Using Your Nervous System to Enhance Your Immune System

00:00:00.200 | - Welcome to Huberman Lab Essentials,

00:00:02.360 | where we revisit past episodes

00:00:04.400 | for the most potent and actionable science-based tools

00:00:07.600 | for mental health, physical health, and performance.

00:00:10.360 | I'm Andrew Huberman,

00:00:12.920 | and I'm a professor of neurobiology and ophthalmology

00:00:15.600 | at Stanford School of Medicine.

00:00:17.840 | Today, we are discussing the immune system,

00:00:20.800 | and we are also discussing how the nervous system

00:00:23.360 | can be used to activate and control the immune system.

00:00:27.640 | The first topic we have to attack is the question

00:00:31.320 | of what is the immune system and how does it work?

00:00:34.120 | I'd like to just take a moment

00:00:35.220 | and do a sort of brief immune system 101.

00:00:40.280 | Really simple, cover the basic elements of the immune system

00:00:43.620 | so that everyone listening or watching this

00:00:46.100 | can get a clear sense of how the immune system functions

00:00:49.640 | and what its basic parts are.

00:00:51.740 | It's actually really simple

00:00:54.060 | because it is truly elegant in design.

00:00:56.880 | You have three main layers of defense for your health.

00:01:01.880 | And the first of those three is a physical barrier

00:01:06.920 | that we call your skin.

00:01:08.880 | And that might seem kind of obvious,

00:01:10.260 | but everything about you is contained in this compartment

00:01:15.080 | that is boundaried by your skin.

00:01:18.360 | If you've ever had a cut,

00:01:19.640 | you essentially have a breach of the boundary

00:01:22.440 | that is your immune system.

00:01:24.480 | Still in category one,

00:01:26.320 | your body and your external surface,

00:01:28.480 | you have openings to that surface.

00:01:31.760 | So what are those openings?

00:01:32.640 | Well, let's start at the top and work our way down.

00:01:35.480 | A primary site of potential infection are your eyes,

00:01:39.440 | you have your ears, you have your nostrils,

00:01:41.320 | you have your mouth.

00:01:42.320 | Okay. Those are going to be the primary sites

00:01:44.560 | by which things can get into your system.

00:01:47.280 | And you need to put things into your system.

00:01:48.640 | You need to drink and eat,

00:01:49.680 | and you need to get light into your system.

00:01:51.200 | That's why you have those openings.

00:01:52.720 | And then of course, along the back of your throat,

00:01:56.440 | all the way down to your stomach and your digestive system,

00:01:59.840 | and through your intestines and out your rectum,

00:02:01.920 | you have a tube that you are basically a series of tubes.

00:02:06.040 | I've said that before in this podcast,

00:02:07.440 | and this is one such tube by which you extract nutrients

00:02:10.120 | from the outside environment.

00:02:11.800 | But all along that tube,

00:02:14.120 | including your nose and your mouth,

00:02:16.800 | it's lined with mucus.

00:02:18.800 | And while mucus might seem kind of gross to some of you,

00:02:20.960 | the more you learn about mucus,

00:02:22.040 | the more you realize that mucus is really, really cool.

00:02:25.080 | because mucus essentially acts as a filter,

00:02:27.820 | as a trap for bacteria and viruses,

00:02:31.080 | and it has certain ways of scrubbing

00:02:33.900 | or killing those bacteria and viruses.

00:02:37.280 | Now, inevitably, bacteria, viruses,

00:02:40.920 | and parasitic infections are going to make their way

00:02:44.640 | into our body.

00:02:45.960 | But whether or not they are killed off

00:02:48.000 | or whether or not they take over and cause us harm

00:02:50.960 | is going to be determined by layers two and three.

00:02:54.480 | So layers two and three are the so-called innate immune system

00:02:59.160 | and the adaptive immune system.

00:03:01.020 | So the innate immune system

00:03:02.720 | is what I would call the second layer of defense.

00:03:04.720 | It's very fast.

00:03:05.820 | So this innate immune system is this rapid response.

00:03:09.500 | When something enters our system

00:03:11.860 | and our body doesn't recognize it,

00:03:14.380 | it's something that's either a bacteria, virus, or parasite.

00:03:18.440 | And the innate immune system involves the release

00:03:22.260 | of particular cells that are waiting, dormant, ready to attack,

00:03:26.300 | whatever this invader is.

00:03:27.900 | And some of these cell types you've heard of before.

