright artificial light is somewhere around 1000 lux, and ordinary room light is somewhere around 100-200 lux. This is due to the amount of light scatter present. Even if you have a very bright bulb sitting right next to you, it won’t be enough to get the cortisol released at the appropriate time. To do this, you need to get outside. Generally, if it’s bright outside and there is no cloud cover, the light can be indirect.

You don’t have to be staring into the sun, please don’t damage your eyes. We can’t regenerate those neurons yet and restore vision that’s lost, but if you have to blink, that means it’s too bright. It’s fine to blink of course, please do if you need to. To get the most out of the sunlight, it is recommended to get outside for 10 minutes, or five minutes should suffice, but 10 minutes is sure to suffice. If it’s a cloudy day, dense overcast, you’re probably going to need about 30 minutes. If it’s light cloud broken cloud cover, it’s probably going to be somewhere between 10 and 20 minutes. For those who can’t get outside or are on an airplane and it’s bright overhead, artificial lights or ordinary room lights, it’s going to take you about six hours of light. By the time you reach the middle of your wakeful period, it’s too late. You won’t be able to shift your clock and your cortisol will start drifting later and later. Therefore, it is vital to get this light on a regular basis, to get that cortisol released early in the day.

Getting sufficient sunlight first thing in the morning is the best way to make sure that you time your cortisol appropriately. This is important for optimal levels of energy and great sleep. Throughout the day, most of us have jobs, families, and commitments, so it can be difficult to focus on optimizing our health. However, having a healthy level of energy is essential to be able to move about, learn, and do various things. So please try to get that sunlight within the first hour if it is within your protocols to do so.

Life can provide stressors, such as a difficult coworker, not getting the raise or vacation you expected, or any other disappointment. This can cause increases in cortisol and epinephrine. It is important to understand that cortisol should be high in the morning, but then you can expect increases in cortisol and adrenaline throughout the day based on unpleasant events. For example, traffic and emails that ask you to fill out a form can stress someone out, even if they don’t lose their cool. However, it is key that these blips in cortisol and epinephrine should not last too long or be too frequent, otherwise you will be in a state of chronic cortisol or epinephrine elevation.

The system of stress was designed to increase alertness and mobilize us towards things, as well as to get us frustrated and provide the opportunity to change behavior. If we find ourselves getting stressed and staying stressed, there are tools such as the double inhale exhale and the physiological sigh that can help. The energy we experience during stress is actually a healthy hormonal and neural system working. Cortisol, when released into the bloodstream, binds to receptors in the brain, such as the fear centers, threat detection centers, and areas involved in learning, memory, and neuroplasticity. This is why neuroplasticity, the brain’s ability to change itself in response to experience, is first stimulated by attention and focus, and often a low-level state of agitation. Knowing this, we can be less troubled by the little stress increases we experience throughout the day.

There are ways to leverage stress, epinephrine, and cortisol in ways that serve you. To do this in a deliberate way, there are also ways to increase your level of stress threshold, making it less likely for epinephrine and cortisol to be released. I often get asked about practices like Wim Hof breathing (also known as tummo breathing), ice baths, and high intensity interval training. All of these have utility, but it is important to consider how you use them and how often you use them. The same practices that can enhance your immunity can also deplete it. It is important to be mindful of how you use these practices.

Excuse me, they can improve it, meaning they can improve your immune system. The key is how often you use them and when. In light of the scientific literature, I want to review how to build practices into your daily or maybe every other day routine that can help buffer you against unhealthy levels of cortisol and epinephrine. This means avoiding cortisol increases that are too great or that last too long, as well as epinephrine increases that are too great or last too long. There are numerous negative effects that come with having too much cortisol or epinephrine for too long, such as Cushing syndrome, abdominal fat accumulation, and sleep disturbances. I want to arm you with the tools to address these issues before talking about the dark side. If somebody tells you something troubling or you see a text message that’s upsetting, you can use the tools you have to address the situation.

When you do that, it will cause an immediate increase in epinephrine and cortisol in your brain and body. Even if you love or hate the cold, or you go out for high intensity interval training, weightlifting, hot yoga, or any other activity, you will increase your epinephrine and cortisol levels. There is simply no way around this. However, if you decide to sit down and do some deep breathing, it will still cause an increase in your epinephrine and cortisol levels. We all hear about the benefits of deep breathing, so it is important to remember that even with this activity, your levels will still increase.

You’re going to get big increases in epinephrine and cortisol when you engage in activities like high intensity interval training, weight training, and cold exposure. Multiple studies have supported this. While these activities may be stressful, you can cognitively reframe them as something positive. For example, you can tell yourself that you love exercising. Though getting into the cold doesn’t feel good, you can tell yourself that it is good for you and that you will enjoy it when you get out. All of these activities will increase your alertness and energy levels. In an upcoming episode, we will discuss how to do these activities in the optimal way.

