The Nerve That Controls Inflammation — and How to Activate It | Dr. Kevin Tracey

Key Takeaway

Take a deep breath when stressed—it's scientifically sound advice. Inhale slowly for 3 seconds (two short breaths to fill lungs completely), then exhale through pursed lips for 7 seconds. This creates six breath cycles per minute, activating your vagus nerve to slow your heart rate and potentially reduce inflammation. Do this for 5-10 minutes daily. While large clinical trials are still needed, this simple practice costs nothing, takes minutes, and has measurable cardiovascular benefits.

Episode Overview

Dr. Kevin Tracy, a leading researcher in vagus nerve function, explains how this crucial nerve network connects the brain to major organs and regulates everything from heart rate to immune response. He discusses the emerging science of bioelectronic medicine, the limitations of current vagal tone measurements, and evidence-based practices like breathwork that may improve vagus nerve function, while cautioning against unproven claims flooding social media.

Full Transcript

Transcript of The Nerve That Controls Inflammation — and How to Activate It | Dr. Kevin Tracey from 10% Happier. Auto-generated from episode audio; may contain minor errors.

Dr. Kevin Tracy, welcome to the show. Thanks for having me on, Dan. It's really great to be here. I look forward to chatting. Yeah, me too. All right, let me let me start with a big basic question, which is what is the vagus nerve? And just for people listening, it's not like Las Vegas, it's v a g u s. So, what is this vagus nerve? Well, it's a media sensation. Lately, there are billions of web impressions and social media posts. So, we'll start with with with the answer to your question in very basic terms.

It's The vagus nerve is a structure that runs from your brain down your neck to the organs in your body that you don't think about all day long. And we call it the vagus nerve, but it's a paired structure. So, you have two of them, like you have two thumbs and two kidneys. One on each side. In the brain, it it starts at about the level of your ears, ears, ears, travels down the neck with your carotid artery, where you can feel your pulse in your neck.

your neck. your neck. And when it enters the chest, it starts sending branches to your heart, your lungs, and down in your abdomen, innervates your liver and your pancreas and and and your intestines and even your spleen. your spleen. your spleen. And all day long in these two bundles of nerves, the the the information is running back and forth from the body to the brain and and the brain to the body. But what's really important about the answer to this question is I've said there's one vagus nerve.

We call it the vagus nerve when you actually have two. But inside of each of those two are 100,000 fibers. So, So, So, you really have 200,000 vagus nerves connecting the organs in your body to your brain. your brain. your brain. If memory serves, because this is not the first time the vagus nerve has come up on this show, as you can imagine, we've been we've been around for a while. while. while. Um Um Um Vagus Vagus Vagus is Latin for wandering. Uh so, this is a sort of a long set of paired uh wandering uh wandering uh wandering uh nerves that go through our torso.

The the the word is derived from the Latin for for wandering or meandering. And that is correct. I don't particularly like that name. Um Um Um I think I for bringing it up. I've already pissed you off and we're only like 2 minutes into our acquaintance. Yeah, no, no. I'm I'm not angry. I've gotten over it. It goes back 2,000 years, so I've gotten over it. Back in Back in Back in in the in the beginning, if in the in the beginning, if you will, Galen, one of the first physician scientists, physician scientists, physician scientists, uh noticed the vagus nerve and he called it the pneumogastric nerve, cuz he deduced that it was a major nerve connecting the brain to the lungs, pneumo, and the stomach, gastric.

gastric. gastric. And he also proved that if you cut it in living animals, that it that it killed them. And to this day, it's the only nerve in your body that if you cut it on both sides, it's it's lethal. it's lethal. it's lethal. And so, over for many centuries, almost 15 centuries, it was some it was referred by many other people as the pneumogastric nerve or the great even some even called it the great nerve of Galen, Galen's great nerve. And so, I think that's a much better name, because when you look at the vagus nerve today under an electron microscope and you see 200,000 fibers, 100,000 on each side.

And you know that each of them has a specific origin and a specific destination. And each and every fiber is carrying the electrical information that controls a specific function, a function and a in a nerve fiber that was honed by millions of years of evolution to give a very precise way for the brain to establish set points on the physiological output of your organs. It's elegant, it's beautiful, and it to me me me meandering or wandering doesn't describe the precision and the elegance and the importance of it.

I think it's just great, which is why I named my book The Great Nerve. Great Nerve. Great Nerve. Fair point. Um that lands. that lands. that lands. Um let let's just say a little bit more about the aforementioned greatness. Um Uh I'll I'll phrase it like this. You've kind of answered this a little bit, but but let's put a really fine point on it. For my average listener, why should I care about my vagus nerve? Primarily because it is conducting the information between your body and your brain that keeps you healthy.

healthy. healthy. When when your heart, for instance, starts to beat a little faster than normal, normal, normal, signals in your vagus nerve slow it down. down. down. When your immune system starts to cause inflammation that can be dangerous to your health, your health, your health, the vagus nerve signals slow it down. When When When you breathe, every breath you take, your body optimizes the delivery of air into the lungs and blood into the lungs in a synchronized, harmonious way. Those are controlled by signals in the vagus nerve.

vagus nerve. vagus nerve. So, why should we care So, why should we care about it? Well, the science underlying its importance has stood the test of time for centuries. And we're living in an era today where, as I remarked remarked remarked when we started chatting today, there are billions of web impressions. And some of those web impressions tell you to do this, that, or the other thing for your vagus nerve. And some of those recommendations may be based in some scientific truism about its importance to your health.

But let the buyer beware. A lot of these recommendations are based on people selling things. A lot of these recommendations are based on on on minimal, if you will, or sometimes no clinical trial data done in any sort of rigorous or randomized controlled way. And so, it we are in an era where there's a a lot of information about the importance of the vagus nerve, and some of it's based in hard science, some of it we know to be true, some of it we know to be false, and some of it we know should be studied further.

And so, it's a very important topic now, a very it's a very important topic now, because one has to sort through all this information. information. information. I'm trying to grapple with why it's become such an important topic now. Would you feel Do you think it's because people feel like their nervous systems are out of whack? Um I I've just noticed anecdotally that when we give a podcast episode episode episode a title like how to regulate your nervous system, this episode will probably have a title like that.

Those episodes do really well. I think we are living in an era where we have very powerful tools to image the brain, the human brain, even, to study how it functions. We have a a tremendous interest, as you say, in how the brain works and how the mind works and how consciousness works. Again, these are very popular words and tags in social media and on the internet. internet. internet. And a convergence, I think, of of new technology technology technology to study the nervous system, the brain, the nerves, and and and their functioning, I think is is sort of converging on on a cultural phenomenon where anxiety and depression have been on the rise for many years.

You can't pick up a a a report anymore about the state of health care. health care. health care. And this is a global phenomenon. This isn't just a US phenomenon with with a rising rates of of anxiety and depression to the point where these rising rates of anxiety and depression are are outpacing our ability to provide enough caregivers and therapists. So, I think people are looking for understanding in how the nervous system works, how the brain works, how the mind works. works. works. And they are grabbing onto some things that are scientifically validated and some things that are not.

All right, so this conversation is going to stay within the confines of uh the evidence-based. the evidence-based. the evidence-based. And when we venture out of it, we will signal clearly. Um Okay, let me do my magic trick of channeling Um Um Um I say this facetiously or semi-facetiously, channeling the mind of of of my listener. I suspect people are wondering, okay, how do I know whether my vagus nerve is functioning correctly? I think the term for that is vagal tone. So, like, how's my vagal tone?

