--:-- Andrew Huberman: Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance.
--:-- Andrew Huberman: Today we are discussing the immune system, and we are also discussing how the nervous system can be used to activate and control the immune system. The first topic we have to attack is the question of what is the immune system and how does it work? I'd like to just take a moment and do a sort of brief immune system 101, really simple, cover the basic elements of the immune system so that everyone listening or watching this can get a clear sense of how the immune system functions and what its basic parts are.
--:-- Andrew Huberman: It's actually really simple because it is truly elegant in design. You have three main layers of defense for your health. And the first of those three is a physical barrier that we call your skin. And that might seem kind of obvious, but everything about you is contained in this compartment that is boundaried by your skin. If you've ever had a cut, you essentially have a breach of the boundary that is your immune system.
--:-- Andrew Huberman: Still in category one, your body and your external surface, you have openings to that surface. So what are those openings? Well, let's start at the top and work our way down. A primary site of potential infection are your eyes, you have your ears, you have your nostrils, you have your mouth, okay? Those are going to be the primary sites by which things can get into your system. And you need to put things into your system, you need to drink and eat, and you need to get light into your system, that's why you have those openings.
--:-- Andrew Huberman: And then of course, along the back of your throat, all the way down to your stomach and your digestive system and through your intestines and out your rectum, you have a tube that you are basically a series of tubes. I've said that before in this podcast, and this is one such tube by which you extract nutrients from the outside environment. But all along that tube, including your nose and your mouth, it's lined with mucus.
--:-- Andrew Huberman: And while mucus might seem kind of gross to some of you, the more you learn about mucus, the more you realize that mucus is really, really cool because mucus essentially acts as a filter, as a trap for bacteria and viruses, and it has certain ways of scrubbing or killing those bacteria and viruses.
--:-- Andrew Huberman: Now, inevitably, bacteria, viruses, and parasitic infections are going to make their way into our body, but whether or not they are killed off or whether or not they take over and cause us harm is going to be determined by layers two and three. So layers two and three are the so-called innate immune system and the adaptive immune system.
--:-- Andrew Huberman: So the innate immune system is what I would call the second layer of defense, it's very fast. So this innate immune system is this rapid response. When something enters our system and our body doesn't recognize it, it's something that's either a bacteria, virus, or parasite. And the innate immune system involves the release of particular cells that are waiting, dormant, ready to attack whatever this invader is.
--:-- Andrew Huberman: And some of these cell types you've heard of before, the most typical one are the so-called white blood cells. So the white blood cells will actively go to the site of invasion and will start to encapsulate or try and surround that given invader. The other names of these different cell types of things like neutrophils, macrophages, natural killer cells, just a few of the many types of immune cells.
--:-- Andrew Huberman: They work in concert with two other assistants, and those assistants are called the complement proteins. Complement proteins exist in the blood, and what they do is they travel to sites where there's an invasion, and they mark certain things for being engulfed and eaten. And so they sort of put an eat me tag on it.
--:-- Andrew Huberman: And then there are the cells that are either damaged from the injury or from the parasite, or are suffering because of the bacteria or the virus itself. And the cells of your body will also release an alarm signal, which is not an eat me signal, but a help me signal. And those help me signals come in the form what we call cytokines.
--:-- Andrew Huberman: And the cytokines are things like interleukin one, interleukin-6, tumor necrosis factor alpha. The interleukin is shouting out, help me. The complement proteins are coming in and saying, eat this and tagging the invader with an eat me signal. And then the killer cells and the white blood cells are doing the job of trying to kill off that thing. That's the innate immune system.
--:-- Andrew Huberman: So your skin and your mucus lining plus your innate immune system are a beautiful, two-layered set of defenses against various kinds of invaders and infections. And then there's the third type, which is the adaptive immune system. And you'll notice that leading up until now, I haven't said the word antibody at all.
--:-- Andrew Huberman: And that's because it is the job, not of the skin or the mucus or the microbiome or the innate immune system to produce antibodies that can recognize specific invaders, but rather it is the job of the adaptive immune system to create antibodies against bacteria, viruses, and even parasites, and even physical intruders to your system.
--:-- Andrew Huberman: So the adaptive immune system has this incredible ability to show up at the site of invasion or infection or inflammation. And what it does is it actually attaches to and creates a sort of an imprint of the shape of whatever invader happens to be there. And then using that imprint in concert with some other cells creates antibodies that are specific to recognize that invader should the body ever have that invader inside of it again.
