The Science of Regulating Your Nervous System | Dr. Kevin Tracey

Plus: How to increase vagal tone, improve heart health, and reduce inflammation. Kevin J. Tracey, MD, is president and CEO of the Feinstein Institutes for Medical Research at Northwell Health https://feinstein.northwell.edu/, a pioneer of vagus nerve research and author of the recent book, The Great Nerve: The New Science of the VagusNerve and How to Harness Its Healing Reflexes. https://www.penguinrandomhouse.com/books/746339/the-great-nerve-by-kevin-j-tracey-md/ Join Dan and Emmy Award-winning journalist Allison Gilbert at 92NY on May 17th for a live conversation about how mindfulness can deepen connection and combat loneliness, available in person and via streaming. Register here. https://www.92ny.org/event/dan-harris-with-allison-gilbert Join Dan, Sebene Selassie, and Jeff Warren for Meditation Party, a 3-day immersive retreat at the Omega Institute in Rhinebeck, NY, October 16–18. Grab your in-person spot here https://www.eomega.org/workshops/meditation-party, or sign up to livestream here https://www.eomega.org/workshops/meditation-party-livestream! This episode is sponsored by: BetterHelp — Online therapy, matched to your needs. Get 10% off your first month at https://www.betterhelp.com/happier Spark — Clean energy and focus with zero sugar. Get 30% off and free shipping with code HAPPIER at https://www.drinksparkcom https://www.drinksparkcom/

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:04Dan Harris?

  This is the 10% Happier Podcast. I'm Dan Harris.

• 0:18Dan Harris?

  Hello, party people. How we doing? I have noticed, and you will hear me mention this to my guests today, I have noticed that when we do episodes about regulating your nervous system, those episodes do really well. I think the reason for this is pretty clear. We are in an era where many of us feel like our nervous systems are totally out of whack. So today, we're going to talk about how to regulate your nervous system, but we're going to specifically talk about the vagus nerve. That's V A G U S, which has been getting a lot of attention these days. There's a lot of talk online about how to improve your so-called vagal tone. And you will hear my guest express some skepticism about some of the people making these claims. But anyway, my guest is a true expert in this field,

• 1:01Dan Harris?

  and he's going to talk about the importance of the vagus nerve and what he personally does, given his understanding of the physiology and the data, to improve the functioning of his own vagus nerve, and by extension, his mental health, his heart health, and his immune response. He's also going to talk about something called bioelectric medicine and how this might be the next big wave in treating chronic diseases. My guest is Dr. Kevin J. Tracy. He's a neurosurgeon. He's the president and CEO of the Feinstein Institutes for Medical Research at Northwell Health, and he's the author of a book called "The Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes."

• 1:43Dan Harris?

  Before we dive in, just a quick heads up that I've got two live, in-person events coming up. On May 17th, I'll be at the 92nd Street Y in New York City. I will guide a meditation. I'll talk about how the practice can help you navigate a chaotic world, and then I'll take your questions. And then in October, I'll be doing my annual meditation party retreat with Sebene Selassie and Jeff Warren. It's a weekend thing at the Omega Institute in upstate New York. It's super fun. We teach a bunch of different styles of meditation, but there's also time for Q and A and socializing and pickleball, whatever you're into. I have to say, and you've heard me say this before, but it's really important to know that one of the best ways to improve your meditation practice is to do it in the carpool lane, and that's

• 2:28Dan Harris?

  what this weekend is all about. I will put links for both events in the show notes. We'll get started with Dr. Kevin J. Tracy right after this.

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• 3:36Dan Harris?

  Dr. Kevin Tracy, welcome to the show.

• 3:39Speaker 03

  Thanks for having me on, Dan. It's really great to be here. I look forward to chatting.

• 3:43Dan Harris?

  Yeah, me too. All right, 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 V-A-G-U-S nerve?

• 4:00Speaker 03

  Well, it's a media sensation lately. There are billions of web impressions and social media posts. So we'll start with the answer to your question in very basic terms. 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 starts at about the level of your ears, travels down the neck with your carotid artery, where you can feel your pulse in your neck. And when it enters the chest, it starts sending branches to your heart, your lungs,

• 4:41Speaker 03

  and down in your abdomen, innervates your liver and your pancreas and your intestines and even your spleen. And all day long, in these two bundles of nerves, the information is running back and forth from the body to the brain 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 you really have 200,000 vagus nerves connecting the organs in your body to your brain.

• 5:19Dan Harris?

  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 around for a while. Vagus is Latin for wandering. So this is a sort of a long set of paired wandering nerves that go through our torso.

• 5:40Speaker 03

  The word is derived from the Latin for wandering or meandering, and that is correct. I don't particularly like that name.

• 5:51Dan Harris?

  Well, I apologize for bringing it up. I've already pissed you off. We're only like two minutes into our acquaintance.

• 5:58Speaker 03

  Yeah, no, no, I'm not angry. I've gotten over it. It goes back 2,000 years, so I've gotten over it. In the beginning, if you will, Galen, one of the first physician scientists, noticed the vagus nerve and He called it the pneumogastric nerve because he deduced that it was a major nerve connecting the brain to the lungs, pneumo, and the stomach gastric. And he also proved that if you cut it in living animals, 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 lethal. And so, over for many centuries, almost 15 centuries, it was referred by many other people as the pneumogastric nerve or the great nerve of Galen, Galen's great nerve.