And how do I know? And then, of course, you know, what do I do about it, which we will get to. You're absolutely correct. The the term vagal tone is widely used. And we have to, I think, be very careful about semantics here. I got to keep coming back to this point, cuz it it really is important, but you have 200,000 vagus nerve fibers. And each and every one of them has a specific job description and a specific path and a specific origin and a specific insertion or beginning and end.

and end. and end. And you can walk and chew gum. You may be able to chew gum and play the piano. Your nervous system can do lots of things simultaneously, drive a car and tell a joke, because individual neurons control very specific individual functions. functions. functions. When people talk about vagal tone, you we have to put this in the context of what it is we can measure about the vagus nerve. One thing we can measure quite easily is our resting heartbeats. Resting heartbeats Resting heartbeats Resting heartbeats are controlled are controlled are controlled by a balance between the input from the vagus nerve to the heart, which tends to slow it down, and the inputs from the sympathetic nerves to the heart, which tend to speed it up.

it up. it up. If you have a lower resting heart rate, you would have by this explanation, uh tendency to have higher activity in your vagus nerve fibers to your heart as compared to the activity of the sympathetic nerves to your heart, and hence your heart rate is slower. Now, Now, Now, that's that that's one way to to describe vagal tone. Where you have to be careful is some people extract that to all 200,000 fibers. Now, the five the fibers that go to your heart, whether they're a few hundred or a few thousand, it's not 200,000.

And many assume that if the fibers to your heart are working, then the the vagus nerve fibers to your lungs and the vagus nerve fibers to your gut and the vagus nerve fibers to your pancreas are also working. I I There's no proof of that. And we're limited by what we can actually measure. actually measure. actually measure. In in the lab, we can we can study the vagus nerves in animals, and we can literally, it sounds unbelievable, but you can literally study the activity of individual fibers.

And and laboratories uh like like my lab with Sangeeta Chavan at the Feinstein Institute here in New York, but other labs at Harvard and at the Karolinska Institute in Sweden and all around the world, laboratories are actually going fiber by fiber in animals to identify the function of each and every fiber. And in even in human studies, which are uh being led by Stavros Ano's at the Feinstein Institute, Institute, Institute, well, he's looking at at cadavers and doing detailed uh autopsies, if you will, will, will, on the vagus nerve of of of deceased humans to to describe the path of each and every fiber.

So, we're still working through the basic anatomy in human beings of each and every fiber. So, to to say that when your heart rate is slow, is slow, is slow, then then you have great vagus tone, that's that's the description people use, and I understand why, but it doesn't necessarily mean that all 200,000 fibers are in good shape. I can imagine where imagine where imagine where uh instances where nerve damage or even infection in the vagus nerve can affect some fibers, but not all of them.

We saw this in victims of COVID in some very famous uh studies in Spain that started in Spain and been replicated elsewhere that showed victims of COVID, many of them had severe damage to their vagus nerve, nerve, nerve, and there was virus in some of the fibers, and there was inflammatory cells causing damage around some of the fibers. So, fibers. So, fibers. So, we have to be careful. That is what people talk about, but we need to really be thoughtful about how it works and and what it means.

Okay, so I take your caveat that we have these very crude ways of measuring vagal tone that really don't capture the complexity and, to use your term, greatness of uh of the thing we're trying to to to capture. Um That being said, you you mentioned heart rate as one, again, very rough way to get a sense of how we're doing. Um I've sometimes heard, and I believe you write about, not just your resting heart rate, but also heart rate variability. Uh is it worth saying more about that with all the caveats that we've just you and I have just that you've issued and I've repeated?

I've repeated? I've repeated? The heart rate variability term is, again, widely used and and held by many to be extremely important. And as you as you as you just pointed out, it is complicated. It's let's let's go down to let's go down to some again some simple definitions. definitions. definitions. Heart rate variability is fundamentally a a a a calculation, a series of calculations based on a fundamental simple measure, and that fundamental simple measure, what is actually being recorded, is the distance in time between individual heartbeats.

individual heartbeats. individual heartbeats. So, each time your heart beats, some number of milliseconds goes by until your next heartbeat. And if you watch what happens even when you feel your own pulse in your wrist and you take a big slow breath in and a long exhale out, you can feel your you can feel your heartbeat literally accelerate a little bit during the big inhalation, and then slow down during a long slow exhalation. That slowing down is the vagus nerve sending its signals to your heart to prolong the time to the next heartbeat.

That's how it works. And so, And so, And so, in this context of high vagal tone that we're discussing, we're discussing, we're discussing, the more times your vagus nerve is firing, the more variability there will be between your individual heartbeats. And so, that's where this term heart rate variability comes from. Now, heart rate variability, this variation is is closely linked, but not the same thing as respiratory sinus arrhythmia, which is the phenomenon I just described where inhalation causes an acceleration of heartbeat, and exhalation causes a deceleration of heartbeat.

And that evolutionary mechanism is is physiology's way of trying to optimize or pair up the maximum amount of air delivery with the maximum amount of blood delivery into the lungs at the same time, so you get effective gas exchange. So, putting all that together, people have collected these measures of instantaneous heartbeats and subjected them to sometimes very complicated um mathematical mathematical mathematical uh uh uh uh analyses. uh analyses. uh analyses. And things like fast Fourier transformations and other algorithms. And when you do that, you can you can find some predictions that can be confirmed with pharmacology studies that area in in in in a spectral analysis called the high frequency domain is probably is probably is probably the closest thing we have to indicating the vagus nerve activity to the heart.

So, what's wrong with that? Why why why why why is there still no consensus, frankly, on how to measure heart rate variability or how to use it? Because all the algorithms are different. The algorithm in your Fitbit that calculates heart rate variability is different than the algorithm in your various watches and other wearables. The algorithms they use in physiology labs may be different than the algorithms that are used in a cardiovascular test. cardiovascular test. cardiovascular test. It matters if you're lying down or sitting up when you have the test.

It matters if you had a cup of coffee for breakfast or something else to eat or drink or nothing to eat or drink. The the the these variables all influence heart rate variability. It matters if you you collect the data for 5 minutes or or 12 hours. So, So, So, the the issue isn't whether heart rate variability is interesting, the issue isn't whether the vagus nerve has an influence on heart rate variability. The the the the questions that remain are what are you supposed to do personally with this this information?

In order to answer that that question, you and your listeners know this as well as anybody, in order to answer that question, you need large randomized, well-controlled, highly replicated clinical trials. That's where the whole thing breaks down. We don't have those. This episode is sponsored by BetterHelp. May is Mental Health Awareness Month and a reminder that whatever you're dealing with, you do not have to deal with it alone. I actually just uh came through a little bit of a depressive episode in my life. It's super difficult, but I got a ton of help from my therapist, also my family and friends, but my therapist in particular was just super available, really helpful with insights and recommendations and medication tweaks.

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clearly saying. clearly saying. So, how do we get a sense then of how we're doing and then what to do as a result? result? result? I think if you're a an elite athlete with unlimited resources, you can control for many of the things I said. You can work with skilled professionals who are expert in recording heart rate variability the same way every time in the same sort of controlling all the the variables that can be controlled. And by by knowing your own baseline again in a very controlled situation by knowing your own heart rate variability baseline baseline baseline and having and having and having standardized methods for following it over time, there may be some value in in watching trends in your own heart rate variability.

