What You've Been Told About the Vagus Nerve is WRONG (& How to Increase HRV Based on *Science*!) With Dr. Navaz Habib and JP Errico.

My name is Ben Greenfield, and on this episode of the Boundless Life Podcast—

and that's really one thing that's been misunderstood or overlooked is the connection of these immune cells to the vagus nerve and the vagus nerve back down to those immune cells. It really is a bidirectional pathway specifically to the immune cells that are present in every organ of the body.

Welcome to the Boundless Life with me, your host, Ben Greenfield. I'm a personal trainer, exercise physiologist, and nutritionist, and I'm passionate about helping you discover unparalleled levels of health, fitness, longevity, and beyond.

Today's podcast, great one on all things vagus nerve. I learned quite a bit including things that I thought I knew about HRV function and vagus nerve, which were frankly wrong. All the shownotes are going to be at BenGreenfieldLife.com/VagusPodcast, V-A-G-U-S-N-E-R-V-E. US Podcast. Great conversation with Navaz and JP. Let's do this. I had the pleasure a few months ago of being on a panel at a conference on all things vagus nerve. And, another guy on that panel was Dr. Navaz Habib. I met him at this event and realized he knows a lot about the vagus nerve. He gave me this book that he wrote. I'll hold it up if you're watching the video version. It's called Activate Your Vagus Nerve. Just chock-full of a lot of stuff that goes beyond just the ho-hum, "Yeah, it's a nerve, snakes through your body and you should work on your HRV, bro." So, Navaz has this great book. And then, as if that weren't enough, JP Erico is also on the call. JP is kind of in the science innovation and medical technology side. Of all things vagus nerve. And so, he kind of knows a lot about vagal nerve stimulation. And, both he and Navaz co-host a podcast called the Health Upgrade, right, guys?

The Health Upgrade Podcast.

That's correct.

Yeah. Okay, cool. And, by the way, Dr. Habib, I know you're big into functional medicine, but what exactly do you do on the medical side of things? Are you still practicing or anything like that?

I have my chiropractic license, so I am a DC by profession, but it's heavily on the consultative side now.

Ben Greenfield: Got it. Okay. Alright, cool. Well, this is going to be fun, guys. We get to put on our propeller hats and dive into all things vagus nerve. So, like I mentioned, it's kind of one of those things where just like people say, "Oh, the mitochondria are the powerhouses of the cells," and they just kind of stop there. Sometimes I think people don't really get a good explanation of what the vagus nerve actually is. And, some people probably even think that it's part of that city in Nevada called Las Vegas, which it isn't, spelled differently. So, how do you describe the vagus nerve in terms of a little bit deeper, we got time scientific explanation?

So, I'll take a stab at that. Dr. Habib is definitely the expert when it comes to the clinical applications of Vagus nerve stimulation. And I am the science guy. I wrote a book that if you really want to dig into the science, it's The Vagus Immune Connection, which is, you know, goes into the deep science of it all. But basically, the vagus nerve is one half of your autonomic nervous system. And for those of you out there who think about the autonomic nervous system and don't really know what that means, it's in control of all the things that you don't consciously think about. So You know, Ben, as you're sitting there or standing there walking on your treadmill, everything from your balance to your heart rate, your respiration rate, your metabolic function, even at the cellular level, is being controlled by your autonomic nervous system. So, your autonomic nervous system is basically the control system that determines how everything in your body functions that you're not consciously monitoring. Okay? And we think of ourselves being human beings as because we can fly to Disney World and we can buy things on Amazon and, you know, we've got, you know, internet access anywhere in the world, that that's what really matters. But 99.9% of what our bodies and our lives are all about actually is not something we consciously think about. And that's where the vagus nerve, and the sympathetic nerve chain control your autonomic function. The vagus nerve is what we call the parasympathetic side, and the sympathetic nerve chain is the sympathetic side. And, we'll get into what those mean.

So, the vagus nerve act or is responsible for modulating parasympathetic like the rest and digest function.

Exactly.

What nerve did you say does the sympathetic side?