If you struggle with energy and alertness, it can be beneficial to have a protocol built into your day to deliberately increase your levels of epinephrine and cortisol. This can be done by taking a cold shower or doing deep breathing exercises such as Wim Hoff or tummo type breathing. These activities can help to release adrenaline into your system and will give you more energy. It is important to understand that the body does not differentiate between different types of stress, such as a troubling text message, ice, tummo breathing, or high intensity interval training. Reframing the stress and telling yourself that you enjoy it can help. However, it is important to get clearance from your doctor before attempting any of these activities.

The way that a molecule impacts your body and brain is not going to change. I chuckle when people tell me that all I have to do is say “this is good for me” – no. What I tell myself is that I enjoy it, which liberates other molecules such as dopamine and serotonin that help buffer the epinephrine response. I have talked about this in a previous episode, but dopamine is the precursor to epinephrine, and cortisol is made from cholesterol. So, if I tell myself I’m enjoying something, it can increase my epinephrine level, as long as I’m not lying to myself. This is not really cognitive reframing, but a chemical substance that is occurring.

Dopamine gives you more epinephrine, resulting in a bigger amplitude epinephrine release which gives you a sense of control. To increase levels of energy, especially during the daytime or when alertness is desired, there is a protocol anyone can use. This practice should be done consistently, such as every day, every third day, or every fourth day. Examples of this practice include an ice bath or cold shower, or the cyclic inhale exhale breathing protocol. To demonstrate this protocol, one can do 25-30 rounds of inhaling more deeply and then feeling warm. People in the yoga community say this is generating heat.

Inhale and exhale deeply 25 or 30 times to release adrenaline and norepinephrine in your body and brain, making you more alert. Follow this with an exhale hold, holding your breath for 15 to 30 seconds. Always do this on dry land and never near water, as it can be dangerous. If you feel comfortable, you can do an inhale and hold. All these activities are just a form of stress.

Cold exposure and high intensity interval training, weight training, and other forms of exercise can have health promoting effects. These include increasing brown fat thermogenesis and metabolism, as well as cardiovascular effects. Additionally, these practices can help to build a system that can better buffer increases in epinephrine and cortisol from life events. Finally, there is scientific data to support that one can leverage specific protocols to increase their immune system on demand.

There is a biological mechanism that is very important if you want to increase energy and your immune system, as well as buffer stress in real time. This means taking certain protocols, such as cold water, ice baths, exercise, etc., and making a small but powerful adjustment in how you perform them. In order to make this adjustment, it is important to understand the mechanism, so you know if you are doing it correctly.

Cortisol is released from the adrenals and can bind to receptors in the body and brain. It can even bind to the amygdala, also known as the fear center, because it can cross the blood brain barrier.

Cortisol can be released in the body and cross the biological barrier, which is like a fence that keeps things out of the brain. However, cortisol has passing rights and can make it through. On the other hand, epinephrine is polarized and the shape of it prevents it from passing through the blood brain barrier. This is why it is released both from the adrenals in the body and from the locus coeruleus in the brain. This is powerful as it allows the body to enter states of readiness and alertness while the mind remains calm.

There are ways to do this, such as getting morning light to time the cortisol increase, and picking from the pallet of exercises or tools to increase epinephrine. Additionally, if one wants more energy or to increase their immune system’s ability to combat infections, this is also possible.

There are a lot of ways to increase adrenaline released from the body. Cold water, exercise, or confrontations with other people are all effective. At a biological level, it is identical. If you like to go online and place comments or read things that agitate you, you can use that as an opportunity. However, I suggest taking care of yourself and others in less destructive ways. The simplest way to increase adrenaline is through a cold water or breathing protocol. For example, a cold shower can be stressful and will increase epinephrine, alertness, and adrenaline.

Practicing resilience can help us stay calm in the mind while being stressed in the body. We can do this by telling ourselves it is good for us, emphasizing our exhales, and engaging in activities such as exercise or music. At a mechanistic level, we are trying to have adrenaline released from the adrenals, but not have epinephrine released from the brain stem to the same degree. We are not trying to grind it out, zone out, or distract ourselves; rather, we are trying to shift our cognitive relationship to the body stress response.

I’m sure some of you out there are shouting, “Yeah, that’s exactly like whatever, whatever, whatever.” I agree. This is in many ways a self-directed kind of stress inoculation, but we’re not talking about this as stress inoculation. We’re talking about this as a way to increase energy and focus.