• 6:43Speaker 03

  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 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 to me, meandering or wandering doesn't describe the

• 7:27Speaker 03

  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.

• 7:33Dan Harris?

  Fair point. That lands. Let's just say a little bit more about the aforementioned greatness. I'll phrase it like this. You've kind of answered this a little bit, but let's put a really fine point on it. For my average listener, why should I care about my vagus nerve?

• 7:51Speaker 03

  Primarily because it is conducting the information between your body and your brain that keeps you healthy. When your heart, for instance, starts to beat a little faster than normal, signals in your vagus nerve slow it down. When your immune system starts to cause inflammation that can be dangerous to your health, the vagus nerve signals slow it down. 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.

• 8:35Speaker 03

  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 when we started chatting today, there are billions of web impressions. 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 minimal, if you will,

• 9:19Speaker 03

  or sometimes no clinical trial data done in any sort of rigorous or randomized control way. And so we are in an era where there's 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 because one has to sort through all this information.

• 9:45Dan Harris?

  I'm trying to grapple with why it's become such an important topic now. Do you think it's because people feel like their nervous systems are out of whack? I've just noticed anecdotally, when we give a podcast episode a title like "How to Regulate Your Nervous System", this episode will probably have a title like that. Those episodes do really well.

• 10:11Speaker 03

  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 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. And a convergence, I think, of new technology to study the nervous system, the brain, the nerves and their functioning, I think, is converging on a cultural phenomenon where anxiety and depression have been on the rise for many years.

• 10:54Speaker 03

  You can't pick up a report anymore about the state of healthcare. And this is a global phenomenon. This isn't just a US phenomenon with a rising rates of anxiety and depression to the point where these rising rates of anxiety of depression 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. And they are grabbing onto some things that are scientifically validated and some things that are not.

• 11:33Dan Harris?

  All right. So this conversation is going to stay within the confines of the evidence based. And when we venture out of it, we will signal clearly. Okay, let me do my magic trick of channeling. I say this facetiously or semi facetiously, channeling the mind 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.

• 12:15Speaker 03

  You're absolutely correct. The term vagal tone is widely used. And we have to, I think, be very careful about semantics here. I'm gonna keep coming back to this point. 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 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. When people talk about vagal tone, we have to put this in the context of what it is we can measure about the vagus nerve.

• 13:00Speaker 03

  One thing we can measure quite easily is our resting heartbeats. Resting heartbeats 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. If you have a lower resting heart rate, you would have, by this explanation, tendency to have higher activity in your vagus nerve fibers to your heart compared to the activity of the sympathetic nerves to your heart, and hence your heart rate is slower. Now, that's one way to describe vagal tone.

• 13:43Speaker 03

  Where you have to be careful is some people extract that to all 200,000 fibers. Now, the fibers that go to your heart, whether they're a few hundred or a few thousand, it's not 200,000. Many assume that if the fibers to your heart are working, then 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. There's no proof of that. And we're limited by what we can actually measure. In the lab, 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.

• 14:24Speaker 03

  Laboratories, like my lab with Sangeet Shivan 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. Even in human studies, which are being led by Stavros Zanos at the Feinstein Institute, he's looking at cadavers and doing detailed autopsies, if you will, on the vagus nerve of deceased humans to describe the path of each and every fiber. We're still working through the basic anatomy and human beings of each and every fiber.

• 15:09Speaker 03

  So to say that when your heart rate is slow, then you have great vagus tone, 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- 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. Some very famous studies in Spain that started in Spain have been replicated elsewhere that showed victims of COVID, many of them had severe damage to their vagus nerve, and there was virus in some of the fibers, and there was inflammatory cells causing damage around some of the fibers.

• 15:53Speaker 03

  So we have to be careful. That is what people talk about, but we need to really be thoughtful about how it works and what it means.

• 16:01Dan Harris?

  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 the thing we're trying to capture. That being said, you mentioned heart rate as one, again, very rough way to get a sense of how we're doing. I've sometimes heard, and I believe you write about, not just your resting heart rate, but also heart rate variability. Is it worth saying more about that with all the caveats that you've issued and I've repeated?

• 16:40Speaker 03

  The heart rate variability term is, again, widely used and held by many to be extremely important. And as you just pointed out, it is complicated. Let's go down to some simple definitions. Heart rate variability is fundamentally 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. So each time your heart beats, some number of milliseconds goes by until your next heartbeat. If you watch what happens, even when you feel your own pulse in your wrist, and you take a big,

• 17:22Speaker 03

  slow breath in and a long exhale out, 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- In this context of high vagal tone that 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 closely linked, but not the same thing as respiratory sinus arrhythmia,

• 18:07Speaker 03

  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 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 mathematical analyses, things like fast Fourier transformations and other algorithms. And when you do that,

• 18:51Speaker 03

  you can find some predictions that can be confirmed with pharmacology studies that an area in spectral analysis called the high-frequency domain is probably the closest thing we have to indicating the vagus nerve activity to the heart. What's wrong with that? 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.

• 19:34Speaker 03

  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. These variables all influence heart rate variability. It matters if you collect the data for five minutes or 12 hours. So 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 questions that remain are, what are you supposed to do personally with this information? In order to answer 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

• 20:19Speaker 03

  have those.

• 20:21Dan Harris?