That's fair. Where where it gets to be problematic is when you you see things online online online on social media that if your heart rate variability is above or below this number, then you know, this means that you're you're you're shortening your lifespan or you're at risk for this, that, or the other thing or you have or or your underlying condition could be caused by this, that, or the other thing. There we just don't have enough information. What's fascinating though about all this, and I think this goes back to one of your earlier questions about why people are so fascinated in the vagus nerve today nerve today nerve today is we can all agree that a population with a lower resting heart rate has a has a higher vagus nerve activity at rest than a population with a faster resting heart rate.

And that if you look at enormous population studies, whether it's the Framingham study out of Massachusetts over many decades or a even larger study out of France the one thing that predicts longevity in a population is a slower resting heartbeat from all-cause mortality. So, given the choice and knowing what we know today may not be a perfect explanation for everything, we'd all still rather have a lower resting heart rate and higher vagal tone as we're defining it today. Okay, so that's good to know in the abstract, but not so helpful for me as an individual, right?

I mean I mean I mean given everything we've said. So, I think we you're I think So, I think we you're I think what you're saying is we've got to live with the fact that it's hard to measure vagal tone for a lot of reasons. And yet, your book goes into great detail about things we can do to improve it even though we can't measure get a baseline reading or at least most of us can't. So can't. So can't. So let's talk about those things we can do to, you know, regulate our nervous system, specifically the vagus nerve.

You you talk about a lot of them. Um Um Um So so I'm going to I'm tempted to go through them right now. Is that cool with you? with you? with you? Absolutely. I think we might we might set up a introductory framework by saying what what grandma told you to do and and hopefully your primary care physician physician physician tells you to do. Get a good night's sleep, avoid anxiety, eat a balanced diet, watch your weight, exercise regularly, try to have a a positive attitude and close personal ties and social bonds and give something back to your community.

The beauty of that is all of those things tend to slow resting heart rate. Right. Yeah. So Yeah. So Yeah. So that we can say that we can say on a population basis. And so grandma was right and your doctor's right, perhaps. perhaps. perhaps. The other thing that grandma said when we were freaking out is take a deep breath. Absolutely. And that's a very cuz many of the things you just listed like get a good night's sleep, give back to your community, it's a a a you know, we could we could we could say a lot more about each of those, but take a deep breath is very very practical and you have some uh pretty um achievable instructions in the book.

So, maybe maybe let's start right there. It's a Pascal's wager for me, Dan. I do I do a lot of these things because I believe my data that increasing vagus nerve activity can reduce inflammation when we do it either in the lab or in clinical trials with a device implanted on the vagus nerve of people with excessive inflammation like rheumatoid arthritis. And this is now FDA approved and and and and I know how all that works. What I don't know is if things like big breaths which we'll talk about are activating the vagus nerve's fibers to to to my immune system to slow down inflammation inflammation inflammation in a in a way that would be sort of parallel or similar to the signals that are slowing down the heart.

Now, maybe they are, so I do it. And what I do is I I take a big breath in on three. Uh Uh Uh as in as in as in human human men talks about a lot of physiological sniff, you know, towards the end. So, two sort of big breaths over 3 seconds to fill your lungs. lungs. lungs. And then through pursed lips, I like a a long slow exhalation up to the count of seven. So, now you've just breathed in for three and out on seven, that's 10 seconds, which is a rate of about six per minute.

Six complete breath cycles per minute and that has been shown in many physiology studies to amplify, if you will the vagal effect on heart rate variability measures. And so, that's one and you can feel your you can if you do that for a few minutes, you can actually feel your resting heart rate slow down over that time. And so, we've stimulated the vagus nerve to the heart. Hopefully, as I would say, maybe we've stimulated the fibers that slow inflammation. The data are pretty pretty clear, pretty pretty good from many many independent studies about the effects on the cardiovascular system as we've just been talking There's very little data on the fact that this intervention has a a reproducible effect on the immune system.

It might. There are some suggestive studies. suggestive studies. suggestive studies. But they are they don't come up to the level of level of level of large randomized well-controlled clinical trials, which is which frankly is why is why is why these some of these recommendations haven't reached the mainstream in general medical practice because physicians are held accountable for what they recommend to their patients. And absent the those large trials and absent replication of those large trials and absent the [snorts] physician societies and and and groups making recommendations based on those large trials, it's very difficult for for physicians to make these recommendations and then be held accountable without that backup.

So, that's kind of where we are. Do I do it? Yes, I do. It's a Pascal's wager. I I enjoy doing it. I meditate. I I do breath work. And and I hope that it's that it's improving my cardiovascular health and I hope I'm stimulating my vagus nerve to reduce the inflammatory burden in my body, but I haven't proved it. Okay, I have a million questions that I've written down. I will get to them in some semblance of order. Pascal's wager, is that the the French philosopher who is like, I don't know if God's real, but I'm going to believe in him because the odds I I I don't want to bet against him and find myself at the pearly gates having having having wagered the wrong way?

Exactly. Exactly. Exactly. You brought up inflammation. I kind of know what that means and it's embarrassing to admit this since both of my parents are doctors and my wife is a doctor and I've hosted this show for 10 years and we talk a lot about um the mind-body connection. Um But can you remind me what inflammation is and why you've brought it up? Inflammation is the body's response to an injury or infection. It it's how the immune system deals with an invasion, an injury from from whether it's cutting your cutting your hand on a knife or or an infection, whether it's a virus or a bacteria that makes its way into your body.

When we talk about inflammation, we're back to Galen again, the guy from 2,000 years ago who described it as redness, pain swelling pain swelling pain swelling and um uh and heat at the site of that injury or infection. So, if you have an infected mosquito bite, that's what you see. You see redness, pain swelling, heat. And heat. And heat. And this this terminology has stood the test of time more than 2,000 years. That that's that's what it means today and then. But in the modern era, we've we've gotten pretty good in the laboratory at discovering and following the molecules and the cells that produce the redness, the heat, the pain, and the swelling.

And those molecules have names like cytokines, which were very popularly which were which were popularized during COVID, cytokine storm, because these molecules can cause not only the signs of inflammation that you see, but they can also cause damage in the organs in your body that you can't see. can't see. can't see. So, cytokines with names like TNF and IL-1 drive inflammation in the kidneys in lupus. They drive inflammation in the brain in multiple sclerosis. And in rheumatoid arthritis, they drive inflammation in the joints, which can be disabling in rheumatoid arthritis patients.

The reason this whole conversation comes up in the context of the vagus nerve is because 25 years ago my colleagues and I discovered very unexpectedly that signals in the vagus nerve were like the brakes in your car turning off inflammation. And I keep talking about the individual 200,000 fibers. We've mapped the fibers that turn off inflammation in the body of animals, and we have a pretty good idea what they are in humans as well. And the signals in these fibers turning off inflammation can be activated using a using a using a small device, a battery-powered device, that's implanted in the neck on the vagus nerve.

And this is now being used to treat patients with rheumatoid arthritis. arthritis. arthritis. And this is striking, Dan, because the only patients that are being allowed to be treated right now with this device are patients who are are are not having benefit from all the other drugs that are out there for treating inflammation. So, this is a whole new way of thinking about treating inflammation, and it's rooted in understanding how the vagus nerve nerve nerve controls the immune system. The whole area we call today we call it bioelectronic medicine.

bioelectronic medicine. bioelectronic medicine. I'm going to get into bioelectronic medicine in a in a big way briefly. But But But I began this line of questioning because you were saying in the spirit of Pascal's wager that you do breathwork. Uh but you don't yet know because we don't have the tools to measure it whether it is uh improving vagal tone in a way that reduces inflammation. Exactly correct. And And And I can imagine and I I again I so so this is the line of questioning I want to go down for a little bit before we get to bioelectronic medicine.