The reason is that epinephrine when released in the body has a profound effect on the immune system and when released in the brain has a profound effect on the ability to learn and remember information and to be alert.

We’re talking about splitting the location, separating the location from which you have epinephrine, adrenaline released. So let’s say you are doing this practice simply to wake up, okay, cold shower will do that, exercise will do that.

The ability to stay calm in mind while having heightened levels of adrenaline and presumably cortisol as well in the body. But the cortisol is going to circulate everywhere.

Cortisol can be managed through self-soothing and calming techniques. When cortisol levels are high, the body is primed to resist infection. A scientific study has explored how increasing adrenaline in the body can improve immune resistance. This phenomenon is well known, as increased stress can protect against infection in the short term.

The classic data for this phenomenon is based on the work of Bruce McEwen, who was at the Rockefeller University in New York. His decades of work had a great impact. The more recent study is immediately actionable and can be used to help manage cortisol levels.

The work that has been done has explored how inducing stress can enhance the function of the immune system in the short term, lasting from one to four days. Subjects were exposed to some sort of infection, either bacterial or viral, and induced stress. Surprisingly, brief bouts of stress, which are associated with cortisol and epinephrine release, were able to increase immune system function. This makes sense when understanding how epinephrine works in the body and brain – it is the signal by which the nervous system can inform immune organs, such as the spleen, to go in combat infections. The nervous system provides the signal that liberates the killer cells and tells them there is a problem.

The duration here is really important because if stress stayed too high for too long, then it can hinder the immune response. However, for a period of about one to four days, stress can actually protect you by increasing the immune response. This effect is governed by epinephrine, adrenaline released from the adrenals and not from the brain, as they explored whether the effect exists in the presence of an adrenalectomy. Without the adrenals, this effect does not exist.

So, if you want to increase your immune system in the short term, you want to increase your epinephrine in the short-term. This can be done through short bouts of intense exercise, exposure to cold water, or cyclical breathing. Caffeine can also increase epinephrine and dopamine, but it should not be consumed chronically.

Caffeine can increase epinephrine levels, which can improve immune system function. This can be done by drinking caffeinated beverages such as coffee and tea, but also by breathing exercises, cold exposure, and exercise. It is recommended to do one of these activities two or three times a week, especially if you are in a setting with a lot of children or work in a healthcare setting.

I don’t want anecdotal data to ever be misunderstood as anything but anecdotal data. Anecdotally, I can say that I’ve had instances where I’ve felt a throat tickle coming on or some sinus infection, and I will do the cyclic breathing that I described before – 25, 30 breaths exhale hold, 25 30 breaths exhale hold, 25, 30 breaths exhale hold, and then big inhale hold. Most times I didn’t get full blown sick, but I also take other precautionary measures to get sleep, et cetera. So whether or not it was causal, or whether or not it’s just correlated I don’t know.

However, there’s a human study that I definitely want to point out to you, because it was published more recently than the McEwen work. It was published in the Proceedings of the National Academy of Sciences for the USA, because there are Proceedings of the National Academy of Sciences for many other countries as well. The title of the paper is “Voluntary activation of the sympathetic nervous system” – that’s the system that causes fight or flight AKA stress, and causes release of adrenaline – “and attenuation of the innate immune response in humans.” This is Kox et al. PNAS, Proceedings to the National Academy of sciences, 2014. coli endotoxin, which is a nasty, nasty little molecule that can make you very, very sick.

Wim Hof breathing is much like the breathing protocol that I’ve described several times now in this podcast. It is also called tummo breathing and other people from other cultures and communities have called it other things. The naming really isn’t important, although I do think Wim is a pioneer in trying to bring these practices to the general public more broadly and was involved in this study. The study was done in the Netherlands and was communicated by Dr. Tamas Horvath at Yale. I mentioned all that and Horvath is a terrific scientist, I’m familiar with his work over many years.

They injected people with E. coli endotoxin, which is a nasty, nasty little molecule that can make you very, very sick. Here’s what they did: they incorporated the ever famous Wim Hof breathing.

The people who engaged the breathing protocol had groups that did sorts of breathing to increase adrenaline release. They found that the response to the E. coli was quite different in these people. Remarkably, they found that the fever, vomiting, and other negative effects of E. coli were greatly attenuated by engaging the adrenaline system, in this case using breathing. They also looked at inflammatory cytokines such as IL-6, which were reduced. It should be noted that you don’t need to use the breathing protocol to get adrenaline release; other things such as cold exposure, high intensity interval training, etc. can also do the job.

