- Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm
a Professor of Neurobiology and Ophthalmology at
Stanford School of Medicine. Today, we are discussing
the immune system, and we are also discussing
the nervous system, which is the brain, spinal cord, and the connections of
the brain and spinal cord with all the organs of the body. We are also going to discuss
how the nervous system can be used to activate and
control the immune system. Now, about 10, 20 years ago, if somebody said that
the mind could control the immune system, they'd
probably get laughed out of most academic conferences. And certainly the work
wouldn't be published in quality journals, but
nowadays there are dozens, if not hundreds of quality
peer-reviewed studies on how the mind and how the nervous system can control activation
of the immune system. This is a wonderful
growing body of research. And just to give you a hint of where we are headed with
this, just this last week, there was a paper published in "Nature" which is the apex journal
for scientific publishing, premiere journal, extremely stringent, a paper published in "Nature" from Qiufu Ma's lab at
Harvard Medical School, explored how acupuncture can reduce inflammation in the body. And I will describe this study
in a bit more detail later, but what they discovered was
that by stimulating the body in particular ways at
particular sites on the body, they were able to liberate
certain cells and molecules that enhance the function
of the immune system, and potentially can be used to combat different types of infection. And just to give you another little hint, they found that a particular
type of organ tissue called fascia, some of you
may have heard of fascia, fascia surrounds our muscles. Just to look at it, you might think it's a
kind of useless tissue, it's sort of like a dense bag in which the muscles are contained. Well, it turns out that those dense bags are much smarter than we thought. They don't have a mind of their own, but by stimulating the fascia in a particular location on the body, there's a pathway leading
out of that fascia directly to an organ
called the adrenal medulla, I'll explain what all this means, that could liberate particular chemicals that had a potent
anti-inflammatory effect. So what we're basically saying is that the nervous system
acts as a set of highways between the different
tissues of your body, calling into action the immune system, liberating particular molecules
that can reduce inflammation and lead to faster healing. And I will explain how all of that works as well as some other
non-acupuncture methods for activating and enhancing the function of the immune system. So, today, we're going
to be talking all about healing with the mind in
a completely non-mystical, non-abstract sense. Before we begin, I'd like to
emphasize that this podcast is separate from my teaching
and research roles at Stanford. It is, however, part
of my desire and effort to bring zero cost 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 ROKA. ROKA makes eyeglasses and sunglasses that are absolute suburb quality. I've spent a lifetime
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"Huberman" at checkout. Okay, let's talk about the immune system, and the nervous system,
and how the two interact, and how you can control your immune system to serve you better. We are going to talk a lot
of mechanistic science, a little bit of detail,
you'll learn some new language around the immune system; names of the different
cell types and so forth, but I promised to make it all very clear, regardless of your background. We are also going to
discuss a lot of tools. And I think many of you are
probably here because you want to know what you can do in order to boost or enhance the function
of your immune system. That's a very reasonable question to ask. I want to begin by just
acknowledging that if one were to put that question into the internet, you would get back a lot of answers. And there is now a sort of
generic form of that answer that deserves our respect, but is not going to be the
topic of conversation today. I just want to tip my hat to it, however, and list off a few of
the things that we know set us up to be healthier than we would be if we didn't do these things. So the first of course is
the foundation of all mental and physical health, which
is to get adequate sleep. Meaning enough sleep,
whatever it is for you that you require, to get deep sleep, so it's
got to be of high quality, and to time that sleep correctly. Meaning you can't sleep
during the day one day, and at night the next day, and expect your system to function well. I've talked a lot about
that before on this podcast. You need a relatively
consistent sleep schedule most of the time, about 80% of the time, or even better would be 90% of the time. But the realities of life
make it that we can't always go to bed at the same time and wake up at the exact same time. Okay, so we need sleep. We do need sunshine. Why do we need sunshine? Because it sets our rhythm
into a regular state where the genes in all of our cells can be expressed at the correct times. We're sort of a factory
of cells, if you will, and that factory can only
run properly if it knows when certain things should be active and when certain cells
should not be active. And the best way to coordinate
all of those activities of all the cells is to
get sunshine in your eyes in the morning and again in the evening, and not to get too much
bright light in your eyes in the middle of the night. That's just foundational. And then any lists that you'll find on any number of websites
on the internet would say, "Okay, get good sleep,
get sun, get exercise." How much exercise? We should all be getting
150 to 180 minutes of zone two cardio. That's cardiovascular
exercise where we can just barely hold a conversation
or maybe not, per week. We should be eating well. We're always told we have
to get good nutrition. What good nutrition means to
you is going to be different than what it means to somebody else. But we acknowledge that food intake and quality of food in particular,
avoiding processed foods, that's going to be important. Social connection is important. Hydration is important. You're starting to get the picture. We can take all that,
acknowledge it as useful and foundational for
mental and physical health. But of course there are many
people who still struggle with getting ill too often, or with not being able to heal from physical injuries and wounds, or from various bacterial
and viral infections quickly enough or deal
with chronic disease. And so, today's really about how you can take all of that information,
acknowledge it, and follow it. But in addition to that, there are things that
you can do to leverage your nervous system in order
to enhance the function of your immune system in very robust ways. So that's where I'd like to
shift the conversation to. The first topic we have to
attack is the question of what is the immune system
and how does it work? I think many of you have heard
of antibodies or killer cells or the various organs of
the body that are involved in the immune system, like the bone marrow,
the spleen, the thymus, and the lymph nodes. 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. For some of you, this might be too basic. It might be a little bit of background that you already know. I think for most of you,
this information will be new. And I promise you, you
don't need a biology or medicine background in
order to understand this. It's actually really simple because it is truly elegant in design. You have three main layers
of defense for your health. These are the three things
that are constantly at work to protect you from invasion
and illness from bacteria, from viruses, and from parasites. 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. And your skin is a very important aspect of your immune system. If you've ever had a cut, you essentially have a
breach of the boundary that is your immune system, and you would notice a number
of things would happen. You might get some
swelling around that cut. You might get a scab, likely
you would get a scab over time. If it got dirty, there were
some bacteria that got in there, you might see some accumulation
of white blood cells, what's called puss. I know it's kind of gross,
but that's what that is. It might take on a yellow tint
because of the accumulation of some dead cells there. But basically your skin
is the primary barrier through which you keep
things from the outside that could harm you from
getting to the inside. Now, still in category one, your body and your external surface, you have openings to that surface, right? You're not just a round or a body shaped completely covered up with skin. You have openings, 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, but bad things, meaning
things that can harm you, can get into those systems. 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 on 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. 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. Now, the mucus is constantly
being turned over, as we'll talk about later, the chemistry of that
mucus is really important in order to make sure that certain things don't make it into your system, and other things are allowed
to move through your system and you can extract nutrients from them. So the reason I'm talking
about this first category of barrier for immune
system in such detail is I'd like you to envision
yourself as a human, of course, but as a human that is a clear
entity from everything else. And you have to bring in the right things and you have to keep out the
wrong things or kill them. 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. So the innate immune
system is what I would call the second layer of defense. It's very fast. So whether or not it's
bacteria, virus, or parasite, what happens when you have
something enter your body, maybe you swallowed it, maybe
got in through your eyes, maybe you shook somebody's
hand who is carrying a particular kind of illness,
and then you wiped your eyes. And I've talked about
on this podcast before, very soon after we meet another person, usually within 30 seconds,
believe it or not, most people wipe that person's chemicals somewhere on their face or
on their body's surface. This has been demonstrated
over and over again. If you want to learn more about that, we did an episode all
about chemical signaling, where you can learn about it. I know it sounds weird and you
might say, "I don't do that," but indeed you do, most of
the time most everybody does. Okay, so, this innate immune
system is this rapid response when something enters our system and our body doesn't recognize it. It's not food, it's not clean air, 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. 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 are things like neutrophils, macrophages, natural killer cells are just a few of the many types of immune cells. So there's kind of like
an ambulance system, but rather than go and
try and heal something like a paramedic would,
they go there and they try and surround and kill
whatever this invader is. They work in concert with
two other assistants, and those assistants are
called the compliment proteins. Compliment 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. So they sort of put an "eat me" tag on it. They basically put a