I can imagine people listening thinking okay, don't I I want my immune system respond when I get bit by a bug, uh when I, you know, mistakenly slice my finger while I'm chopping onions, whatever. I want my immune system to respond um um um in an acute way. I want the inflammation to be there when I need it. The problem is that many of us are dealing with chronic inflammation where the immune system is on alert without cause in a way that can be severely degrading to our health.

Am I right about Am I articulating that correctly? You are articulating it perfectly. I like to describe the chronic inflammation that occurs with autoimmune conditions like rheumatoid arthritis or inflammatory bowel disease. It's almost as if the immune system is calling in the the the the full power of of the army and the navy and the air force uh to the site of a of a few elderly residents protesting the food in their nursing home. And and this is this is we don't know what has in in many of these conditions, we don't know what the trigger is to this immune response, but you're 100% right.

There's a ongoing attack, persistent, ongoing, steady attack of the immune system against the body's normal tissues in these conditions, and that is the problem. The other problem, and you your your your question framed this, the other problem with this is how we treat it today. So, these patients with these chronic conditions are being treated with powerful immunosuppressive drugs. And it's a trade-off because the immunosuppressive drugs have their own side effects. As you said, you want you want an appropriate amount of inflammation to heal your wound and to fight off your infection in your fingertip.

fingertip. fingertip. But if you immunosuppress, if you suppress the entire immune system, you impair those abilities to fight off infection, and you impair those abilities to heal your wounds. And now you end up with a whole host of new problems. So, the the side effect, the black box warnings of many of the drugs used today to treat autoimmune conditions, include the risk of cancer, the risk of sepsis, the risk of tuberculosis and and leukemia. And that's because the drugs themselves are suppressing the immune system so that it's no longer able to do its job.

When we developed the the the theory of vagus nerve control of of inflammation, what one of the things that's so appealing about it is evolution selected this mechanism to control inflammation. And evolution would not select a mechanism that has immunosuppressing side effects, and that's that turns out to be the case. Okay, so let's go back to breathwork. We don't know um whether doing breathwork will increase vagal tone in a way that reduces the bad kind of inflammation. But But But is isn't there evidence, and you may have stated it already, that breathwork can just help your vagus nerve or vagal tone in other ways?

Breathwork will increase vagal tone as measured by the effects on your heart. And there are some small studies looking at breathwork, if you will, to reduce levels of inflammatory markers in your blood. Where we have to be cautious there there there is we don't have a hemoglobin A1C for inflammation. Some people talk about measuring a marker called CRP. And that is one way of looking at sort of the total accumulated inflammation in your body. But it's not perfect. It's far from perfect. It's okay. Other people look at other cytokine markers like IL-6 or other uh of these inflammatory molecules that can accumulate in your blood.

But we don't have a hemoglobin A1C for inflammation. Hemoglobin A1C, when you get that number from your doctor, that that tells you how how much glucose has been happening sort of in your in your body for many days or weeks before that test. It's a it's accumulate it's a cumulative marker of of the total glucose exposure. We don't have that marker for studying inflammation, which makes it very hard to draw conclusions about a specific breathwork, and that's the other problem, Dan. Breathwork is not breathwork is not breathwork breathwork.

There are many many many different styles of breathwork that people practice. There's the box breathing. There's the three in seven out. There's There's There's uh rapid breathing breathing breathing and breath holding, and the list goes on and on and on. There There's as many different kinds of breathwork as there are sort of breathwork teachers. And so And so And so we have to compare when we do these kinds of studies and make recommendations recommendations recommendations based on randomized clinical trials, we have to compare the same kind of breathwork in the same kind of person to draw the same kind of conclusion using tools to measure inflammation that are imprecise.

And the result is you go in the literature, you go in the peer-reviewed medical literature now, and you see all kinds of confusing reports, many of them done on on studies of 10 or 20 people, not replicated, not well controlled, well controlled, well controlled, sometimes where the the methods in which the study was done are are are poorly presented. So, you're not even sure what they did. And then you go online and you try to make sense of all this, and you bump into billions of web impressions.

So, that's what kind of where we are. But you as the guy who lives in this world very deeply have decided, yeah, I'm going to do a couple minutes of what I think is called straw breathing, where you're it breathing in very deeply through the nose and then breathing out through the mouth, lips pursed. pursed. pursed. You're going to do a couple minutes of this every day because there's enough evidence that it is good for your heart and at least directional evidence that it could reduce inflammation.

That's right, Dan. You've got it right. I combine it with meditation, takes 5 or 10 minutes, and it is called straw breathing. I think the importance of it is the breathing at six breaths a minute. So, a 10 10-second cycle per breath because that tends to optimize the correlation between the respiratory processing of of gas exchange and the delivery of blood from the heart through the pulmonary circuit to optimize that. So, yes, I do. I do that in in the hopes that it's a healthy habit.

habit. habit. And it makes me feel And I like the way it makes me feel. So, that's good, too. Yeah, you know, I was just going to say that. that. that. I sometimes joke that it's Remember those old Colt 45 ads, the the malt liquor in the '90s days to I think Billy Dee Williams was in the ads, and and the the the slogan was works every time. And I find that when I do a couple deep breaths, it just feels good. I mean, I can't I I there's no I can't I'm not willing to draw any like hard and fast scientific conclusions based on that, but it seems strongly suggestive that something positive is happening.

happening. happening. I I agree. My experience supports that. So, So, So, Okay, I just I'm doing this interview one day after returning from Nosara, which is in Costa Rica. It's on the Pacific coast. It's It's kind of this like wellness haven. I don't go there for the wellness stuff, but I go there to hang out with my friends, but it's beautiful and there's all this wellness mishigas happening in the in the in in Nosara. And there are all these breath work classes offered all over town.

And um um um you know, I'm just wondering for for people listening, they may they may hear you talk about the the potential No, the benefits both real and potential of doing a few minutes of breath work, but what about all these breath work classes? You're not I'm not hearing you, Kevin, say that you do those. I know you've done some studies with Wim Hof, who's who's kind of a well-known breath work uh and and cold plunge um evangelist. Uh evangelist. Uh evangelist. Uh But so what what about Should people consider going to these breath work classes or is just doing a few minutes of straw breathing uh sufficient?

I I really can't comment on that. I think people have different resources and time is a resource and money is a resource and and and they have different motivations and interests. I think we don't know enough about it to make a broad recommendation to a population. You hinted before when we were talking about you'd rather be in the population with the slower heartbeats at rest than the faster heartbeats at rest because on a population level there's a chance that population statistically significantly good chance they're going to live longer than the other population.

But as you pointed out, you can't apply [snorts] [snorts] [snorts] a population statistic analysis to an individual. That was true, we'd all know which lottery ticket to buy. We don't We just don't know how to do just don't We just don't know how to do that. that. that. You look at these the amount of money that's spent on these wellness clinics. And if it makes people feel better, great. great. great. My My only caveat in in in in having this conversation and one of the reasons I wrote the book is people should go into this with eyes wide open.

There these these classes cost money. People are are marketing them. People are making money. And where the marketing makes claims, there it becomes caveat emptor. You know, let the buyer beware. Because Because Because if someone's sick and they have enough money to to spend it on one of these classes and they go in on on because they they've they've understood that the class is going to cure their whatever autoimmune condition and they don't and they spend their money I mean, that's not a good scenario. That That's not a good scenario where where people are marketing things or stretching claims beyond what is supported by um first by scientific mechanistic understanding laboratory studies, but second by clinical trials.