  Okay, so let's talk about what we can do. If you're saying that using your wearables to get a sense of your vagal tone, whatever that even means, using your wearables to get a sense of it is a bit groping around in the dark, which is what you're very clearly saying. How do we get a sense then of how we're doing and then what to do as a result?

• 20:47Speaker 03

  I think if you're a elite athlete with unlimited resources, you can control from any of the things I said. You can work with skilled professionals who are expert in recording heart rate variability the same way every time, controlling all the variables that can be controlled. By knowing your own baseline and having standardized methods for following it over time, there may be some value in watching trends in your own heart rate variability. That's fair. Where it gets to be problematic is when you see things on social media that if your heart rate variability is above or below this number, then this means that you're shortening your lifespan, or you're at risk

• 21:29Speaker 03

  for this, that, or the other thing, 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, is we can all agree that a population with a lower resting heart rate has a higher vagus nerve activity at rest than a population with a faster resting heart rate. And if you look at enormous population studies, whether it's the Framingham Study out of Massachusetts over many decades, or even larger study out of France, the one thing that predicts longevity in a population

• 22:13Speaker 03

  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.

• 22:31Dan Harris?

  Okay, so that's good to know in the abstract, but not so helpful for me as an individual, right? I mean, given everything we've said, 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, let's talk about those things we can do to, you know, regulate our nervous system, specifically the vagus nerve. You talk about a lot of them. I'm tempted to go through them right now. Is that cool with you?

• 23:06Speaker 03

  Absolutely. I think we might set up an introductory framework by saying, "What Grandma told you to do, and hopefully, your primary care 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 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.

• 23:36Speaker 03

  So, that we can say on a population basis. So Grandma was right, and your doctor's right, perhaps.

• 23:44Dan Harris?

  The other thing that Grandma said when we were freaking out is, "Take a deep breath."

• 23:49Speaker 03

  Absolutely.

• 23:52Dan Harris?

  And that's a very, because many of the things you just listed, like, "Get a good night's sleep, give back to your community," we could say a lot more about each of those, but "take a deep breath" is very, very practical, and you have some pretty achievable instructions in the book. So, maybe let's start right there.

• 24:14Speaker 03

  It's a Pascal's wager for me, Dan. 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 with people with excessive inflammation, like rheumatoid arthritis. And this is now FDA approved, 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 fibers to my immune system to slow down inflammation 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.

• 24:55Speaker 03

  And what I do is I take a big breath in on three. As Andrew Huberman talks about, a lot of physiological sniff, you know, towards the end, so two sort of big breaths over three seconds to fill your lungs. And then through pursed lips, I like 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. If you do that for a few minutes, you can actually feel your resting heart rate slow

• 25:40Speaker 03

  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 clear, pretty good, from many, many independent studies about the effects on the cardiovascular system, as we've just been talking about. There's very little data on the fact that this intervention

• 26:05Speaker 03

  Has a reproducible effect on the immune system. It might. There are some suggestive studies, but they don't come up to the level of large randomized, well-controlled clinical trials, which frankly is why 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 those large trials, and absent replication of those large trials, and absent the physician societies and groups making recommendations based on those large trials, it's very difficult 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.

• 26:50Speaker 03

  It's a Pascal's wager. I enjoy doing it. I meditate. I do breath work. And I hope 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.

• 27:08Dan Harris?

  Coming up, Dr. Kevin Tracy talks about what inflammation is and why it matters for your health and the difference between breath work and meditation.

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• 28:20Dan Harris?

  Okay, I have a million questions that I've written down and we'll get to them in some semblance of order. Pascal's wager, is that the French philosopher who was like, I don't know if God's real, but I'm gonna believe in him because I don't want to bet against him and find myself at the pearly gates, having wagered the wrong way?

• 28:41Speaker 03

  Exactly.

• 28:43Dan Harris?

  Okay. You brought up inflammation. I kinda 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 the mind-body connection. Can you remind me what inflammation is and why you've brought it up?

• 29:02Speaker 03

  Inflammation is the body's response to an injury or infection. It's how the immune system deals with an invasion, an injury from, whether it's cutting your hand on a knife, or an infection, whether it's a virus or a bacteria that makes a 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, and heat at the sight 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 this terminology has stood the test of time, more than 2,000 years. That's what it means today and then.

• 29:45Speaker 03

  But in the modern era, 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 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. 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

• 30:30Speaker 03

  arthritis patients. The reason this whole conversation comes up in the context of the vagus nerve is because 25 years ago, my colleague 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 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.

• 31:14Speaker 03

  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 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 controls the immune system. The whole area we call today, we call it bioelectronic medicine.

• 31:40Dan Harris?

  I'm gonna get into bioelectronic medicine in a big way briefly. But I began this line of questioning because you were saying, in the spirit of Pascal's wager, that you do breath work, but you don't yet know, because we don't have the tools to measure it, whether it is improving vagal tone in a way that reduces inflammation.

• 32:04Speaker 03

  Exactly correct.

• 32:05Dan Harris?

  And 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, I want my immune system to respond when I get bit by a bug, when I mistakenly slice my finger while I'm chopping onions, whatever, I want my immune system to respond 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 articulating that correctly?

