The Healing POWER of the Vagus Nerve | Dr. Kevin Tracey

The Healing POWER of the Vagus Nerve | Dr. Kevin Tracey

Your body and all its organs are connected. 
Each and every cell, almost of your body, is connected to a nerve ending, and those 
nerve endings are receiving information about the status of your cells and your organs all 
the time, how much glucose is in your liver, how much carbon dioxide is in your 
lungs, how fast your heart is beating,   how much pressure there is in your stomach 
or your intestines. There is an overwhelming amount of information in your body that is 
constantly transmitted through sensory nerves, many of them in the vagus nerve, not all, but many 
of them in the vagus nerve, up into your brain. Welcome to passion struck. Hi. I’m your host, John 
R miles, and on the show, we decipher the secrets, tips and guidance of the world’s most inspiring 
people, and turn their wisdom into practical advice for you and those around you. Our 
mission is to help you unlock the power of intentionality so that you can become the best 
version of yourself. If you’re new to the show, I offer advice and answer listener questions. On 
Fridays, we have long form interviews the rest of the week with guests ranging from astronauts to 
authors, CEOs, creators, innovators, scientists, military leaders, visionaries and athletes. Now 
let’s go out there and become passion struck. Absolutely thrilled today to welcome Dr, Kevin 
Tracy to passion struck. Hey Kevin, how are you today? Good John, thanks for 
having me on. And how are you I’m doing great, and I’ve been 
looking so forward to this episode,   because we’re in the middle right now of 
doing a series on redefining wellness, and I think one aspect of that people 
are not very aware of is the vagus nerve. And you have just written a great book 
came out in May called the Great nerve,   the new science of the vagus nerve and how to 
harness it, healing reflexes. What originally drew you to the vagus nerve was there a personal 
or clinical moment that sparked your interest? There was, I am a neurosurgeon. I spent 
years after medical school and at the New York Hospital corner Medical Center training 
to be a neurosurgeon, but I also spent several years in laboratories at the New York Hospital 
and at the Rockefeller University next door, studying inflammation. And so I had a decade or 
more of thinking about the underlying molecular causes of inflammation. And as a neurosurgeon, 
I was interested in finding ways to develop therapies based on what we had learned and were 
learning then about the molecular mechanisms of inflammation. What my colleagues and I learned 
in the 1980s was that one way of thinking about inflammation, well, first of all, what is 
inflammation? It’s the redness, the heat,   the pain and the swelling that occurs at the 
sites of injury or infection in the body. So another way of thinking about inflammation, 
as scientists do, is what are the molecules and the cells that cause the underlying inflammation, 
the redness, the pain, the heat and the swelling. And then in the 1980s my colleagues and I 
realized that molecules called cytokines, things like TNF and IL, one made by white 
blood cells, have a very important role in   causing inflammation, and that overproduction 
of cytokines can actually be the driving cause of inflammation In some conditions. And 
knowing this, it was possible for us to do experiments with molecules called monoclonal 
antibodies. And these monoclonal antibodies, we showed, were able to stop inflammation in 
baboons with serious inflammation. That really leads to the question that drove the research 
for me for the last 30 years, which is if, if your body can make molecules that cause serious 
inflammation, then how did evolution put in place mechanisms to stop that inflammation or control 
it? If inflammation has the capacity to do great harm there, there must be evolutionarily ancient, 
conserved mechanisms that keep it in balance. They keep it restrained. And so I was a neurosurgeon. 
I’m a neurosurgeon thinking about inflammation, and it would be nice to say that I had an original 
idea, or the dream about what the solution would be. But actually what happened was surprising, 
unexpected result in the laboratory, and here at the Feinstein institutes, in my laboratory, 
here with Sangeeta Shivan and my colleagues, years ago, there was an experiment done looking 
at the effect of putting an anti inflammatory and experimental molecule into the brains of 
animals with a stroke. Yeah. And the idea was, if we stop the inflammation around the stroke in 
the brain, that the stroke would be smaller and there’d be less brain damage. And we did that, and 
it worked beautifully. What we didn’t expect is that, by putting the anti inflammatory molecule 
directly into the brain of these mice and rats, that the inflammation in the body of these animals 
would also be stopped. And this made no sense at all. There was no plausible way to understand 
why a very small amount of a drug in the brain, not enough to go through the whole body, 
would stop inflammation through the body,   and to make 25 years of work very short. What 
we had discovered is that the brain was sending signals through the vagus nerve, and the vagus 
nerve was acting like the brakes on your car to stop cytokine production and to stop the onset of 
inflammation. And that really changed everything. And that simple, unexpected experiment set us on a 
path of research that’s gone on now for 27 years. That is an amazing story, and what an inflection 
point. I know some people are familiar with the vagus nerve because it’s becoming more 
talked about, but there might still be listeners today who haven’t heard of it yet. 
The interesting thing is, it touches every vital function. How would you explain its 
role to someone with no medical background? Let’s begin with where it is and where 
it goes. So the vagus nerve starts at the bottom of your brain, at about the level 
of your ears, and travels down your neck. We call it the vagus nerve, but you actually have 
two of them, like two thumbs or two kidneys, so one on each side. So these vagus nerves travel 
down each side of your neck, across your chest and into your abdomen, and along the way, sends out 
branches or projections that touch all the organs that you don’t think about all day long, your 
heart, your lungs, your liver, your pancreas,   your intestines. Now we’ve said there’s two 
vagus nerves. Actually. Inside each of those vagus nerves is a bundle of nerve fibers, 100,000 
individual nerve fibers on each side of your neck. Now knowing this, it’s good to think of it, 
perhaps, like a transatlantic cable running between New York and Paris, and it can and it 
carries. This cable can carry information going in either direction from the body to the brain 
or from the brain back to the body’s organs. And that’s exactly what it’s doing all day long, 
the signals traveling in your 200,000 vagus nerve fibers are the basis of the reflexes that 
allow your brain and nervous system to control the function of your organs and to keep them in 
on a in a harmonious Balance. So for instance, you take a breath in and the air fills your 
lungs. That expansion of your lungs causes changes in pressure and changes in carbon dioxide. 