So, you have the sympathetic nerve chain, which is basically the opposite of that. It runs along your spinal, spinal bones, your vertebral bodies on the anterior side. So, basically, your spinal cord sits on the backside of the spinal cord. On the front side, you've got a series of nerve bundles, basically, they're all connected that run down the front of your spine and they merge with the spinal cord nerve roots to control a lot of organ function, a lot of tissue function, a lot of of smooth muscle function, like whether your pancreas is releasing pancreatic fluids or bile is going into your intestines. All of that is controlled by smooth muscles that are being controlled by your sympathetic nervous system and balanced by your parasympathetic.

The balance is the key. And so, there isn't a single sympathetic nerve, there is a full chain and a full chain ganglia series that sits, as JP mentioned, on the front of the spinal column. And those chains, they're bilateral, there's right side, left side, and there's a ton of nerves that come out of there. The vagus nerve is unique to this because it does the opposite function of the rest, digest, recover functionality, but it's the only nerve generally that does it within the thorax and the abdomen. There isn't another single nerve that's a controlling mechanism here.

So, is this related to— so, when you say the front side of the body and the back side of the body, I often hear in correlation to discussions about the nervous system the terms dorsal, and I think the other one is ventral.

Ventral, ventral, yeah.

Does that have something to do with the nerves on the front and the back of the body?

It's not directly nerves on the front and back of the body, What it's actually talking about is the developmental process and the evolutionary process. So the dorsal vagal are kind of the basic vagus nerve specific tools that are available since we've evolved as mammals, right? So these are the first parasympathetic controls that were really just focused on turning on rest and digest systems. When we are in a dorsal vagal, as it's mentioned, and this is in the polyvagal theory, so we're talking more psychological theoretical concepts. The dorsal vagal is almost a deer-in-the-headlights experience. When there is stress, it doesn't know what to do. Where the ventral vagal, which is the more evolutionarily new vagus nerve that we have as humans and that other animals do have, but we tend to have it at the highest functionality, that ventral vagal state allows us to go into almost like a flow parasympathetic control state, which is kind of that goal of can we control our physiology while still being consciously capable of functioning within the world and cognitively capable. So, that's where the definition or the words dorsal and ventral vagal actually came from. It's the evolutionary timeline, not the physical dorsal and ventral within the body.

So, if the dorsal vagal causes a little bit of a deer-in-the-headlights freeze type of approach and the vagus nerve itself is more parasympathetic than sympathetic. Is it an inaccurate description when people say sympathetic nervous system is fight, flight, or freeze if the vagus nerve is involved with the sympathetic part of the brain?

Yes and no. Yes and no. And, JP has a good way to explain this.

Yeah. I would describe it this way. When you're scared, your first response is to fight. Or run away. But when you're cornered, when an animal gets cornered, there's this process of fawning and then freezing that is still part of, physiologically, part of that sympathetic activity. The dorsal-ventral way of thinking about vagal function is actually not physiologically accurate. It's actually, I think, a mistake in polyvagal theory because when you're in that freeze moment where you're Bambi in the headlights, that's still a sympathetic response. So the sympathetic nervous system is really in control of that, even though it appears like you've reached some sort of maximal suppressed, digested, restored state. Because you're not moving.

The reason for this is because physiologically it looks like you're in a parasympathetic state because you're in a shutdown state, but you're not actually digesting when you're in that freeze state to begin with. You're not resting. You are in a stress state. You just don't know what to do. So there's no reactivity that can occur. So physiologically it looks like the, the vagus nerve is turned on and you're in a parasympathetic state, but in reality it's very much a sympathetic state.

Right. You're saying if we're playing possum, we still could be very, very stressed out.

Oh, exactly.

For sure.

Alright.

So, we're poking holes now in the polyvagal theory and perhaps there's a little bit of an error in the dorsal application of that. Good to know. Rewriting the textbooks already, guys.

It's a great theory and I don't want to diss it, but at some level, I think physiologically it needs to be.

Okay. Alright. So, in terms of terminology here, The other two terms that I often hear when people are talking about the vagus nerve and the way that interacts with the body is or are afferent and efferent, like AFF and EFF, afferent and efferent. Why are those two terms used? I mean, how does it apply to the brain talking to the body versus the body talking to the brain?

