Passion Struck with John R. Miles - Dr. Kevin Tracey on How the Vagus Nerve Fights Rheumatoid Arthritis | EP 650

Episode Date: August 14, 2025

In this episode of Passion Struck, John R. Miles sits down with Dr. Kevin Tracey, a pioneer in neuroimmunology, to explore the remarkable healing potential of the vagus nerve. Dr. Tracey explains how this hidden superhighway between the brain and body regulates inflammation and how targeted stimulation is providing life-changing results for patients with rheumatoid arthritis, Crohn’s disease, and other autoimmune conditions. Together, they dive into the science, personal stories, and future implications of using bioelectronic medicine to treat disease without drugs — potentially rewriting the rules of modern healthcare.Visit this link for the full show notes.Go Deeper: The Ignited Life SubstackIf this episode stirred something in you, The Ignited Life is where the transformation continues. Each week, I share behind-the-scenes insights, science-backed tools, and personal reflections to help you turn intention into action.Subscribe🔗  and get the companion resources delivered straight to your inbox.Catch more of Dr. Kevin Tracey: https://feinstein.northwell.edu/institutes-researchers/our-researchers/kevin-j-tracey-mdIf you liked the show, please leave us a review—it only takes a moment and helps us reach more people! Don’t forget to include your Twitter or Instagram handle so we can thank you personally.How to Connect with John:Connect with John on Twitter at @John_RMilesFollow him on Instagram at @John_R_MilesSubscribe to our main YouTube Channel and to our YouTube Clips ChannelFor more insights and resources, visit John’s websiteSee Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Coming up next on Passionstruck. 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 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 Passionstruck. 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 turned 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 Passionstruck. Welcome back, friends, to Passion Struck Episode 650, the show where we explore the science of human potential, the art of intentional living, and the stories that ignite lasting change. Whether you've been with us for years, or this is your first time, thank you so much for being

here. You're now part of a global movement committed to living with intention, leading with purpose, and unlocking the life you were meant to live. Let me ask you this. What if your body already had the blueprint to heal itself? What if the key to reversing inflammation, common thread, behind most modern diseases wasn't in a pill bottle, but in a single nerve running from your brain through your body. And what if the next great medical revolution is not about creating new drugs, but about harnessing ancient reflexes your body has had all along? That's exactly what today's guest, Dr. Kevin Tracy, has spent his career uncovering. Dr. Tracy is a neurosurgeon, pioneering scientist and president and CEO of Feinstein Institutes for Medical Research. He's also

the co-founder of Set Point Medical, the company behind the first FDA-approved vagus nerve implant for rheumatoid arthritis, a breakthrough that could change the way we treat autoimmune disease forever. In this riveting conversation, we explore how the vagus nerve, made up of over 200,000 fibers acts as the body's superhighway for healing. While stimulating it can regulate inflammation, restore immune balance, and even impact mental health. We discussed the ancient Buddha breathing practice he once discussed with the Dalai Lama, and what it revealed, feels about claiming the body's healing reflexes. We go into the science behind the FDA-approved neurostimulation device and what it means for the future of medicine, and why Kevin believes

we're only scratching the surface of what neuroimmune modulation can do. If you missed last Friday's solo episode, The Absorption Gap, I am packed why so many wellness routines fail, and the hidden science that explains it. Earlier this week, Wolfgang LinkedIn joined me for a powerful discussion on chronic worry and emotional resilience. Both pair perfectly with today's episode. Want more insights like this? Join our substack at the ignitedlife.net. My free weekly newsletter for behind-the-scenes notes, book insights, and tools to help you live intentionally. And if you found value in today's episode, please consider leaving a review on Apple and Spotify. I'd love to hear your thoughts on today's episode. Now, let's dive into this groundbreaking conversation

with Dr. Kevin Tracy. Thank you for choosing Passionstruck and choosing me to be your host and guide on your journey to creating an intentional life. Now, let that journey begin. Absolutely thrilled today to welcome Dr. Kevin Tracy to Passionstruck. Hey, Kevin, how are you today? Good, John. Thanks for having me on, and how are you? I'm doing great, and I have 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 Vegas nerve. And you have just written a great book came out in May called The Great Nerve, the new science of the Vegas nerve and how to harness it's healing reflexes. What originally drew you to the Vegas nerve? Was there

a personal or clinical moment that sparked your interest? There was. I am a neurosurgeon. I spent years after medical school at the New York Hospital Corona 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 I 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 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 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 a dream about what the solution would be,