Those pressure changes and carbon dioxide changes are activating vagus nerve fibers, probably a 
few 100 of them that travel up into your brain, and now your brain knows that your lungs expanded 
and that carbon dioxide levels are changing, the brain and brainstem process that information 
and reflexively, without you thinking about it, respond to adjust things like your heart rate and 
your blood pressure. And this is the fundamental operating principle of the vagus nerve. It’s a 
conduit for reflexes that keep all your organs functioning in harmony, so that you don’t have to 
think about doing it. Imagine you’re sitting in the doctor’s office, and she taps your knee with 
a rubber hammer, and she taps your patellar tendon that stretches. That’s the knee. The nice patellar 
tendon is stretched by the thump of the rubber hammer that causes signals to go up the sensory 
nerves into your spinal cord, and immediately there is a motor signal that returns to your 
quadriceps femoris muscle, your thigh muscle, and boom, your leg pops up, and you said, who 
did that? This is happening all day long to control the organs that balance your physiology, 
that keep everything in what we call homeostasis, which is health. Homeostasis and health depend 
on healthy reflexes in your vagus nerve. So I wanted to take this a little bit different 
direction. I think that’s a great baseline. I   had a conversation a few years ago with Dacher 
keltners professor at the University of Berkeley, and our conversation was all around his book 
that was about awe, but in this discussion, he was telling me that. But when you experience 
awe, it can connect to the vagus nerve, and it is what influences your emotions. 
I didn’t really understand the science behind that, and I was hoping you might 
be able to explain it to some extent. The simple answer is, nobody completely 
understands it. John, when you’re talking about 200,000 individual nerve fibers, each with an 
evolutionary history that dates back millions or hundreds of millions of years, each has a specific 
root, a specific origin, a specific destination or insertion, and each has a specific function. 
When someone tells me they want to stimulate their vagus nerve, I like to joke, okay, there’s 200,000 
of them. Which one do you want to stimulate? And we don’t know. We don’t know enough to give a 
simple answer to your questions. Let me give you, let me give you an example about some a 
few things we do know Steve lieberlissa,   a brilliant researcher at Harvard Medical School 
in Boston, did a beautiful study some years ago, and he’s followed it up with others, but I’ll just 
talk about one. And he asked a question in mice, which have about 5000 vagus nerve fibers. In mice, 
how many vagus nerve fibers control breathing. Now breathing is pretty important. The vagus nerves 
pretty important. I think most people, at first   blush, would think it would be an enormous number 
controlling breathing. It turns out it’s about 100 fibers control and within those 100 fibers, a few 
dozen might control the inhalation or the maximal inspiration volume, another few 100 might a few 
dozen fibers might control the duration of breath, holding between inspiration and expiration, 
and down the list, a few dozen more control   expiration. Think about that. It’s amazing 
if something as important as breathing, which does require for healthy, normal breathing. Does 
require a healthy, normal vagus nerve functions. But if we’ve accounted for 100 or 200 fibers in 
breathing, well, what are the other 4800 fibers doing? Now, if you go to heart rate control, 
which is another area with hundreds of millions, if not billions, of web impressions on social 
media, there’s again, a similarly small number of fibers project in the vagus nerve from the brain 
stem to two different sites in the heart, and when the vagus nerve signals traveling into the heart 
increase, heart rate tends to slow. And so you can study that as an isolated phenomenon. So you 
can in a physiology lab, either in animals like there’s a beautiful let me do one more example out 
of New Zealand. You can study sheep, as was done recently in New Zealand a couple of years ago, 
and you can attach all kinds of sophisticated monitors and electrodes to a sheep as it runs 
on a treadmill. And if you can imagine it sounds like a Far Side cartoon, right sheep running on 
a treadmill in a lab, you can almost imagine them smoking a cigarette afterwards, or something 
in the Far Side cartoon. But the question the   investigators asked and answered was really simple 
and elegant. So we all know that the vagus nerve is the rest and digest part of the nervous system, 
and it opposes the fight or flight or sympathetic part of the nervous system. So the vagus nerve 
is parasympathetic and the fight or flight is   sympathetic. Now we all know when you exercise, 
you increase your sympathetic nervous system, you get pumped up. Your heart rate increases, 
your blood pressure increases. That’s all true. What they proved by looking very carefully at 
the signals traveling in the vagus nerve and in the blood flow through the coronary arteries 
and in cardiac output measurements that they   did in these sheep is that when the sympathetic 
nervous system was up regulated during exercise, it didn’t turn off the vagus nerve signals. It 
turned the vagus nerve signals were also turned on. They were both on and when, in fact, both 
were important, because when they cut off the vagus nerve signals in these sheep, the coronary 
artery blood flow decreased and the workload, or the efficiency of cardiac and muscle function 
decreased. So in order to have optimal performance during exercise, it was actually a synergistic 
effect, or an additive effect, between the sympathetic and parasympathetic systems working 
together. So just in those three examples, right heart rate, breathing and exercise, you see 
how complicated your question is. 80, 80% of the 200,000 fibers in human vagus nerves are sensory. 