--:-- Andrew Huberman: Now that's why it's called the adaptive immune system. And in many ways it creates a memory of a prior infection so that these antibodies can be made anytime that same invader comes back again. All right, and so this is the basis of what we call immunity.
--:-- Andrew Huberman: Now there are a lot more details to the adaptive immune system, but I just want to emphasize a few points that might be relevant. First of all, the name of the antibodies that are created sometimes come in the form of IgM and IgG, things of that sort. This isn't a full deep dive immunology class, but Ig stands for immunoglobulin, okay? So the immunoglobulins are part of the adaptive immune response in creating antibodies.
--:-- Andrew Huberman: If you hear IgM, the IgM is the first of the adaptive immune responses, and it tends to come on earlier. So if somebody is immunopositive for IgM for a particular type of viral or bacterial invader, that means that it was a fairly recent infection. Later, one creates, the adaptive immune system, I should say, creates an IgG, which is the more stable form of the specific antibody that's going to recognize a given invader.
--:-- Andrew Huberman: So IgG tends to come up a little bit later. So just to recap, something gets into your system, then there's the innate response, which is a more general response of trying to contain and combat the infection or invader. And then the adaptive response is the one that generates the antibodies. First, the IgM response, the immunoglobulin M response, and then the immunoglobulin G response, IgG response.
--:-- Andrew Huberman: So how do we keep these three barriers or these three defense systems to infection tuned up? One of the key ways we can do that is to keep that mucus lining in really good shape. And what does that mean? Well, the mucus lining needs to turn over quite often, and it needs to be the correct chemistry to be a trap for the bad stuff and for it to be permeable to the good stuff, to the nutrients that we need.
--:-- Andrew Huberman: And it is now very clear from hundreds, if not thousands of studies, that the best way to do that is to maintain a healthy so-called microbiome. The microbiome being these little bacterial organisms that are good for us, that live all along our mucus pathways, and even in our eyes.
--:-- Andrew Huberman: Now, just to be really clear, it's not just about the gut microbiome. We actually have a microbiome in our eyes. We have one that's specific to our mouth. We have a nasal specific microbiome. There's one all along the gut and the species of microbiota that live all along the digestive tract differ from the mouth to the throat, to the stomach, intestines, and to the rectum.
--:-- Andrew Huberman: It's well established that there are healthy microbiota that live all along that length and they differ along that length. This is a reminder that whenever possible, unless eating or speaking, you want to be nasal breathing, not breathing through your mouth. Your nose is a much better filter for viruses and bacteria than is your mouth.
--:-- Andrew Huberman: And so be a nose breather, not a mouth breather. You will combat more of the infections that you are constantly confronted with. The other way to try and keep out bad things and to avoid getting sick is the advice that your mother and certainly my mother gave me which is to not touch your eyes after touching other people or touching other surfaces.
--:-- Andrew Huberman: And the reason to avoid doing that is the eyes are a primary entry point for a lot of bacteria and viruses. And then the third way to keep a healthy line of defense for your entire mucus tract is to enhance the proliferation of good gut microbiota. The best way to enhance the quality of your gut microbiome and the mucus lining that serves as this protective layer all along your body is to ingest two to four servings a day of fermented foods, low sugar fermented foods.
--:-- Andrew Huberman: It helps reduce the activity of certain cytokines. When people have a healthy gut microbiome, There are fewer cells in the body being infected from outside infections, and therefore less of a reason for cells to be crying out help because they are thriving, not suffering. Things like sauerkraut, things like natto, if you can access that, kimchi, pickles, again, low sugar sources are going to be the sources that are going to be most effective for this.
--:-- Andrew Huberman: I'd like to take a quick break and acknowledge our sponsor, AG1. By now, many of you have heard me say that if I could take just one supplement, that supplement would be AG1. The reason for that is AG1 is the highest quality and most complete of the foundational nutritional supplements available.
--:-- Andrew Huberman: What that means is that it contains not just vitamins and minerals, but also probiotics, prebiotics, and adaptogens to cover any gaps you may have in your diet and provide support for a demanding life. For me, even if I eat mostly whole foods and minimally processed foods, which I do for most of my food intake, it's very difficult for me to get enough fruits and vegetables, vitamins and minerals, micronutrients, and adaptogens from food alone.