IL-10, an anti-inflammatory cytokine, was increased. Additionally, there were some inflammatory cytokines that were increased. This leads to the point that you can control your immune system by finding a way to increase adrenaline. This runs counter to the common belief that stress will lead to illness. To control adrenaline and cortisol, one should learn to turn them on and off. For example, cortisol can be turned on with light in the morning and turned off when it spikes due to life events. This ability to control adrenaline and cortisol can turn on energy and focus in the immune system. Ultimately, this is the most important point from today’s podcast and it does not matter which protocol is used to get adrenaline in the system, such as a cup of coffee and running up a hill five or six times.

Using an ice bath or a cold bath can help to shut off an emotional response. Additionally, epinephrine and cortisol have powerful benefits on the brain, such as increased energy and improved learning. To make sure these hormones are released properly, it is important to get light exposure early in the day. This will increase energy levels throughout the day and time the release of thyroid hormone. For this reason, getting light exposure early in the day is a non-negotiable practice.

I try to get as much light exposure early in the day without fail. This helps to regulate my circadian clock, which is regulated by cortisol. This cortisol secretion begins to rise during sleep and peaks shortly after waking. This triggers the release of hormones for thyroid, which is important for metabolism and energy. It is very important to have thyroid in check, so I make sure to get the light exposure I need.

Epinephrine and cortisol are hormones that are released in response to stress. Everyone has a story of being so stressed that they couldn’t remember something, such as when sitting down to an exam. I personally experienced this once, where I completely blanked despite not being sleep deprived. It was very difficult to pull myself out of this situation, but I eventually managed to do it. Most people think of stress as an inability to perform, but most of the time increases in epinephrine (provided they are not through the roof) lead to improved performance.

Epinephrine has been shown to be beneficial for memory tests, learning new information, and physical performance. When blood levels of epinephrine are low, performance is not very good. However, when blood levels of epinephrine are high (up to about 1500 to 1700 pg/mL), performance increases significantly.

It is important to note that if one becomes too stressed, they may become too focused on their bodily response, rather than the task at hand. Epinephrine and cortisol are both nootropics, or smart drugs, that we make internally. However, this does not mean that one should have high epinephrine levels during an exam.

That’s going to increase your learning and memory.

Epinephrine increases immediately after learning can enhance memory and learning performance. The timing is essential, as it helps to consolidate the information and engage the proper mechanisms in the brain for neuroplasticity. This phenomenon is not necessarily evolved for us to do what we want and learn what we want, but it does allow us to do that. An example of this is when we are alert and primed after seeing a particularly gory accident. The adrenaline and epinephrine released into the brain and body increases learning and memory.

Not only will you not forget the event, but you will remember everything that led up to it. This is because your brain and body’s primary concern is safety, which is the neuro-biological explanation for Maslow’s hierarchy of needs. This leads to heightened awareness and alertness for everything that preceded the spike in adrenaline and cortisol.

If you need to learn something better, taking Adderall or a lot of coffee beforehand is actually driving the process in the wrong direction. This is because past a certain point, you are actually degrading learning and performance. The time to do this is toward the end or immediately after the learning, as this mechanism is not simply devoted to negative events, but works to make sure that the hippocampus, which encodes memories, is primed.

To ensure good learning, non sleep deep rest (NSDR) or a good night’s sleep after learning is recommended. Additionally, as the learning event tapers off, make sure that epinephrine levels are not tapering off as well. This may be one of the reasons why the 90 minute cycle (the so-called ultradian cycle for learning) works, as it takes a few minutes to get into the rhythm of learning.

It is no coincidence that podcasts are typically 90 minutes long. At the end of this time frame, you will start to feel fatigued as your body is no longer able to secrete epinephrine at the same level. To increase your alertness and memory for the information, breathing exercises, cold showers, ice baths, hard runs, or hit training can be used. After that, a non-sleep deep rest and a good night’s sleep will enhance the learning process.

Caffeine can be used to prime the learning process by drinking it towards the tail of the learning episode, which is counter-intuitive to many. I, myself, use caffeine in the form of coffee, mushroom coffee, and mate. Recently, a study titled “Habitual Coffee Drinkers Display a Distinct Pattern of Brain Functional Conductivity” was published in Molecular Psychiatry. The study found that drinking coffee chronically changes brain conductivity.

People who drank coffee habitually every day had changes in their brain circuitry, such that there was a shift or a bias toward anxiety even when they don’t ingest caffeine. It appears that caffeine increases connectivity between the brain areas that relate to anxiety, which could be a good thing or a bad thing depending on the individual. For people prone to chronic panic or anxiety attacks, it is not a good thing. However, some people might use caffeine in healthy ways, such as to increase overall levels of alertness. To maximize its benefits, one should delay caffeine intake for two hours after waking up and drink it later in learning and focus sessions as a way to enhance plasticity.