• 32:44Speaker 03

  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 full power of the army and the navy and the air force to the site of a few elderly residents protesting the food in their nursing home. And in many of these conditions, we don't know what the trigger is to this immune response, but you're 100% right. There's an ongoing attack, persistent, ongoing, steady attack of the immune system against the body's normal tissues in these conditions, and that

• 33:26Speaker 03

  is the problem. The other problem, and 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 an appropriate amount of inflammation to heal your wound and to fight off your infection in your 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 side effect, the black box warnings of many of the drugs used

• 34:08Speaker 03

  today to treat autoimmune conditions, include the risk of cancer, the risk of sepsis, the risk of tuberculosis 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 theory of vagus nerve control of inflammation, well, 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 turns out to be the case.

• 34:44Dan Harris?

  Okay, so let's go back to breath work. We don't know whether doing breath work will increase vagal tone in a way that reduces the bad kind of inflammation. But, isn't there evidence, and you may have stated it already, that breath work can just help your vagus nerve or vagal tone in other ways?

• 35:09Speaker 03

  Breath work will increase vagal tone as measured by the effects on your heart.

• 35:15Dan Harris?

  Got it.

• 35:15Speaker 03

  And there are some small studies, looking at breath work, if you will, to reduce levels of inflammatory markers in your blood. Where we have to be cautious 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 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 IL6 or other of these inflammatory molecules that can accumulate in your blood. But we don't have a hemoglobin A1C for inflammation.

• 35:59Speaker 03

  Hemoglobin A1C, when you get that number from your doctor, that tells you how much glucose has been happening sort of in your body for many days or weeks before that test. It's a cumulative marker 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 breath work. And that's the other problem, Dan. Breath work is not breath work is not breath work. There are many, many, many different styles of breath work that people practice. There's the box breathing. There's the three in, seven out. There's rapid breathing and breath holding. And the list goes on and on and on.

• 36:43Speaker 03

  There's as many different kinds of breath work as there are sort of breath work teachers. And so we have to compare when we do these kinds of studies and make recommendations based on randomized clinical trials. We have to compare the same kind of breath work 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 studies of 10 or 20 people, not replicated, not well controlled, sometimes where the methods in which the study was done 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

• 37:28Speaker 03

  and you bump into billions of web impressions. So that's kind of where we are.

• 37:32Dan Harris?

  But you, as the guy who lives... In this world, very deeply, have decided, yeah, I'm gonna do a couple of minutes of what I think is called straw breathing, where you're breathing in very deeply through the nose and then breathing out through the mouth, lips pursed. You're gonna do a couple of 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.

• 38:03Speaker 03

  That's right, Dan. You've got it right. I combine it with meditation. Takes five or 10 minutes. It is called straw breathing. I think the importance of it is the breathing at six breaths a minute, so a 10-second cycle per breath, because that tends to optimize the correlation between respiratory processing 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 the hopes that it's a healthy habit. And I like the way it makes me feel, so that's good, too.

• 38:38Dan Harris?

  Yeah, you know, I was just gonna say that. I sometimes joke that it's, remember those old Colt 45 ads, the malt liquor in the 90s they used to run? I think Billy D. Williams was in the ads and the slogan was "Works Every Time." And I find that when I do a couple of deep breaths, it just feels good. I'm not willing to draw any like scientific conclusions based on that, but it seems strongly suggestive that something positive is happening.

• 39:04Speaker 03

  I agree. My personal experience supports that.

• 39:08Dan Harris?

  So I'm doing this interview one day after returning from Nosara, which is in Costa Rica. It's on the Pacific coast. 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 Nosara. And there are all these breath work classes offered all over town. You know, I'm just wondering for people listening, they may hear you talk about the benefits, both real and potential, of doing a few minutes of breath work. But what about all these breath work classes? I'm not hearing you, Kevin, say that you do those. I know you've done some studies with Wim Hof, who's kind of a well-known breath work and cold plunge evangelist. Should people consider going to

• 39:53Dan Harris?

  these breath work classes? Or is just doing a few minutes of straw breathing sufficient?

• 39:58Speaker 03

  I really can't comment on that. I think people have different resources and time is a resource and money is a resource 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 statistically significantly, good chance they're going to live longer than the other population. But as you pointed out, you can't apply population statistic analysis to an individual. If that was true, we'd all know which lottery ticket to buy. We

• 40:42Speaker 03

  just don't know how to do that. The amount of money that's spent on these wellness clinics, and if it makes people feel better, great. My only caveat in having this conversation, and one of the reasons I wrote the book, is people should go into this with eyes wide open. These classes cost money. People 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 if someone's sick and they have enough money to spend it on one of these classes, and they go in because they've understood that the class is going

• 41:23Speaker 03

  to cure their whatever autoimmune condition, and they don't, and they spend their money, that's not a good scenario. That's not a good scenario where people are marketing things or stretching claims beyond what is supported by, first by scientific mechanistic understanding, laboratory studies, but second by clinical trials. And, you know, I've seen this happen. I've seen healthcare, call them aficionados, or people very strident about these do it yourself practices, and I've seen them interact with patients who are crippled with rheumatoid arthritis. And when you say to someone with a severe autoimmune condition, well, you know,

• 42:05Speaker 03

  I do my pushups and my situps, and that's why I don't have this, that, or the other thing. Well, don't you think if doing a few situps or a few pushups would cure a serious condition like rheumatoid arthritis, that more people would know about it and everybody would be doing it? Of course. It's not that simple. And so that's where we have to be careful. 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 to keep this knowledge away from other people. It just means it's complicated.