--:-- Andrew Huberman: For that reason, I've been taking AG1 daily since 2012. When I do that, it clearly bolsters my energy, my immune system, and my gut microbiome. These are all critical to brain function, mood, physical performance, and much more. If you'd like to try AG1, you can go to drinkag1.com slash Huberman to claim their special offer.
--:-- Andrew Huberman: Right now, they're giving away five free travel packs plus a year's supply of vitamin D3K2. Again, that's drinkag1.com slash Huberman to claim that special offer. Next, I'd like to talk about what's called sickness behavior. Sickness behavior is a suite of responses that we tend to all undergo when we are feeling sick.
--:-- Andrew Huberman: The main thing about sickness behavior is that it tends to involve a slowing of our usual levels of activity. People start to feel lethargic or they feel like the activities that previously they could do with relative ease are very difficult for them or somewhat overwhelming.
--:-- Andrew Huberman: The other thing you start to see is that people and animals, by the way, stop grooming. They stop taking care of themselves, not necessarily stop showering, although oftentimes that's the case, but they will stop doing their hair. They'll stop putting on makeup, depending on whether or not they did that before, they might stop.
--:-- Andrew Huberman: Animals will stop licking and grooming themselves. People will stop taking care of their cosmetic appearance. Now, it's not just because they don't care how they look when they're sick. It's because there's this overall suppression of certain kinds of activities and an enhancement of other kinds of activities.
--:-- Andrew Huberman: And this is really important. Sickness behavior is actually a motivated state. It's a state that's designed to accomplish certain things. One of the other features of sickness behavior, in addition to being lethargic, loss of grooming, will be a loss of appetite, right? Oftentimes people who have a great appetite normally just won't feel hungry at all.
--:-- Andrew Huberman: When we have that, we can be kind of irritable. We don't want to do certain things and we just want to be left alone. Things are harder. How? Why? Well, there's a known pathway, which is the so-called vagus nerve that connects the body and the brain, signals to particular brain sites to engage this category of motivational state that we call sickness behavior.
--:-- Andrew Huberman: The vagus nerve is a very extensive nerve pathway. It's the 10th cranial nerve comes out of the back of the brainstem, heads into the body and branches out extensively to innervate or connect to many of our organs, including our lungs, our heart, our gut, et cetera.
--:-- Andrew Huberman: And all of those organs are also able to send neural signals back up to the brain. We sometimes hear the vagus as the route to calming ourselves down. Unfortunately, that's more or less a myth that I don't know how it got propagated.
--:-- Andrew Huberman: There have now been many studies of the vagus in various contexts, including in sickness behavior. And it's very clear that the vagus nerve is the fast pathway by which an infection in the body is signaled to the brain, to a particular location in the brain called the hypothalamus, which harbors a lot of different types of neurons.
--:-- Andrew Huberman: Neurons, for instance, in the pre-optic area that increase body temperature and fever, right? That's one of the most important things is to increase body temperature in order to, It's the body's attempt to kill off this invader because many viruses and many bacteria don't survive well at elevated heat.
--:-- Andrew Huberman: That's the function of a fever. It also sends input to areas of the brain that change your perception of the outside world. One of the most obvious of these, obvious once I tell it to you, is photophobia, right? I love bright sunshine. I love bright lights when I want to be alert, But most people, when they are sick, when there's an inflammation response in the body, they feel like bright lights are kind of aversive.
--:-- Andrew Huberman: They get a well-described kind of classical photophobia. And that's mediated by a pathway that goes from your eye to an area of your thalamus, called the anterior nucleus of the thalamus. Then from there up to the outer lining of the brain, which is the meninges, just sort of on the outside of the brain, where the brain starts to interface with some of the other connective tissues.
--:-- Andrew Huberman: It can actually create a photophobia and a headache when one is ill. And the last element I'd like to talk about is the rest. There's something that gets triggered from the body to the brain, to the hypothalamus, and there are nuclei there that promote the desire to sleep even during the daytime, what would normally be the active phase of your circadian cycle.
--:-- Andrew Huberman: Now, that is really interesting because what's happening here is you've got multiple pathways that are saying, avoid light, reduce your amount of behavior, heat up all the things that are making you sick. This is sickness behavior, and it's going from your body to your mind to make you do the right thing.
--:-- Andrew Huberman: Now, there's also a slow pathway that's purely mediated by the blood, so-called humoral factors, not because they're funny, but humoral factors are factors of the blood. As you have an infection for many hours or days, the amount of IL-6 and IL-1 and tumor necrosis factor and other inflammatory cytokines is starting to increase such that the total amount in your circulation gets high enough and is communicated to the brain.