00:03:30.760 | The most typical one are the so-called white blood cells.

00:03:34.020 | So the white blood cells will actively go to the site of invasion

00:03:38.260 | and will start to encapsulate or try and surround that given invader.

00:03:43.500 | The other names of these different cell types are things like neutrophils,

00:03:47.300 | macrophages, natural killer cells.

00:03:49.740 | There's just a few of the many types of immune cells.

00:03:52.480 | They work in concert with two other assistance.

00:03:57.660 | And those assistance are called the complement proteins.

00:04:01.180 | Complement proteins exist in the blood.

00:04:04.220 | And what they do is they travel to sites where there's an invasion

00:04:08.060 | and they mark certain things for being engulfed and eaten.

00:04:13.140 | So they sort of put an eat me tag on it.

00:04:15.980 | And then there are the cells that are either damaged from the injury

00:04:20.860 | or from the parasite or are suffering because of the bacteria or the virus itself.

00:04:26.340 | And the cells of your body will also release an alarm signal,

00:04:32.220 | which is not an eat me signal, but a help me signal.

00:04:35.100 | And those help me signals come in the form what we call cytokines.

00:04:39.100 | And the cytokines are things like interleukin one, interleukin six,

00:04:43.100 | tumor necrosis factor alpha.

00:04:44.980 | The interleukin is shouting out, help me.

00:04:46.820 | The complement proteins are coming in and saying, eat, eat this,

00:04:49.900 | and tagging the invader with an eat me signal.

00:04:52.580 | And then the killer cells and the white blood cells are doing the job

00:04:55.900 | of trying to kill off that thing.

00:04:57.620 | That's the innate immune system.

00:04:59.340 | So your skin and your mucus lining plus your innate immune system

00:05:05.340 | are a beautiful two layered set of defenses

00:05:10.460 | against various kinds of invaders and infections.

00:05:13.740 | And then there's the third type, which is the adaptive immune system.

00:05:17.260 | And you'll notice that leading up until now,

00:05:19.500 | I haven't said the word antibody at all.

00:05:22.300 | And that's because it is the job, not of the

00:05:25.460 | skin or the mucus or the microbiome or the innate immune system to produce antibodies

00:05:31.900 | that can recognize specific invaders, but rather it is the job of the adaptive immune system

00:05:37.300 | to create antibodies against bacteria, viruses, and even parasites,

00:05:42.900 | and even physical intruders to your system.

00:05:46.900 | So the adaptive immune system has this incredible ability to show up at the site of invasion

00:05:53.340 | or infection or inflammation.

00:05:55.340 | 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.

00:06:06.340 | 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.

00:06:18.780 | Now, that's why it's called the adaptive immune system.

00:06:21.780 | And in many ways it creates a memory of a prior infection so that these antibodies can be made any time that same invader comes back again.

00:06:32.220 | All right.

00:06:33.620 | And so this is the basis of what we call immunity.

00:06:36.220 | 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.

00:06:43.220 | So first of all, the name of the antibodies that are created sometimes come in the form of IgM and IgG, things of that sort.

00:06:55.060 | This isn't a full deep dive immunology class, but Ig stands for immunoglobulin, okay?

00:07:02.060 | So the immunoglobulins are part of the adaptive immune response in creating antibodies.

00:07:07.180 | If you hear IgM, the IgM is the first of the adaptive immune responses, and it tends to come on earlier.

00:07:17.020 | 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.

00:07:26.020 | Later, one creates the adaptive immune system, I should say, creates an IgG, which is the more stable form of the specific antibody

00:07:35.020 | that's going to recognize a given invader.

00:07:38.500 | So IgG tends to come up a little bit later.

00:07:40.540 | So just to recap, something gets into your system.

00:07:44.700 | Then there's the innate response, which is a more general response of trying to contain and combat the infection or invader.

00:07:51.980 | And then the adaptive response is the one that generates the antibodies.

00:07:54.980 | First, the IgM response, the immunoglobulin M response,

00:07:59.260 | and then the immunoglobulin G response, IgG response.

00:08:03.660 | So how do we keep these three barriers or these three defense systems to infection tuned up?

00:08:11.180 | One of the key ways we can do that is to keep that mucus lining in really good shape.

00:08:17.020 | And what does that mean?

00:08:17.780 | 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.

00:08:32.020 | 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.

00:08:39.540 | The microbiome being these little bacterial organisms that are good for us, that live all along our mucus pathways and even in our eyes.