What happens when you take a big breath, as I said in the first example, which. Classically used as 
a way to start a relaxation therapy, for instance, is you see that during that inhale, you actually 
speed up your heart rate a little bit. And that has to do in part, with the fact that you’ve 
changed the volume and pressure in your lungs by inhaling because you lowered your diaphragm 
so you’ve made a bigger volume, so the pressure   drops that causes your heart to twist a little 
bit on its access. You can see that on an EKG, and it causes your pulse to speed up. If you feel 
your pulse carefully, and you take a three second inhale, you can actually feel your heart speed 
up a little bit, and then when you exhale slowly for seven seconds through say, pursed lips, you 
can actually feel your heart slow down again. So what you’re seeing is a real time effect of the 
incoming signals in the vagus nerve to the brain, which is coordinating the outgoing signals 
through the sympathetic nervous system and the   vagus nerve to increase and decrease your heart 
rate, and this is all done so that your breathing is coordinated with your heart rate changes, so 
that your blood is optimally oxygenated. Now, is that stimulating your vagus nerve, or is it a 
lot more complicated than that? That’s the semi medium long form answer to your question. 
And we’re just getting started, really. I was going to ask this question later on, but since 
you were just talking about cheap and exercise, I’ll jump to I think it’s chapter 10 in your book, 
where you write that things like cold exposure, breath work, meditation. You were 
just talking about breath work,   stimulate vagal tone. Can you walk us 
through why these practices are so effective? You said they’re effective. I didn’t. What I say 
in the book is that whether it’s breath work or exercise, various types of cognitive behavioral 
therapy and meditation, there’s a grain of truth in all of those things, in some people, done in 
some ways, to culminate in a lower resting heart rate. If you look at a group of subjects, 
and one subject has a lower heart rate, resting heart rate than another, and other health 
factors and medications are all equivalent, then that’s one sort of quick and easy way 
to estimate that the activity of The vagus nerve fibers to the heart in the patients or the 
subjects with the lower heart rates, is higher than the vagus nerve activity in the group 
of subjects who have a higher heart rate. So why is that? Well, that’s because we can be 
pretty certain that the fibers to the heart, vagus nerve fibers to the heart that tend to slow 
heart rate seem to have more activity, as I said, all of the things being equal, if the heart 
rate slower in one group than another, okay,   that we know we can’t connect all the dots without 
looking at, as I said, animals modern with very sophisticated Technology in a laboratory, we 
can’t connect all those dots between input, vagus nerve sensory fibers and output. So 
in the case of deep breathing or meditation, associated with breathing in on three and 
out on seven, by changing your breathing,   you are changing the vagus nerve signals 
associated with inspiration and expiration, which changes the vagus nerve signals going to 
the heart. And that doesn’t mean necessarily, that when you breathe in and activate those 
vagus nerve fibers associated with the lungs and heart that you’re also associating all the 
other vagus nerve fibers, the other the other fibers of the 200,000 fibers, to your stomach, 
for instance, or your intestines or your liver. There’s no evidence that because you activate one 
vagus nerve fiber, you’re activating all of them. And so the questions are interesting, because 
there are clinical studies of correlation between conditions or behaviors that lower heart rate and 
outcomes or quality of life measures that seem to improve, so as a across the board recommendation, 
the things that tend to lower the pop the heart rate of a population, are things that are 
good for your well being and mental health, regular aerobic exercise, eating a balanced diet, 
meditative practices or cognitive behavioral practices or avoid. Getting stress and anxiety, 
getting enough sleep, having a having hobbies and being well integrated into cognitive activities 
and social activities, all of these things, you can find evidence in fairly good studies that all 
of those practices are associated with decreasing heart rate. Therefore you could say increasing 
vagal tone. There are also studies looking at a more now popular lately, measure of what’s called 
vagal tone, looking at heart rate variability, which is a little more complicated, but suffice it 
to say, these correlations do not prove causality, and that’s really the rub. That’s really 
the answer to your question. There’s a lot   of correlative data of meditative practices, 
lower heart rate, feeling better. Does that mean that you feel better because you stimulated 
your vagus nerve, maybe, but it’s not proved. So begs the question, with 200,000 fibers that 
are constantly transmitting data, how in the heck does the body prioritize what gets acted 
on first? Is it like competing radio signals? That is why I wrote the book, was to try to break 
down that very question into understandable sound bites. So the first thing you have to get your 
head around to understand the answer is that your body and all its organs is connected. 
Each and every cell, almost of your body, is connected to a nerve ending, and those 
nerve endings are receiving information about the status of your cells and your organs all 
the time, how much glucose is in your liver, how much carbon dioxide is in your lungs, how fast 
your heart is be is beating, how much pressure there is in your stomach or your intestines. It 
there is an overwhelming amount of information in your body that is constantly transmitted through 
sensory nerves, many of them in the vagus nerve, not all, but many of them in the vagus nerve 
up into your brain. Now, if you were the little person standing inside your brain looking down 
at the information coming up the vagus nerve, you would be seeing a second to second report of 
the status of the health and function and outputs of all your organs. Which makes sense, right? 