• 42:40Dan Harris?

  Yes.

• 42:41Speaker 03

  That's the warning. Now, people go to these places, and they have a great time, and they love it, and they meditate, and they do breathwork all day long, and they come back to work. A week later, they feel like a million bucks. That's great. 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're not there yet. Maybe someday we will be.

• 43:05Dan Harris?

  Well said. You have a few times mentioned, and to be a little cute here, in the same breath, breathwork and meditation. To me, those are two actually quite distinct disciplines. So let's talk about meditation. What evidence is there for meditation having benefit for your vagus nerve?

• 43:28Speaker 03

  There's a lot of evidence for the health benefits of meditation, whether it's anxiety and depression, or blood pressure control. There's overwhelming evidence. And I think that's great. But the reason I separate breathwork and meditation in this conversation with you is because when I tried to write about those chapters in my book, what I found out was in almost zero cases do the clinical studies of meditation control for the type of breathwork, and vice versa. You could argue that every time you pay attention to your breath for five or 10 minutes, whether it's 4-4-4 box breathing, or straw breathing, as you said, or in on three, out on seven,

• 44:11Speaker 03

  you could argue that by paying attention to your breath, it is a form of meditation.

• 44:15Dan Harris?

  Yes.

• 44:16Speaker 03

  And vice versa, when you do different meditative practices, whether it's chanting, or whether it's some sort of transcendental meditation, or some sort of mindfulness... You inevitably, in that practice, breathe differently than when you're going about your day-to-day activity. So separating the breath work from the meditation is very, very difficult. I don't think that the overwhelming majority of studies that have been done out there in a controlled way have handled that very well. What do we know? We know that meditation affects regions of the brain 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

• 45:01Speaker 03

  implanted on their vagus nerve in their neck. So it's interesting, right? Do we know how it all works? No, absolutely not.

• 45:08Dan Harris?

  Just to say 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 school in which I've studied, which is kind of old-school Buddhism. You might be watching your breath while you meditate. You might be focusing your mind on the sensations of the body breathing, but you aren't manipulating the breathing. That's the key distinction for me.

• 45:48Speaker 03

  No argument. You are the expert on meditation. I am not. I would agree with you that during Buddhist-style meditations, you may not be consciously controlling 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 actually pretty certain that those changes were not the same in everybody. So separating the effect, if you will, of the meditation practice, the style, the method, from its modulating or modifying your breath work.

• 46:30Speaker 03

  It's very hard to sort through that 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 from there into a gazillion other brain regions, including the origin of the sympathetic nervous system. Those sympathetic signals go back down the sympathetic nerves. So now you've activated your vagus and your sympathetics. And this is why your heart speeds up. Your heart speeds up.

• 47:15Speaker 03

  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 exhalation. So when you think about all these things, I just gave four. Two in, two out. You have another, 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 meditation as an important part of a healthy lifestyle. I think it is. And I don't have any hesitation with suggesting some sort of breath work, either separately or together with meditation.

• 48:00Speaker 03

  It's also healthy and a good, healthy habit. But 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 oftentimes proposing arguments that are not supported by what we do know to be true.

• 48:15Dan Harris?

  There's a lot of bullshit out there, no question about it.

• 48:17Speaker 03

  Yeah, I'm so glad you said that, and I didn't have to.

• 48:21Dan Harris?

  Yeah, I'm in the eye of the storm. 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. We have to do a lot of policing.

• 48:35Dan Harris?

  Coming up, Kevin talks about some more tools for supporting your vagus nerve and what bioelectric medicine is and how it could change treatment of chronic disease.

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• 49:52Dan Harris?

  Okay, but let's keep working down the list of things that you, Dr. Tracy, do, given everything you know about the importance of the great nerve, the vagus nerve. Another thing on your list is cold. Say more about that.

• 50:08Speaker 03

  Cold is fascinating. I really thought when I got to that chapter that I would be overwhelmed with clinical results. And, once again, I was disappointed. In most of the clinical trials, specifically on the relationship between cold and inflammation, which is where the angle I'm pursuing here, most of those studies are 10 or 20 people, a typical number, many of them with no controls, and many of them with unclear methods in how they measured, what they measured, whether it was in the inflammation responses or the cardiovascular responses. But I did come away encouraged that there is evidence to support.

• 50:51Speaker 03

  Careful cold exposure to being anti-inflammatory. And I think the way most people do it, there's actually two separate anti-inflammatory mechanisms. First of all, you shouldn't do any sort of cold exposure without checking with your physician. Make sure that your heart 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, even when you get used to it, it's uncomfortable. And for that first few seconds or minute after the acute cold exposure, it almost feels like you can't breathe. It feels like all the air goes out of your body.

• 51:36Speaker 03

  And if you feel your pulse, you'll feel your heart rate accelerate. You're having a massive fight or flight 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 not the same as a low-grade chronic fight or flight response, which is pro-inflammatory. But anyways, I like anti-inflammatory, so I suffer through it. 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.

• 52:16Speaker 03

  And that's an important transition from fight or flight to sort of higher Vegas 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 has 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 when you get into your 60s and 70s, inflammation in your arteries is the source of progressive

• 53:01Speaker 03

  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, if cold exposure is lowering my inflammatory burden, which I hope it is doing, and there is some evidence that it does that in these clinical studies, then that's why I do it. I don't do it every day, I think a few times a week, and I still hate it. Every time I do it, I still hate it. But when I get out, it feels great. I feel really happy, and I like that, too. So.