00:08:49.060 | 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.

00:09:01.060 | There's one all along the gut and the species of microbiome that live all along the digestive tract differ from the mouth, to the throat, to the stomach, intestines, and to the rectum.

00:09:11.860 | It's well-established that there are healthy microbiome that live all along that length, and they differ along that length.

00:09:17.380 | This is a reminder that whenever possible, unless eating or speaking, you want to be nasal breathing, not breathing through your mouth.

00:09:26.260 | Your nose is a much better filter for viruses and bacteria than is your mouth.

00:09:33.300 | And so be a nose breather, not a mouth breather.

00:09:36.100 | You will combat more of the infections that you are constantly confronted with.

00:09:40.580 | 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,

00:09:49.060 | which is to not touch your eyes after touching other people or touching other surfaces.

00:09:56.260 | And the reason to avoid doing that is the eyes are a primary entry point for a lot of bacteria and viruses.

00:10:03.140 | 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.

00:10:16.180 | The best way to enhance the quality of your gut microbiome and the mucus lining that serves as this protective layer

00:10:24.020 | all along your body is to ingest two to four servings a day of fermented foods, low sugar fermented foods.

00:10:31.220 | It helps reduce the activity of certain cytokines.

00:10:34.500 | When people have a healthy gut microbiome, there are fewer cells in the body being infected from outside infections

00:10:40.820 | and therefore less of a reason for cells to be crying out help because they are thriving, not suffering.

00:10:46.580 | Things like sauerkraut, things like natto, if you can access that, kimchi, pickles.

00:10:52.100 | Again, low sugar sources are going to be the sources that are going to be most effective for this.

00:10:57.140 | Next, I'd like to talk about what's called sickness behavior.

00:11:00.740 | Sickness behavior is a suite of responses that we tend to all undergo when we are feeling sick.

00:11:07.940 | The main thing about sickness behavior is that it tends to involve a slowing of our usual levels of activity.

00:11:14.260 | People start to feel lethargic or they feel like the activities that previously they could do

00:11:20.100 | with relative ease are very difficult for them or somewhat overwhelming.

00:11:25.060 | The other thing you start to see is that people and animals, by the way, stop grooming.

00:11:29.460 | They stop taking care of themselves.

00:11:31.540 | Not necessarily stop showering, although oftentimes that's the case, but they will stop doing their hair.

00:11:36.980 | They'll stop putting on makeup.

00:11:38.340 | Depending on whether or not they did that before, they might stop.

00:11:42.420 | Animals will stop licking and grooming themselves.

00:11:45.780 | People will stop taking care of their cosmetic appearance.

00:11:49.460 | Now, it's not just because they don't care how they look when they're sick.

00:11:52.980 | It's because there's this overall suppression of certain kinds of activities and an enhancement of other kinds of activities.

00:11:59.700 | And this is really important.

00:12:01.220 | Sickness behavior is actually a motivated state.

00:12:05.620 | It's a state that's designed to accomplish certain things.

00:12:09.380 | One of the other features of sickness behavior, in addition to being lethargic, loss of grooming,

00:12:14.260 | will be a loss of appetite, right?

00:12:18.500 | Oftentimes people who have a great appetite normally just won't feel hungry at all.

00:12:22.740 | When we have that, we can be kind of irritable.

00:12:25.940 | We don't want to do certain things and we just want to be left alone.

00:12:28.900 | Things are harder.

00:12:30.660 | How?

00:12:31.220 | Why?

00:12:32.020 | Well, there's a known pathway, which is the so-called vagus nerve that connects the body and the brain,

00:12:39.380 | signals to particular brain sites to engage this category of motivational state that we call sickness behavior.

00:12:48.100 | The vagus nerve is a very extensive nerve pathway.

00:12:51.620 | It's the 10th cranial nerve, comes out of the back of the brainstem, heads into the body,

00:12:57.700 | and branches out extensively to innervate or connect to many of our organs, including our lungs, our heart, our gut, etc.

00:13:06.020 | And all of those organs are able also to send neural signals back up to the brain.

00:13:10.900 | We sometimes hear the vagus as the route to calming ourselves down.

00:13:16.420 | Unfortunately, that's more or less a myth that I don't know how it got propagated.

00:13:21.620 | There have now been many studies of the vagus in various contexts, including in sickness behavior,

00:13:27.860 | and it's very clear that the vagus nerve is the fast pathway by which an infection in the body is

00:13:35.780 | signaled to the brain to a particular location in the brain called the hypothalamus, which harbors a lot

00:13:40.580 | of different types of neurons.