chemical tag onto invaders that then allows those white
blood cells, neutrophils, macrophages, natural killer cells to say, "Ah, I need to basically kill this thing, and then wrap it in a
body bag and send it off. Kill that thing, wrap in a
body bag and send it off." And I'm using the analogy of the body bag, but in the sense it's the right one rather because these cells that
come in and kill things, the way they do that is actually to engulf the invading bacteria, virus or parasite. So they actually surround it. And when you see puss or you see infection in maybe a cut on the skin
or something like that, or even in an ingrown hair
that gets some bacteria in it, that puss and the white part, I know it's kind of gross to talk about, but those are the white blood cells, oftentimes it's dead cells, and that's the dead invader sitting there. So it's trying to create
an isolated compartment 'cause it wants to keep it
in that part of the body. Okay, so you've got the
innate immune system, the compliment comes
through blood and helps it by tagging certain things
with an "eat me" signal. 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 of what we call cytokines. And the cytokines are
things like interleukin-1, interleukin-6, tumor
necrosis factor alpha. You may have heard of these
things if you are at all curious about or have been learning
about the health space, online health space, especially
in the last few years, inflammation is all the buzz word now. Everyone's talking about inflammation, inflammation, inflammation. What do we mean when we say inflammation? Well, inflammation is a physical response, but it's also a chemical response. And many times the markers of
inflammation that are measured in people or in animal models
where this research is done, are things like
interleukin-1, interleukin-6, tumor necrosis factor alpha. So when those go up in the blood, it's a sign that somewhere there's a cell that's saying "help me, help me." And is secreting these
things which calls in those neutrophils, macrophages,
natural killer cells, and white blood cells, okay? And it might help to remember all this, by just telling people
that what interleukin means is to communicate, right? So the interleukin is
shouting out "help me," the compliment 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. 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, 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. So, the adaptive immune system
has this incredible ability to show up at the site of invasion or infection or inflammation. It's called there by various cues, including the cytokines that
we talked about earlier. 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. So if that particular
invading bacteria or virus has a contour that's kind
of rippled or kind of spiky or whatever shape it happens to have, it creates an imprint of that. 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. 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. This is the basis of what
we call an enhanced ability to combat certain types of infections. And it's really a wonderful, and I mean, I can't even state how
incredible this really is, that all of our bodies
have this capacity, right? We have something called leukocytes. These are essentially white blood cells. We have red blood cells
and white blood cells, and they both are derived from
the same type of origin cell. It's a stem cell. When you hear stem cell,
a stem cell just means a cell that can become many
different types of other cells. We sometimes hear about stem
cells in terms of people that are getting injections of stem cells or the potential therapeutic effects or potential of stem cells. But we all harbor certain
stem cells within us as well, that can become lots of
different cell types. And there's one particular
type of stem cell, which is the hematopoietic stem cell, which can give rise to red blood cells and white blood cells. And in general, these
reside in the marrow, at least in adults. So, in our bone marrow, we have this ability to make certain cells that can go out when they
are called out chemically, they get called out to sites of infection and create antibodies, and then maintain those
antibodies in our system, or have a memory of that
particular infection so that if the infection comes back again, we can kill it off immediately. And it doesn't have to pass
through these multiple stages of first, the innate response, then the adaptive
response, taking some time. 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 a part of the adaptive immune response
in creating antibodies. 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. So IgG tends to come
up a little bit later. So, just to recap, something gets into your
system through your eyes, through some hole in your skin,
a cut, through your mouth, sexually transmitted
diseases come in through the mucus membranes that
are on the genitalia or in the genitalia, sexually transmitted
disease, airborne disease, gets into the mucus, somehow
gets into the bloodstream. 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. So, how do we keep these three barriers or these three defense
systems to infection tuned up? Well, leaving aside the list of things that I mentioned before that generally enhances their function, things like sleep and
sunlight and good nutrition, et cetera, the sort of generic
things for good health, 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. 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. 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, into the rectum. It's well-established that
there are healthy microbiota that live all along that length, and that they differ along that length. There's also a urethral microbiota, and there's a vaginal
microbiota that promotes health of that environment as well. So how is it that one can
maintain the healthy microbiota and not favor growth of harmful bacteria, or allow that mucus lining
to become too permeable to the bad stuff that can
come in from the environment? Well, as far as we know, there are three main ways to do that. The first two are purely
structural and mechanical. It's very clear now from work, some of which was done at
Stanford, but elsewhere as well, that the nasal microbiome
is particularly good at scrubbing bacteria, at preventing certain types of infections. So, 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. The mouth contains certain
structural features, even organs and cell
types that can protect against incoming infection, but you don't want to be a mouth breather for a variety of reasons. And there's a terrific book called "Jaws: A Hidden Epidemic," which was written by my colleagues, Sandra Kahn and Paul Ehrlich at Stanford, and Stanford Medicine with a foreword by Jared Diamond and Robert Sapolsky. So it's really a lot of
heavy hitters on that book that talks about the increase in infection that one gets when
breathing through the mouth, as opposed to the nose. Now, of course, during hard exercise, one breathes through the mouth, that's not necessarily bad. When one is eating or speaking, that's not necessarily bad at all. I guess it depends on what you're saying. That was a joke. But in general, when possible you want to be breathing through your nose. Many people have trouble
breathing through their nose because of so-called deviated septums or chronically collapsed sinuses. The best way to dilate
those sinuses is actually to breathe through your nose. So it can take a little bit of time, but there is some
plasticity to the sinuses. And so, be a nose breather,
not a mouth breather, you will combat more of the infections that you are constantly confronted with. I should mention that
we are always bombarded with different types of bacteria, viruses, and parasites in our environment. And the goal of course, is to reinforce your immune system, so you can keep these things
at bay and not get sick. There's actually a
paper that was published in Cell Reports, "Cell Press Journal," excellent journal that showed
that the nasal microbiome, it has particular species of microbiota that are good at fighting off infection. There has not been a direct
link between particular patterns of nasal breathing and
the nasal microbiome yet, but oxygenation of that environment by breathing through your nose, turns out to be quite important overall for enhancing it as a filter. So don't just think of
your nose as something to smell foods and to bring in air. It's also an active filter for
things that could invade you. 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. And as I mentioned earlier, we tend to do this subconsciously. But the reason to avoid
doing that is the eyes are a primary entry point for
a lot of bacteria and viruses. You're constantly lubricating
the surface of your eyes with the so-called lacrimal glands, and tears and things of that sort. If you've ever noticed when
you wake up in the morning, you have some sleep in your eyes, you know the kind of crusty stuff in the corners of your
eyes or on your eyelashes, that sleep, that crust
are actually dead bacteria that you've successfully
battled during the night. Okay, that's what that is. It's not the accumulation
of some healthy tissue. It's the accumulation of that
your healthy mucus membranes and tears and other things
that are specifically combating those bacteria. So, I know that sounds a little bit gross, but that's what that is. So you're wiping away the
casualties of a battle that you fought at night. So during the daytime, you
don't want to introduce viruses and things to your eyes
as much as possible. It is a primary site of entry. This is why people wear
goggles in surgical units and things of that sort, to try and avoid getting
things into their eyes. Very, very important. 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. I've talked about this
before a bunch of times on the podcast, but these
are data from my colleague, Justin Sonnenburg's lab at Stanford Med. And there, I just wiped my eyes. Yep, you got me. But a paper published
in the journal "Cell," which is a absolutely spectacular journal, really points to the fact that when people eat fermented foods,
two to four servings per day, it helps reduce the activity
of certain cytokines. Now, you know what those are, right? Cells make cytokines to call
out, "help me, help me." To reduce the amount of cytokines, the so-called inflammatom. Now that doesn't render
those cells more vulnerable. The reason they saw a
reduction in IL-6 and IL-1, and some of these other cytokines is because 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. So, don't wipe your eyes,
keep your hands clean, everyone tells you that, right? But keep your hands clean,
don't wipe your eyes, be a nasal breather, not a mouth breather, unless you're speaking,
exercising or eating, and keep a healthy gut microbiome by eating two to four servings
a day of quality, low sugar, fermented foods, things like sauerkraut, things like natto if you can access that. I've tried it before, it's interesting. It's sort of an acquired
taste, kimchi, pickles, again, low sugar sources
are going to be the sources that are going to be
most effective for this. So now you're armed with three
ways to enhance the function of your immune system and
combat infection that is, I like to think separate from the typical type of information that you