--:-- Andrew Huberman: And it tends to enter the brain through a particular type of tissue that's really interesting called choroid, C-H-O-R-O-I-D. the choroid starts releasing and responding to these cytokines, the inflammatory cytokines. And then the brain actually starts to experience all sorts of changes in terms of inflammation to neurons.
--:-- Andrew Huberman: Your memory tends to get poor. Your cognition tends to get poor. These are transient things most often. These, eventually these things will pass, but this is deep into sickness when you're really feeling lousy. You can't read, you can't watch a movie, you can't do anything. If you ever get sick and you just can't be bothered by anything, it's probably because you've had that fast response from the body and you've also had this slower response where you literally have a set of tissues in your brain that are sending out these inflammatory signals.
--:-- Andrew Huberman: And now your whole brain is starting to cope or is trying to cope with this infection. So you've got a slow pathway and a fast pathway. That all sounds really terrible. So now I'd like to talk about what you can do to reduce the probability of getting sick. And there are actually things that one can do as you start to get sick.
--:-- Andrew Huberman: And once you're sick, to accelerate the healing process by flipping the equation. Up until now, we've been talking about how the body activates certain areas in the brain to create sickness behavior that's very much like depression. You're probably all familiar with this from any time you've had a cold or a flu or something really lousy or an injury.
--:-- Andrew Huberman: Now let's flip the equation and ask, what can we do with our nervous system in order to enhance the function of our immune system in order to be able to heal and recover from illness and injury more quickly. We all know what we should do. We should all hydrate, drink some water, and go to sleep. Right? That's what we are all told.
--:-- Andrew Huberman: But there are actually things that you can actively do in order to get your immune system to deploy a more robust response at that early phase of potential infection. Let's focus first on the rest component. Yes, of course, we are all told that we should take a hot shower and go to sleep you know and get nine or 10 hours of sleep
--:-- Andrew Huberman: But there an interesting way of looking at sleep specifically for its role in enhancing the immune system During sleep, and in particular during sleep that's associated with the early stage of any kind of viral or bacterial infection, the so-called glymphatic system is much more active than it would be normally.
--:-- Andrew Huberman: What's the glymphatic system? The glymphatic system with a G is a system in the brain by which debris that accumulates throughout the day, but in particular, debris that accumulates under conditions of neuroinflammation and inflammation of the body is cleared out or is washed out of the brain.
--:-- Andrew Huberman: And the activity of this glymphatic system is extremely important for the recovery from infection of any kind. There is a way that you can increase the activity of your glymphatic system under normal circumstances. Because of the mechanics of the glymphatic system, it turns out that if you elevate your heels by about 12 degrees, it doesn't have to be exactly 12, as you sleep by putting maybe a rolled pillow or two pillows underneath your feet, by having the head below your legs, it seems that there's more glymphatic washout or clearance during sleep.
--:-- Andrew Huberman: So I would say, if you're not feeling well, yes, take the hot shower. Yes, get into bed and go to sleep, but elevate your feet to try and increase the activity of the glymphatic system. Some might even consider that if you have to be awake, that you might want to be awake with your feet elevated above your head.
--:-- Andrew Huberman: Now that might not be practical for the workplace, but it might be practical for a short nap during the day or something of that sort. I'd like to take a quick break and acknowledge one of our sponsors, Element. Element is an electrolyte drink that has everything you need and nothing you don't.
--:-- Andrew Huberman: That means the electrolytes, sodium, magnesium, and potassium in the correct amounts, but no sugar. Proper hydration is critical for optimal brain and body function. Even a slight degree of dehydration can diminish cognitive and physical performance. It's also important that you get adequate electrolytes.
--:-- Andrew Huberman: The electrolytes, sodium, magnesium, and potassium, are vital for functioning of all the cells in your body, especially your neurons or your nerve cells. Drinking element dissolved in water makes it very easy to ensure that you're getting adequate hydration and adequate electrolytes.
--:-- Andrew Huberman: To make sure that I'm getting proper amounts of hydration and electrolytes, I dissolve one packet of Element in about 16 to 32 ounces of water when I first wake up in the morning, and I drink that basically first thing in the morning.