00:13:42.180 | Neurons, for instance, in the pre-optic area that increase body temperature and fever, right?

00:13:47.220 | That's one of the most important things is to increase body temperature in order to,

00:13:51.060 | it's the body's attempt to kill off this invader because many viruses and many bacteria don't

00:13:59.380 | survive well at elevated heat.

00:14:01.220 | That's the function of a fever.

00:14:02.660 | It also sends input to areas of the brain that change your perception of the outside world.

00:14:09.540 | One of the most obvious of these, obvious once I tell it to you, is photophobia, right?

00:14:16.340 | I love bright sunshine.

00:14:17.780 | I love bright lights when I want to be alert.

00:14:19.940 | But most people, when they are sick, when there's an inflammation response in the body,

00:14:24.500 | they feel like bright lights are kind of aversive.

00:14:27.540 | They get a well-described kind of classical photophobia.

00:14:30.980 | And that's mediated by a pathway that goes from your eye to an area of your thalamus,

00:14:37.780 | called the anterior nucleus of the thalamus.

00:14:41.060 | Then from there up to the outer lining of the brain, which is the meninges,

00:14:46.260 | just sort of on the outside of the brain where the brain starts to interface with some of the other

00:14:50.900 | connective tissues.

00:14:51.700 | It can actually create a photophobia and a headache when one is ill.

00:14:56.180 | And the last element I'd like to talk about is the rest.

00:14:59.140 | There's something that gets triggered from the body to the brain, to the hypothalamus,

00:15:03.700 | and there are nuclei there that promote the desire to sleep even during the daytime,

00:15:10.100 | what would normally be the active phase of your circadian cycle.

00:15:13.300 | Now, that is really interesting because what's happening here is you've got

00:15:18.660 | multiple pathways that are saying avoid light, reduce your amount of behavior,

00:15:24.820 | heat up all the things that are making you sick.

00:15:27.540 | This is sickness behavior, and it's going from your body to your mind to make you do the right thing.

00:15:33.620 | Now, there's also a slow pathway that's purely mediated by the blood, so-called humoral factors,

00:15:41.060 | not because they're funny, but humoral factors are factors of the blood.

00:15:45.140 | Now, if you have an infection for many hours or days, the amount of IL-6 and IL-1 and tumor necrosis factor and

00:15:56.100 | other inflammatory cytokines is starting to increase such that the total amount in your circulation gets high

00:16:03.460 | enough and is communicated to the brain.

00:16:06.100 | And it tends to enter the brain through a particular type of tissue that's really interesting called

00:16:11.380 | choroid, C-H-O-R-O-I-D.

00:16:14.660 | The choroid starts releasing and responding to these cytokines,

00:16:19.220 | the inflammatory cytokines, and then the brain actually starts to experience all sorts of changes

00:16:27.060 | in terms of inflammation to neurons.

00:16:29.460 | Your memory tends to get poor.

00:16:31.140 | Your cognition tends to get poor.

00:16:33.300 | These are transient things.

00:16:34.980 | Most often, eventually, these things will pass.

00:16:37.620 | But this is deep into sickness when you're really feeling lousy.

00:16:40.420 | You can't read.

00:16:41.060 | You can't watch a movie.

00:16:41.940 | You can't do anything.

00:16:42.580 | So if you ever get sick and you just can't be bothered by anything,

00:16:46.660 | it's probably because you've had that fast response from the body,

00:16:49.940 | and you've also had this slower response where you literally have a set of tissues in your

00:16:54.580 | brain that are sending out these inflammatory signals.

00:16:58.340 | And now your whole brain is starting to cope or is trying to cope with this infection.

00:17:02.900 | So you've got a slow pathway and a fast pathway.

00:17:05.060 | That all sounds really terrible.

00:17:07.620 | So now I'd like to talk about what you can do to reduce the probability of getting sick.

00:17:13.620 | And there are actually things that one can do as you start to get sick.

00:17:19.060 | And once you're sick, to accelerate the healing process by flipping the equation.

00:17:24.340 | Up until now, we've been talking about how the body activates certain areas in the brain

00:17:29.140 | to create sickness behavior that's very much like depression.

00:17:31.860 | You're probably all familiar with this from any time you've had a cold or a flu or something

00:17:35.140 | really lousy or an injury.