It begins with the input. Now the inputs are relayed through a number of centers in the brain 
stem and called nuclei, which function like the router in your house, where the information comes 
in from the internet, and the router distributes   it to your iPhone or to your kids laptop or to 
whatever, all through the house. It’s, it’s, parses all the information. In the case of your 
brain stem, the all the information comes in from the body, and the brain routes it through 
different networks. Now each network is capable of sending a response back to the body. Now, just 
like the knee jerk reflex we talked about before, reflexes tend to act in opposition to the input, 
so the tendon stretches so your leg bounces up because your thigh muscle contracts. In the 
case of, say, too much pressure in your stomach, the incoming signal going up the vagus nerve 
would say the pressure in the stomach is high. The descending signal from the brain would say, we 
better relieve that pressure, either by relaxing   the stomach or contracting it to propel the 
food down to the next station. And you do that for every single input, 1000s and 1000s of input, 
each one very specific. Each one induces a highly specific reply reflex output. So you almost have 
to think about it to the scientific the correct answer. There’s philosophical and psychological 
answers you could talk about all day long,   but the scientific, physiological answer has 
to be answered one fiber at a time, in and out. I just wanted to go through a hypothetical here. 
Let’s say I was a former military person served in combat, and let’s say you get injured on the 
battlefield and your vagus nerve is severed. What happens to an individual? Can it be repaired? 
I understand if it’s severed on both sides, it causes instant death. But how 
does that disrupt your functions? The important point you just made bears a little 
explanation for those who haven’t read the   book. But the vagus nerve is the only nerve in the 
body that if you cut it on both sides, you die, which is interesting, if you cut the spinal cord 
high enough up, you die. But as a nerve, the   cranial nerve arising from the brain, so it has. 
These very important functions, you can survive a vagus nerve injury being damaged on one side, and 
whether it can be repaired or not, really depends on the nature of the injury and how quickly the 
neurosurgeon could get in there to reconnect fibers in the hopes that some would grow back. 
But a more common example, rather than a vagus nerve injury. Actually we saw during covid So near 
the end of the covid pandemic, there were a series of studies that came out. It started in Spain 
from researchers looking at autopsies people who had died of severe covid, covid 19, and when they 
looked at the vagus nerve of these cadavers, they found that the vagus nerve, many of these deceased 
patients had the SARS virus, the covid virus, in their vagus nerves. And there was evidence 
that the vagus nerves were damaged, and there was evidence of inflammation in and around the 
vagus nerve. Now we know that vagus nerve damage or dysfunction will actually, you could think of 
it as damaging the brakes in your car, the brakes that normally suppress inflammation. And so we 
know, if you cut the vagus nerves and animals and subject them to any inflammation stress, that 
the inflammation is much, much worse, much more lethal, much more dangerous, if the vagus nerve 
is not working, and we know if you stimulate the vagus nerve in these inflammation conditions 
that you can stop inflammation. So knowing that the covid victims had damage to their vagus nerve 
has opened a whole new field of research asking if the vagus nerve can slow down inflammation 
and covid or SARS can damage the brakes damage the vagus nerve. Is that why some people have long 
covid? Do they have underlying vagus nerve damage? And so some studies have continued in addressing 
this question, and there is now evidence with MRI scans and high sensitivity ultrasound studies that 
have been published. And in fact, some patients, some covid survivors who have long covid do have 
evidence in their vagus nerve damage. So the work continues because, again, it’s a correlation. It’s 
very interesting, but it does improve causality, but it’s an important question you’re asking. 
When you go into fields like rheumatoid arthritis, inflammatory bowel disease and other conditions 
of auto autoimmunity or autoimmune illnesses, and you ask, what is the evidence for vagus 
nerve dysfunction in those patients. It turns out there’s a lot of evidence so in rheumatoid 
arthritis patients, and several studies have now demonstrated this, including one that my 
colleague Sangeeta Siobhan and I here at the   Feinstein institutes in New York, one that we 
published we measure heart rate variability, which we said is a surrogate marker for vagus 
nerve activity to the heart. And what we found was that patients with autoimmune conditions 
have poorer vagal tone. They had less heart rate variability, more heart rate variability 
associated with more vagal tone than subjects who are healthy and did not have autoimmune 
conditions. Very interesting. Again, correlation, it does improve cause and effect, but there’s 
a tremendous interest in this. Can we use heart rate variability as a surrogate marker for the 
fibers in the vagus nerve that stop inflammation? The question is, maybe, and if so, does that 
answer your question, that how much evidence is there for vagus nerve damage in contributing to 
subsequent conditions? There’s growing evidence. Well, since you just brought up rheumatoid 
arthritis, I’m going to go here, because just days ago, the FDA approved the set point system, 
which is an implantable device you co developed as a treatment of rheumatoid arthritis. That is 
such a landmark achievement, something you’ve been working on for decades. What does this moment mean 
for you, personally, into the future of medicine, there’s huge implications for this to be clear, 
set point, medical is a company that I co founded in 2007 based on the science that came out of my 
laboratory at the Feinstein Institute. I did not develop the device. The company developed the 
device over many years. The company was founded in order to develop new devices that would target 
the vagus nerve in order to reduce inflammation in patients with rheumatoid arthritis and other 
autoimmune conditions. And the number of people that worked on that project and brought this idea 
to life are too many to name. Over the years, they’ve been. Many dozens, if not hundreds, 
of people at set point who conceived of how   to design the device, build the device, launch 
the clinical trials, design the clinical trials, fund the clinical trials, and then ultimately 
to produce a 24,000 page document for the FDA to review, which culminated just last week, 
as you point out in the FDA approval for the setpoint medical device as an immunoregulator to 
true rheumatoid arthritis patients. So hats off to Murthy, the CEO and his team at setpoint 
for doing this and leading the charge. What it means is a tremendous new therapeutic option 
for one and a half million patients in the United States who are should be eligible as possible 
patients because they have rheumatoid arthritis, which is not responding or getting better 
from the currently available drugs. The currently available drugs are drugs called 
biologics and jacks or Jack inhibitors, these drugs work terrifically well in some 
patients, and there’s a lot of good that can be said about them, but for about half the 
patients that take them, they don’t work well, or don’t work at all. And more importantly, 
even in the patients that are deriving benefit from the drugs. The drugs have significant side 
effects. These drugs all cause immunosuppression, which means that the immune system is suppressed 
to the point by these drugs that patients are at risk for serious complications of secondary 
infections, tuberculosis, sepsis, even some forms of cancer. So patients, in general, 
that I’ve talked to would prefer a therapy with less side effects, and that’s exactly what 
the setpoint device offers. The setpoint device is about the size of a multivitamin. It’s called 
an immunoregulator. It sits on the vagus nerve in the neck at about the level of your Adam’s apple 
and the safety profile in the clinical trial, which led to the FDA approval, is absolutely 
terrific. All the detailed information about safety and patient eligibility and effectiveness 
are on the setpoint medical website, and you can steer your listeners to that for the detailed 
information and how it works and the science behind it that came out of my laboratory 
that’s detailed in my book The Great nerve. I wanted to go there next. How does it actually 
stimulate the vagus nerve and reduce inflammation? Because that, to me, was remarkable, because, as 
you were just saying, the current drugs are only working at most on about 50% of the rheumatoid 
population. If I have that figure correct, you do have the figure correct. It’s somewhere 
between 40 and 50% of patients today benefit from those rheumatoid arthritis drugs, and these are 
drugs that have immunosuppressing side effects and sometimes cost between 50 and $100,000 a year. 
