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,
premier journal, extremely stringent.
A paper published in Nature from Chufu 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
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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 promise 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.
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
where 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 pus.
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 in this podcast,
and this is one such tube by which you extract nutrients
from the outside environment.
But all along that tube, including your nose and your mouth,
it’s lined with mucus.
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.
And 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 it got in through your eyes,
maybe you shook somebody’s hand
who was 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 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,
just a few of the many types of immune cells.
So this is 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 complement proteins.
Complement proteins exist in the blood.
And what they do is they travel to sites
where there’s an invasion and they mark certain things
for being engulfed and eaten.
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, and natural killer cells to say,
ah, I need to basically wrap,
you’ll kill this thing and then wrap it in a body bag
and send it off, kill that thing,
wrap it in a body bag and send it off.
And I’m using the analogy of the body bag,
but in a sense it is one, 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 pus or you see infection
in maybe a cut on the skin or something like that,
or even in a ingrown hair that gets some bacteria in it,
that pus and that the white part,
I know it’s kind of gross to talk about,
but those are the white blood cells.
And those are the dead, oftentimes it’s dead cells.
And that’s the dead invader sitting there.
So it’s trying to create an isolated compartment
because it wants to keep it in that part of the body.
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
what we call cytokines.
And the cytokines are things like interleukin one,
interleukin six, tumor necrosis factor alpha.
You may have heard of these things.
If you are at all curious about,
or been learning about the health space,
online health space, especially in the last few years,
inflammation is all the buzzword now.
Everyone’s talking about 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,
excuse me, where this research is done
are things like interleukin one, interleukin six,
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,
but by just telling people that what interleukin means
is to communicate, right?
So the interleukin is shouting out, help me.
The complement proteins are coming in and saying, eat,
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 that 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,
just 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
of 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 hemopoietic 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’re 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 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, and to the rectum.
It’s well-established that there are healthy microbiota
that live all along that length,
and 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 forward 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 reads 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.
It 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 Report,
Cell Press Journal, excellent journal that showed
that the nasal microbiome 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 and that,
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’re 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 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 Sonnenberg’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 inflammatome.
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, you know, get good sleep, good nutrition,
good social connection, et cetera.
All 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
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,
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 happened 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 stop showering,
although oftentimes that’s the case,
but they will stop doing their hair.
They’ll stop putting on makeup.
You know, 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, you know,
so not running around so much or running at 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 and your groin,
your armpits, around your throat,
around your, 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 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
that are 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.
Now, I don’t want to see anyone take this to 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 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 in 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,
you know, 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.
You know, a back injury or a slip 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.
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,
The vagus nerve is a very extensive nerve pathway.
It’s the 10th cranial nerve,
comes out of the back of the brainstem,
heads into the body and branches out extensively
to innervate or connect to many of our organs,
including our lungs, our heart, our gut, et cetera.
And all of those organs are able also
to send neural signals back up to the brain.
We sometimes hear the vagus
as the route to calming ourselves down.
Unfortunately, that’s more or less a myth
that I don’t know how it got propagated.
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
in order to, it’s the body’s attempt
to kill off this invader.
Because many viruses and many bacteria
don’t survive well at elevated heat.
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 lippy polysaccharide
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.
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.
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 range,
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,
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
because you wiped your eyes or 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’ve 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 because 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 because they’re funny,
but humoral factors are factors of the blood.
As you have an infection for many hours or days,
the amount of IL-6 and IL-1 and tumor necrosis factor
and other inflammatory cytokines
is starting to increase such that
the total amount in your circulation gets high enough
and is communicated to the brain.
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.
That 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 this 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 any time 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 what 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.
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 Raphae nucleus
start releasing more serotonin.
And that 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 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 washout 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 Reveri, R-E-V-E-R-I.com.
Reveri 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 Reveri.
It’s a great thing that,
especially for people that are challenged
with meditation could use
because you just listen to the script,
involves deep relaxation.
I would suggest using that script,
but with, 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
on 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, 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 increasing,
excuse me, 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 it 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, very interesting study.
The title reveals where I’m going with this.
It’s effect of a single finish 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-minute 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
that 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.
So 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 the 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
that 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.
So 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 feed a fever part makes sense to me,
that 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 fast
do increase the amount of adrenaline,
also called epinephrine, in the brain and body.
And as we’ll next explain,
epinephrine, 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 epinephrine release in the brain
and adrenaline release in the body.
It’s the so-called fight-or-flight system
when it’s really active,
but it’s the system that’s active when we are wide awake.
And we already talked about the innate immune system.
That’s that first line of defense
after the skin barrier, of course,
whereby some infection comes into the body
and there’s this rapid response of increasing inflammation.
And that’s also about the time that you first feel lousy.
So when you start to feel like,
oh, I think I’ve got something.
I don’t feel right, a headache.
I feel nauseous, I’m heating up.
I don’t feel good.
That’s the innate immune system kicking in.
So what they did in this study,
and by the way, I should say they,
this is the first author is Cox, K-O-X.
Last author, last name Pickers, 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.
There’s a bacteria, which makes people,
all people feel terrible.
See, 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 lowers inflammation,
increased after endotoxin administration.
And that was triggered by an increase in epinephrine,
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 pro-inflammatory TNF-alpha
tumor necrosis factor alpha, IL-6, interleukin-6,
which you should all be familiar with now,
as pro-inflammatory 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.
They both, both sets of subjects
have been injected with E. coli.
So you know everyone’s getting the same amount
placed into their system.
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 in the world does this work?
Why does this work?
Well, to make a long story short-ish,
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 epinephrine
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,
because 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 TUMO breathing
as it’s been described historically
in the science and physiology community
and in my laboratory, because 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 sea 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 TUMO 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.
Ah, ah, ah, ah, ah, ah, ah, ah.