00:17:36.420 | Now let's flip the equation and ask, what can we do with our nervous system in order to enhance

00:17:44.020 | the function of our immune system in order to be able to heal and recover from illness?

00:17:48.980 | And injury more quickly.

00:17:50.100 | We all know what we should do.

00:17:51.860 | We should all hydrate, drink some water, and go to sleep.

00:17:54.980 | Right?

00:17:55.940 | That's what we are all told.

00:17:57.940 | But there are actually things that you can actively do in order to get your immune system

00:18:04.020 | to deploy a more robust response at that early phase of potential infection.

00:18:13.140 | Let's focus first on the rest component.

00:18:15.220 | Yes, of course, we are all told that we should take a hot shower and go to sleep,

00:18:20.020 | you know, and get nine or 10 hours of sleep.

00:18:21.780 | But there's an interesting way of looking at sleep specifically for its role in enhancing the immune

00:18:29.700 | system.

00:18:30.420 | During sleep, and in particular during sleep that's associated with the early stage of any kind of viral

00:18:35.300 | or bacterial infection, the so-called glymphatic system is much more active than it would be normally.

00:18:42.580 | What's the glymphatic system?

00:18:43.940 | The glymphatic system with a G is a system in the brain by which debris that accumulates throughout the

00:18:51.300 | day, but in particular debris that accumulates under conditions of neuro inflammation and inflammation

00:18:58.100 | of the body is cleared out or is washed out of the brain.

00:19:02.420 | And the activity of this glymphatic system is extremely important for the recovery from infection

00:19:10.580 | of any kind.

00:19:11.540 | There is a way that you can increase the activity of your glymphatic system under normal circumstances.

00:19:17.380 | Because of the mechanics of the glymphatic system, it turns out that if you elevate your heels

00:19:23.940 | by about 12 degrees, it doesn't have to be exactly 12, as you sleep by putting maybe a rolled pillow

00:19:29.220 | or two pillows underneath your feet, by having the head below your legs, it seems that there's

00:19:35.620 | more glymphatic washout or clearance during sleep.

00:19:39.220 | So I would say if you're not feeling well, yes, take the hot shower, yes, get into bed and go to sleep,

00:19:44.660 | but elevate your feet to try and increase the activity of the glymphatic system.

00:19:48.900 | Some might even consider that if you have to be awake, that you might want to be awake with your

00:19:54.980 | feet elevated above your head.

00:19:57.380 | Now that might not be practical for the workplace, but it might be practical for a short nap during the

00:20:02.740 | day or something of that sort.

00:20:04.180 | So I would like to do an in-depth analysis of a study that has achieved some prominence out there,

00:20:10.420 | not just in the scientific literature, but on the internet, because it relates to how particular

00:20:17.540 | types of breathing can impact the immune system and the ability to combat infection.

00:20:23.940 | The title of this paper is Voluntary Activation of the Sympathetic Nervous System and Attenuation of the

00:20:30.180 | Innate Immune Response in Humans.

00:20:32.340 | This is a paper that was published in PNAS, which is the Proceedings of the National Academy of Sciences,

00:20:38.900 | USA.

00:20:39.460 | It's a very prestigious journal, and I just want to describe the basic contour of the study.

00:20:44.740 | I'll explain the findings, and then I want to go in-depth and explain the mechanistic basis for

00:20:50.260 | these findings and the protocol that we can all export from these findings.

00:20:55.380 | So here we go.

00:20:57.300 | So first of all, a couple of terms so that everybody is on the same page.

00:21:00.740 | The sympathetic nervous system is one division of our nervous system.

00:21:06.100 | It's a set of neurons down the middle of our spinal cord and in our brain

00:21:10.180 | that generally lead to a heightened state of arousal and alertness.

00:21:15.620 | It's associated with epinephrine release in the brain and adrenaline release in the body.

00:21:19.700 | It's the so-called fight-or-flight system when it's really active,

00:21:24.100 | but it's the system that's active when we are wide awake.

00:21:27.700 | And we already talked about the innate immune system.

00:21:32.500 | That's that first line of defense after the skin barrier, of course,

00:21:36.020 | whereby some infection comes into the body and there's this rapid response of increasing

00:21:42.020 | inflammation.

00:21:42.820 | And that's also about the time that you first feel lousy.

00:21:46.660 | So when you start to feel like, "Oh, I think I've got something.

00:21:48.820 | I don't feel right.

00:21:49.700 | A headache.

00:21:50.340 | I feel nauseous.