--:-- Andrew Huberman: I'll also drink Element dissolved in water during any kind of physical exercise that I'm doing, especially on hot days when I'm sweating a lot and losing water and electrolytes. Element has a bunch of great tasting flavors. I love the raspberry. I love the citrus flavor. Right now, Element has a limited edition lemonade flavor that is absolutely delicious.
--:-- Andrew Huberman: I hate to say that I love one more than all the others, but this lemonade flavor is right up there with my favorite other one, which is raspberry or watermelon. Again, I can't pick just one flavor. I love them all. If you'd like to try Element, you can go to drinkelement.com slash Huberman, spelled drinkelement.com slash Huberman, to claim a free Element sample pack with a purchase of any Element drink mix.
--:-- Andrew Huberman: Again, that's drinkelement.com slash Huberman to claim a free sample pack. Next, I'd like to do an in-depth analysis of a study that has achieved some prominence out there, not just in the scientific literature, but on the internet, because it relates to how particular types of breathing can impact the immune system and the ability to combat infection.
--:-- Andrew Huberman: The title of this paper is Voluntary Activation of the Sympathetic Nervous System and attenuation of the innate immune response in humans. This is a paper that was published in PNAS, which is the Proceedings of the National Academy of Sciences USA.
--:-- Andrew Huberman: It's a very prestigious journal. And I just want to describe the basic contour of the study. I'll explain the findings, and then I want to go in depth and explain the mechanistic basis for these findings and the protocol that we can all export from these findings. So here we go.
--:-- Andrew Huberman: So first of all, a couple of terms so that everybody is on the same page. The sympathetic nervous system is one division of our nervous system. It's a set of neurons down the middle of our spinal cord and in our brain that generally lead to a heightened state of arousal and alertness.
--:-- Andrew Huberman: It's associated with epinephrine release in the brain and adrenaline release in the body. It's the so-called fight or flight system when it's really active, but it's the system that's active when we are wide awake. And we already talked about the innate immune system.
--:-- Andrew Huberman: That's that first line of defense after the skin barrier, of course, whereby some infection comes into the body and there's this rapid response of increasing inflammation. And that's also about the time that you first feel lousy. So when you start to feel like, oh, I think I've got something. I don't feel right, a headache. I feel nauseous. I'm heating up. I don't feel good. That's the innate immune system kicking in.
--:-- Andrew Huberman: So what they did in this study, they injected people with E. coli, which is a bacteria, which makes people, all people feel terrible. These people voluntarily signed up for this study. However, some of the subjects in this study performed a behavioral protocol that can best be described as cyclic hyperventilation.
--:-- Andrew Huberman: So they're comparing controls that do just sort of a basic meditation versus people that do this intense breathing followed by some breath holds. In the intervention group, the breathing group, plasma levels of anti-inflammatory cytokine IL-10. So this is a cytokine that lowers inflammation, increased after endotoxin administration, and that was triggered by an increase in epinephrine and adrenaline.
--:-- Andrew Huberman: So in other words, doing a particular pattern of breathing allowed an anti-inflammatory cytokine to be turned on. And they discovered that levels of pro-inflammatory TNF-alpha, tumor necrosis factor alpha, IL-6, interleukin-6, and interleukin-8, which you should all be familiar with now, as pro-inflammatory cytokines, were lower in the intervention group.
--:-- Andrew Huberman: Finally, flu-like symptoms were lower in the intervention group. So this is an amazing finding, right? These are human subjects. One group of subjects is doing this breathing protocol. The other group of subjects is just meditating. They both, both sets of subjects have been injected with E. coli. So you know everyone's getting the same amount placed into their system.
--:-- Andrew Huberman: How in the world does this work? Why does this work? First of all, what is this magical pattern of breathing? Some of you may recognize this as so-called Wim Hof breathing. The breathing that is so-called Wim Hof breathing is very similar, not exactly the same, but very similar to Tummo breathing as it's been described historically.
--:-- Andrew Huberman: In the science and physiology community, refer to it as cyclic hyperventilation, which just means repeated deep breaths in and out, and then there are these retention. So because I'm here in the hot seat anyway, I might as well demonstrate it for you so you know what this looks like.
--:-- Andrew Huberman: It involves 20 to 30 deep inhales and then exhales through the mouth, followed by a exhale of all one's air and a breath hold, that's the retention, And then at some point, 15 to 60 seconds later, repeating the 25 or 30 breaths, and then again, a breath hold with lungs empty.