Okay, so let’s assume I did that for 30 breaths.
I can already feel myself perspiring a little bit.
You’re heating up, that’s the release of adrenaline.
It’s caused by that breathing pattern.
And then exhaling all of one’s air,
no speaking in between like I’m doing.
And then sitting lungs empty
until one feels the impulse to breathe,
and then repeating for several rounds,
two or three or even four rounds.
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 brainstem
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.
Coarse 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 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,
then I’m happy to revise that statement.
But in any case,
doing that pattern of breathing that I just described
greatly increases a 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 of you who 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 you go from seven,
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 these 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 epinephrine.
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 epinephrine,
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 really hard,
or you’ve been a caretaker for somebody else
or studying for exams,
and people around you are getting sick
and you’re just powering through it,
and you’re not getting sick,
but then you stop,
you turn in your final exam,
you stop taking care of somebody else,
or you finally stop and rest,
or you go on vacation and then you get sick.
Well, you’ve just experienced the effect
that adrenaline, epinephrine can have
in activating your immune system
by way of the nervous system
in order to keep fighting and combating infection.
And that brings us to a larger theme,
which is that stress and combating infection or a wound
is not one unique system.
It’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 epinephrine,
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 have 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.
You know, 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 a,
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 epinephrine 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 epinephrine 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 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 interventions, excuse me,
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,
These are chemicals in your nervous system
and body that promote states of alertness.
Dopamine, of course,
is part of the reward and motivation pathways.
They explored the levels of these molecules in blood,
in plasma, during and after this breathing protocol.
And it was interesting, as I mentioned before,
epinephrine showed robust increases
compared to the control group.
Norepinephrine, significant increases occurred
in the breathing group,
but in the cyclic hyperventilation retention breathing group,
of course, but less so.
And dopamine levels actually dropped somewhat.
But this is very interesting
because there’s a new and emerging literature,
largely from ISA, A-Y-S-A, Roll’s 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 everything worse at some level.
Outcomes to neurodegeneration,
performance in physical endeavors and mental endeavors.
If stress is too high for too long,
people experience different challenges
and essentially every major psychiatric disorder,
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 catecholamines.
And what Issa Rolls’s 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 Issa 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
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 structural 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 Vegas 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 DPDTT.
So let’s just call it the DPDTT
to the dorsal medial hypothalamus.
Not a lot of Ds.
It shouldn’t mean anything.
Doesn’t really matter what we call it,
but what’s important is conceptually,
it’s a pathway that originates in sites of 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 associative learning.
So maybe, you know, like my pilot V5s,
which I love so much,
you know, 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 ISA 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 or 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 this so-called mesolimbic reward pathway
and could reduce the size of tumors,
could accelerate wound healing,
could greatly accelerate the passage from a state of illness
to a state of health and wellbeing.
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, take it anywhere from 500 to 750 milligrams
can increase dopamine because tyrosine
is a dopamine precursor, of course,
things like mucunipurines, 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 are, I would not recommend them at all.
I’m not recommending them 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 a 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 epinephrine, 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
doubling or more of baseline dopamine levels
and epinephrine 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 it 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 catecholamines, 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 epinephrine system,
things that are of the pseudofed variety
prevent or reduce congestion
because of the way that they cause release of epinephrine.
And some of the effects on dilating the bronchioles
and dilating the nasal passages and so forth.
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 epinephrine 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 epinephrine 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 they 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,
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 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
of 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 a decent number of subjects,
randomized trial, double-blind.
Both cases saw significant decreases in nasal obstruction,
improved ability to smell, improved sleep,
daily working cytokine,
inflammatory cytokines were reduced as well,
reduction nasal itching,
all the stuff that you’d like to experience,
I can imagine, after taking two grams,
two grams, not milligrams, 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, 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 cells are these little bubbles
that contain histamine that go to that site
and release their histaminergic contents
and cause swelling and inflammation
of whatever cells are affected locally.
That’s cause, 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 characteristic
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 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 antihistamine,
antihistamine, in order to deal with seasonal allergies,
for instance, you’re dealing, you’re, excuse me,
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 symptomology equally on par
with some of the major prescription
and over-the-counter drugs for that.
One cautionary note, spirulina does,
can carry some side effects for people
that are, 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
nutritious read or diet soda
for reasons that they understand.
It could 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 a 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
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 Chufu Ma’s lab at Harvard Medical School.
Chufu, 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 Chufu’s lab looked at stimulation of the body
with so-called electroacupuncture,
so these are needles where it’s a small bit
of electrical current, low level of electrical current,
is passed into the needle and therefore into the body.
They located sites on the body that can increase inflammation
by way of releasing inflammatory cytokines.
These areas included the abdomen
and they found areas on the body,
such as the lower limbs 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 experience
that physical experience that he’d ever been through
going through this rolfing procedure.
Maybe some of you 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 PROC-R2 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
and near the calf and thigh.
And then they send another wire up into the spinal cord
and to a region of the hind brain
in the back of your brain, kind of near your neck
called the medulla, in the medulla oblongata.
That neuron also has a name called the DMZ, doesn’t matter.
And that neuron connects to the adrenal gland
to release our good old friends,
the catecholamines, noradrenaline, adrenaline, and dopamine,
or norepinephrine, epinephrine, and dopamine.
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 is all this saying?
This is saying that activation of the deep fascial tissue
causes a chain of neural reactions
that leads eventually to the release of norepinephrine,
noradrenaline, adrenaline, and dopamine.
And once again, lowers inflammation,
very much like the breathing study
that we talked about earlier
in the pattern of cyclic 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 a particular 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,
like just a figment of my imagination.
There’s actually a mechanism,
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 our two 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 I really, terrific work, Chufu 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 is Complementary 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 discuss 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.
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