So not everybody can even afford these drugs. So the point is, really that other options are 
going to be welcomed. The way it works is based, as we talked about in the beginning, on 27 
years of work in my laboratory and now also in dozens of laboratories around the world by 
hundreds of other people, the science of this is actually very well mapped out. I actually 
like to say when I’m lecturing about this,   that in many ways, we understand the science 
of how the vagus nerve stops inflammation better than we understand how some of the 
biologics actually work. The way it works   is that signals arise in the brain or brain stem, 
which is where the vagus nerve begins. As I said, at about the level of your ears, these signals 
travel down fibers. And in the human vagus nerve, we estimate it’s about 1000 fibers are sufficient 
to do this. It could be more. Could be less. In mice, we estimate it’s a few 100, these 1000 
fibers travel down your neck, down your chest, into your abdomen. There they terminate. They end 
on a bundle of neurons called a ganglion, which in turn sends additional nerve fibers into your 
spleen. In the spleen, The electrical information is converted to chemical information. That means 
that the signals that we can in mice anyways, we can actually begin the signaling process with 
very sophisticated electrodes and other methods directly in the brain of the mouse. We can follow 
the signals all the way into the spleen, where the   electrical signals are converted into chemical 
signals called norepinephrine and acetylcholine. The acetylcholine actually comes from white 
blood cells called lymphocytes or T cells, that are activated by the neuro norepinephrine that’s 
being released by the nerve endings in this plane. Now the acetylcholine being made by the T cells 
is the. Signal to the other white blood cells, called monocytes and macrophages, to stop making 
cytokines. It also does something else. It causes these monocytes to change their behavior. So one 
behavior of a monocyte, we call m1 and that’s the angry, attacking white blood cell, and that’s 
the white blood cell that goes to your joints,   if you have rheumatoid arthritis, and causes the 
redness and the pain and the swelling. But in the spleen, the signal from acetylcholine made by 
the lymphocytes actually causes those monocytes to switch and become what we call him to or tissue 
repairing monocytes. If you have tissue repairing monocytes leaving your spleen because your vagus 
nerve was stimulated, those tissue repairing monocytes can increase the healing in the joints 
rather than increase the damage. Now, all of this is based mostly on work and mice and rats and 
other animals in the lab, because it’s very hard to do these kinds of studies in humans, but 
surrogate measures of everything I said has also been found in human clinical studies, and that’s 
why so many people are optimistic when you look at the results of the first clinical trials, and 
when you look at the results from the most recent clinical trial of 242 pages, patients, 75% of the 
patients after one year of vagus nerve therapy with the immunoregulator. From set point, 75% of 
those patients were using the immunoregulator as their main stay of therapy. They were no longer 
using biologics or jacks, and that’s huge, because that means that you’re not only gaining clinical 
benefit for the pain and swelling in the joints, but you’re also avoiding the risks of the black 
box warnings on those immunosuppressive drugs. Thank you so much for going into that, and I want 
to read something from your book. You write that   today we know that there are billions of synapses 
in the nervous system that are activated when the vagus nerve is stimulated, which you were 
just talking about. Thus, by accessing the vagus nerve with an electrode in your neck, 
we’re beginning to learn how to modulate the   physiological harmony of your body and brain. That 
sounds like an enormous discovery that not only is going to help rheumatoid arthritis, but this 
could go on to help so many bodily functions. Where do you see the potential of where 
this could go beyond just this apparatus, the potential is great because we can apply the 
methods that we use to mapping what we call the inflammatory reflex, which are the signals 
I just described, the signals. When you have inflammation in your body, the vagus nerve detects 
the inflammation. That’s the sensory input. That’s the rubber hammer tapping your knee. That’s the 
input signal the brain responds with the other signals I just described that travel from the 
brain to your spleen to stop the inflammation,   to counteract it. That’s the output. So by 
approaching questions of body brain function and the relationship between conditions that cause 
diseases in the brain or diseases in the body that influence the other and vice versa. By approaching 
these seemingly extraordinarily complex questions, one nerve fiber at a time, you can begin to 
develop enough knowledge we call that molecular mechanisms, or neurophysiological mechanisms, to 
now intervene with therapies. So again, you have 100,000 vagus nerve fibers on each side, a very, 
relatively small number appear to be sufficient to stop inflammation in patients with rheumatoid 
arthritis, or at least to make it significantly better. Now, imagine we’re doing that today 
with the devices we use by putting in a very small amount of current. The current only flows 
for one minute a day at 400 micro amps. That’s nothing. 400 micro amps through that. Some patients that I’ve met from the clinical 
trial are sleeping through it. The device is programmed in some of these patients to fire at 
430 in the morning, and some patients literally   sleep through the stimulation. The other thing 
it tells you, because it’s only 400 microamps, is we’re not stimulating all 100,000 fibers. 