Nootropics generally fall into two categories: one that increase blood glucose and one that do not. The former can improve performance and enhance learning in some situations. The latter includes a cocktail of different things such as caffeine, culinary trick stimulation, etc. that are not tailored to the individual. I don’t particularly enjoy this topic because I don’t like the name “smart drugs”. It implies that there is only one kind of “smart”, when in reality there are many kinds such as creativity, task switching, strategy building, and strategy implementation. We will provide a link to the full paper online.

I’m not suggesting people take these things, but here’s just a list of a few of them. Some of them are legal, some of them are gray market, and some of them are illegal. Piracetam, oxiracetam, and aniracetam, all the Tams, elevate blood glucose, which is how they work. The neural effects that you hear are secondary or tertiary to the fact that they just increased blood glucose. We know this because if you block the blood glucose effect, you block the nootropic effect.

Others include, and definitely don’t take these please, amphetamine and cocaine. Those will increase learning in the short term in particular dosages, but because they increase blood glucose. Painful stimuli or stress will also improve learning by way of increasing blood glucose. Stress and epinephrine that’s associated with it not only improve performance during the learning about, but as I mentioned before, having epinephrine come up afterward will increase the retention of that information in the longterm.

We have discussed ways to increase energy and immune system function using cortisol and epinephrine. However, it is important to note that if these hormones are chronically elevated or elevated too high, they can have detrimental effects. Additionally, there is a whole category of nootropics that do not impact blood glucose, but instead work by increasing cholinergic system activity. These include choline, lecithin, Physostigmine, and phosphodiesterase. Therefore, there are other sources of energy than just food, such as neural energy, which is created by neurotransmitters that create alertness, focus, and the willingness and ability to move.

We normally hear about the negative impacts of stress, such as insomnia, weakened immune system, and increased body fat. To ameliorate these effects, there are ways to adjust cortisol and epinephrine levels, even when stressed. Additionally, there is a literature on why comfort foods are desired under conditions of chronic stress, which can help us better understand how to prevent or reduce the effects of chronic stress.

Mary Dallman’s work showed that when cortisol levels are high, we seek out comfort foods high in fat and sugar. This phenomenon is caused by a negative feedback loop, where high levels of cortisol shut down the releasing hormones in the brain and pituitary. Mary Dallman’s work at the University of California San Francisco showed that the hormones cortisol, testosterone and estrogen, when too high, are read out by neurons in the brain and pituitary, causing the production of these hormones to shut down. This feedback loop is what causes us to seek out comfort foods when we are stressed.

Chronic stress can cause a negative feedback loop between the adrenals, brain, and pituitary, leading to the release of high levels of glucocorticoids (e.g. cortisol). This can cause a cascade of stress, leading to further stress, and can even affect gene regulation and transcription. To avoid this, it is important to learn to turn off the stress response. Studies have shown that chronic stress can lead to increased consumption of sugar and fat; subjects have even been willing to eat lard. It is therefore important to reduce chronic stress in order to maintain health.

The real key to understanding the relationship between stress and food is to learn to shut off the stress response. Studies have shown that if the system is kicked into motion for too long, then a shift towards anxiety occurs. This is due to the fact that body fat receives neural innervation, which causes it to release hormones that in turn feed back to the brain and make us crave sugary and fatty comfort foods. Interestingly, short-term stress can actually block hunger by activating the bombesin system.

Bombesin is a peptide hormone named after some sort of toad, Bombina bombina. Initially, it was sequenced from the toad before it was discovered in humans. Bombesin reduces eating and stress liberates bombesin, making you want to eat less. However, chronic stress causes positive feedback changes, which amplify the stress response over and over. Short-term stress is great, but long-term stress is really bad and has other negative effects. To control these effects, you need to know that stress can make you go gray.

The rate at which people go gray depends on genetic factors. There are two ways in which people go gray. The first is due to the presence of a stem cell niche in each follicle. This stem cell produces more of the given hair cell which is made up of peroxide groups. The second way is due to the pigmentation of the hair which is controlled by melanocytes. Sunlight can increase levels of certain hormones which can reduce hunger and improve testosterone and estrogen levels. The sympathetic nervous system, which is responsible for the liberation of adrenaline and epinephrine, can also drive the depletion of melanocytes in hair stem cells.