The vagus nerve is a bidirectional highway, meaning that there are signals going body to brain and brain to body. What's really important to note is about 80, 83% of the signals on the vagus nerve are afferent, meaning they're coming from the organs, from other tissues to the brain. It's a vast majority afferent, vast majority up to the brain. The effect from the brain to the organs of the body is close to between 15 and 18%. That's where the distinction comes from. So, We tend to think of the parasympathetic and kind of the brain-body control as the primary mechanism by which vagus nerve does its work. In reality, it's a lot more information up to the brain. And this is exactly the way these afferent fibers, AFF fibers, are the ones that are signaling from the microbiome up, right? It's what's signaling from the liver up to the brain, telling us what's going on with the Kupffer cells, what's going on with the toxic burden within the liver, what's going on within blood sugar levels. In the bloodstream, what's going on in other areas of the body. We even have the one area of sensation that is coming up from the auricle of the ear to the nucleus tractus solitarius where all of the afferent fibers of the vagus nerve come into. And that's where we relay that the signals into the central nervous system through the brainstem.

And then we do our executive function, figure out what we should be doing. And then the efferent fibers are turned on through the dorsal motor vagus nucleus. And that's the parasympathetic efferent pathways that then turn on the rest, digest, recover and signal to the immune cells. And that's really one thing that's been misunderstood or overlooked is the connection of these immune cells to the vagus nerve and the vagus nerve back down to those immune cells. It really is a bidirectional pathway specifically to the immune cells that are present in every organ of the body. That's where the vagus nerve does its amazing work.

Ben Greenfield: The idea of 80-plus percent of the vagal nerve function being the afferent, the body back to the brain, makes me think a little bit about this idea of HRV. And, maybe one of you guys can explain the link between the HRV and the vagus nerve. But, as a part of this potentially convoluted question, fellas, the attempts to increase HRV can range from thinking positive thoughts, meditating, yoga, singing, chanting, humming, gargling, et cetera. But, I think a lot of people might think you got to do something to your brain to increase HRV. And, it sounds like it might be a little bit more realistic to think about things that we would do with our body. I don't know if that's correct if the majority of nerve fibers are more afferent. But, what I'm wondering is what's the link between HRV and the vagus nerve? And, based on the understanding that 80-plus percent of the information is afferent, body to brain, how would that then influence the things we could do to potentially increase HRV?

So I'm going to just chime in real quickly, and then Dr. Habib has a very good understanding and explanation for HRV. But think of the, of the vagus nerve as your body's or your brain's primary sensory, or a sensory nerve that gives it the information as to what's going on in the body. I mean, we, we know that our eyes are connected to parts of our brain that see, see through the optic nerve. The optic nerve is carrying lots of bits of information that need to be absorbed and analyzed and understood, but meaning has to be drawn out of that. So, you know, when we look out and we see a giant red blob running, you know, moving down the street, that's probably going to be like a fire engine or something like that. And we recognize that it's a fire engine long before there's a complete analysis done in the brain of that visual information. The same thing is true of all the bodily information that's coming up through the vagus nerve into the brainstem. The brainstem's job is to extract meaning out of those signals that are coming in. That could mean I have to go to the bathroom. It could mean I hurt my leg, I just banged it into a table. It could mean I'm hungry. It could mean I'm tired. It could mean any one of a number of different things. And the brainstem's job is to gather all of that information that's coming up and extract meaning out of it, and then changing our behavior accordingly. So, for example, if you feel sick, you know, I will often ask the question, why does a gastrointestinal bug that's affecting my digestive system, why does it make my back hurt? Why does it give me a headache? Why does it make me feel tired? Why does it give me all of these other symptoms that aren't really associated with the, the location of that infection? And the reason is because all of that information is coming up into the brainstem and is being interpreted, and it creates the brain's response. And most of what we experience, those feelings of being sick, are actually coming as a result of that interpretation of those signals. That's why two people— I mean, I've been married for 20 years. My wife and I have, on dozens of occasions, been carrying the same infection, et cetera, where one of us feels terrible and is sick and the other one doesn't feel anything at all. And that's a function of just how the brainstem is interpreting all of that information coming up into it from the vagus nerve. And so how your vagus nerve is functioning literally is going to determine whether or not something is a subclinical infection for you or whether or not you're actually going to get sick. And, that's the larger issue that ties into how heart rate variability is basically a function of how your brainstem has responded to the information coming up through the vagus nerve.