but actually what happened was a surprising unexpected result in the laboratory. And here at the Feinstein Institute's in my laboratory here with Sengita Chavon 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. 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 Vegas 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, it sends out branches or projections that touch all the organs that you don't think about all day long, your heart, your lung, 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 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 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 hundred 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 pateller tendon that stretches that's the knee the knee the tether 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 quadricepsumorous 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 to keep everything in what we call homeostasis, which is health. Homeostasis and health depend on healthy reflexes in your Vegas 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 Dacre Kellner's professor at the University Berkeley. And our conversation was all around his book. That was about awe. But in this discussion, he was telling me that 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 Lieberliss, 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 5,000 vagus nerve fibers. In mice, how many vagus nerve fibers control breathing? Now, breathing is pretty important. The vagus nerve is 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 hundred 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 4,800 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 increased, 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 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 fighter 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 upregulated during exercise, it didn't turn off the vagus nerve signals. 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% 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 is 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've 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 purse lips, you can actually feel your heart slowed 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 sheep 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 breathwork 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, the 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's 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, 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 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 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 avoiding 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. 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 it 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 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 brainstem 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 kid's laptop or to whatever, all through the house. It sparses all the information. In the case of your brain stem, 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, thousands and thousands 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 should bear 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 it has 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, of 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 Vegas nerves. And there was evidence that the Vegas nerves were damaged and there was evidence of inflammation in and around the Vegas nerve.

Now, we know that Vegas nerve damage or dysfunction will actually, you could think of it as damaging the brakes in your car, the brakes that normally suppress inflammation. So we know if you cut the Vegas nerve, 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, 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 doesn't prove 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-immunity

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 in several studies have now demonstrated this, including one that my colleagues, Sangita Shaban and I here at the Feinstein Institute's in New York,

one that we published, we measured 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, Setpoint 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, there have been many dozens, if not hundreds of people at Setpoint who conceived of how to design the device, build the device, launch the clinical trials, design the clinical funds, 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 set point medical device as an immunoregulator to treat rheumatoid arthritis patients. So hats off to Murthy, the CEO, and his team at Setpoint for doing this leading the charge. What it means is a tremendous new therapeutic option for one and a half million patients in the United States who 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 set point device offers. The set point 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 Adams apple and the safety profile in the clinical trial, which led to the FDA approval, it's absolutely terrific. All the detailed information about safety and patient eligibility and effectiveness are on the set point medical website. 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 Nerd.

I want 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 some, you know, sometimes cost between $50,000 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, a brainstem,

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 a thousand fibers are sufficient to do this. It could be more, it could be less. In mice, we estimate it's a few These thousand 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 norapinephrine and acetylcholine. The acetylcholine actually comes from white blood cells called lymphocytes or T cells that are activated by the norapherin that's being released by the nerve endings in the spleen. 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 m2 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 founded 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 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 joint, 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, 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 microamps. That's nothing. 400 micro-a-sleep 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 4.30 in the morning, and some patients literally sleep through the stimulation. The other thing it tells you, because it's only 400 micro-amps,

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 increased attention? Can we follow the fibers that go into the locus serulius, which then are relayed up into the basal four, brain colonergic system or to the 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 guidepost 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 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 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 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 TBIs 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 have time, we're always looking for good people. That is the right question. And again, 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 benefits. 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. 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, poured 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%. Oh my 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-review journal, and it was picked up by the press around the world because it speaks to what you said. Can we link Vegas 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 a hundred new questions. So this will have to all be pursued. But it's a really interesting time for the answer to that question. Wow. And I want to ask one follow on to this. The other thing, I haven't done any episodes on this recently, but in the past I've done a few on this. One of the most fascinating was with Dr. David Yaden, who's at Johns Hopkins, is he's been trying to study silo-cybin and its effects on these same types of conditions. And the thing he told me, was right now talk therapy, its efficacy is somewhere around 30%, where psilocybin and BMA are

showing as high as 65 to 70% efficacy. And it goes back to the question I asked earlier about breathwork, meditation. Could some of these mind-altering drugs also be having an impact on the vagus nerve? Yes, they absolutely could. When you look at the clinical effects of these various drugs, some of them slow heart rate. So again, using our simplest definition of vagus nerve stimulation, if you consume a drug and your heart rate slows, and presumably we're talking about drugs that affect primarily the brain, not a beta blocker or something that slows your heart through.