get such as get good sleep, good nutrition, good social
connection, et cetera. All of that stuff still holds true, but these three other points
I think can really make a substantial difference
in terms of bolstering the immune system, your immune system. I do want to mention,
because these names are going to come up several times
during this episode, that while interleukins like IL-6 and IL-1 encourage inflammation, they
are these "help me" signals that call in cells to gobble up invaders. There are some interleukins
that are anti-inflammatory. And the one that I'd like
to highlight in particular, because it will come up
again in a little bit is interleukin-10. So not all of the IL, insert number, not all of the interleukins
are inflammatory, some are anti-inflammatory. So that's an important
point to keep in mind as we go forward. Next, I'd like to talk about what's called sickness behavior. And indeed there is a category of behavior that we call sickness behavior
that is very informative as to the things that we can
do to avoid getting sick. Now, this notion of sickness behavior goes back several decades or more. And it's a very interesting way of looking at the function of the immune system, because what it does is it
bridges us from this thing that we're calling the immune
system where it's T-cells, and B-cells, and cytokines and leukocytes, and it starts taking us into the realm of the nervous system, because of course the nervous
system controls behavior. So sickness behavior
is a suite of responses that we tend to all undergo
when we are feeling sick. So this is going to vary
from person to person, but there's some general
categories of things that we all do and that
happen to all of us after we are wounded or sick or dealing with an infection of any kind. And by examining sickness
behavior in some detail, it can be really informative as to routes that we can take to health. So 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. 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 stopped 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. 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. 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. And there are several theories
as to why this would be. One prominent idea in
the literature is that it's to discourage vomiting and diarrhea, which of course can be
infectious to other people. So, that's a theory. I don't know that that's
ever been tested directly, but that's one idea. The other idea is that it's
simply to harbor more resources for sake of repair. And I want to talk about
that because we are all told to get extra sleep when we
aren't feeling well or to rest. But just like any good
two or three-year-old constantly asks, "why, why?" Good scientists, good
people who are interested in health information
should always be asking why. Why should I get more sleep? What happens in sleep that I should get more sleep when I'm sick? Why shouldn't I just push through this? And there are a couple of reasons for this that have been established
in the literature. The first is that there does
seem to be something useful about slowing circulation when we are ill. One idea that has some data to support it is that when we slow our
circulation, our blood circulation, so not running around so
much or running it all, but rather lying down, getting
extra rest, maybe sleeping, maybe even just remaining still, is that the lymphatic system, which carries a lot of the
immune-related cells and fluids, is able to ramp up its levels of activity. So, this is interesting, right? So reducing circulation of the blood, but increasing circulation
of the lymphatic system. You've all probably been familiar
with the lymphatic system when you're combating an infection, your lymph nodes can get sore. You've got lymph nodes behind your ears, in your groin, your
armpits, around your throat, around near your thyroid,
in your throat, et cetera. So, that's the other reason. Now, some people, when they get sick, psychologically go into
a very vulnerable state where they really, really want people, other people to take care of them. You've probably witnessed this, or you feel this way yourself. About 50% of people have that response. They really want to be taken care of. Now, when you think about it
from an adaptive perspective, this makes sense, right? A member of our species is
ill and they more or less will cry out for help
in one form or another to the other members of their
species to take care of them. And of course this will be
especially apparent in cases where people are young enough
or incapacitated enough that they can't actually
get resources on their own. If you've ever been really sick, just getting up and going to
the fridge or to the restroom can feel like a monumental task. So about 50% of people report
or describe seeking of help and support when they are sick. But you could also
imagine how this would be a very non-adaptive response because it increases the
opportunity to spread infection to the caretaker. So that's an interesting consideration. Another 50% of people seem
to have the opposite response when they're sick. So, somehow, regardless of how they were prior to getting ill, the sickness behavior that's engaged by these neural circuits in the brain, they are indeed neural
circuits in the brain, create a stay away from me. I don't want to be bothered. I want to be left alone. I don't want to be taken care of, right? It's not stubbornness. It's literally a lack of interest or a disinterest in social
connection when one is sick. And you see this in animals too, some animals will seek out
other members of their species. Others, like my unfortunately now passed away bulldog, Costello. When he was sick I always knew
because he would go around the back of the house and
he would just hide there. He would just take himself
away from everybody else. He did not want to be taken care of. And it was just a natural response to him. I don't think he was trying to prevent me from getting whatever it was that he had. So if ever somebody doesn't
want to be taken care of, or if they do want to be taken care of, realize that people tend to fall into these two bins naturally, and animals tend to fall into these bins. Regardless of what species
they are, it's about 50/50. And again, this sickness
behavior is a motivated state. It's designed to slow
circulation of the blood, increase circulation of the lymph, and the other killer cells in the body, reduce the probability of
infecting others by reducing, its thought, diarrhea and vomit, but also breathing on others,
interacting with others. And in some cases it will activate this, I don't want to call it a regressed state, but many people feel somewhat more... If they are adults,
they feel more childlike when they are ill and they want to be taken care of very badly. Some of it might be learned. Some of it might be innate. We don't know, but the sickness
behavior is very interesting for a couple of reasons. First of all, it mimics another state that has been described in
the neuroscience literature, which is major depression. And in both sick individuals, sick from bacterial or viral infection, and in people with major depression, it's been shown that
there are robust increases in the levels of interleukin-6 and tumor necrosis factor alpha. So there is an idea now circulating
that depression involves these inflammatory
cytokines being very active. And we know that illness involves inflammatory cytokines being very active. So if you think about it, the similarity between major
depression and being sick ought to be able to point us
in a direction of interventions that could help us either prevent illness or move through illness more quickly. But as we head in that direction, because indeed that's the case, I just want to emphasize
that sickness behavior is what provides this bridge
between the immune system and the nervous system. And what we'll soon see also
is that healthy behavior, behavior that allows
us to avoid infection, also points to a clear bridge between the nervous system and the immune system. That it isn't just that we have a brain and body and our organs, and
then we have an immune system. That's true, but they're
interacting all the time. And this is going to lead us to a place where it's going to be very
clear and not at all surprising how certain patterns of
thinking and certain behaviors that we can elect to take can help enhance our immune system function and vice versa. There are two other features
of sickness behavior definitely worth pointing out. One is a theory, which is
that the reduced appetite, in particular appetite for
protein rich foods when sick, is thought to be an attempt,
a subconscious attempt, of the organism to
reduce the amount of iron that it's taking in. Now, typically the amount of iron intake that's recommended or
more or less is for men, it's about eight milligrams per day. For women, it's anywhere from
18 to 27 milligrams per day, depending on whether or
not they're pregnant, lactating or menstruating, et
cetera, the ranges can vary. But, and indeed, it's
true that if iron levels in the blood go too high, like
over 45 milligrams per day can be very toxic to the system. But the theory that's prominent
in the biology literature and in the health literature
is that the reduction in appetite is actually an attempt to reduce iron intake specifically because many bacteria and
other forms of infection seem to thrive when levels of
iron in the blood are high. And I don't want to see
anyone take this too extreme and suddenly do an iron deprivation diet in order to get well. But it's an interesting
theory that I'd be remiss if I didn't mention,
because it makes good sense. Iron is actually attached to hemoglobin and red blood cells in the bloodstream. Normally that can help us quite a lot. It's also in muscle,
I should mention that. Iron can be a sequestered into muscle, and iron serves a lot of
important health promoting roles, but by reducing appetite and
thereby reducing iron intake, it does reduce the
capacity of certain things, including infections to
travel in certain compartments within the body. So, again, that's just theory, but I think many of you
are probably familiar with not having an
appetite when you're sick. The other thing that's
very typical of people with major depression is loss of appetite, not always but often loss of appetite. So, here again, we have loss of appetite in sickness behavior, loss of
appetite and major depression, and perhaps not surprisingly
one of the major symptoms of sickness behavior and major depression that map more or less onto one another is loss of libido or interest, not just in social interactions, but in sex and reproduction. And so, again, if you think
about sickness behavior and depression, they
are very, very similar. Okay, so sickness behavior
and major depression have certain core features in common. We need to therefore ask
ourselves why and how does being sick influence the way
that we think and perceive our environment and impact our appetite, whether or not we want
to be cared for more or cared for less? Again, people tend to diverge
into two different bins there, and believe it or not, the pathway for this has been identified. When we have an infection
someplace in our body, and it could be up in our head, it could be a sinus infection,
it could be an ear infection, or I should also mention