And, by the way, this is super interesting because I was always under the impression, whatever, I get sick, my wife gets sick, we've also been married for 23 years. Hers manifests in maybe a headache and a sore throat, mine manifests in, say, nausea and a sore throat, that doesn't mean the sickness hit her head and her throat, but for me, it hit my gut and my throat. It means that the brainstem is simply interpreting the immune system dysfunction in different ways.

And, it's running a program. I like to describe it as the sick program. Your brain has 90, 95% of the time there's information coming into, up into the brainstem with, you know, some subclinical infection somewhere where you broke the skin on your leg or you've got some, you know, virus that's been passed to you by your kids or something. And your brainstem is interpreting the information coming up into it and saying, hey, listen, the immune system has this handled. I don't have to change my behavior. I can go about my day. Because everything that I normally do isn't going to impact this sickness that needs to be managed. But when that signal comes up and it's strong enough, it will then cause your brain to flip into sick mode. And that is really designed to change your behavior. It's not— it'd be great if we could have like a little running scroll at the bottom of our vision that said, Hey, you know, you've got a little infection in your knee and we're working that out. Don't worry about it, go about your day. But we don't have that. So what we have is how we feel. And so when we start to feel sick and we get a headache or we get tired or we get nauseated, all of these things are programs that are running in the brainstem in order for you to change your behavior so that the immune system can handle what it needs to handle. Why do we get nauseated? Because your immune system doesn't want you up running around or eating. It doesn't want you eating because it wants to use your liver's production of ketone bodies and fatty acids to run its job, which is to, you know, power the immune system. Interestingly, your nerve cells and your immune cells are somewhat unique in the body in that they don't require insulin in order to take up glucose. That's a really fascinating fact, which we'll get into, I think, at some point. But there's a lot— the sick program is what really makes you feel bad. And if you can control how that sick program is activated or not activated, you can change how you feel, which is why things like fibromyalgia, you know, endometriosis, And many of these disease conditions that are, they make you feel bad all over, are really a function of how your brain is interpreting the inbound signals.

Yeah, and from a tribal survival standpoint, it also makes sense that sickness may debilitate you with something like nausea or joint pain to also protect other people from being infected by you. Simply because you have no desire to go out and party and shake hands and kiss people.

Exactly, that's why you wanna lie down in a dark place away from everybody else. You get a little moody, you don't wanna eat, you don't wanna be around other people. You're absolutely right. There is that sort of evolutionary protection of everybody else too.

Dr. Abib, yeah, the HRV piece, what do you think about that part of my question?

The way I interpret this is HRV is a sign of the signaling capacity of the vagus nerve. So, how strong are the signals in being able to be passed from point A to point B along the nerve? It is a nerve overall, so we need to look at it in that nerve way. So, the simplest analogy that I can provide is think of a really, really thick electrical wire that has a lot of insulation, many electrical wires running through it, and the capability of that wire is much stronger in being able to send these electrical signals. Think like Tesla charging wire is significantly thicker than a USB-C wire that connects between your wall and your cell phone, right? So the thickness of the wire is going to determine the signaling capacity and how much electrical signaling capability there is within that nerve. Now, the thicker the nerve, the thicker the insulation, the more capability there is, but the quality of that nerve or the quality of that insulation matters significantly as well. So if you think of a frayed wire that's been bent and crumpled and ripped open and maybe some mice have gotten in and eaten that insulation off, the signaling capacity is going to decrease.