• 53:37Dan Harris?

  So what's your routine? How many times a week and where are you doing it? Shower, bath? How many minutes?

• 53:42Speaker 03

  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, which activates the trigeminal nerve, the fifth cranial nerve, and that can participate in what's called a diving reflex. And the diving reflex is what sea mammals like whales and seals use when they're submerged 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 vestigial diving reflexes.

• 54:26Speaker 03

  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, and pulled out and resuscitated and is totally fine." That's because babies have very, very strong diving reflexes. That's a good indicator that you've stimulated your vagus nerve.

• 54:46Dan Harris?

  And I think you talk about in the book that merely splashing cold water in your face can have some anti-anxiety benefits.

• 54:56Speaker 03

  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. It's not totally comfortable if the water's very cold, but it's a lot easier than cold water immersion in a shower or a tub. And a lot of people do that.

• 55:19Dan Harris?

  I have a great friend, his name is Robbie Hammond, shout out to Robbie Hammond, who is really at the forefront of what he calls bathing culture. Bathhouses are popping up all over the country, all over the world. They're part of ancient civilization, but they're having a resurgence in Manhattan. I live near Manhattan and there's just, and Brooklyn, and there's tons of them popping up all the time. And Robbie takes me to these places. And it's a combination of sauna, hot tub some places, and cold plunges. And some of these places are like fucking medieval, like with the cold plunges at like right above freezing. And I get in there and my feet and hands are throbbing and it's horrible. What you're describing of just making the shower cold, which I think brings it down

• 56:04Dan Harris?

  into the 50s. And so it's not like at 34 or something like that. And just doing that for a couple of minutes, that sounds like I'm actually gonna start doing that now, right after this podcast, as opposed to getting in a cold plunge, which I hate.

• 56:19Speaker 03

  So I jumped in the Baltic Sea in winter once outside of Solskjaerbad in Stockholm. And I have had the experience you describe of going from the sauna into the ice water. And 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, soldiers or infantry, quote-unquote, volunteer for this. They put on a wet t-shirt and a bathing suit and they hose them down and put them in a cold room with a fan on. They will lower their body temperature, but you can get sufficient

• 57:04Speaker 03

  physiological responses from a cold shower for several minutes that are much more tolerable, as you said, much safer. Frankly, there have been drownings in cold tubs, as you know, and do elicit physiological responses that point to an effect on reducing inflammation. So, yes, it is doable. You don't have to invest in a tank in your backyard that's refrigerated year-round. You can do it with a cold shower. Where we are today, people are making money selling tubs. People are making money teaching people how to sit in cold tubs. That's a reality of our culture and our times. And people are not making money doing large clinical trials that are well-controlled and randomized.

• 57:47Speaker 03

  That's the fundamental disconnect to everything we've been talking about for the last hour. If there was a way people could get rich doing the clinical trials, we would have all the answers.

• 57:56Dan Harris?

  Yeah. Oh, man. I'm not anti-capitalist, but there are flaws in the system, no question.

• 58:03Speaker 03

  I love, I start companies, I try to move ideas from my lab into clinical development. I see the advantages of a capitalist system that can make technology broadly available to millions of people around the world and change the course of civilization. But I find it frustrating that we don't have simple answers to these simple things because people can't get rich doing it.

• 58:24Dan Harris?

  Yeah. Okay, on the subject of cold, what about saunas, the opposite of cold? Is there any evidence to indicate that sitting in a sauna can improve your vagal tone and maybe reduce inflammation by extension?

• 58:39Speaker 03

  I don't have a lot of good information on that. I don't have a good answer to that question. I think the safest answer is to say that what is another good indicator of vagal tone, whether it's coming out of a hot sauna, or whether it's coming out of an aggressive, sort of a VO2 max, aggressive cardiac workout. What is a very good, useful indicator of vagal tone is how quickly, how soon, your heartbeat goes back down to a slow rate. So, a lot of people follow those kinds of signals in their health regimes, and in their personal fitness tracking. Again, it's best for that kind of personal

• 59:21Speaker 03

  assessment and monitoring if you're working with somebody who's really trained in this and has the best equipment. And because there are, once again, a lot of generalizations about you want your heart rate to recover at this speed, 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 assessments to individual people without having established sort of long-term baselines and controlling for all the variables like diet, exercise, sleep, and stress. That being said, heart rate recovery, you want your vagus nerve to come right on after these stressful events and predominate over your fight or flight, so you get back to baseline quickly. That's a sign of good health and

• 1:00:06Speaker 03

  homeostasis balance.

• 1:00:09Dan Harris?

  Okay, real quick, before we get to bioelectric medicine, the fourth thing on your list of things we can do to increase vagal tone is, and you just finished referencing this in passing, exercise. What should we know about that?

• 1:00:24Speaker 03

  Check with your physician, but if you can exercise regularly, of course, watching your diet and your weight all along the way, there's overwhelming evidence that fit people, not just athletes, but people who exercise regularly have lower resting heart rates than non-exercisers or couch potatoes or unfit people. We're very confident in the clinical data that Aerobic fitness is associated with lower resting heart rate. We're a lot less certain on the heart rate variability measures, frankly. There's very conflicting evidence from good exercise studies that one particular exercise regime or another does or does not improve heart rate variability.