through sympathetic nervous system. But if you take cellosybin, one of the other psychoactive drugs and your heart rate slows, then you have quote unquote stimulated your vagus nerve. Have you stimulated the vagus nerve fibers to your pancreas? No one knows. Have you stimulated the vagus nerve fibers

to your immune system? No one knows. So the problem isn't with saying vagus nerve stimulation. The problem is with assuming that the vagus nerve fibers all have to fire together. All of us can walk and chew gum at the same time. Some people can play the piano and carry on a conversation at the same time. That's because each of those neurons in your body, in your brain and in your spinal cord and in your autonomic nervous system,

all of these neurons, as I said before, they have a specific origin, a specific destination, and a specific function. And they can operate separately. And so treating the vagus nerve as a solid copper wire, which is what, frankly, much of the self-help advice in those billions of web impressions is based on the idea, well, you can hum and you stimulate your vagus nerve. And then your life is better because you've stimulated your vagus nerve. Well, maybe, right? So you have, again, a few hundred or a thousand fibers of your vagus nerve in your neck, branch off and go to your voice box, go to your larynx. And they are very important signals that control your vocal cords. So when you hum, those

fibers in your vagus nerve are very busy controlling your vocal cords. Does that mean that the fibers controlling your heart are activated? No. Does it mean the fibers to your pancreas and stomach are activated? No. And the answer is maybe they are, but we don't know that. The fact that you hum and feel better may be because you've slowed your breathing. And when you slow your breathing, you change your carbon dioxide levels. And when you change your carbon dioxide levels, you get different feedback to your brain. Every one of these, quote, unquote, simple things is doing thousands of other things to your body. They could also be influencing your state of mind and how you feel. So, yes, humming stimulates the branches of your vagus nerve to your voice box. But whether it, I can't stress

this enough, the differential activities of the individual fibers is really the opportunity to do better for our future knowledge and for our future patients. There's no harm in talking about the vagus nerve as a solid copper wire. There wouldn't necessarily be much harm in that, except that a lot of people are trying to profiteer from it and sell things that will do this, that, the other thing on your neck or somewhere else to stimulate your vagus nerve when there's no evidence that actually is stimulating your vagus nerve.

And so the profit margin fits into this. And as a scientist and as an inventor, I also do worry about how some of this outright false information actually dilutes the importance of the important new science that comes out and has supported things like this FDA approval. Kevin, one of the reasons I am 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 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 that 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 of 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 set point 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. Setpoint is launching clinical trials very soon in multiple sclerosis. The preclinical data for that are fascinating. We can 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 psoriotic arthritis. And I'm aware of preclinical 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 friends 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 workfulness biohacking and

paper I look like a prime example everyone of someone who's trying to do everything right John I think you look great 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't 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 Vegas 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, by meditate, five minutes, ten 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, are doing these

healthy things is probably a safe bed, a passive. Scal'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, 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 or a device directly on the vagus nerve and reanimate those signals with 400 microamps. 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 helpful thing to him. And we're standing on a stage in front of about a thousand 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 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 Vegas 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 Vegas Nerve and how to harness its healing reflexes, to me as a must read. It's 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 curiously. 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 BioElectronic

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. And that's a wrap. What a fascinating deep dive into the hidden superhighway that connects our brains, bodies, and healing potential. Dr. Tracy's work invites us to reconsider everything we think we know about treating disease. He reminds us that sometimes the most advanced medicine is not about creating something new, but rediscovering and

activating the healing tools our bodies have had for millennia. As you reflect on today's conversation, ask yourself, if stress reduction, breath work, and meditation be doing more for your immune system than you realize. If inflammation is the common threat in so many illnesses, what simple practices could you start today to claim that fire? And how might the science of vagus nerve stimulation reshape health care in the decades to come? You can learn about Dr. Tracy's work in his book, The Great Nerve, at passionstruck.com, and follow set points, ongoing breakthroughs at setpointmedical.com. Want to watch the full interview, head over to our YouTube channel and subscribe so you'll

never miss a conversation like this. Coming up next on PassionStruck, Christopher Wong-Mickleson and Jennifer Toasty Karears, join me for a timely and insightful conversation on meaningful work. Exploring how to align your career with your values, navigate burnout, and reclaim a sense of purpose in what you do every day. When we feel our work is deeply meaningful, we are less sensitive to maximizing our rewards that we get from it. For example, if I'm paid, if I'm doing a task that's deeply meaningful, and I know that I have, I'm being paid on a per task

basis, like a piece rate kind of compensation scheme, I will do more work, the more meaningful my work. I'm not totally insensitive to money. I'm not totally clueless about money. If it stands to be more money made, I'll expend more effort. The interesting thing that we were able to disentangle in our study, though, is the same relationship held when workers were salaried, meaning I can do more work, but I'm not necessarily additionally compensated for it. Thank you for being part of this movement. Your commitment to growth and intentional living fuels everything we do. And remember, the fee for this show was simple. If something resonated with you, share it with someone who needs to hear it. Until next time, live life, passion struck.

Thank you.