--:-- Andrew Huberman: Okay, so let's assume I did that for 30 breaths. I can already feel myself perspiring a little bit. You're heating up, that's the release of adrenaline. It's caused by that breathing pattern. And then exhaling all of one's air, no speaking in between like I'm doing. And then sitting lungs empty until one feels the impulse to breathe. And then repeating for several rounds, two or three or even four rounds.
--:-- Andrew Huberman: Basically this study looked at people doing cyclic hyperventilation with retention, three rounds of 25 to 60 breaths, followed by exhale hold in between of various duration, but in general, 15 to 60 seconds is typical. So what's going on here? How is the breathing leading to these shifts in, or I should say reduction in inflammatory cytokines and an increase in the liberation of these anti-inflammatory cytokines?
--:-- Andrew Huberman: This is beyond the scope of this discussion, but that it's actually the release of epinephrine, aka adrenaline, that's causing this reduction and inflammation. And that's actually supported by something that you've probably experienced before, which is if you've ever worked, worked, worked, worked really hard, or you've been a caretaker for somebody else or studying for exams, and people around you are getting sick and you're just powering through it and you're not getting sick, but then you stop, you turn in your final exam, you stop taking care of somebody else, or you finally stop and rest, or you go on vacation and then you get sick.
--:-- Andrew Huberman: Well, you've just experienced the effect that adrenaline, epinephrine can have in activating your immune system by way of the nervous system in order to keep fighting and combating infection. And that brings us to a larger theme, which is that stress and combating infection or a wound is not one unique system It the same stress system that you use to combat psychological stress So when you very very stressed at least in the short term, because you release so much adrenaline and epinephrine, you're actually better able to combat infections and you reduce inflammation and the whole feeling lousy response, right?
--:-- Andrew Huberman: Remember, reduced flu-like symptoms here. So this pattern of breathing is actually a very useful tool. And I confess, I use this pattern of breathing Anytime I am at the initial stages of getting some sort of bug, if I feel like I've been running myself ragged, or if I somehow, for whatever reason, have a tickle in my throat, or I have that kind of sensation in my nose, like I might have caught a bug of some sort, I will do this pattern of breathing.
--:-- Andrew Huberman: I've been doing it consistently, gosh, for the last four years or more. Now, this is just anecdotal reports, but I find that it allows me, indeed, to either have those early symptoms disappear or it allows me to just kind of push through and harder longer. I don't suggest people continue to push through exposure to infections. Obviously you don't want to infect other people, nor do you want to crash and suddenly get a massive illness of some sort because you stopped doing this breathing.
--:-- Andrew Huberman: But I do think it's a useful tool. It's a purely behavioral intervention that has been shown here. And now there are additional studies on the way to enhance the function of your immune system and to reduce inflammation. And this is, to me, one of the most concrete examples of a zero-cost tool that bridges the activation of the nervous system through breathing with the immune system by way of releasing adrenaline and thereby reducing the terrible effects or feelings of lousiness from a, in this case, an E. coli infection.
--:-- Andrew Huberman: There's one last very interesting feature of this study that I want to emphasize, and that was that they actually measured the so-called catecholamine concentrations. Catecholamines are things like dopamine, epinephrine, norepinephrine. These are chemicals in your nervous system and body that promote states of alertness.
--:-- Andrew Huberman: Dopamine, of course, part of the reward and motivation pathways. They explored the levels of these molecules in blood, in plasma, during and after this breathing protocol. And it was interesting, as I mentioned before, epinephrine showed robust increases compared to the control group.
--:-- Andrew Huberman: Norepinephrine, significant increases occurred in the breathing group, but in the cyclic hyperventilation retention breathing group, of course, but less so. And dopamine levels actually dropped somewhat. But this is very interesting because there's a new and emerging literature, largely from Aysa, A-Y-S-A, Roll's lab in Israel.
--:-- Andrew Huberman: What her laboratory has shown is that motivational state and mindset has a powerful impact on various aspects of the immune system that were thought to be independent of the brain and mind and thinking. They explored the well-established psychological phenomenon that when cancer patients or very ill people or people who are suffering from very debilitating injuries, when people had or reported a sense of hope, their rates of recovery were much higher, right?