00:21:51.620 | I'm heating up.

00:21:52.500 | I don't feel good."

00:21:53.380 | That's the innate immune system kicking in.

00:21:56.580 | That's what they did in this study.

00:21:58.900 | They injected people with E. coli.

00:22:01.460 | There's a bacteria which makes people, all people feel terrible.

00:22:06.500 | These people voluntarily signed up for this study.

00:22:08.660 | However, some of the subjects in this study

00:22:12.980 | performed a behavioral protocol that can best be described as cyclic hyperventilation.

00:22:20.100 | So they're comparing controls that do just sort of a basic meditation versus people that do this intense

00:22:25.540 | breathing, followed by some breath holds.

00:22:27.780 | In the intervention group, the breathing group, plasma levels of anti-inflammatory cytokine IL-10.

00:22:33.940 | So this is a cytokine that lowers inflammation, increased after endotoxin administration and that was triggered by an increase in epinephrine and adrenaline.

00:22:46.420 | So in other words, doing a particular pattern of breathing allowed an anti-inflammatory cytokine to be turned on.

00:22:51.780 | 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.

00:23:06.980 | Finally, flu-like symptoms were lower in the intervention group.

00:23:11.620 | So this is an amazing finding, right?

00:23:13.780 | These are human subjects.

00:23:14.900 | One is one group of subjects is doing this breathing protocol.

00:23:18.420 | The other group of subjects is just meditating.

00:23:20.500 | They both, both sets of subjects have been injected with E. coli.

00:23:25.620 | So, you know, everyone's getting the same amount placed into their system.

00:23:30.020 | How in the world does this work?

00:23:31.220 | Why does this work?

00:23:32.340 | First of all, what is this magical pattern of breathing?

00:23:35.300 | Some of you may recognize this as so-called Wim Hof breathing.

00:23:38.500 | The breathing that is so-called Wim Hof breathing is very similar, not exactly the same, but very similar to TUMO breathing, as it's been described historically.

00:23:48.900 | In the science and physiology community, refer to it as cyclic hyperventilation, which just means repeated deep breaths in and out.

00:23:56.740 | And then there are these retention.

00:23:58.020 | So I'm, because I'm here in the hot seat anyway, I might as well demonstrate it for you so you know what this looks like.

00:24:04.820 | 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.

00:24:16.580 | That's the retention.

00:24:17.620 | And then at some point, 15 to 60 seconds later, repeating the 25 or 30 breaths.

00:24:24.340 | And then again, a breath hold with lungs empty.

00:24:28.100 | I'm not going to do the whole thing right now, but it goes something like this.

00:24:36.100 | 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.

00:24:47.860 | It's caused by that breathing pattern.

00:24:49.620 | And then exhaling all of one's air, no speaking in between like I'm doing.

00:24:53.620 | 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.

00:25:05.620 | Basically, this study looked at people doing cyclic hyperventilation with retention, three rounds of 25 to 30 breaths, followed by exhale hold in between.

00:25:17.380 | This study looks at a couple of various duration, but in general, 15 to 60 seconds is typical.

00:25:22.580 | So what's going on here?

00:25:23.620 | 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?

00:25:38.660 | This is beyond the scope of this discussion, but that it's actually the release of epinephrine, aka adrenaline,

00:25:44.900 | that's causing this reduction in inflammation.

00:25:48.340 | And that's actually supported by something that you've probably experienced before, which is if you've ever worked, worked, worked, worked, worked really hard,

00:25:57.140 | or you've been a caretaker for somebody else, or studying for exams, and people around you are getting sick,

00:26:02.660 | and you're just powering through it, and you're not getting sick, but then you stop, you turn in your final exam,

00:26:08.420 | you stop taking care of somebody else, or you finally stop and rest, or you go on vacation, and then you get sick.

00:26:14.500 | You get sick.

00:26:15.140 | 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.

00:26:28.340 | And that brings us to a larger theme, which is that stress and combating infection or a wound is not one unique system.

00:26:37.620 | It's the same stress system that you use to combat psychological stress.

00:26:41.060 | So when you're very, very stressed, at least in the short term, because you release so much adrenaline and epinephrine,

00:26:47.700 | you're actually better able to combat infections and you reduce inflammation and the whole feeling lousy response, right?

00:26:53.700 | Remember, reduced flu-like symptoms here.

00:26:55.700 | 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.