many of these same mechanisms can also be the consequence of a wound or an injury to the body. A back injury or a slipped disc or I guess it's called a herniated disc is the way that you hear it described. 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. Many of you have probably
heard of the vagus, V-A-G-U-S, vagus. The vagus nerve is a very
extensive nerve pathway, as 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. And all of those organs are
able also to send neural signals back up to the brain. We sometimes hear of
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. You have lots of different
pathways in the vagus Usually vagal stimulation
actually creates more arousal and alertness, although it
does have multiple pathways, but 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. Neurons, for instance,
in the preoptic area that increase body
temperature and fever, right? That's one of the most important things is to increase body temperature, it's the body's attempt
to kill off this invader because many viruses and many bacteria don't survive well at elevated heat. That's the function of a fever. A fever actually has a functional role. So, in biology, we like complicated words, so we call anything that
increases body temperature or creates a fever, a pyrogen. Many years ago, in my undergraduate years, I was working on pyrogens, injecting something
called lipopolysaccharide into the belly, which
then gives you a fever. The way it does that is LPS causes an inflammation response in the gut. The gut doesn't know what is happening. The stomach cells don't
know what's happening. So they just start secreting
the IL-6, the IL-1, all those cytokines, the killer
cells migrate into the gut. That's why you sometimes
get a stomach ache when you don't feel well, you have a flu, or something like it. A neural signal, electrical
signals get sent up to the hypothalamus. The hypothalamus says, oh,
I don't know what's going on out there, but there's a
signal something's going on. Let's just heat up the body. Let's just start cooking
whatever it is out there. And of course you don't
want fever to go too high because you can kill brain cells. But within a particular range
the fever is a functional and adaptive response, okay? So if you're taking drugs
to try and lower the fever that might make you feel more comfortable, but actually that's limiting
the response that your body is creating in order to try
and kill off that invader. And again, you don't want
fever to go too high. This is going to vary depending on age. You can look up online what the tolerable ranges are for fever. But when you're trying
to lower body temperature when you have a fever, unless you're heading into
dangerous levels of heating up, that's actually the wrong
way to take your system if you do indeed want to
kill off that invader. Okay, so the vagus nerve
is the quick response. 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. We all have different
levels of light sensitivity, 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. 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. This is work that was
done by Clifford Saper at Harvard Medical School. It's really beautiful work. And 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. We'll talk more about these later. It can actually create a
photophobia and a headache when one is ill. So, here's the pathway: Some invader gets into your system 'cause you wiped your eyes or
it got in through your mouth. You didn't listen to your mother and got in through your eyes. You're feeling sick. Something's going on there. You have a stomach ache because of all the inflammation there, the signal goes up from your vagus nerve. You're heating up with a fever. You've got photophobia
because you've activated this pathway by which what would
normally be tolerable light is triggering this thalamic
nucleus, the anterior thalamus, that's projecting up to the meninges. You got a headache in
response to looking at light. It's basically triggering
an overall pathway to get you to go into a
quiet, dark place and rest. 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 we think we know which
hypothalamic area it is. It's the supraoptic nucleus, we think. Supraoptic 'cause it's right above your so-called optic chiasm, If you want to look up where that is, it's right above the roof of your mouth. 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. 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. Now there's also a slow pathway that's purely mediated by the blood, so-called humoral factors. Not 'cause 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. 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. Choroid is really interesting. It's kind of this fluffy tissue that sits in your ventricles. The ventricles are the
spaces in your brain, and the spaces in your
brain have what's called cerebral spinal fluid in them. The cerebral spinal fluid contains a number of important things, but 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, your memory tends to get poor, your cognition tends to get poor. These are transient things most often. 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. So 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 the slower response where you literally have a
set of tissues in your brain that are sending out these
inflammatory signals. 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
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 anytime you've had a cold or a flu
or something really lousy or an injury. 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. So let's say you are in that
unfortunate circumstance of waking up one day or coming home, and you've got that tickle in your throat, or when you breathe, your nasal passages
don't feel the same way. You've got a little bit of a headache. You're feeling kind of off. We all know what we should do. We should all hydrate, drink
some water and go to sleep. Right, that's we are all told, 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, and get nine or 10 hours of sleep. But there's an interesting
way of looking at sleep, specifically for its role in
enhancing the immune system. And there's a wonderful review, I'll put the review in the
captions that looked specifically at the literature surrounding
sleep that is different because it occurs in support
of the immune system. So normally when we go to sleep, we have slow-wave sleep predominantly in the early phase of the night, and then over time as we
sleep longer and longer, we get more so-called REM,
rapid eye movement sleep. I talked all about this
on the episodes on sleep. Of course you have slow-wave
sleep and REM sleep throughout the night always, but it's the fraction of slow-wave sleep to REM sleep that shifts, and they have different
functions, et cetera. There is some evidence
that the sleep associated with an infection, in particular,
early stage of infection, is associated with elevated
levels of serotonin in the brain that either through an adaptive mechanism or for whatever reason,
the neurons in the brain of the so-called raphe nucleus start releasing more serotonin. And that serotonin and
its related pathways can help enhance some of
the immune system function that could combat the infection. There is starting to be some data, and I emphasize starting because it's not a very robust literature yet, looking at whether or not
supplementing precursors to serotonin like 5-HTP, which can be taken in a supplement form or consuming foods that
increase serotonin naturally. So these would be any foods that contain high levels of tryptophan. You can look up what those are. So, white meat turkey, for instance, certain complex carbohydrates can often be rich with tryptophan. That consuming those foods can enhance the amount of serotonin
that's available in the brain and blood and thereby
lead to the particular quality of sleep that
allows for more deep healing or for when I say deep healing, I mean for a more robust immune response. Now, again, those are still emerging data. What is very clear, however, is that 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. What's the glymphatic system? The glymphatic system is actually a relatively recent discovery. I mentioned lymph and the
lymphatic system earlier, 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. And the activity of this glymphatic system is extremely important for the recovery from infection of any kind. And it's now becoming clear,
is important for recovery from traumatic head injury, and maybe even from psychological trauma. So, the glymphatic system can
be thought of more or less as a plumbing system that
runs through the ventricles, but also mainly through
the lining that sits between the brain and the skull and some of the other tissues
and things of that sort. The choroid is involved as well. Brain imaging reveals
the glymphatic system is very active during deep sleep. And there's this kind of wash
out of the glymphatic system. And I am aware of some
studies that are ongoing now where augmenting the serotonin
system through either supplementation of tryptophan or 5-HTP or even serotonin itself,
these are laboratory studies, is being looked at for
its capacity to increase the amount of circulation
in the glymphatic system. And the idea is that it might,
and I want to underscore might, potentially lead to more
rapid recovery from injury and illness and potentially
ramp up, if you will, the activity of the immune system. So, it essentially is a
ramping up of the activity of the immune system. Now, regardless of whether
or not you decide to, for instance, supplement with
5-HTP before sleep or not, I'll talk about what that
might look like in a moment, 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. And this is without taking any compound to adjust the serotonin system. 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. 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. The glymphatic system is not
just active during sleep. It's also active during
certain phases of waking, in particular when we are in
a deep state of relaxation. So as many of you probably
know I'm a big proponent of self-hypnosis because of the quality scientific literature on this. If you're interested in self-hypnosis, you can go to Reverie, R-E-V-E-R-I.com. Reverie is a cost-free
app for Apple and Android that was developed by my
colleague, David Spiegel, and others at the Stanford
University School of Medicine, based on quality studies
and peer reviewed data, showing that deep states
of relaxation can be used to improve pain management, improve transition time to sleep, and a number of other things. You can select the
various sort of outcomes that you're seeking using Reverie. It's a great thing especially for people that are challenged with
meditation could use, because you just listened to the script. It involves deep relaxation. I would suggest using that
script, or the script for sleep, but with feet elevated
to increase activity of the glymphatic system. Now, if you do decide
that you want to test out this serotonin hypothesis on your own, obviously check with a doctor. I'm not a doctor, I'm a professor. So, I'm professing things,
not suggesting things, but 5-HTP is a supplement
that I've talked about before on this podcast that I
actually do not recommend for most people for sake of sleep, because it can disrupt the