And And And you know, I've seen this happen. I've seen I've seen um health care uh call them aficionados or people very strident about these do-it-yourself practices and I've seen them interact with patients who were crippled with rheumatoid arthritis. rheumatoid arthritis. rheumatoid arthritis. And when you say to someone with a with a severe autoimmune condition, well, you know, I do my push-ups and my sit-ups and that's why I don't have this, that, or the other thing. Well, don't you think if doing a few sit-ups or a few push-ups would cure a serious condition like rheumatoid arthritis, then more people would know about it and and and everybody would be doing it?

Of course. It's not that simple. And so that's where we have to be careful. That because people get swept up in these People want simple explanations and simple solutions and sometimes things are just complicated and just because something's complicated doesn't mean there is a conspiracy that that that keep keep keep to keep this knowledge away from other people. It just means it's complicated. And so that that's the warning. Now, people go to these places and and they have a great time and they love it and they meditate and they do breath work all day long and they come back to work a week later, they feel like a million bucks.

That's great. But but but but to turn around and say that we understand everything about how this works and therefore we should be marketing this, that, or the other thing to other populations of people, we just We're not there yet. Maybe someday we will be. Well said. Okay, so you you have a few times times times mentioned and to be a little cute here in the same breath um uh breath work and meditation. meditation. meditation. To me, those are two actually quite distinct distinct distinct uh disciplines.

Uh so let's talk about meditation. What evidence is there for meditation having benefit for your vagus nerve? nerve? nerve? There's a lot of evidence for the health benefits of meditation, whether it's anxiety and and and depression or or blood pressure control. There's overwhelming evidence. Uh and I think that's great, but the reason I separate breath work and meditation in this conversation with you is because when I tried to write about those chapters in my book when I tried to write about those chapters, what I found out was in in almost zero cases do the clinical studies of meditation control for the type of breath work and vice versa.

vice versa. vice versa. You could argue that every time you pay attention to your breath for 5 or 10 minutes, whether it's uh 4-4-4 box breathing or straw breathing as you said or in on three, out on seven you [snorts] could argue that by paying attention to your breath, it is a form of meditation. of meditation. of meditation. And vice versa, when you do different meditative practices meditative practices meditative practices uh whether it's chanting or or or whether some sort of transcendental meditation or some sort of mindfulness you inevitably you inevitably you inevitably in that practice breathe differently than when you're going about your day-to-day day-to-day day-to-day uh activity.

So separating [snorts] the breath work from the meditation is very very difficult. I I don't think I don't think that the the overwhelming majority of of studies that have been done out there in a controlled way have have handled that very well. So what what do we know? We know that meditation affects regions of the brain uh uh uh and that that seem to have increased activity depending on what kind of meditation you're doing. And we know that many of those regions are also activated in patients who have a vagus nerve stimulator surgically implanted on their vagus nerve in their neck.

So it's interesting, right? Do we know how it all works? No, absolutely not. Just just to say on the on the disambiguation between breath work and meditation, I think you can mindfully do breath work. Meaning you can manipulate your breath and be mindful while you're doing it. So that would count as a kind of meditation. But in meditation as I understand it, there is no manipulation of the breath, at least in the in the school in which I've studied, which kind of old school Buddhism. Um you you might be watching your breath while you meditate at you might be focusing your mind on the sensations of the body breathing but you aren't manipulating the breathing.

Um and so that's that's the key distinction for me. No argument. You are the expert on meditation. I am not. I would I would agree with you that that during during during uh Buddhist style meditations that that that you may not be consciously controlling your breath your breath your breath but I would bet you a dollar if we looked at 20 people at their respiratory rate before they started their meditation, during it, and afterwards that we would see changes. And I would be uh actually pretty certain that that those changes were not the same in everybody.

And so so separating the effect if you will of the meditation practice, the style, the the method the method the method from its from its from its modulating or or modifying your breath work work work um it's it's very hard to sort through that in sort of in a scientific way. The importance of it is with every breath you take, you are in fact stimulating your vagus nerve. So you take that big inhalation we keep talking about and you've expanded your lungs, you've increased the pressure of the air in your chest.

That activates signals that travel up your vagus nerve. Those signals go into a part of your brain called the nucleus tractus solitarius. They're relayed up from there into a gazillion other brain regions, including the origin of the sympathetic nervous system. system. system. Those sympathetic signals go back down the sympathetic nerves. So now you've activated your activated your activated your vagus and your sympathetics. And this is why your heart speeds up. Your heart speeds up. That sends new signals up your vagus nerve into your nucleus tractus solitarius, which sends signals over to your dorsal motor nucleus of the vagus, which sends signals back down to your heart to slow it down during during exhalation.

So when you think about all these things, that's just I just gave four. Two in, two out. You have another, you know, you know, you know, several thousand to go just to explain the simple inspiration, expiration, and establishing of a regular cadence to your breath work. So I don't have an issue with with meditation as an important uh part of of a healthy lifestyle. of of a healthy lifestyle. I think it is. Uh and I don't have any um hesitation with suggesting some sort of breath work either separately or together with meditation is also healthy and a good healthy habit.

But how how it all works in the nervous system, it's complicated. We don't fully understand it. And people that say they have a simple answer are often times proposing arguments that are not supported by what we do know to be true. There's a lot of [ __ ] out there, no question about it. Um Yeah, I'm so glad you said that I didn't have to. to. to. Uh yeah, I'm in the eye of the storm. I get I get pitches all the time from people who are making claims either as people who want to advertise on the show or come on the show and talk to my listeners and we have to do a lot of policing.

of policing. of policing. Um okay, but let's keep working down the list of things that you uh Dr. Tracy do given everything you know about the importance of the great nerve, the the vagus nerve. Um Uh another thing on your list is cold. Say more about that. Cold is fascinating. I really thought when I got to that chapter chapter chapter that I would be overwhelmed with clinical results. And once again, I was disappointed. Most of the clinical trials on the specifically on the relationship between cold and inflammation, which is which is where the where the angle I'm I'm pursuing here.

pursuing here. pursuing here. Most of those studies are 10 or 20 people, typical number. Many of them with no controls and many of them with sort of unclear methods in how they measured what they measured, whether whether whether it was in the inflammation responses or the cardiovascular responses. cardiovascular responses. cardiovascular responses. But I did come away encouraged uh that there is evidence to support careful careful careful cold exposure cold exposure cold exposure to being anti-inflammatory. And I think the way most people do it, there's actually two separate anti-inflammatory mechanisms.

mechanisms. mechanisms. So um first of all, you you shouldn't do any sort of cold exposure without checking with your physician. Make sure that your heart can can can take it. But if your physician says it's okay, what a lot of people do is they get into a cold bath or a cold shower. Now, what happens? Well, if you've ever done it, you know that it's extraordinarily uncomfortable. Even when you you you even when you get used to it, it's uncomfortable. uncomfortable. uncomfortable. And for that first few seconds or minute after the acute cold exposure, you can actually it almost feels like you can't breathe.

It feels like all the air goes out of your body. And if you feel your pulse, you will you'll feel your heart rate accelerate. You're having a massive fight or flight response. response. response. Now, the good news here is that an acute massive fight or flight response like that is actually anti-inflammatory and we can talk about that. It's it's not the same as a low-grade low-grade low-grade chronic fight or flight response, which is pro-inflammatory. But anyways, I like anti-inflammatory. anti-inflammatory. anti-inflammatory. So I suffer through it and and here's where it gets interesting.

If you stand there under that cold water for a minute or two or three, after some period of time, you'll notice that you still hate it, but it's almost like I'm watching it happen to somebody else. else. else. And I think that's a that's an important transition from fight or flight to sort of of of higher vagus tone, if you will. And when I check my pulse, as you get adapted to the cold, I didn't say enjoy it, but as you get adapted to it, you can actually feel your pulse start to slow down.