I interpret that in a dynamic sense as that's what it looks like when the HRV is low because the signaling capacity of the vagus nerve is decreased. What that means is we can fix it because this is a dynamic thing within the body. We're not simple wires that are present. We have cells that are there to help support the lining. We have the specific insulating cells around our nerves that produce the, the insulation of those nerve fibers. So, can we provide the right inflammatory control pieces to rebuild that wire signaling capability? And that's how we can get our HRV to increase. So it is a dynamic process, which is why we can have higher and lower HRV.

Now, when a gut bug shows up or when a virus shows up in our, in our lungs, what that's doing is it's telling our body through HRV becoming lower in those instances that it's time to rest, it's time to go into an inflammatory control mode and to not go out and and shake hands and kiss and do all these things tribally, and also to rest, take in fluids, and allow the, the immune system to do its job of clearing out the, the virus, the, the initiating trigger, and the liver to be able to clear the toxins out of the body. So the HRV is low as a sign of what's happening within the body in those dynamic processes. But when HRV is chronically low, it's because those wires have become frayed and there's chronic inflammation that's present breaking it down.

Ben Greenfield: Okay. Alright. And then, also based on that original question I asked about the afferent versus the efferent fibers and the majority of them being afferent, does that mean if I did want to say increase HRV that I would be more successful if I were to do something with my body, say, I don't know, exercise versus if I were to do something with my brain, say meditate?

I would say that both are effective. Remember that HRV, I mean, I realize this is probably going back to a really basic level, but HRV is basically a measurement of the balance between sympathetic and parasympathetic activity that controls the rate at which your heart is beating. So your heartbeat should not be a metronome. I mean, you do not want to have your heart rate at, you know, every single second beating exactly the same time frame between each beat. When you breathe in versus breathing out, it changes how your heart rate is flowing so that while you're, you know, That's why when you go out and you're, you know, let's say you're shooting at target practice or something like that, or out doing archery or something like that, people, you watch them, they take in deep breaths, they hold them for a second or a few seconds, they breathe out slowly. They're trying to get that sympathetic activity lower, parasympathetic level higher, so that they can be very, very true and accurate with their, with their firing because they're controlling how their heart is beating. That's why you get these, these yoga, yoga specialists. So the yogis in, in Tibet are able to lower their heart rate and raise their heart rate and lower metabolic rates, et cetera, because they've become so in tuned with the autonomic nervous system that they can consciously control it. So meditation, And positive mental attitude and gratitude behavior is just as powerful and just as potent as a sauna or a cold plunge. What you're trying to do is generate a resilience. You don't necessarily— sympathetic activity gets a bad rap because we talk about it in as, as pro-inflammatory or damaging and, and promoting depression and anxiety and other things. That's not true. I mean, if you go out and play a game of basketball, you're activating your sympathetic nervous system, but you do it for short periods of time. Short periods of time, that's like a hormetic stress.

It's right, a hormetic stress are necessary for cellular resilience.

Exactly. And it's true of neurologic resilience as well. So when you, when you take short bursts of these things, I always tell people, go out for a 3-mile run. That's great for you. Go out for a 30-mile run. You know, if you're— if you've trained for it, great. You go out for a 300-mile run. There's not a lot of people that are going to survive that. Okay. You need rest.

And nobody for whom it would actually be biologically beneficial.

Yeah, exactly. Exactly. You might do it for some Centurion, you know, context, but I mean, the baton death march is not a good thing.

So the goal here is autonomic flexibility, the ability to shift between sympathetic and parasympathetic on demand and to recover quickly following these short bursts of sympathetic activity. So exercise, but then recovery post-exercise. What I really want to emphasize on this specific call, because I know a lot of your audience is on the exercise-positive biohacking side of things, what we want is not only to do the exercise, but to shift out of the exercise state into a calm, rested, recovered state. So building that recovery protocol post-exercise initiates that autonomic flexibility. And that's where you're going to boost HRV because HRV comes down simply to how quickly can you go into sympathetic state and come back into parasympathetic state.