We’re stimulating a small subset of fibers that is sufficient to stop the inflammation. 
Now, as knowledge of the vagus nerve anatomy and the vagus nerve function continues 
to grow, will it be possible someday to identify the fibers that are traveling up into 
the brain to activate the pathways, for instance, associated with increase. Least attention. Can 
we follow the fibers that go into the locus coeruleus, which then are relayed up into the 
basal forebrain cholinergic system or to the dope dopaminergic systems of the brain? Can we identify 
the individual fibers that participate in reflexes that might explain why so many patients with 
vagus nerve stimulators say that it improved their quality of life because it made them feel happier. 
This was the basis. It was clinical observations decades ago, actually, in the 1990s of patients 
who had vagus nerve stimulators implanted to treat epilepsy, and many of these patients reported to 
their physicians, I feel happier. I feel better. The device is not helping my epilepsy for one 
reason or another, but I want to leave it in   because my outlook on life has improved. That 
actually led to clinical trials using Vagus Nerve Stimulation therapy to treat patients with severe 
depression that is not responding to advanced talk therapy or medical therapy. Well, what happened? 
Well, 50% of the time, give or take, patients get significantly better with the vagus nerve 
stimulation. Well, what about the other 50% Why doesn’t it help them? It’s back to your question. 
We don’t understand the mechanism. If we knew in advance which patients would benefit from Vagus 
Nerve Stimulation therapy, we could screen them and not implant the 50% of the patients in which 
it doesn’t benefit. We can’t answer that question, because we’re not sure of the underlying reflex 
circuits that are dictating the beneficial response or the absence of a response. So your 
question is spot on, because the basic principles of mapping reflex circuits in the vagus nerve 
can serve as a guide post for developing new therapies for other conditions that may or may 
not be mediated by other vagus nerve fibers. Kevin, I wanted to go back to my example of being 
in the military, and I know that one of the things that has been a result of people being in the 
20 years of war that the United States was in, in Afghanistan and Iraq is a lot of people 
were exposed to bomb blasts, which caused, almost like if you were in a football game, lots 
of trauma that keeps on repeatedly happening, and it’s caused a lot of people to feel The 
symptoms of having traumatic brain injuries because of this constant trigger event. I guess 
it’s the same thing that leads football players to getting CTE. And I understand that one of 
the causes for dementia is might also be related to this, where, for whatever reason, the amyloid 
plaques aren’t getting flushed through the system. Where I’m going with all of this is, is 
there any correlation to all these things,   and potentially, the vagus nerve being at 
the center of what’s causing these ailments? I don’t like to put it at the center, 
because each of those are so different   conditions. So post traumatic stress 
syndrome is extremely different than CTE, the football repeated concussion injury syndrome, 
and that’s very different than Alzheimer’s, where there’s a convergence in the story 
is all three of those conditions have implicated a role for inflammation in 
in contributing to those conditions or making them worse. And so you can ask the 
question, it’s fair to ask the question. Let me reframe it. I guess where I was going to 
this is inflammation on the brain, which seems to be the same thing across all of them. And 
what’s interesting to me is oftentimes PTSD has overlapping symptoms that a TBI or repeated TV 
eyes that would bring about, or CTE would bring about, which mirrors some of the symptoms that 
you would experience with dementia or Alzheimer’s. John, you are asking the question like a savvy 
researcher, and there’s openings in my lab if you’re FY, we’re always looking for good people. 