There is a rate of aging that we will undergo based on our genetics, but stress can make us go gray. Recently, a paper from Zang et al in the Nature journal (2020) showed that the activation of stress in various forms will deplete melanocytes stem cells. You do not need to worry about an ice bath, hard exercise or breathing increasing your levels of stress to the point where you go gray – it is chronic stress that is the issue. To offset the stress effects on graying of hair, you can practice something that helps you regulate stress on a consistent basis, such as non sleep deep breath or meditation.

Having a practice to keep stress at bay and offset the negative effects of chronic stress is essential. Sunlight stimulates melanocytes, not just in skin, but in hair, so getting ample sunlight is important. Additionally, understanding the difference between acute and chronic stress is key. Chronic stress can lead to depression, elevated cortisol, and other negative effects. Therefore, it is important to have a practice in place to regulate stress.

Low thyroid hormone is associated with depression and having a consistent schedule of light, feeding, exercise and sleep is the most powerful thing one can do to buffer against negative effects on mental and physical health. Additionally, one can take supplements, prescription drugs, etc. For those with Cushing’s, a chronic elevation of cortisol, there are prescription drugs that can be used. Most people are dealing with a situation of fluctuating stress levels, and any stress that lasts more than a few days is considered chronic. My lab has done experiments measuring stress in people over time.

People vary tremendously in their ability to have a really hard day and then fall deeply asleep. That’s going to be the ultimate reset is the ability to sleep well more or less undisturbed each night, although one or two wake ups during the night, probably not going to be too detrimental provided they’re not too long, and you’re not viewing light during those wake-ups or your phone.

If you feel like you’re chronically stressed and you’re veering toward some of the negative effects of stress, there are some simple things that people can do in terms of supplementation. All supplements of course have to be checked out for their safety margins for you, because they going to differ from person to 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 Ashwagandha and it has a powerful anxiolytic anti-anxiety effect. You’re welcome to go to examine.com and for zero cost you can see their so-called human effect matrix. Ashwagandha has many uses. It’s been used to enhance power output in athletes, it has been shown to modestly increase testosterone, it has been shown to modestly adjust things like low density lipoprotein cholesterol, the so-called bad cholesterol in quotes.

Ashwagandha has been shown to have a profound effect on anxiety, with nine peer-reviewed, independent studies funded by organizations with no vested interest in the answer. It has a very strong effect on cortisol, with a reduction of 14.5 to 27.9% noted in otherwise healthy but stressed humans. Six studies have also indicated that the effect of Ashwagandha is significantly larger than many other supplements. Some people have raised concerns about taking Ashwagandha chronically, but if anyone has specific studies to indicate why it is not good, they should put it in the comment section or let the speaker know.

In the comment section on YouTube would be best. The studies that I’m referring to did explore both genders, with a reasonably high number of subjects (64 or more). The study was conducted over a period of one to six months, so these were long-term studies. That’s great, as it is preferable to see results from a long-term study rather than an acute study. Subjects included males and females of various ages, both overweight and non-overweight. Blood draws and saliva tests were conducted to measure cortisol levels, with saliva being the best way to measure free cortisol. It turns out that cortisol can also be measured from ear wax, which sounds gross but is nonetheless a valid method.

Ashwagandha may be beneficial for those dealing with chronic stress or a stressful period in their life. It has been found to reduce cortisol levels and depression, as well as low density lipoprotein. Additionally, research has indicated that it can lower C-reactive protein, which is a marker of negative health effects. Six quality studies have been independently supported and point to significant reductions in otherwise healthy adults. For more detailed information, readers can visit examine.com and search for Ashwagandha.

Cardiovascular health and macular degeneration are notably reduced due to heart palpitations being reduced. Serum T3 and T4, hormones from the thyroid, have increased from a previous episode. Symptoms of OCD, both obsessions and compulsions, have decreased. Obsessions are of the mind, while compulsions are of behavior. Lowering cortisol has many downstream benefits, such as lowered heart rate, insomnia, improved memory, decreased pain, increased quality of life, decreased reaction times, and more. All of these stem downstream of decreased cortisol.

If one were to decide to take ashwagandha in order to reduce cortisol levels, it is best to take it later in the day or in the evening. It is not known to cause insomnia and this was not listed as one of its major effects on examine.com. I, personally, take ashwagandha from time to time if I’m chronically stressed or am not sleeping well. Despite my knowledge about sleep and sleep protocols, I still struggle to get a solid night of sleep due to my dog’s sundowners. I take ashwagandha before sleep and with my last meal of the day, which is at least two hours before I go to sleep. Dosages can vary, so it is best to go with what is on the bottle from a reputable brand.