00:27:04.340 | If I feel like I've been running myself ragged, or if I somehow, for whatever reason, have a tickle in my throat,

00:27:10.340 | or I have that sensation in my nose, like I might have caught a bug of some sort, I will do this pattern of breathing.

00:27:18.020 | I've been doing it consistently, gosh, for the last four years or more.

00:27:22.660 | Now, this is just anecdotal reports, but I find that it allows me, indeed, to either have those early symptoms disappear,

00:27:32.900 | or it allows me to just kind of push through and harder longer.

00:27:36.900 | I don't suggest people continue to push through exposure to infections.

00:27:41.700 | Obviously, you don't want to infect other people,

00:27:43.540 | nor do you want to crash and suddenly get a massive illness of some sort because you stop doing this breathing.

00:27:50.260 | But I do think it's a useful tool.

00:27:51.940 | It's a purely behavioral intervention that has been shown here.

00:27:56.340 | And now there are additional studies on the way to enhance the function of your immune system

00:28:02.340 | and to reduce inflammation.

00:28:03.860 | And this is, to me, one of the most concrete examples of a zero cost tool that bridges the

00:28:11.860 | activation of the nervous system through breathing with the immune system by way of releasing adrenaline

00:28:19.300 | and thereby reducing the terrible effects or feelings of lousiness from a, in this case, an E. coli infection.

00:28:28.260 | There's one last very interesting feature of this study

00:28:31.780 | that I want to emphasize.

00:28:33.300 | And that was that they actually measured the so-called catecholamine concentrations.

00:28:38.100 | Catecholamines are things like dopamine, epinephrine, norepinephrine.

00:28:41.460 | These are chemicals in your nervous system and body that promote states of alertness.

00:28:47.780 | Dopamine, of course, part of the reward and motivation pathways.

00:28:52.820 | They explored the levels of these molecules in blood, in plasma during and after this breathing protocol.

00:29:00.420 | And as interesting, as I mentioned before, epinephrine showed robust increases compared to the control group.

00:29:06.340 | Norepinephrine, significant increases occurred in the breathing group, but in the cyclic hyperventilation retention breathing group, of course, but less so.

00:29:18.420 | And dopamine levels actually dropped somewhat.

00:29:19.940 | And dopamine levels actually dropped somewhat.

00:29:20.980 | But this is very interesting because there's a new and emerging literature,

00:29:27.700 | largely from Aysa, A-Y-S-A, Rohl's lab in Israel.

00:29:33.540 | What her laboratory has shown is that motivational state and mindset has a powerful impact

00:29:41.220 | impact on various aspects of the immune system that were thought to be independent of the brain and mind and thinking.

00:29:48.260 | They explored the well-established psychological phenomenon that when cancer patients or very ill people

00:29:58.740 | or people who are suffering from very debilitating injuries, when people had or reported a sense of hope,

00:30:07.140 | their rates of recovery were much higher, right? Sounds very subjective.

00:30:11.940 | But what is a sense of hope? A sense of hope is a sense of the future.

00:30:17.380 | A sense of the future is tightly associated with the dopamine system.

00:30:21.060 | And so what they've discovered and through other studies from other groups have discovered is that

00:30:26.260 | stimulation of the dopamine pathway, either simply by thinking about a future, ideally a positive future,

00:30:33.940 | but thinking about a positive future leads to activation of this so-called mesolimbic reward pathway

00:30:38.660 | and could reduce the size of tumors, could accelerate wound healing, could greatly accelerate the passage

00:30:46.660 | from a state of illness to a state of health and well-being.

00:30:49.940 | It's because this reward pathway and the fact that it's related to a sense of the future

00:30:56.340 | seems to liberate entire systems within the body that make inflammatory cytokines go down

00:31:03.060 | and anti-inflammatory cytokines go up exactly as was demonstrated in the beautiful PNAS study where

00:31:12.020 | breathing, cyclic hyperventilation, was used to increase epinephrine, increase norepinephrine,

00:31:18.580 | and to augment the catecholamine system. So I think that the bridges between these studies are really

00:31:25.940 | relevant. There was a very exciting article published from Chu Fu Ma's lab at Harvard Medical School

00:31:30.740 | and the title of the article is "A Neuroanatomical Basis for Electroacupuncture to Drive the Vagal Adrenal Axis"

00:31:38.820 | when Chu Fu's lab looked at stimulation of the body with so-called electroacupuncture. So these are needles

00:31:45.940 | where a small bit of electrical current, low level of electrical current is passed into the needle and