That is the right question. And again, to go to break it down to first principles, individual 
nerve fibers, individual molecular targets,   individual molecular mechanisms, you really 
need to connect the dots by asking those kinds of questions. So let’s start with the question of 
post traumatic stress, and we’ll start top down. So in PTSD, there’s good evidence in many of 
those patients that some percentage of them, I don’t know if it’s half, I think it’s about 
half, can gain significant benefit improvement from various cognitive behavioral therapies, 
and some can even be. Guided by, say, an app, and there’s some exciting new advances in and 
actually some consensus arising on the best cognitive behavioral or talk therapy approaches 
that have helped a lot of people with PTSD. So that’s good. What’s also known, and this goes back 
many years again, to patients who had vagus nerve stimulators, originally implanted for epilepsy 
that if you have, if you give cognitive tests and attention testing to volunteers before and 
after you turn on the vagus nerve stimulators in their neck, which is presumably driving signals 
up into the router in your brain that we talked   about that their attention improves and their 
and their ability to learn and to and remember actually improves as well. So that’s amazing, 
right? The driving vagus nerve signals is good   for your cognition and attention. So knowing that 
and knowing also that those behaviors are good for neuroplasticity, and knowing that neuroplasticity 
or brain remodeling is a really important part of the clinical response to say, talk therapy or 
cognitive behavioral therapy, investigators recently put all those things together and they I 
don’t know if you saw the news, maybe that’s why you’re asking me. But there’s a recent report 
out within the last month or so of a clinical trial implanting vagus nerve stimulators and this 
and these simulators were timed not to not work all day long, but to only deliver a pulse, 
a simulation of the vagus nerve in the neck, driving signals up into the brain timed with 
the function of the app. And what they found in these PTSD patients is the effectiveness 
of the app went from 50% I think, to 100% gosh, I realized it was that high. It’s unbelievable. You can Google it and double check 
all the facts, but there was a tremendous clinical response. This study was published in a very 
high impact, peer reviewed journal, and it was picked up by the press around the world because it 
speaks to what you said. Can we link vagus nerve therapies to these complex, difficult to treat 
brain therapies. Now that’s the most advanced of the three. There are theories and hypotheses being 
pursued for CTE and Alzheimer’s, and there’s hope, but the first clinical trial results appear to 
be in for PTSD. And what remains to be seen, of course, is that trial will have to be 
replicated. And with every new discovery,   whether it’s in the lab or in the clinic, there’s 
100 new questions, so this will have to all be pursued, but it’s a really interesting 
time for the answer to that question. Wow. Kevin, one of the reasons I’m so 
excited about having you on the podcast, I’ve been looking forward to this interview so 
much, is the bigger picture. So we’ve talked a lot about today inflammation, and inflammation 
is the common thread across most modern diseases. So if you think about this from a larger 
perspective, that inflammation is at the root cause of why so many millions of people 
around the world are suffering, and the research is starting to point to the vagus nerve as helping 
to turn that tide. It just speaks to how large the work that you’ve been doing over the past two 
decades could potentially be to influencing so many people’s lives in a better way. My question 
from that is, do you believe Modern medicine is shifting fast enough to embrace this kind of 
integrative systems level thinking to help people I don’t know John, I hope that the adoption 
of this therapy in first, obviously rheumatoid arthritis, because that’s what the FDA approval 
is for, will drive an explosion of interest in some of the other conditions you’re specifically 
referring to, heart disease and stroke, cancer, diabetes, metabolic syndrome, obesity, all of 
it. These conditions account for the mortality of two thirds of the people who die on planet 
Earth every year, 40 of the 60 million people who die on planet earth according to the who 
die of those in a couple of other conditions, and they all are either caused by inflammation or 
made worse by inflammation. So the question you ask is the big question, and my hope is that the 
ongoing research that’s already occurring around the world, thinking about treating inflammation 
using vagus nerve stimulation and other, frankly, other possible nerves that control other types 
of inflammation that this work will accelerate how quickly it gets adopted into medical 
practice? Well, that’s one of the main   reasons. Is that. I wrote, my book is to provide 
a platform for people to begin to talk about it, to share the same language and background. There’s 
a chapter in there called FAQs for patients to ask their doctors. Those questions are written for the 
patients, the answers are written for the patients   and the doctors. Most doctors haven’t thought 
about the vagus nerve since medical school, and you asked specifically about adoption, 
a couple things have to happen. There have   to be a lot more clinical trials. The rheumatoid 
arthritis idea is launched. I think that will gain traction quickly, because patients are looking 
for it, and I know this because setpoint medical launched its clinical trial for 242, patients, and 
they had almost 30,000 patients go on the portal and try and enroll in the trial. So there’s an 
enormous demand and interest in that population. Set Point is launching clinical trials very soon 
in multiple sclerosis. The pre clinical data for that are fascinating. We could talk about 
it. I’m aware of other clinical trials for   inflammatory bowel disease, Crohn’s disease, 
ulcerative colitis. I would not be surprised to see clinical trials for psoriatic arthritis. 
And I’m aware of pre clinical studies, laboratory studies and small clinical trials looking at 
diabetes and looking at inflammation associated with other conditions affecting other organs. So 
this is an incredibly exciting time, I think, if you’re a patient or have a family member or friend 
suffering from one of these conditions, things are   not going fast enough. And why is that? Well, you 
really, if you think about it, you don’t really want your doctor chasing every shiny object. 
Medicine has a conservative side to it with good reason. Things take time to work out the molecular 
mechanisms and to understand how they really work. Things take time to build new devices that are 
proven safe and reliable. Things take time to change business practices and workflows and payer 
behavior and regulatory behavior. There’s no bad people doing this. It’s just that you want to 
do it right. You want to know what you’re doing, and that takes time putting all that aside. 
I think we’ve launched with this FDA approval and all the science behind it, and all the 
engineering that setpoint did behind it. I think we’ve launched a new era, and I think 
it might go faster than people are realizing. Kevin, I have one last thing I wanted to talk 
to you about this week prior to me putting your episode out, I did a solo episode on something 
that I’m calling the absorption gap. And let me explain this to you. I host an alternative 
health podcast, so I’ve had lots of people on this show talking about cold plunges to functional 
medicine to clean eating to better sleep. So I’ve put myself through this like a living experiment. 
So I’ve tried to optimize myself by clean eating, structured sleep, intense workouts, breath 
work, mindfulness, biohacking. And on paper, I look like a prime example everyone of 
someone who’s trying to do everything, right, John, I think you look great. 
Well, I think it’s working. The thing behind it, though, is I didn’t feel 
great. My energy was flat. My mind was foggy at times, motivation was gone. And it wasn’t that 
I was burned out, but I came up with this concept called the absorption gap, and I wanted to run 
it by you, because there’s this concept in soil science called hydrophobic soil. It’s when soil 
comes damaged through drought, erosion, overuse, it can absorb water. And I’m wondering if 
the same thing was happening to me. I was throwing so many inputs at my body that my body 
couldn’t absorb it, and I’m wondering if there’s any link between this and the vagus nerve somehow 
getting blocked, the inputs are getting blocked, and so it’s not getting the stimulation it needs. 