normal architecture of sleep and create a deep sleep
early in the night, and then a spontaneous
waking with some trouble to get back to sleep. And that's because of the
way that the serotonin system and the melatonin system interact. However, under conditions
where one is feeling like they might have an infection or an early stage of illness, in that case, 5-HTP might
be a useful supplement in order to access these states of sleep that are not typical. They're not the typical deep
sleep that you would achieve when you're feeling healthy. These are states of sleep
that are specifically there in order to try and repair
some of the immune system related inflammation that's occurring. If you'd like to explore
the 5-HTP approach and you feel it's right and safe for you, and you've talked to your doctor, it's 300 to 500 milligrams
taken about 30 to 60 minutes before going to sleep for the night. That's the typical protocol. Not incidentally,
increasing serotonin is also one typical approach for the
treatment of major depression. This is the basis for things like SSRIs, selective serotonin reuptake inhibitors, like Prozac and Zoloft, and so forth. The 5-HTP approach is
a much milder approach than prescription drug, of course, but will allow more serotonin to be synthesized and/or released. Now, for those of you that are
interested in learning more about the glymphatic system,
it's a fascinating system, and you might want to do a deep dive there in terms of the behavioral protocols, and what's known about it, there's a wonderful article called "The Glymphatic System:
A Beginner's Guide." This is a scientific article. The first author is Jessen is
the last name, J-E-S-S-E-N. If you put in "Jessen,
The Glymphatic System: A Beginner's Guide," you
can access the full length manuscript easily online. It'll show up immediately in your search. And in a really interesting way, the glymphatic system
has now also been tied to the iron deposition system. Earlier we were talking
about iron and how, of course, getting enough
dietary iron is important, but if levels of iron are too high it isn't good for a number of reasons. There's a very interesting article that just came out last year called "Dysfunction of the glymphatic
system might be related to iron deposition in
the normal aging brain." So, we're starting to see these links between iron levels being too high, the glymphatic system not being
active enough and so forth, leading to sickness
behavior, inflammation, and maybe even damage to
neurons associated with aging. We can flip that on its
head and say that increasing the activity of the glymphatic system, feet elevated during deep sleep, maybe even feet elevated
above the head while awake, during a nap or doing a Reverie script once a day or something of that sort, could increase the activity
of the glymphatic system, lowering iron to a point
that's probably below the typical intake during
periods of infection, perhaps, I should say, can enhance the glymphatic
system and vice versa. And then you've got this specialized sleep that's related to sickness behavior that seems to have heightened
levels of serotonin that might be augmented
by ingesting 5-HTP. Again, not on a regular basis. I don't suggest that people take compounds that increase serotonin
unless it's prescribed to you for depression or something, but not doing by supplement
with tryptophan or 5-HTP on a regular basis, but
only under conditions where as I mentioned, you
might be starting to feel sick or you're coming down with something, or you're combating
some sort of infection. So if we consider the
advice that we typically get when we're not feeling
well of take a hot shower, get into bed and go to sleep, and we've now touched on
ways to potentially increase the efficacy of the sleep part through the glymphatic and the serotonin system. What about the take a hot shower part? Is that good advice? Well, it turns out it is, and there's actually a
way to do even better. There's a study, a very interesting study, the title reveals where
I'm going with this, it's "Effect of a single
Finnish sauna session on white blood cell profile
and cortisol levels." In this case, it was done in
athletes and non-athletes, which is kind of nice. This involves taking
athletes and non-athletes and exposing them to sauna. It wasn't particularly hot. It was 96 degrees, which isn't cool, but it's not really hot. Nowadays you hear about people
doing very, very hot sauna. The humidity of the sauna,
if you want to know, is 15 plus or minus 3%. But basically what they found
was that just one 15 minutes sauna session could really increase white blood cell profiles and
could adjust cortisol levels in ways that were beneficial
for combating infection. And now there are many
other studies like this. Now, this should immediately
make sense based on what we said before about fever; heating up can actually
help combat infection. But for those of you that have listened to the episodes on temperature, what you probably know is
that when you get into a sauna or any kind of hot environment, your body is also going to be actively pushing to cool itself off. So, there's probably an increase in heat, there is an increase in heating, but then afterwards
your body will cool off, maybe even with a dip below baseline. I do want to provide a cautionary note that if you are already running a fever, getting into a sauna could
take your body temperature into dangerously high levels, dangerously meaning you can kill neurons. And once you kill neurons,
they do not come back. So, please don't kill your neurons. I don't recommend getting into a sauna if you're already running a fever. So this would be something
to do at the initial stage of an infection or if you're
feeling a little bit off. So this is kind of a ramping
up or a super protocol of the typical advice of take
a hot shower and get into bed. That is good advice. Now we're talking about a hot sauna, probably showering off
and then getting into bed, maybe augmenting serotonin. I know many people don't
have access to sauna. So, in that case, a
very hot bath or shower, don't scald yourself, of course, but as hot as you can comfortably tolerate or right at that edge
of what you can tolerate would be a good idea. Some people I've heard are creating saunas in their bathrooms by running hot water and creating a ton of steam. Anything that really heats you up, but not to dangerously high levels is going to be beneficial. If you have access to a sauna, terrific. This again was only 15 minutes. They'd had a cool off session. Would you get more of an increase? People always want to know
if you did it twice as much, would you get twice an increase? Those data don't really exist yet. However, if you are
interested in maximizing the effects of sauna, it is clear that a cool
off period is important. So it's not that a 15
minute sauna is good, and a 30 minute sauna is better. If you are going to take
that route of exploring more, it does seem that doing a
15 minute heating period followed by a five to 10
minute cooling period, and then getting back into
the heat can be beneficial. And this is interesting. It gets to the mechanisms by
which the hypothalamus areas, the areas of the hypothalamus, that is, that generate increases in body heat, the activation of those
neurons occurs as you heat up and then were you to just stay
in that heated environment, they would actually shut
off and some other neurons would be handling the job so to speak. But by getting in and out
of the heated environment, you actually force that
system to send repeated pulses of these cortisol lowering
and white cell stimulating signals to the body. Some of you have probably
heard the phrase, "feed a fever, starve a cold." I don't know who first said that. I couldn't find the
citation, but we hear this. And we can speculate that
the reason that phrase, "feed a fever, starve a cold" came to be is because of the adaptive
function of fever, that increases in body
temperature make it challenging for intruding viruses
and bacteria to survive. Even though, of course, highly
elevated body temperatures pose a danger to the
host organism, to you. Feeding, eating does cause an
increase in body temperature through the so-called
thermogenic effect of food. So I can understand the
logic of feed a fever. It would mean that when you have a fever, it's your body's natural
attempt to heat up and kill some invading thing. And by eating, you would further increase your body temperature. Why you would want to starve
a cold, I don't know, however. Maybe it's because when your
nasal passages are congested, it's uncomfortable to eat
or something of that sort. So the feet of fever
part makes sense to me, the starve a cold part is
still mysterious to me. I couldn't find any logical
reason why that would be good. There are communities out
there that believe that fasting is a viable way to combat
certain types of infection. Fasting, in particular, prolonged fasts, do increase the amount of adrenaline, also called epinephrin,
in the brain and body. And as we'll next explain, epinephrin, adrenaline does have a powerful effect on the various inflammatory cytokines and on the immune system in general. So, let's talk about a behavioral protocol that anyone can use; it
doesn't involve any equipment, you don't need a sauna, you
don't need anything at all, that has been demonstrated
in excellent peer reviewed research to enhance the
function of the immune system and actually allow people
to combat infection in very dramatic ways. 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. 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. It's a very prestigious journal. For those of you that know PNAS, you know that there are certain
papers published in PNAS, or there used to be that
were not peer reviewed. In recent years, I think
all of them have moved to peer reviewed papers. So this is a peer reviewed,
very high quality study. 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. 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. It's associated with
epinephrin 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. 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, "ugh, 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. So what they did in this study, and by the way, I should say they, this first author is Kox, K-O-X, last author, last name
Pickkers, P-I-C-K-K-E-R-S. What they did was they
exposed human subjects to an endotoxin. In other words, they
injected people with E. coli, which is a bacteria which makes people, all people feel terrible. Makes you nauseous,
fever, vomiting, diarrhea, it's very unpleasant, okay? 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. My lab works on these types
of breathing protocols. This is not work that my lab did, but basically subjects hyperventilate, followed by breath
retention, by breath holds, and I'll explain exactly what they did. They also looked at other
forms of behavioral protocols, but let's focus on that one. 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. I'm just paraphrasing here,
in the intervention group, the breathing group, plasma levels of
anti-inflammatory cytokine IL-10, so this is a cytokine that
is lowers inflammation, increased after endotoxin administration. And that was triggered by an increase in epinephrin and adrenaline. So, in other words, doing a particular pattern