00:31:52.340 | therefore into the body. They located sites on the body that can increase inflammation by way of releasing

00:31:59.940 | inflammatory cytokines. These areas included the abdomen and they found areas on the body such as the

00:32:06.660 | lower limbs or the hind limbs in this case that can stimulate the vagal adrenal reflex

00:32:12.740 | and can lead to reduced inflammation. And what was really interesting is that they figured out that

00:32:20.740 | it was activation of nerve endings that resided in the fascia. The fascia is a really thick sheath of

00:32:28.500 | tissue that surrounds muscle. And so what they discovered is there's a specific population of neurons,

00:32:34.500 | those neurons have a name as they often do in science. Name isn't important, but if you want

00:32:38.660 | to look it up, it's the PROK-R2 neurons, P-R-O-K-R2 neurons. And they send a connection deep into the

00:32:47.780 | limb fascial tissue. And then they send another wire up into the spinal cord and to a region of the hind

00:32:55.860 | brain, brain in the back of your brain, kind of near your neck called the medulla, in the medulla oblongata.

00:33:01.220 | That neuron also has a name called the DMZ. Doesn't matter. And that neuron connects to the adrenal gland to

00:33:07.060 | release our good old friends, the catecholamines, noradrenaline, adrenaline and dopamine or norepinephrine,

00:33:14.180 | epinephrine and dopamine. So what is all this saying? This is saying that activation of the deep fascial tissue

00:33:20.580 | causes a chain of neural reactions that leads eventually to the release of norepinephrine,

00:33:28.180 | noradrenaline, adrenaline and dopamine. And once again, lowers inflammation very much like the breathing

00:33:35.540 | study that we talked about earlier in the pattern of cyclic hyperventilation with retention leading to

00:33:40.100 | reductions in inflammation. Okay. So thus far, we've been discussing how one can prevent

00:33:46.660 | getting sick or when one starts to feel ill, how one might be able to shorten the course of that

00:33:52.660 | infection by ramping up the activity of the immune system. But what about when you're already

00:33:58.420 | experiencing symptoms? There are many ways to address that at the symptom level. You're probably

00:34:03.940 | aware of all the over-the-counter medications, many of which focus on the epinephrine system. You know,

00:34:10.580 | things that are of the pseudofed variety prevent or reduce congestion because of the way that they cause

00:34:18.180 | release of epinephrine and some of the effects on dilating the bronchioles and dilating the nasal

00:34:24.660 | passages and so forth. I'm not going to speak to whether or not those are good or bad choices.

00:34:30.660 | They do have a couple of effects that are not so great for the course of treating the underlying cause,

00:34:37.060 | which are, first of all, they can cause dehydration. So you have to make sure that you're hydrating well,

00:34:42.340 | both fluids and electrolytes. And they also can interfere with sleep. There is an interesting

00:34:49.380 | alternative choice. And when I say alternative, I do mean alternative. The choice I'm referring to is

00:34:54.820 | spirulina, which is actually a form of algae. There are some really nice studies and some data

00:35:00.340 | and also an understanding of the mechanism by which spirulina can have potent effects in reducing what's

00:35:05.940 | called rhinitis, which is a fancy word for congestion of the nose and inflammation of the nose.

00:35:11.780 | These looked at humans. So this is not a mouse study. This is a study on humans.

00:35:15.780 | Both sexes are males and females. In one case, looking at a hundred plus subjects,

00:35:22.260 | 129 subjects, the other 65 subjects. So a decent number of subjects, randomized trial,

00:35:26.900 | double-blind, both cases saw significant decreases in nasal obstruction, improved ability to smell,

00:35:35.460 | improved sleep, daily working cytokine, inflammatory cytokines were reduced as well.

00:35:43.220 | Reduction nasal itching, all the stuff that you'd like to experience, I can imagine,

00:35:48.660 | after taking two grams, two grams, not milligrams, but two grams of spirulina.

00:35:53.540 | Once again, we've covered a lot of information. Today, we learned about the immune system,

00:35:57.220 | the adaptive immune system, the innate immune system, and the nervous system and how those interact.

00:36:02.260 | And throughout, we discuss protocols that can allow you to tap into this relationship between the nervous

00:36:07.540 | nervous system and immune system and hopefully avoid end or shorten the course of any illnesses,

00:36:13.780 | injuries or inflammation that you might encounter.

Using Your Nervous System to Enhance Your Immune System | Huberman Lab Essentials

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