Examine.com mentions a range of dosages that people have used in various studies to different effects. It is important to remember that cortisol is made from the cholesterol molecule, as are estrogen and testosterone. Because of this, ingesting certain substances can increase cortisol and decrease estrogen and testosterone, as they are competitive. One such substance is liquorice, which contains a substance called glycyrrhizin. This substance increases cortisol, although not hugely, but it is significant.

Research has looked at the effects of stress on people of different ages, from 18 to 29 for both males and females, and from 30 to 64. It was found that serum cortisol, testosterone, and estrogen increased substantially, as well as blood pressure. This is due to cortisol increasing in order to engage the stress response. Other hormones associated with stress also increased. It was also discovered that licorice and some of the compounds in black licorice can increase stress, so it is not recommended to be ingested during periods of chronic stress.

Whether or not anyone has had positive effects of using licorice to increase cortisol and other contexts, let me know. It is very interesting that the chemistry of licorice increases stress hormones, and therefore we would probably want to avoid it in conditions of chronic stress. Additionally, if we are trying to optimize testosterone and estrogen, liquorice seems like a bad idea.

One instance where we might want to use licorice would be if we are traveling and trying to wake up at a particular location, because licorice has these effects on cortisol which is associated with the waking phenomenon, alertness, and energy. However, we should be careful to time it so that we are not getting two cortisol increases throughout the day.

We should also make sure to do all the other things correct for jet lag and adjusting to jet lag. These include timing our feeding, using temperature, using exercise, and using light to adjust to jet lag more quickly.

The other compound that deserves attention is apigenin, which is found in chamomile. Apigenin has been discussed previously.

Ashwagandha and Apigenin are two compounds that have been shown to have various effects. One is that it is a mild anti-estrogen. It also has an anxiolytic effect of reducing anxiety. I take 50 milligrams of it before bedtime, however, it is important to decide if it is safe for you or not. The major source of action is to calm the nervous system by adjusting things like GABA and chloride channels, and it also has a mild effect in reducing cortisol.

Ashwagandha and Apigenin together are considered to be the most potent commercial compounds in supplement non-prescription form that one could use if they are interested in reducing chronic stress, especially late in the day by way of reducing cortisol late in the day. Cortisol and epinephrine 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 up for days and days, but you do want to have a practice in order to increase them in the short term.

We should talk about protocols that can set a foundation of cortisol and epinephrine that is headed towards optimal. Optimization is always going to be a series of regular practices that you do every day, such as sleeping and eating at specific times. Certain foods have a profound effect on energy levels, which I’m referring to as neural energy, epinephrine and cortisol. Fasting and timing one’s eating are two sides of the same coin, even if you’re on a standard three meal a day diet. Whenever you’re asleep or not ingesting any calories, you are fasting.

Fasting is a great way to increase epinephrine. Anytime our blood glucose is low, cortisol and epinephrine are going to go up. While there are several different kinds of fasting, if we fast for too long, that is considered stress. However, this doesn’t mean it doesn’t have other beneficial effects. For example, running a marathon is considered stress, but it can also have positive effects. Therefore, it’s important to think about stress mechanistically, as epinephrine and cortisol. I will do an entire episode on optimizing food intake for performance in the sports context, but in the meantime, fasting is a great way to increase epinephrine.

Anytime we haven’t eaten for four to six hours, levels of epinephrine and cortisol are going to go up pretty substantially. There’s an exception to that, which is if you are used to eating on the clock every two hours or every hour being half hour late, or being even 10 minutes late on that schedule will induce stress, most of that psychological stress, but also the release of things like ghrelin that are going to make you hungry.

One thing that many people do to great benefit is they follow a so-called circadian eating schedule. They eat only when the sun is up, they stop when the sun is down, more or less. Another way to think about this is they stop eating a couple hours before sleep and they eat more or less upon waking, assuming that they’re waking up more or less around the time of the sunrises, maybe plus or minus two hours.

Skipping breakfast and delaying caffeine for 90 minutes to two hours is a habit I have. I typically don’t eat until lunchtime around 11:30 or 12:00. Occasionally, I will snack on almonds or walnuts earlier in the day if I’m feeling hungry or if I just happen to see them. I also have a habit of being a “drive by eater” and picking up blueberries or nuts and putting them in my mouth. However, I try not to do this off other people’s plates. I get a cortisol increase and energy boost early in the day from the sunlight.

I have a little bit of agitation sometimes early in the day, but my ghrelin system is used to kicking in right around noon. To maintain my epinephrine levels, I usually eat meat and salad, or something of that sort, or fish and salad (although I don’t particularly like the taste of fish). I’m assuming I’m in a slightly elevated state of epinephrine and cortisol throughout the day.