of breathing allowed an anti-inflammatory
cytokine to be turned on, whereas that was not
the case in the subjects that did not do this
particular breathing protocol. And they discovered that levels of proinflammatory TNF-alpha,
tumor necrosis factor alpha, IL-6, interleukin-6 and interleukin-8, which you should all be familiar with now, as proinflammatory cytokines were lower in the intervention group. Whereas these IL-10 levels that are anti-inflammatory went up. 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. Both sets of subjects have
been injected with E. coli. So, you know everyone's
getting the same amount placed into their system. This is very, very interesting. And it leads to the question
that every good scientist, two year old or health
information seeker asks, which is why? How? How in the world does this work? Why does this work? Well to make a long story shortish, because I am going to go into depth here, the reason it works is
because the sympathetic nervous system, the so-called stress part of our nervous system, it's
not really called that, but the part of our nervous
system that triggers stress from mild stress, to severe
stress, even to panic, causes the release of
adrenaline and epinephrin in the brain and body. And under normal circumstances, when we have some sort
of invading infection, our body is able to push back on that, to resist it by engaging
the stress response. So what's happening here is
there's a behavioral protocol involving the nervous
system, 'cause all behaviors are generated from the
nervous system of course. A behavioral protocol that
people are deliberately employing that allows them to activate
the sympathetic nervous system, which in turn allows them to
activate the normal pathways by which immune system
function is enhanced. Okay? Now, the reason I'm
underscoring this is that the common interpretation of
this study is that somehow it blocks the normal immune response, but that's not really
what's happening here. Yes, there's a reduction
in inflammatory cytokines and there's an increase in
anti-inflammatory cytokines, but that's not really the same thing as blocking the immune response. This could just as easily
be viewed as enhancing the immune response and
combating the intruder, in this case, E. coli. So, let's parse this study
a little bit more closely. First of all, what is this
magical pattern of breathing? Some of you may recognize this as so-called Wim Hof breathing. Wim, of course the Dutchman. I think his occupation online used to be listed as daredevil, believe
it or not, on Wikipedia. That's a pretty cool occupation. Wim is best known for his
activities with cold exposure, he holds multiple world records for that, swimming under icebergs
and other incredible feats, that you definitely
don't want to try unless you're extremely skilled and really know what you're doing, as he does, but also for the use of breath work. 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. In the science and physiology community and in my laboratory, 'cause
I run a university laboratory, we refer to it as cyclic hyperventilation, which just means repeated
deep breaths in and out. And then there are these retentions. 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. There are variations on
this, so with respect to Wim, with respect to Tummo practitioners, with respect to the cyclic
hyperventilators everywhere, this is one general theme of it. 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. There are variations on this, but in our laboratory and
in this particular study, it looks something like this. Okay, I'm not going to do
the whole thing right now, but it goes something like this. [Andrew deeply breathing] 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. [Andrew deeply exhaling] 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. Now some people will also
introduce a big inhale and breath hold at the end and find that indeed they can
hold their breath much longer than they normally would be able to. Because the trigger to
breathe is normally activated by increases in carbon
dioxide in our blood. We have neurons in our brain stem and in our various regions
of our brain, actually, that respond to when
carbon dioxide is too high and trigger the reflex to breathe. But when we exhale deeply, we blow off a lot of carbon dioxide so we don't feel that impulse
to breathe come quite as soon. Basically this study
looked at people doing these cyclic hyperventilation
with retention, 25 or 30 breaths, then the retention, 25 or 30 breaths, then retention, 25 or 30 breaths, then the retention. So, three rounds of 25 to 30
breaths followed by exhale, hold in between of various duration. But in general, 15 to
60 seconds is typical. What happened physiologically? This is one of the
reasons I like this study. What happened physiologically? Well, a couple of things. Of course, blood oxygenation drops. You would expect that
based on hyperventilation and especially based on the exhale of so much carbon dioxide. We could explain why that is, but blood levels of oxygen drop. The pH, the alkalinity
of the body goes way up. This is very interesting. If you look up this paper, you can look at Figure One,
Panel C, the pH goes way up. People become alkaline. You've heard before of alkaline water. I hate to say this, I'll probably lose some friends for this, but yeah, don't waste your money
on drinking alkaline water. You can't really shift the
alkalinity of your body. There are cases where some
compartment in your body needs to be more alkaline than the rest. Your gut is a different
alkalinity than other areas of your body, et cetera, but
ingesting high alkaline water isn't going to shift
your overall alkalinity. If someone can send me a quality reference that shows different than I'm happy to revise that statement. But in any case, doing
that pattern of breathing that I just described
greatly increases the pH. Greatly, I should say,
it doesn't send it off into dangerous levels. It takes it from 7.4 to 7.6, which is a significant
increase in alkalinity. So, as pH levels, for those
you remember high school or college chemistry, as the
numbers on the pH go down, you're becoming more acidic, as they go up, you're
becoming more alkaline, okay or more basic. So, these subjects went from 7.4 to 7.6 during the breathing, and then afterwards it returned to normal. But that shift in alkalinity is thought to be important here. So, what's going on here? How is the breathing
leading to the shifts in... Or I should say reduction
in inflammatory cytokines and an increase in the liberation of these anti-inflammatory cytokines. Well, the authors make some good arguments as to why it's not the shift in pH per se, or the shift in carbon
dioxide levels in the blood, but rather it's the release of epinephrin. And there's some good reason
to believe why that's the case. It's beyond the scope of this discussion, but that it's actually
the release of epinephrin, AKA adrenaline, that's
causing this reduction in inflammation. 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, 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 stopped taking care of somebody else, or you finally stop and
rest or you go on vacation, and then you get sick. Well, you've just experienced
the effect that adrenaline, epinephrin 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's the same stress system that you use to combat psychological stress. So when you're very, very stressed, at least in the short term, because you release so much
adrenaline and epinephrin, you're actually better
able to combat infections and you reduce inflammation and the whole feeling
lousy response, right? 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've caught a bug of some sort, I will do this pattern of breathing. 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. 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, in this case, an E. coli infection. Now, I'd like to focus on a
couple of important points that I haven't heard
discussed broadly elsewhere, which is that the hyperventilation and the breath retention
are both important. So you can't simply
hyperventilate to get this effect at the level of epinephrin release and reduction in inflammatory cytokines. It's been shown before that
the hyperventilation phase and the hypoxia, which is
a low oxygen saturation due to the breath retention, they both combine to increase
epinephrin adrenaline levels. So, you have to do the 25 or 30 breaths, and then the retention. 25 or 30 breaths then the retention, meaning that the exhale
with the breath hold, in order to get the full effect. I'd also want to provide a
critical cautionary note. Don't do this anywhere near
water or while driving a car. These things might seem kind of obvious, but obviously in the off
chance that you black out or something like that,
it could be disastrous. So, please be careful. And again, don't try and
push the breath hold. The moment you feel the impulse
to breathe, just breathe. And it did seem that the three
rounds of 25 to 30 breaths with breath hold retentions in between was the ideal protocol. 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, epinephrin, norepinephrine. These are chemicals in your
nervous system and body that promote states of
alertness, 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, epinephrin showed robust
increases compared to the control group, norepinephrine, significant
increases occurred in the breathing group, 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 Asya, A-Y-S-A Rolls' lab in Israel. 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. So this brings us back to
something that we discussed at the very beginning of this episode, which is that 20, 30 years ago, the idea that you could
heal the body with the mind was considered kind of quackery. I think that there was an
intervening period up until now where people might've said,
"sure, if you're stressed out, it's going to make things worse." I mean, I think everyone
agrees that stress makes every thing worse at some level, outcomes to neurodegeneration, performance in a physical
endeavors and mental endeavors. If stress is too high for too long people experience different challenges and essentially every
major psychiatric disorder, everything suffers, but in the short term, stress can actually be
beneficial in the ways that we just described. And stress, if we break it down is really a neurochemical state, right? It's the release of these catacholamines. And what Asya Rolls' laboratory has shown is that when the so-called dopamine system and at several episodes, I described there are
multiple dopamine systems, but the so-called
mesolimbic reward pathway involving areas like the
nucleus accumbens, et cetera. When the reward system that's
associated with dopamine and norepinephrine is activated, you see incredible effects,
including for instance, highly significant reduction
in tumor size in cancers. Now, why would that be? How is it that mindset,
dopamine and tumors, and tumor growth are somehow linked? We now know how this
occurs largely through the incredible work of
Asya Rolls and others. So, now I'd like to turn our
focus to how it is specifically that certain mindsets
impact the immune system in ways that we can
actually point to specific biological pathways and
also specific protocols related to mindset. I guess a simple way to frame