Does any of that correlate with your research? I don’t know. It correlates with a lot that 
we know about the vagus nerve. But what I always like to caution people about in this 
frame, well, first of all, full disclosure,   I like you. I try to eat a balanced diet, I try 
to watch my weight, I try to exercise regularly. I try to get enough sleep. I meditate five 
minutes, 10 minutes, twice a day. I do these   things because I believe the data that these 
lifestyle strategies are good for overall health, are good to increase vagal tone and are good to 
reduce inflammation in the body. Does that mean it works through the vagus nerve? Nobody knows. And 
what I always like to caution people of not you, but your listeners, is. Are doing these 
healthy things, is probably a safe bet, a Pascal’s Wager. The issue is, however, if there 
is an underlying structural problem, say, damage to the vagus nerve, like we saw in some patients 
with covid, then if the wires are damaged, right, if the connections are severed or are not 
functioning, then these things don’t work equally well. Point this out, because sometimes I see this 
in social media. I see this online. Well, they should this patient with this horrible condition, 
rheumatoid arthritis, or some other autoimmune   condition. Well, they should exercise more, and I 
cured my rheumatoid arthritis because I changed my diet and I get more sleep and my joints don’t hurt 
anymore. Good for those people that can do these lifestyle changes and have some benefit to their 
health, but shame on them for hinting or blaming the patient when we just don’t know everything 
about the underlying cause. There may be an underlying condition in the vagus nerve of some 
patient where the only way to reactivate those signals is going to be to put an immunoregulator, 
a device directly on the vagus nerve and reanimate those signals with 400 micro amps. And that may 
not be able to be accomplished with a few extra sit ups or push ups. So I see both sides of this. 
You can structure very interesting psychological arguments about mind and body, brain and body 
connections. I tend to actually believe that illness in the body, 100% affects the brain, 
and illness in the brain, 100% affects the body. My favorite conversation on this topic was 
actually with the Dalai Lama some years ago, when I presented this idea of the vagus nerve 
stopping inflammation as a healthful thing to him, and we’re standing on a stage in front of about 
1000 people in Venetian, New York, at his facility there on the top of a beautiful mountain. And he 
asked me this vagus nerve, where is it? And I told him, runs from the brain down both sides of the 
neck, across the chest and abdomen. And he said, is there one or two? I said, there’s two. And he 
said, Is it in the front or the back? I said, it’s in the front. And then he smiled at me and nodded. 
And we went on to something else. Afterwards, I was still standing on stage, and a monk came 
up to me wearing bright orange robes. I’ll never forget it. And he said to me, Do you know why His 
Holiness asked you those questions? And I said, No. He said, because there’s an indo Tibetan 
ancient meditative practice that envisions a cloud of energy, a blue a cloud of blue energy over the 
head, and then during the meditation, we channel that down the neck, on both sides, down the chest 
and into the abdomen. And I said, Cool. And the monk smiled and said, Yeah, it’s very cool. And so 
this connectivity between state of brain and state of body is real. The vagus nerve is a critical 
conduit connecting them what each vagus nerve fiber is doing with each particular intervention 
and modality important research questions. Kevin, this has been one of my most 
favorite conversations I’ve had in a   long time. And your book, The Great nerve, 
the new science of the vagus nerve and how to harness its healing reflexes, to me, 
is a must read. Such great work you put in that book, examples everything else, if 
a listener wants to learn more about you,   your work and these recent breakthroughs, 
where are the best places for them to go? For the general listener, the best place, I 
think, would be those really curious about it, start with my book that I tried to cover the 
basics in a very understandable language for patients, the resources I think, can 
be best found on the setpoint medical website. The other for those in the greater 
New York area, we recently launched a center for bio electronic medicine at Northwell 
Health, and that website also has a links to a phone number and a patient navigator 
that some patients may find very helpful. Kevin, such an honor to have you on the 
show. Thank you so much for joining us. John, thanks for having me on, 
and congratulations on the work you do and are doing and all the good work 
you’ve done. Thank you for having me on.

What if the key to reversing inflammation, healing chronic illness, and restoring balance to your body isn’t a drug — but a single nerve?

In this powerful conversation, Dr. Kevin Tracey — neurosurgeon, scientist, and pioneering researcher — reveals the groundbreaking science of the vagus nerve and how it can be harnessed to treat rheumatoid arthritis, autoimmune disorders, PTSD, depression, and more.

We explore:
• How the vagus nerve acts as the body’s “control switch” for inflammation
• The discovery that changed medical science forever
• FDA approval of a breakthrough implant for rheumatoid arthritis
• The potential to treat conditions from Alzheimer’s to long COVID
• Practical insights on breathwork, meditation, and lifestyle for vagal tone

Whether you’re a patient, health professional, or simply curious about how your body heals itself, this episode will inspire and inform you with cutting-edge science and real-world hope.

Time stamps
0:00 Show’s Intro and guest “Dr. Kevin Tracey”
1:58 Introduction to the vagus nerve and the show
3:22 – Discovery of the vagus nerve’s role in inflammation
06:17 – How the vagus nerve keeps your organs in harmony
09:50 – The link between awe, emotions, and the vagus nerve
13:00 – Breathwork, meditation, and vagal tone: what the science says
17:58 – How the brain prioritizes vagus nerve signals
23:15 – Vagus nerve damage and its impact on disease
30:05 – FDA approval of SetPoint’s rheumatoid arthritis device
37:47 – Expanding vagus nerve therapy to other conditions
46:30 – PTSD, traumatic brain injury, and vagus nerve research
51:10 – The bigger picture: inflammation and modern disease
57:35 – Closing thoughts and where to learn more

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