Now, we've got back to the argument we've been talking about. We have evidence that at least some of the vagus nerve activity is increased and it's slowing your heartbeat. And I'm hoping that that's also anti-inflammatory. I'm hoping that some of that increased vagus nerve activity is spilling over to my immune system and slowing down any inflammation that might be there because you know, when you get into your 60s and 70s, 70s, 70s, inflammation in your arteries is is the source of progressive atherosclerosis, which leads to heart disease and cancer.

Inflammation in other organs is a setup for cancer. Inflammation in other organs can be a setup for Alzheimer's disease or Parkinson's disease. And so as an all-in factor, all-in factor, all-in factor, if cold exposure is lowering my inflammatory burden, which I hope it is doing, doing, doing, uh and there is some evidence that it does that in these clinical studies, then then that's why I do it. I don't do it every day. I think a few times a week. Um and I still hate it. Every time I do it, I still hate it.

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So what's your routine? It's It's It's How many times a week and where are you doing it? Cold shower, bath, how many minutes? Uh two or three times a week after my regular hot shower. I put it on full cold, step out for a second, put it on full cold, let it get fully cold, step in and I go face first holding my nose because that is a very good way to stimulate the cold sensations to your face, face, face, which activates the trigeminal nerve, the fifth cranial nerve, and that can participate in what's called the diving reflex.

And the diving reflex is what sea mammals like whales and seals use when they submerge to great depths for long periods of time. Their heart rate slows way down and they reduce their metabolism and their oxygen consumption. And so humans have have have vestigial diving reflexes. Once in a while you'll read in the wintertime a little baby will fall through the ice in the swimming pool and be underwater for a long time, several minutes, several minutes, several minutes, and pulled out and and resuscitated and is totally fine.

That's because babies have very very strong diving reflexes. And that's that's a that's a that's a good indicator that you've stimulated your vagus nerve. And And And uh I think you talk about in the book that just that just that just merely splashing cold water in your face can have some anti-anxiety benefits. There there that you can stimulate the diving reflex and slow your heart rate, therefore stimulate the cardiac fibers in the vagus nerve to your heart by simply putting your face in a bowl of cold water or a sink full of cold water.

And it's certainly a lot less pain It's not totally comfortable if the water's very cold, but it's a lot easier than than a than cold water immersion in a shower or tub. And and a lot of people do that. So I I have a a great friend, his name is Robbie Hammond. Shout out to Robbie Hammond, who is really at the forefront of forefront of forefront of what he calls bathing culture. There bathhouses are popping up all over all over the country, all over the world.

They're ancient, you know, they're part of, you know, ancient civilization, but they're they're they're they're they're having a having a having a a resurgence. And and in Manhattan, I live near Manhattan and there's just in Brooklyn and there's tons of them popping up all the time. And Robbie takes me to these places. And and it's a combination of sauna, um hot tub some in some places and cold plunges. plunges. plunges. Um Um Um and some of these places are like [ __ ] medieval like with the cold plunges at like right above freezing and I get in there and you know, like my my feet and hands are throbbing and it's horrible horrible.

Um what you're describing of just making the shower cold, which I think brings it down into the 50s. And so it's not like at 34 or something like that. And just doing that for a couple minutes, that sounds like I'm actually going to start doing that now at right after this podcast podcast podcast as opposed to getting in a cold plunge, which I hate. So I jumped in the ball the Baltic Sea in winter once outside of Saltsjobaden in Stockholm, outside of Stockholm. And I have had the experience you describe of going from the sauna into the ice water and it it it really does suck.

I have to agree with you on that. The showers are a lot easier. And what's really interesting, again, I cite the studies in the book, the references are all there, but if you look at physiology or clinical studies done, usually they're military type studies. studies. studies. Uh Uh Uh soldiers or infantry, quote unquote, volunteer for this. They they put on wet t-shirt and a bathing suit and they hose them down and put them in a cold room with a fan on. And they they will lower their body temperature.

temperature. temperature. But But But I think that you you can get sufficient physiological responses from a cold shower for several minutes that are much more tolerable as you said, uh much safer, frankly. There have been drownings in in cold tubs as as you know. know. know. Uh Uh Uh and and and do elicit physiological responses that point to an effect on reducing inflammation. inflammation. inflammation. So, yes, it is it is doable. You don't have to you don't have to invest in a in a tank uh in your backyard that that's refrigerated year-round.

You can you can do it with a cold shower. Where we are today, people people are making money selling tubs. And uh people are making money teaching people how to sit in cold tubs. And that that's that's a reality of our of our culture and our times. times. times. And people are not making money doing large clinical trials that are well-controlled and randomized. That's the fundamental disconnect to everything we've been talking about for the last hour. hour. hour. If if there was a way people could get rich doing the clinical trials, we would have all the answers.

Yeah. Oh, man. I'm I'm not anti-capitalist, but there are flaws in the system. No question. question. question. I I I love I I I start companies. I try to move ideas from my lab into clinical development. I see the the advan- the advantages of a capitalist system that can make technology broadly available to millions of people around the world and change the course of of human civilization, but I but but I find it frustrating that we don't have simple answers to these simple things because we people can't get rich doing it.

Yeah. Um Um Um Okay, on the subject of cold, I it did um what about saunas? Um the opposite of cold. Um is there any evidence to indicate that um sitting in a sauna can improve your vagal tone um and um maybe reduce inflammation by extension? extension? extension? I don't have a a lot of good information on that. I don't have a good answer to that question. I think that the safest answer is to say that what is uh another good indicator of vagal tone, whether it's coming out of a hot sauna or whether it's coming out of a of an aggressive sort of a VO2 max aggressive uh cardiac workout.

What is a a very good I think and useful indicator of vagal tone is how quickly, how soon your heartbeat goes back down to a slow rate. rate. rate. So, a lot of people follow those kinds of signals in their in their health regimes. regimes. regimes. And in their in their personal fitness tracking. Again, it's it's best for that kind of kind of kind of of of of personal assessment and monitoring if you're working with somebody who's really trained in this and has the best equipment and and because there are there are once again a lot of generalizations about you want your heart rate to recover at this speed from after you've been in this temperature, you've had your VO2 up to this percentage of your VO2 max.

And I just think there we have to be careful before we apply these general um uh assessments to individual uh people without having established sort of long-term baselines and controlling for all the variables like diet, exercise, sleep, and stress. That being said, recovery heart rate recovery, recovery, recovery, uh you want you want you want your vagus nerve to come right on after these stressful stressful stressful uh uh uh events and predominate over your fight or flight so you get back to baseline quickly. That's a sign of good health and homeostasis balance.

Okay, real quick before we get to bioelectric medicine. Uh the fourth thing on your uh list of things we can do to increase vagal tone uh is and you just finished referencing this um in passing, uh exercise. Uh what what what should we know about that? Check with your physician, but if you can uh can uh can uh exercise exercise exercise uh regularly uh of course watching your diet and your weight all along the way there there's there's overwhelming evidence that fit uh people, not not just athletes, but people who exercise regularly have lower resting heart rates than um um um than non-exercisers or couch potatoes or unfit people.

unfit people. unfit people. Uh so, we know we we we are very we're very confident in the clinical data that aerobic fitness is associated with lower resting heart rate. Um we're a lot less certain on the heart rate variability measures, frankly. There's there's very conflicting evidence from good exercise studies that particular one particular exercise uh regime or another does or does not improve heart rate variability. It's very difficult to prove that. There's not a consensus on that. Now, you can go online and you can look at charts for the decline of heart rate variability that occurs with normal aging.