all this would be to say that most of us are
aware that yes, indeed, you can worry yourself sick. We've been told that, you're
going to worry yourself sick. And actually there was a
paper published in "Science," again, one of the top
three journals out there, the top three really being
"Nature," "Science," and "Cell." And then other of course,
excellent journals exist, but this was a paper that came
out in "Science" last year. First author is Kataoka, K-A-T-A-O-K-A, describing psychogenic stress and fever. So this was looking or
asking the question, are there areas of the
brain that actually underlie this notion that we can
worry ourselves sick? And they discovered a new
pathway and they were able to both activate this pathway
independent of worry and stress and see illness occur, and they were able to
inhibit this pathway, block activity in this neural pathway and prevent psychogenic
fever and the worrying of oneself sick. So, they were able to do this
in a very controlled way. I'll just mention the pathway in case you want to look it up in more detail. This is a corticolimbic pathway. So, just to orient us,
the cortex is more or less the outer shell of the brain. It's involved in thinking
and sensation and perceptions and learning and maintenance
of a lot of memories are stored there. We all hear that you learn and
remember in the hippocampus, that's the initial site
of learning and memory, but then that information,
believe it or not, is passed off to the
cortex where it's stored in kind of a long-term
hard drive type storage. So the corticolimbic
pathway is one in which your thoughts, your prior
experiences can literally in a structure way, feed down
onto the areas of the brain that control very basal processes, including temperature regulation. So this is a corticolimbic
hypothalamic pathway. We talked earlier about the hypothalamus as controlling temperature
and a lot of sickness related behavior, right? Remember vagus up to the hypothalamus and all the sleep more,
less appetite, fever. Okay, that's all in the hypothalamus. This is a top-down corticolimbic
hypothalamic pathway, and it has a fancy name. It's the dorsal peduncular
cortex, dorsal tinea tecta. The short of that is the DP/DTT. Let's just call it the DP/DTT, to the dorsomedial hypothalamus. A lot of D's. It shouldn't mean anything. It doesn't really matter what we call it. But what's important is
conceptually it's a pathway that originates insights to the brain that are associated with thinking, with emotion and with prior history, and feeds directly into
an area of the brain that's involved in basic physiological subconsciously controlled processes. So, that's incredible, right? And it points to a physical
pathway by which the way we think about something
changes something core about our physiology. Now, in some ways that
shouldn't be surprising, right? If you think about
something that excites you, your heart rate can increase. You think about something
that terrifies you, your heart rate can increase. So the idea that thinking
controls our physiology is not a new concept at all,
but somehow human beings, we have been challenged with
the idea that we could actually think ourselves into being sick. But this paper from Kataoka
shows that if you expose somebody to a psychological stress, you can actually activate this
pathway and create a fever. And how do they do that? Well, you can do this by exposing subjects to a very stressful real event, and you cue it through
our associative learning. So, maybe, like my PILOT
V5s, which I love so much, we could traumatize me to the PILOT V5 if I had some horrible
experience happen to me while I'm looking at and
concentrating on the PILOT V5. Then you take away the
horrible experience, you give me the PILOT V5, and I start to experience
a lot of the symptoms associated with that terrible event. They were able to do this
using sickness inducing stimuli and so forth. They did all the various derivations and identified this pathway
that when activated, even in the absence of
some horrible event, could create fever and
illness-like behavior and so forth. And if they blocked certain stations along this neural pathway,
they could block that effect. So this is really concrete
evidence, proof, if you will, that there are dedicated
pathways in the mammalian brain, your brain and mine, that allow us to turn
thoughts into illness. That's kind of a depressing idea. What about the inverse? What about turning thoughts into health? Well, that's the work of Asya Rolls. 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 a
reported a sense of hope, their rates of recovery
were much higher, right? 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. Dopamine, again, being
this molecule of reward and motivation and movement, but movement and motivation are
about things that are beyond the confines of our skin
and are about the future. 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 the 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. So there are many, many
studies now starting to wick out related to this. There's also the idea that
augmenting the dopamine system can increase the rate of healing. And so, there are individuals
out there who opt, for instance, to take things
that increase dopamine. Now, obviously drugs of abuse
would not be a good idea in this context, even though
they increase dopamine, they lead to big crashes, they have addictive properties, et cetera. I've talked before on
this podcast about things like L-tyrosine, taking anywhere
from 500 to 750 milligrams can increase dopamine because tyrosine is a dopamine precursor, of course. Things like Mucuna
pruriens, which are L-dopa, the immediate precursor to dopamine. Some of these will lead
to somewhat of a crash in certain individuals. Other people tolerate
them a little bit better. Again, you have to talk to your doctor, you have to figure out
what's right for you. If you have bipolar or
mania or schizophrenia, these things, I would not
recommend them at all. I'm not recommending them at all, I'm just mentioning them
for potential exploration if it's safe and right for you. But the point is this: the dopamine system, when
activated can accelerate healing, it can accelerate the recovery
from injury of all kinds. And that shouldn't come as a mystery or surprise result to us. 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 epinephrin,
increase norepinephrine, and to augment the catecholamine system. So, I think that the bridges
between these studies are really relevant. In one case, I'm talking about potentially taking an over-the-counter
compound to increase dopamine to accelerate healing. In another case, we're
talking about using breathing. There's also the use
of cold water exposure to increase dopamine. I talked about this several episodes ago, but it's been shown that
immersing oneself in cold water up to the neck or so. How cold? Well, it depends on what you can tolerate, but uncomfortably cold, but not so cold that
you become hypothermic, but where it's challenging to get in, but you can stay there for
three to 10 minutes or so, has been shown to lead
to very significant, up to doubling or more of
baseline dopamine levels and epinephrin levels that
go on for several hours. This may be the basis for why
people will do cold showers or ice baths and then get into a sauna. So, what's called
cold-heat contrast therapy, as a way to augment
these neurotransmitters. Today, we've been talking about
how these neurotransmitters can be used to enhance the
function of the immune system. And so just keep in mind that
anytime you're talking about increasing neurotransmitter levels, that can be done pharmacologically
through supplementation, or the can be done
behaviorally through exposure to cold water, for instance, or it can be done even
just simply by breathing in a particular way, cyclic hyperventilation
followed by retention. The catacholamines,
noradrenaline, dopamine, and norepinephrine are
the bridge of activation for the immune system
and the nervous system. They are the way that the
nervous system calls out to the immune system,
"Aha, we have a problem. We need to counter this." So you can think of them,
them meaning dopamine, epinephrine, and norepinephrine, as being able to deploy larger
amounts of immune cells, all the types of immune
cells that we talked about at the beginning of the episode. 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? The runny nose, stuffed
up nose, congestion, headache, et cetera. Well, there are many ways to address that at the symptom level. You're probably aware of all the over the counter medications, many of which focus on
the epinephrin system. Things that are of the
Sudafed variety prevent or reduce congestion because of the way that they cause release of epinephrin, and some of the effects on
dilating the bronchioles and dilating the nasal
passages and so forth. 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, and they also can interfere with sleep because as I've talked about
in the episodes on sleep, one of the hallmarks of
deep sleep and in particular REM sleep is that epinephrin,
adrenaline levels are low. This is what allows you to have intense, often very emotionally-laden
dreams during REM sleep and not act those out. And low adrenaline,
epinephrin during REM sleep is basically a signature, a neurochemical signature
of the REM sleep state, which is so vital for
emotional and physical repair and so forth. So, the fact that they can inhibit sleep, the fact that can cause dehydration, the fact that they can make
people feel kind of lightheaded and jittery makes them
not terrific choices for a number of people. 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. Years ago, I think when I
first heard about spirulina, it sounded very much of the kind of 1970s, 80s health food store variety. It seemed really kind
of mystical and wacky, but actually now 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 an inflammation of the nose. Basically, anytime you hear
a word that includes "itis," at least if it's in the
medical or health context, it generally means
inflammation of some tissue. So rhinitis just being
inflammation of the nasal passages, but that's one of the most
uncomfortable symptoms of any kind of infection. So there are two studies
I'd like to highlight just very quickly. One is the effects of
spirulina on allergic rhinitis. And the other is a clinical comparison to the efficacy of spirulina platensis, that's a technical name, and cetirizine for the
treatment of allergic rhinitis. These looked at humans, so
this is not a mouse study, this is a study on humans. Both sexes, so males and females. In one case, looking at 100
plus subjects, 129 subjects. The other, 65 subjects, so
decent number of subjects, randomized trial, double blind. Both cases saw significant
decreases in nasal obstruction, improved ability to smell, improved sleep, daily working inflammatory
cytokines were reduced as well, reduction in nasal itching, all the stuff that you'd
like to experience, I can imagine, after taking two grams, two grams, not milligrams,
but two grams of spirulina. Sometimes had to be
taken for a short while before the effect kicked in. So, that's pretty impressive, I would say, but it doesn't really speak to mechanism, but in exploring the underlying