• 1:01:08Speaker 03

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

• 1:01:51Speaker 03

  Is that a problem of the position the measures are taken in? Is that a problem of? We don't know. All the studies addressing these kinds of things are relatively small and relatively 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 either made somewhat better

• 1:02:36Speaker 03

  or their onset is delayed by regular exercise. Could that be because the exercise is enhancing the vagus nerve signals that turn off inflammation and therefore reduce the inflammatory component of those conditions? Maybe, but we don't know.

• 1:02:53Dan Harris?

  Okay, very helpful. Bioelectric medicine, what is it? And how might it apply to the lives of regular folks listening to this show?

• 1:03:05Speaker 03

  To understand bioelectronic medicine and where it comes from, it's very illustrative to think about where does pharmaceutical or regular medicine come from? 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 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 drug as a therapy. That's the pharmaceutical industry in a nutshell for more than 120 years.

• 1:03:49Speaker 03

  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. Pick a disease, 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. 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.

• 1:04:32Speaker 03

  And we can do that with these battery powered devices. We've done this now successfully for several conditions. I mentioned rheumatoid arthritis before because the company that I co-founded in 2007 recently received FDA approval for their device. The company is Setpoint Medical. It's a vagus nerve simulator and it sits in the neck of patients with rheumatoid arthritis. It's about the size of a fish oil pill. It has the battery, it has the ASIC, the computer chip, it has the leads that control the electrical current flowing into the vagus nerve and it operates, you won't believe this, Dan, for one minute a day.

• 1:05:12Speaker 03

  And for one 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. And patients who are being treated in this way, some of them are having tremendous clinical effects. Some of them are now no longer having to take medications. Others still take their medication, but the medications that used to not be helpful are now appear to be helping them. And then 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

• 1:05:52Speaker 03

  controlled by a battery, a rechargeable battery, that 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, and they're very expensive. In the United States especially, they can go to be $50,000 or $100,000 a year. So patients are looking for options. When Setpoint was doing its definitive trial for FDA approval, they needed 250 or so patients to sign up, and they ended up with 242 people in the trial. But Dan, 30,000 people tried to enter the trial. 30,000.

• 1:06:36Speaker 03

  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.

• 1:06:47Dan Harris?

  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's useful for depression, epilepsy, body weight, and diabetes?

• 1:06:59Speaker 03

  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 of vagus nerve stimulation as a therapy goes back for decades, decades. And why doesn't everybody know about this? That's a long, complicated topic, but let's just break it down really simple for depression. In depression, if you look at the clinical trials, again, done over decades. People with vagus nerve stimulators who are being treated now under FDA-approved treatments in the United States and in Europe and other countries around the world, these are patients who are refractory to all available therapy.

• 1:07:44Speaker 03

  They're depressed despite talk therapy, despite drug therapy, despite electroconvulsive therapy. So what's happening? They have a vagus nerve stimulator implanted, and about 50% of them get significantly better. 50%. So you say, well, 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 loved ones because they were too depressed. And many of them have been able to rejoin society. And so why is it 50%? No one knows.

• 1:08:30Speaker 03

  We don't know how it works in the 50% or why it doesn't work in the other 50%. But I encourage, in my book, I plead with my colleagues to double down on this kind of research. Because if we really understood why half of the people with this severe depression benefited from this FDA-approved therapy, 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 a really important topic. And in the United States, many insurance companies don't pay for this, for depression. There was a sort of a split vote over the years on its approval. And so many insurance companies are waiting, quote unquote, for more data.

• 1:09:14Speaker 03

  It's an enormous opportunity to help a lot of people if we could figure out why it helps half of the people.

• 1:09:20Dan Harris?

  I try to do what I'm about to do rarely because it does feel like I'm abusing my privilege as 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, I mentioned I just got back from vacation 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 they're not papering over their stuff with busyness, sadness can break through. So depression is on my mind. If I, as somebody who I don't have severe, but I do have chronic depression, often comorbid with anxiety, wanted to go ahead and get one of these devices implanted,

• 1:10:05Dan Harris?

  is that a thing I could do if I was willing to pay cash for it, even if my health insurance provider wouldn't do it? Is that a thing I could do? And then what does it look like? Where does it go in the body? How invasive a surgery is it? Just tell me a little bit more about the practicalities here.

• 1:10:22Speaker 03

  The practicalities are all dictated by cost, as you said, one, and second, regulations. If cost is no object, if people have money to pay for the device and the surgical fees and the hospital fees and whatever, you're going to still bump up against the regulatory issues at most medical places. Before we get to that, let's talk specifically about the device because you framed it that way. So the devices that were originally approved in the 1990s as a therapy for epilepsy or depression are like cardiac pacemakers. 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

• 1:11:07Speaker 03

  skin up to the vagus nerve in the neck at about the level of the Adam's apple. The device connects to the vagus nerve. It's almost like a slinky at the end of the wire and you unwrap the slinky and rewrap it around the vagus nerve that holds it in place. I call that generation one. 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 sort of default settings back in the 1980s and 90s when these things were being developed.