We don't know what causes that. Is that a problem in the nerves themselves? Is that a problem in the heart itself? Is that a problem in in the brain networks that control the output to the nerves to the heart? No one knows. We We We see recommendations that you should do this, that, or the other thing to increase your your VO2 max. That does not necessarily or reproducibly reproducibly reproducibly uh uh uh correlate to lasting effects on individual heart rate variability measures. measures. measures. Is that a is that a problem of the measurement?

Is that a problem of the position the the the the the measures are taken in? Is that a problem of We don't know. The All the studies addressing these kinds of things are relatively small and relatively uh poorly controlled. So, should you exercise? Yes, there's overwhelming evidence, overwhelming epidemiologic population-based evidence that exercise is good for your health, it's good for longevity, and it prevents the diseases that we alluded to before that are all caused or made worse by inflammation. The major killers of the human race today, heart disease, cancer stroke, Alzheimer's disease, neurodegeneration, metabolic syndrome, diabetes, obesity, all of those all of those are are are either made somewhat better or their onset is delayed uh by regular exercise.

Could that be because the exercise is enhancing the vagus nerve signals that turn off inflammation and therefore turn reduce the inflammatory component of those conditions? Maybe, but we don't know. Okay. know. Okay. know. Okay. Very helpful. Um Bioelectric medicine, what is it? And how would might it apply to the lives of regular folks listening to this show? To understand bioelectronic medicine and where it comes from, it's it's very illustrative to think about where does where does uh pharmaceutical or regular medicine come from. So, when a when a when a pharmaceutical company or a laboratory wants to make a new drug, they pick a disease.

So, you pick your disease and then you say, "What is the What is the mechanism of that disease? What is the target I can make a drug against?" Having identified the molecule or the target you can then screen libraries of other molecules that fit lock and key into the mechanism target, and you can test those in first in animals and then in people. And then sell the sell the sell the drug as a therapy. That's the pharmaceutical industry in a nutshell for more than 120 years.

years. years. Bioelectronic medicine is different. Bioelectronic medicine says, "We're going to make battery-operated computerized devices to be the drug." And how would you do that? Well, you do it the same way, actually. You start with you pick a disease. You find the molecular mechanism or the target of that disease. But rather than go after a library of drugs to hit the target, you say, "What are the nerves in the body that go to that target?" Because the nerves release their own kind of molecules, neurotransmitters. molecules, neurotransmitters.

molecules, neurotransmitters. If we can find a nerve input to the target that controls it, then we can build these devices to sit on the nerves and essentially control the target through the activity of the nerve. And we can do that with these uh battery-powered devices. battery-powered devices. battery-powered devices. We've done this now successfully for several conditions. several conditions. several conditions. I mentioned rheumatoid arthritis before because the the company that I co-founded in 2007 recently received FDA approval for their device. The company is SetPoint Medical. SetPoint Medical.

SetPoint Medical. It's [snorts] a uh uh vagus nerve stimulator, and it sits in the in the neck of of patients with rheumatoid arthritis. It's about the size of a fish oil pill. It uh has the battery, it has the ASIC, the computer chip, it has the leads that that control the electrical current flowing into the vagus nerve. And it operates, you won't believe this, Dan, for 1 minute a day. And for 1 minute a day it activates the inflammatory reflex that we've been talking about in the vagus nerve that shuts down this dangerous chronic inflammation.

inflammation. inflammation. And patients who are being treated in this way this way this way are some of them are having tremendous clinical effects. The some of them are are now no longer having to take medications. medications. medications. Uh others still take their medication, but the medications that used to not be helpful or now appear to be helping them. them. them. And then a third a third group sometimes it doesn't work well at all. But this is a whole new way of thinking about treating chronic diseases using electrons electrons electrons controlled by a battery, a rechargeable battery battery battery that uh, is essentially replacing drugs in some patients.

And Dan, these are drugs that people don't want to take. They're invasive, many of them they have to be injected. They're immunosuppressive, they have dangerous side effects, we talked about that before. that before. that before. And and they're very expensive. In the United States especially they can go to be 50 or a hundred thousand dollars a year. year. year. So so patients are looking for options. When Set Point was doing its its definitive trial for FDA approval, they needed 250 or so patients to sign up and and and they ended up with 242 people in the trial.

But Dan, 30,000 people tried to enter the trial. 30,000. So patients are looking for options and bioelectronic medicine is an option that's available today for RA, but in the future I think it's going to be available for a lot of conditions. So it's available for rheumatoid arthritis, but there appears to be some evidence and you'll correct me if I'm wrong that it it's useful for depression, epilepsy depression, epilepsy depression, epilepsy uh, uh, uh, weight um, body weight and diabetes? Yeah, we're going to have to do another podcast on that one, Dan, a whole show probably because the approval for depression and epilepsy uh, of vagus nerve stimulation as a therapy goes back for decades.

Decades. And And And why doesn't everybody know about this? Uh, Uh, Uh, there's a there's that's that's a that's a long complicated topic, but let's just break it down really simple for depression. depression. depression. In depression, if you look at the clinical trials again done over decades people with vagus nerve stimulators who are who are being treated now under FDA approved uh, treatments in the United States and in Europe and other countries around the world these are patients who are refractory to all available therapy. They're refractory, they have they're depressed despite talk therapy, despite drug therapy, despite um, sometimes uh, electroconvulsive therapy.

therapy. therapy. So what's happening? They they have a vagus nerve stimulator implanted and about 50% of them get significantly better. 50%. better. 50%. better. 50%. So you say, well uh, 50% is not good enough because you don't want to implant people who are not going to benefit from this device being implanted surgically. Well, that's true, but let me point out to you that in the 50% that do get better, some of these people were suicidal and now they're not. Some of these people couldn't work or take care of their families and their their loved ones because they were too depressed and many of them have been able to rejoin society.

society. society. And so why is it 50%? No one knows. We don't know how it works in the 50% or why it doesn't work in the other 50%. But uh, I encourage in my book I am I I plead with my colleagues to double down on this kind of research cuz if we really understood why half of the people with this severe depression benefited from this FDA approved therapy, then I I if we really understood how it worked in those people, then maybe we could figure out how to make it work in the other half as well.

So it's really important topic and in the United States many insurance companies don't pay for this uh, for depression. Uh, Uh, Uh, there was a sort of a split vote uh, over the years on its approval and so many insurance companies are waiting quote unquote for more data. Um Um Um it's a it's an enormous opportunity to help a lot of people if we could figure out why it helps out if we could figure out why it helps half of the people. Okay, let me just I I I try to do what I'm about to do um rarely because it does feel like I'm abusing my privileges the host of the show, but let me just take myself as an example here.

I have long throughout my whole life struggled with episodes of depression um, actually just I mentioned I would just got back from vacation um, and I was feeling a little bit depressed on vacation, did a little research and found out that that's actually quite common when people get out of their daily routines and um, and they're not papering over their stuff with busyness sadness can sadness can sadness can uh, um, break through. Um, and so so um, depression is on my mind. If I as somebody who I I don't have severe, but I do have chronic depression often comorbid with anxiety wanted to uh go ahead and and get one of these devices implanted, is that a thing I could do if I was willing to pay cash for it even if my uh, um um um health care uh, insurance uh, health insurance provider wouldn't wouldn't do it?