You reminded me of a conversation that I had the other night in which a man was telling me that he had consistently low HRV, but that he seemed to sleep just fine, right? Get in bed exhausted, end of the day, have a great night of sleep. But he said when he wakes up, He's just on like Donkey Kong all day long, can't turn it off. And, one of the things I was explaining to him was, "Well, we need to work on training then for you to be able to, at various intervals throughout the day, shift into a more parasympathetic mode." Whether that be through the use of technologies like say a vagal nerve stimulator or I was telling him about the Shiftwave vibration chair that maybe he could sit in a few times a day. To simple breathwork tactics such as coherence breathwork to simply teach the body using these things like training wheels how to relax throughout the day so he's not in a state of constant sympathetic go-achieve activation.

Ben Greenfield: Yeah. No, I just want to riff on this just for a moment because I don't know if you've done marathons. I'm a long-distance runner. I know you're clearly an athlete. One of the techniques that is, I think, very popular for people who are especially new people in marathon running is something called the, the Galloway technique. And it involves running for 9 minutes and then walking for 1 minute, running for 9 minutes and walk. The very first marathon I trained for, I went out, did the 10-mile run, felt great, came back 2 weeks later, did the 13-mile run and completely bonked. The last 3 miles took me 45 minutes.. And I thought to myself, this is gonna be interminable. I am never gonna be able to make it through a full marathon. But then I learned about this technique where you could go out and you could run for 9 minutes and walk for 1 minute, run for 9 minutes, walk for 1 minute. And I went out and did the 16-mile run faster than I had done the 13-mile run. And when I got done with it, I thought to myself, I am still fresh enough that I could do another 10 miles. And it was such a different way of thinking about how to accomplish the task. I want to tell people, and I tell people all the time, you need to adopt that same strategy in your life. Because as you said, you know, you get up in the morning and in the Western society, if you're a successful person, chances are you get up and you're on like Donkey Kong for 18 hours. You know, that what you need to do is I tell people, when you get to the office or wherever you're going, I want you to watch the clock. And for the last let's say 5 minutes of every hour, I want you to put the phone down, push yourself away from the computer, get up, stretch. Don't ask for permission. Go to the bathroom if you have to, because there's no faster way to amp up your, your sympathetic activity than to either have to go to the bathroom or be thirsty. Okay, go to the bathroom. We're not in kindergarten. We don't have to ask to go. Go to the bathroom, get some water, hydrate a little bit. Call your wife, your husband, your boyfriend, girlfriend, spouse, kids, whatever. Spend 2 minutes on the phone making a plan. You need to break up your stresses. Then you get back 5 minutes later, you're back at it. You run for, you know, it's like, again, just like the marathon training. You run for 55 minutes, then you take 5 minutes and you walk. And you— I'm telling you what you lose at the beginning of the day with these 5-minute breaks, you gain in the back half of the day like 10 times over because you're still energetic. You can get home, you can still be present with your family. You're not tired, you're not exhausted, you're not stressed. It's a great way to incorporate that sympathetic, what I call parasympathetic recovery mode.

You've described my typical workday, and I think there's something mental too, of course, to the idea of intermediate goals. I used Galloway when I used to train. And, you can run a lot farther also because you're simply doing something new every 9 minutes. And, I think it's not just the physiological break and the drop in lactic acid and the shift to different muscles, part of it is just, "All right, I just got to run for 9 minutes 10 times versus run 100 minutes consistently." It's just easier mentally too. And, same thing with the workday, right? I got to write for 55 minutes, in 4 chunks, not a consistent 4 hours. So, Navaz, you had mentioned about the parasympathetic and the sympathetic balance as it relates to HRV and kind of the pacemaking of the heart. But, what confuses me is that if, as we talked about earlier, the vagus nerve is primarily like a parasympathetic system, why is it that when people talk about increasing HRV, they say, "Well, the vagus nerve kind of activates or is responsible for the parasympathetic and the sympathetic feedback into the pacemaker cells of the heart." Is that just basically an inaccurate way to describe it?

I would say that it's a balance between the two sides, right? And, But one of those has to be slightly stronger than the other. And the parasympathetic is kind of the linchpin of this. So the vagus nerve signals that come into the heart are going to kind of take emphasis over the sympathetic signals. And that's why we have this variation that will occur in the heart rate of slowing things down. But it—

Right, right, right. But what I'm saying is the sympathetic signals are not coming from the vagus nerve.