--:-- Andrew Huberman: Sounds very subjective. But what is a sense of hope? A sense of hope is a sense of the future. a sense of the future is tightly associated with the dopamine system. And so what they've discovered and through other studies from other groups have discovered is that stimulation of the dopamine pathway, either simply by thinking about a future, ideally a positive future, but thinking about a positive future leads to activation of this so-called mesolimbic reward pathway and could reduce the size of tumors, could accelerate wound healing, could greatly accelerate the passage from a state of illness to a state of health and wellbeing.
--:-- Andrew Huberman: It's because this reward pathway and the fact that it's related to a sense of the future seems to liberate entire systems within the body that make inflammatory cytokines go down and anti-inflammatory cytokines go up, exactly as was demonstrated in the beautiful PNAS study where breathing, cyclic hyperventilation, was used to increase epinephrine, increase norepinephrine, and to augment the catecholamine system.
--:-- Andrew Huberman: So I think that the bridges between these studies are really relevant. There was a very exciting article published from Chufu Ma's lab at Harvard Medical School. And the title of the article is, A Neuroanatomical Basis for Electroacupuncture to Drive the Vagal Adrenal Axis. Wen Shu Fu's lab looked at stimulation of the body with so-called electroacupuncture.
--:-- Andrew Huberman: So these are needles where it's a small bit of electrical current, low level of electrical current is passed into the needle and therefore into the body. They located sites on the body that can increase inflammation by way of releasing inflammatory cytokines. These areas included the abdomen, and they found areas on the body such as the lower limbs, the hind limbs in this case, that can stimulate the vagal adrenal reflex and can lead to reduced inflammation.
--:-- Andrew Huberman: And what was really interesting is that they figured out that it was activation of nerve endings that resided in the fascia. The fascia is a really thick sheath of tissue that surrounds muscle. And so what they discovered is there's a specific population of neurons. Those neurons have a name as they often do in science. Name isn't important, but if you want to look it up, it's the PROKR2 neurons, P-R-O-K-R2 neurons.
--:-- Andrew Huberman: And they send a connection deep into the limb fascial tissue. And then they send another wire up into the spinal cord and to a region of the hind brain in the back of your brain kind of near your neck called the medulla, in the medulla oblongata. That neuron also has a name called the DMZ, doesn't matter. And that neuron connects to the adrenal gland to release our good old friends, the catecholamines, noradrenaline, adrenaline, and dopamine, or norepinephrine, epinephrine, and dopamine.
--:-- Andrew Huberman: So what is all this saying? This is saying that activation of the deep fascial tissue causes a chain of neural reactions that leads eventually to the release of norepinephrine, noradrenaline, adrenaline, and dopamine, and once again, lowers inflammation, very much like the breathing study that we talked about earlier and the pattern of cyclic hyperventilation with retention leading to reductions in inflammation.
--:-- Andrew Huberman: Okay, so thus far, we've been discussing how one can prevent getting sick or when one starts to feel ill, how one might be able to shorten the course of that infection by ramping up the activity of the immune system. But what about when you're already experiencing symptoms? There are many ways to address that at the symptom level.
--:-- Andrew Huberman: You're probably aware of all the over-the-counter medications, many of which focus on the epinephrine system. You know, things that are of the Sudafed variety prevent or reduce congestion because of the way that they cause release of epinephrine and some of the effects on dilating the bronchioles and dilating the nasal passages and so forth.
--:-- Andrew Huberman: I'm not going to speak to whether or not those are good or bad choices. they do have a couple of effects that are not so great for the course of treating the underlying cause, which are, first of all, they can cause dehydration. So you have to make sure that you're hydrating well, both fluids and electrolytes.
--:-- Andrew Huberman: And they also can interfere with sleep. There is an interesting alternative choice. And when I say alternative, I do mean alternative. The choice that I'm referring to is spirulina, which is actually a form of algae.
--:-- Andrew Huberman: There are some really nice studies and some data and also an understanding of the mechanism by which spirulina can have potent effects in reducing what's called rhinitis, which is a fancy word for congestion of the nose and inflammation of the nose. These looked at humans. So this is not a mouse study. This is a study on humans.
--:-- Andrew Huberman: Both sexes, so males and females. In one case, looking at 100 plus subjects, 129 subjects, the other 65 subjects. So a decent number of subjects, randomized trial, double blind. both cases saw significant decreases in nasal obstruction, improved ability to smell, improved sleep, daily working cytokine, inflammatory cytokines were reduced as well, reduction nasal itching, all the stuff that you'd like to experience, I can imagine, after taking two grams, two grams, not milligrams,