Some people are fasting even longer, pushing out till 4:00 PM or 8:00 PM, or maybe even fasting around the clock. Anytime you’re fasting, you’re increasing epinephrine and cortisol release. You can do all the meditation in the world to keep your mind calm, but you’re closer to that edge of stress and peak stress.

We all eat to suppress cortisol and epinephrine. When we’re hungry, these hormones create an agitation which leads us to seek out food. After eating, typically if it includes carbohydrates, there is a blunting of cortisol and epinephrine in the bloodstream. This is why, for example, when we have had too much coffee to drink and then have a couple of pieces of bread, we might feel the caffeine getting soaked up out of our system. This is because the elevated blood glucose is saturating the effect of caffeine in our system. Eating can also have a calming effect if we are very stressed.

The important point here is that if you want to be alert, you can do that by way of not eating. Of course, please ingest fluids. I know some people water fast out there, but I am yet to see good science on water fasting and why that can stimulate stem cells. After the Nobel prize was given for autophagy, it is true that our cells clean up debris in senescent cells. However, the idea that water fasting is going to promote that is rather amusing. If you know of some great study in a decent journal, please send me the data. In conclusion, I don’t think water fasting is a good idea, nor should you be drinking so much water that you kill yourself. You can actually drink enough water that you die. So, I think ingesting water in healthy amounts is a good thing – stay hydrated.

Staying hydrated and using caffeine may or may not be part of your regimen, but fasting can help to increase your energy levels and prime you for a protocol like breathing, cold exposure, or exercise to help boost your immune system. Additionally, fasting can help increase learning for motor, language, mathematics, and programming. Fasting can increase growth hormone, epinephrine/adrenaline release, and cortisol release, but if life is very stressful, and you are chronically fasting, you are more likely to experience chronic stress and its negative effects, such as lower testosterone and estrogen, graying hair, sleep disturbances, and a weakened immune system.

Our discussion today about epinephrine and cortisol increasing energy and immunity are designed to help you understand when you should be doing certain things and when you should throttle back. If you’re feeling low energy and a little bit under activated, then practices like ice baths and intense breathing could be beneficial. On the other hand, if you’re feeling exhausted and burnt out, then fasting or cold exposure could drive you further into chronic stress. To regulate these hormones, one has to learn how to do so with behavior, nutrition, and possibly supplementation. There are also prescription drugs which can increase or decrease cortisol in cases like Cushing’s Syndrome, which should be discussed with a physician.

Talking to an endocrinologist or a board certified physician is ideal when treating an injury with drugs like corticosteroids, which can reduce inflammation but will also bias the body towards more stress. It is important to remember that cortisol, which is used in corticosteroids, can cross the blood brain barrier and make one more prone to psychological stress.

Having a practice of deliberately increasing adrenaline in the body while learning to stay calm in the mind is beneficial. It is important to learn to separate the brain-body experience and regulate one’s mind when adrenaline levels are high. This can help to regulate one’s actions and avoid negative effects on one’s life and the lives of others. Such practices are straight-forward and cost-free.

You can find any number of ways to increase your adrenaline and stay calm. Exercise is often seen as a way to get energy up. However, today I am discussing deliberately increasing adrenaline while staying calm mentally. This can be very useful when we experience unexpected events or things that we have not sought out. It is also important to be able to regulate adrenaline and cortisol levels. This can be done through supplementation, light, sleep and mental tools. Additionally, it is important to train the system to have a deliberate dissociation between the adrenaline response from the adrenals and the brainstem. After covering this material, it is important to consider if you are in a state of chronic stress or under-activated.

If you like the information that you heard today and want to remember it, perhaps you can go do something to increase your level of adrenaline. Short-term stress is healthy and can be an opportunity to learn how to better control cortisol and adrenaline. We don’t have to be slaves to our hormones and can learn to control them for the benefit of our body and mind. If you’re learning from this podcast, please subscribe on YouTube and hit the notification button. This will let you know when we release new episodes every Monday morning, as well as short clips and special content.

If you haven’t already subscribed on Apple and/or Spotify, please do that. You can also give us a five-star review and leave us a review on Apple. On YouTube is the place to leave us comments, feedback, and suggestions for future episodes. We do read all the comments and are working our way through all the topics.

Today we rounded out the discussion about hormones and are moving to a new topic segment for the next month or so. If you know of anyone who you think could benefit from the information on this podcast, or would enjoy listening to it, please forward it along to them.

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Thank you for joining me for what I hope was an informative and actionable discussion about how to increase energy and the immune system by way of cortisol and adrenaline epinephrine. 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. As a token of appreciation, please use the code thorne.com/u/huberman to get 20% off anything that Thorne makes. And as always, thank you for your interest in science. [upbeat music]