• 1:11:47Speaker 03

  And not coincidentally, what's FDA approved for epilepsy and depression have those settings I just said, and in both cases, it works about half the time. So technically, and I'm not treating you as a physician, Tan, there's my disclaimer too on top of yours. But technically, there might be a path if you could convince a physician to prescribe this for you 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 host the whole procedure. And even if you paid cash,

• 1:12:29Speaker 03

  the physician would still be recommending this therapy off-label. And so there may or may not be additional regulatory requirements depending on the medical center in the hospital. It's not that you can't do it in the United States, but regulations and fear of regulations and compliance and oversight often makes it very difficult or impossible. 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. Now, the Generation 2 device, these are my jargon, but the Generation 2 device is the one like made by one by SetPoint and another one from a company called Microtransponder.

• 1:13:13Speaker 03

  The FDA has approved the SetPoint device to treat rheumatoid arthritis. I fully expect someday there will be additional approvals. There are more clinical trials that have to be done, but I'm actually quite confident you will see expanding use of the SetPoint device for conditions like inflammatory bowel disease and multiple sclerosis. That device is much smaller. It's the size of a multivitamin or a fish oil pill. There's no lead. It sits right on the vagus nerve, almost in like a pea pod, a little silastic pea pod that wraps around the nerve in the device. And the whole thing is completely self-contained. And in the battery in that one, as opposed to the Gen 1, the battery in Gen 2 is fully rechargeable. The patient puts a collar on once a week

• 1:13:58Speaker 03

  and recharges the battery right there in the neck. That's for rheumatoid arthritis, potentially in the future, other inflammatory conditions. I 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. 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. I think it's probably being underutilized in the United States.

• 1:14:39Speaker 03

  I don't know why, maybe because it's new, maybe because not enough people are talking about it. I think it's an important thing. Back to you and others with resources. 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. 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 successful, then you're talking about having impact or benefit for millions and millions and millions of people.

• 1:15:21Dan Harris?

  Real quick before I let you go, aren't there some non-invasive vagus nerve stimulation devices, like something you put in your ear?

• 1:15:28Speaker 03

  Let the buyer beware. We're back to our theme of the day here, Dan. There is a branch of the vagus nerve to your ear. It carries sensory signals from the cartilage of your external ear into your brain stem. 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. Now, as you know, once information goes into your brain, the brain can send that information anywhere it wants. Got 100 billion neurons. At the end of the day, they're all connected. So people call applying a TENS unit, transcutaneous electrical nerve stimulator, electrode to

• 1:16:13Speaker 03

  the ear, they call that vagus nerve stimulation. And it's become jargon and commonplace. Is it the same as putting an 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 on either your cardiovascular system or your immune system? Maybe. There are some studies that suggest, and I've published some of these with my colleagues, and I've seen studies from other laboratories and other research centers from other colleagues that...

• 1:16:49Speaker 03

  When applying these TENS units to the ear, which I prefer to call auricular as in oracle, auricular nerve stimulation. Because 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. And once again, in relatively small studies, 20 subjects, 30 subjects, usually open label, meaning not blinded and not necessarily randomized or well-controlled. But you can see some outcomes. There's pediatric Crohn's disease. Ben San at Northwell, where the Feinstein Institute is in New York. Ben San has reported very significant improvements

• 1:17:33Speaker 03

  in children with Crohn's disease. Cindy Aronow has reported decreased pain in patients with lupus, whose lupus is manifesting as lupus arthritis. Sangita Shivan and others have reported electrically stimulating the ear with a TENS unit decreased the pain and swelling, and even the cytokine responses in the blood of patients with rheumatoid arthritis. So there's all these tantalizing clues about these things. But to me, the marketing and selling of devices with claims are now exceeding the scientific evidence. And so if you like to experiment on yourself, if you can afford to buy these devices, if you want to try putting lots of electrodes

• 1:18:17Speaker 03

  on different parts of your ear and neck, you can do this. Are we at the point where we can make bona fide claims for all of the devices? No. Can we make claims for some of them? Yes. The FDA, for instance, has approved an ear stimulating device 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 from overdosing. So there's clues out there. I know, I'm aware of some recent clinical data. That stimulating the ear, probably vagus nerve branches and trigeminal nerve branches

• 1:19:00Speaker 03

  with a device that does both, may reduce blood loss and bleeding in conditions of 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 simulators can reduce the blood loss. So there's a lot of possibilities out there. I don't like to see the claims get ahead of the data.

• 1:19:25Dan Harris?

  Dr. Kevin Tracy. The new book is called The Great Nerve, The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes. Thank you very much for your time. It's great to talk to you.

• 1:19:37Speaker 03

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

• 1:19:41Dan Harris?

  A true pleasure.

• 1:19:46Dan Harris?

  Thanks again to Dr. Tracy. Great to talk to him. Don't forget to check out my new-ish meditation app. It's called 10% with Dan Harris. It's available over at danharris.com. We've got a growing library of meditations from world-class teachers. We've got ad-free access to this podcast. We've got exclusive livestream events where we teach meditation. Take your questions. We do those every week. DanHarris.com. Join the party. Finally, thank you very much to everybody who worked so hard to make this show. Our producers are Tara Anderson and Eleanor Vasili. Our recording and engineering is handled by the great folks over at Pod People. Lauren Smith is our managing producer. Marissa Schneiderman is our senior producer. DJ Cashmere is our executive producer. And Nick Thorburn of the band Islands wrote our theme.

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