Is that a thing I could do and then what does it look like? Um, you know, where does it go in the body? How invasive is surgery is it? Just tell me a little bit more about the practicalities here. practicalities here. practicalities here. The practicalities are all dictated by uh, cost as you said one and second regulations. And the regulation part would affect if you if cost is no object, if people have money to to to pay this for the device and the surgical fees and the hospital fees and whatever you're going to still bump up against the regulatory uh, issues at most medical places.

Now, before we get to that, let's talk specifically. Before we get to that, let's talk specifically about the device because you framed it that way. that way. that way. So the devices that were originally approved in the 1990s as a therapy for epilepsy or depression are are like cardiac pacemakers. There's a there's a can or a small device maybe a little bigger than a silver dollar that is implanted under the collarbone in the chest. And then there's a wire that is tunneled under the skin up to the vagus nerve in the neck at about the level of the Adam's apple.

And and and the the device connects to the vagus nerve. It's almost like a slinky at the end of the at the end of the wire and you unwrap the slinky and rewrap it around the vagus nerve that holds it in place. Now, I call that generation one. It it fires electric current all day long, 24 hours a day in five minute bursts giving about five milliamps at a time for five minutes and then a five minute pause and then five milliamps all day long, 365 days a year.

And those settings were um, sort of default settings back in the 1980s and 90s when these things were being developed. And and not coincidentally, what's FDA approved for epilepsy and depression have those settings I just said and they in both cases it works about half the time. So technically and I'm not treating you as a physician, Dan. You know, there's my disclaimer too on top of yours. of yours. of yours. Uh, but technically there might be a path if you could convince uh, uh, uh, a a physician to prescribe this for you uh, as a therapy for your anxiety or depression, you would then have to find a neurosurgeon who would be willing to implant the device and a hospital who would be willing to um, you know, host the whole procedure.

And even if you paid cash uh, the the physician would still be recommending this therapy off-label. Right. And so there may or may not be addition additional regulatory requirements depending on the medical center and the hospital. It's not that you can't do it in the United States but uh, regulations and fear of regulations and compliance and oversight often makes it very difficult or impossible. or impossible. or impossible. Um, unless you're following the guidelines of the label of the device, which in this case for depression would be treatment resistant depression in someone who's tried all these other things.

things. things. Now, the generation two device I these are my my jargon, but are my my these are my my jargon, but the generation two device is the one like like like made by one by Set Point and another one from a company called MicroTransponder. The FDA has approved the Set Point device to treat rheumatoid arthritis. I fully expect someday there will be additional approvals. There there are more clinical trials that have to be done, but I I'm I'm I'm actually quite confident you will see uh, expanding use of the Set Point device for conditions like inflammatory bowel disease and multiple sclerosis.

That device only uh, only is much smaller. It's the size of a multivitamin or a fish oil pill. It's uh, there's no lead. It it sits right on the vagus nerve almost in like a pea pod, little silastic pea pod that wraps around the nerve in the device and the whole thing is completely self-contained and the and in the battery in that one as opposed to the gen one, the battery in gen two is fully rechargeable. The patient puts a collar on once a week and recharges recharges the battery right right there in in the neck.

neck. neck. So that um, that's for rheumatoid arthritis and potentially in the future other inflammatory conditions. I don't don't don't see how maybe you could talk someone into implanting that, that would be much harder because the FDA label says it's for rheumatoid arthritis. And then the the third implant that's FDA approved on the vagus nerve is a small device that is designed to enhance neuroplasticity. And it's got an FDA label to improve the recovery and function in the hands and arms of people who've had a stroke.

And there's some remarkable success stories with that. And I think again, I think it's probably being underutilized in the United States. I don't know why. Maybe cuz it's new. Maybe because not enough people are talking about it. I think it's an an important thing. Back to you and and and others with resources. Um buy my book and get the word out because I think that's why I wrote it, Dan. I wrote the book to elevate this conversation and make it something everybody's talking about because because because the questions I don't have the answers and I'm not selling anything.

But the questions I raise are testable hypotheses. And if some of those answers are positive, if some of those clinical trials that are doable turn out to be uh successful, then then then then you're talking about having impact or benefit for millions and millions and millions of people. Real quick before I let you go, uh aren't there some non-invasive uh uh uh vagus nerve stimulation devices like something you put in your ear? Let the buyer beware. And And And we're back to our theme of the day here, Dan.

Dan. Dan. There is a branch of the vagus nerve to your ear. your ear. your ear. It carries It carries It carries sensory signals from the cartilage of your external ear into your brainstem. So technically, when people say vagus nerve stimulation, that's what they're talking about. A teeny little sensory branch that carries information into your brain. your brain. your brain. Now, as you know, once information goes into your brain, the brain can send that information anywhere it wants. Got a hundred billion neurons. At the end of the day, they're all connected.

So, people call people call people call applying a TENS unit a transcutaneous electrical nerve stimulator electrode to the ear, they call that vagus nerve stimulation. And it's become jargon and commonplace. Is it the same as putting a electrode on the vagus nerve in your neck like we've been talking about? Absolutely not. It's different. Might it produce some benefits or effects effects effects on either your cardiovascular system or your immune system? Maybe. Maybe. Maybe. The There are some studies that suggest and I've published some of these with my colleagues and I've I've seen studies from other laboratories and other research centers from other colleagues that that that when applying when applying when applying these TENS units to the ear, which I prefer to call auricular as an oracle, auricular nerve stimulation.

Um cuz there's five There's like five nerves in your ear. So, you don't know if you're stimulating the vagus nerve or the other four or two of them or three of them. So, with this auricular stimulation, you can do clinical studies. studies. studies. And once again, in relatively small studies, 20 subjects, 30 subjects, usually open label, meaning um not blinded and and and not necessarily randomized or well controlled, but you can see some outcomes. There's pediatric Crohn's disease. Bensaid at at Northwell, where where the Feinstein Institute is in New York, Bensaid has reported very significant improvements in children with Crohn's disease.

Cindy Aranow has reported decreased pain in patients with lupus who whose lupus is manifesting as lupus arthritis. Sangeeta Chavan and others have reported that electrically stimulating the ear with a TENS unit decreased the pain and and swelling and even the cytokine responses in patients in the blood of patients with rheumatoid arthritis. So, there's all these sort of tantalizing clues about these things. But to me, the marketing and selling of devices with claims uh are now exceeding the scientific evidence. And so, if you have if you like to experiment on yourself, if you can afford to buy these devices, if you want to try putting lots of electrodes on different parts of your ear and neck, you can do this.

Um Are we at the point where we can make bonafide claims for all of the devices? No. No. No. Can we make claims for some of them? Yes. The FDA, for instance, uh the FDA has approved an ear stimulating device stimulating device stimulating device uh in the treatment of opioid withdrawal, narcotic withdrawal. And that's important, right? Because if you can help people withdraw from narcotics, you can potentially save a lot of lives uh from from from overdosing. So, there's clues out there. I know I'm I'm aware of some recent clinical data that stimulating the ear uh probably vagus nerve branches and trigeminal nerve branches with a device that does both uh may may reduce uh blood loss and bleeding uh in uh in in uh in conditions of of uh there are some patients who have genetic deficiencies in their coagulation system.

And when women have their monthly cycles, they lose a lot of blood. And this company now has evidence that these ear stimulators can reduce the blood loss. So, there's a lot of possibilities out there. I just I don't like to see the claims get ahead of the data. Dr. Kevin Tracy, the new book is called The Great Nerve and the new science of the vagus nerve and how to harness its healing reflexes. Uh thank you very much for your time. It's great to talk to you.

Great talking to you, Dan. And thanks again for having me on. I really appreciate it. appreciate it. appreciate it.