mechanisms for spirulina's effects on reducing rhinitis, it's interesting to find that
spirulina actually can inhibit the formation and/or activity of so-called histaminergic mast cells,
M-A-S-T, mast cells. We haven't talked a lot about mast cells, but they are a very interesting cell type in the immune response. Essentially what they are, are
little packets of histamine. And when we have some sort
of injury or irritant rather to the skin, so a mosquito
bite, for instance, or poison oak or poison ivy, something that causes an itch or something that causes
inflammation internally, doesn't just have to be on the skin, these mast are these little
bubbles that contain histamine that go to that site [hissing], and release their histaminergic contents and cause swelling and
inflammation of whatever cells are affected locally. You might think, well, why
would I want to have a mechanism in my body that would cause
swelling and inflammation? Ah, well then those cells in
turn send out cytokine signals that recruit the very cell
types that we were talking about way back at the beginning of the episode, the cells that are characteristics of the innate immune system that come in, the macrophages and the
other types of cells that will come in and gobble
up the foreign invaders or will help sequester and move away, say the poison from a bite
or from whatever irritant. Again, it doesn't just have
to be at the skin surface. I'm describing an example of
at the skin, for instance, if you've ever had hives of any kind, that almost certainly involved mast cells. So, and when you take an
anti-histamine in order to deal with seasonal allergies, for instance, you're taking a compound that's reducing histamines in mast cells. And spirulina has also been
used quite effectively as a way to treat seasonal allergies
and some of the symptomatology. Equally on par with some
of the major prescription and over the counter drugs for that. One cautionary note, spirulina
can carry some side effects for people that have a genetic mutation leading to something called PKU. These people know who they are. They're very sensitive to phenylalanine. These same people cannot drink any sort of NutraSweet or diet soda for
reasons that they understand. It can be quite dangerous. It's a rare genetic
disorder, but nonetheless, spirulina can be an
issue for those people. For most people, the side effect
profile is pretty minimal. And just to be clear, I
don't have any relationship to spirulina company or anything. I just find it interesting
that there are these compounds that sound rather, forgive the phrase, but rather new-agey because they come from a algae, from a plant. But when you look at the
underlying mechanism, it makes perfect sense. So that's often what we
like to point out here is that if there are these
so-called alternative therapies, alternative because most
people haven't heard of them, it's always nice if they map
to a specific logical mechanism and framework by which
that compound would work, as opposed to just some anecdote of, "Oh, I hear spirulina
is great for allergies." Well, now we know why,
it inhibits mast cells and histaminergic mast
cells in particular. Earlier, I mentioned a new
and very exciting study published as a full article in "Nature." Full article means that
it is a major finding. At the journal, "Nature,"
they have letters, which are important findings. They're still very high
stringency for getting a letter in "Nature" published. But the full articles, generally
there's only one or two per issue in the weekly
edition of "Nature." And just last week, there
was a very exciting article published from Qiufu Ma's lab
at Harvard Medical School. Qiufu I've known for a number of years. His group has done phenomenal
work on the mechanisms of itch and pain and discovering
some of the receptors and pathways for itch and pain. And more recently they've been exploring the mechanistic basis of acupuncture. And the title of the article is, "A neuroanatomical basis for
electroacupuncture to drive the vagal adrenal axis." And while that's a mouthful, now most all of you are probably
familiar with what I mean when I say vagal adrenal axis; vagal meaning of the vagus, and adrenal of the adrenal glands. And so perhaps we should not be surprised, although excited, nonetheless, that when Qiufu's lab looked
at stimulation of the body with so-called electroacupuncture. So, these are needles where 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, or the hind limbs in this case, that can stimulate the
vagal adrenal reflex and can lead to reduced inflammation. And what was really interesting
is that they figured out that it was activation of nerve endings that resided in the fascia. I mentioned earlier what fascia is, but just to remind you, the fascia is a really
thick sheath of tissue that surrounds muscle. If ever you've heard of Rolfing, Rolfing is a form of very intense massage. I've never had this done,
but I've heard about this. It involves among other things, actually separating the muscle away from the fascia somewhat. So it's a very, very deep tissue massage. Actually a good friend
of mine who had this done told me that it was probably the most challenging physical experience that he had ever been
through going through this Rolfing procedure. Maybe some of you have have
been Rolfed, as they say, and can report to the experience, whether or not it was
pleasant or unpleasant, or you felt benefits or not. In any case, this study
isn't about Rolfing per se, but it is about the fascia. 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. And they send a connection deep into the limb fascial tissue, okay? And then they send another connection, the connections we're
referring to are axons, neurons have axons. So a wire in one direction that goes into the deep fascial
tissue of the lower limb, near the calf and thigh. And then they send another
wire up into the spinal cord, into a region of the hind
brain in the back of your brain kind of near your neck
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 catacholamines, noradrenaline, adrenaline, and dopamine, or norepinephrine,
epinephrin, and dopamine. And their release causes a
reduction in inflammation, even in response to an
injection of something called lipopolysaccharide, which
can actually induce fever. So, what does 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 in the pattern of cyclical hyperventilation
with retention, leading to reductions in inflammation. I can't tell you how happy this makes me. I had nothing to do with this work, but the reason it makes
me happy is because I have a particular
fondness for when practices that have existed for many centuries or even thousands of
years, such as acupuncture, such as respiration work,
start to converge with some of the hardcore mechanistic science. And the reason this excites
me is not because we want to take science and erase the previous tools and methods of these ancient
practices, not at all. And it certainly isn't
the case that we just want to name things or rename
things with modern science. What's very exciting is when
we can discover mechanism that explains why certain practices work. First of all, that validates
those as legitimate practices, maybe even insurance
will start to cover them, whereas maybe they previously had not, I don't know what the current status is for insurance coverage of acupuncture. I'm guessing there are places that do it, maybe others that don't. I personally am not somebody
who receives acupuncture. I have in the past, but it's
not that I'm in particular a fan of it, but I think that
there are a number of people that have benefited from it. So, I think that's wonderful. Breath work and respiration
work is something that I've cultivated as a
practice over the years. I mentioned earlier, how
I use it to push back on incoming infections and so forth. And now that doesn't sound like total... You know, like just a
figment of my imagination, there's actually a mechanism, a published mechanism to explain it. But the most exciting
thing to me about all this is that practices that
traditionally have been shrouded in complicated language
or were the unique domain of the practitioners and relied on phrases like the meridians or the chakras, of which I think is
perfectly valid language, but doesn't inform mechanism. And then in a separate community,
the community I come from, the community of scientists, have used language like PROKR2 neurons, medulla oblongata, vagal adrenal axis. And basically no one can
communicate with one another because the language is shrouding. What we're now starting to see
is that at their convergence is a common mechanism. And with that understanding, what's going to be really terrific is as new protocols start to emerge. So in understanding
mechanisms and pathways, and in being able to understand
the base set of practices like breathing, like
electroacupuncture, and so forth, we can now start to daydream
in a very realistic way about the development of new protocols, more effective protocols. Protocols that perhaps one can
do at home without needles, perhaps protocols such as the breathing that you can do anywhere, anytime, and be confident that you're
actually impacting the IL-6 and the IL-8 pathways, reducing
those and increasing IL-10. So we are no longer
wandering around in the fog hearing about these magical
techniques without understanding why they work, nor are we
just seeing a bunch of science that is descriptive, but not mechanistic or pointing to specific protocols. So, I'm just delighted. Again, I had nothing to do with this work, but really terrific work,
Qiufu and colleagues. And I also want to acknowledge a journal as prominent as "Nature"
for featuring this upfront, because I think it really
does mark the beginning of a new path in medicine. And just to underscore that
point a little bit further, the National Institutes of Health, of course has a cancer
institute, an eye institute, that deal with trying to combat cancer and to cure blindness and so forth. And now they have what's called NCCIH, which has complimentary health. And so, there are good
tax dollars being put to the kinds of explorations
that we're talking about that undoubtedly are going
to lead to better treatments for immunological diseases,
neurological diseases, the convergence of the immune
system and the nervous system. Very exciting times and I
hope that by learning about some of this new and emerging
science and hearing about some of the protocols that are
either zero cost or low cost, certainly for respiration that's the case or for the use of heat or cold, or maybe even electroacupuncture
if you have access to that, that we can really see that
we're starting to evolve as a field of health
and medicine and science and ancient practices, and that they're really
starting to converge and have a vector, as we say, in a new and more exciting direction. Once again, we've covered
a lot of information today. We learned about the immune system, the adaptive immune system,
the innate immune system, and the nervous system
and how those interact. And throughout, we discussed
protocols that can allow you to tap into this relationship between the nervous system and immune system, and hopefully avoid
and/or shorten the course of any illnesses,
injuries, or inflammation that you might encounter. If you're enjoying and/or
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