No, no, they're coming from separate sympathetic nerves completely.

Yes, yes, there are sympathetic nerves. I think that is a newsflash for a lot of people.

Yeah, there are, you have both coming in. So our heart has our AV and SA nodes that are the primary internal pacemakers for the heart, but both of those nodes have specific parasympathetic through the vagus nerve and sympathetic through the sympathetic chain ganglia, the cardiac branches that go to the heart. That then will be the sympathetic inputs to the heart. So yes, there are nerves on both sides. It's not all through the vagus nerve.

Okay, got it. And then another kind of clarifying question, JP, if immune cells and nerve cells don't rely upon insulin in order to get glucose into those cells, like you mentioned earlier, I'm just curious, how are they getting energy?

There are multiple pathways for getting glucose into the cell. And, and it doesn't have to be glucose. You can also get ketone bodies and other things into the cell. Mitochondria are relatively flexible, especially if you're in good shape. But, um, the, the pathway for getting, um, glucose into the cell is you've got this, uh, this structure. It's almost like a little, um, lift called a GLUT4 that will extend out to the, the cell, uh, surface and capture the glucose that's outside the cell and bring it in. That process gets activated by insulin in most cells, but immune cells and nerve cells have the ability to internalize and sort of grab the glucose outside the cell and bring it in without insulin being present. But I, but you know, one of the things you said, I just want to riff on for one second. You sort of made a distinguishment or distinguished between nerve cells and immune cells. And it's always been my perspective that the nervous system is part of the immune system. And in fact, the brain itself and the nervous system are built by immune cells. And I'll get into that in one second. But almost all of your nerves have on them cytokine receptors. So they're responsive to immune signaling compounds. And we now know that our immune cells also have on them receptors for neurotransmitters. So they're really two sides of the same coin. We have, I think we all learned during COVID that we have an innate immune system. That's sort of the most basic form of our immune system. And then we have an adaptive immune system that learns. That's why you get vaccines, et cetera. Which ones are the right ones to get and how frequently, that's a separate question. But vaccines and having a virus or something like that that your body experiences and then learns by creating antibodies and memory T cells and other things, that's part of the adaptive immune system. But in each case, with the adaptive and the innate immune system, you have to come in contact with that thing. You have to actually experience the real thing risk of, of dealing with that thing biologically or chemically. We have a proactive immune system, and our proactive immune system is our nervous system. That's the nervous system that withdraws away from fire. It withdraws away from things that are sharp. It recognizes that the water looks murky and green, and I'm not going to drink it. That is the purpose. That is the primary purpose of the brain. And of the nervous system is to protect us, which makes it part of the immune system. And since physiologically it actually has the same receptors, they're sharing communications with one another, with the cytokines and neurotransmitter receptors on the opposing type of cell, they're really part of the same system. They metabolize energy similarly, they function together. So I think we have to think of the immune system and the nervous system really as two sides of the same coin. Now, I mentioned something before, which is that our brains, and really every organ and tissue in our bodies, are actually built— the coordination of it, and actually the physio— physical work that's done to do it— is built by our immune cells. Actually, it's pretty amazing when you go back into embryology to the very earliest stages of human development. This is true of all mammals, all animals. That there's a very small process that takes place at the very beginning, sort of just orienting layers of cells. And within the first 7 days or so, 7.5 days, there's an influx of cells that come from outside the embryo. They're coming from the yolk sac that are progenitors of our very basic, most important immune cells called macrophages., and they, they invade. For example, the microglial cells that are the immune cells of the brain, they go into the neural tube, which at the time is literally just a little tube. It's empty. It has nothing in it. And those microglial cells, they literally form the, or, or promote the construction of the brain from neurogenesis to the, the physical location of those cells, getting rid of cells that shouldn't be there. Making sure that the cells connect, the, the, the myelination, the building of the entire vasculature in the brain in order to make certain that every cell is getting oxygen, the promotion of, of astrocytes and other cells, all of it. Every aspect of that is coordinated and controlled and managed by microglial cells that will then remain with you, the same cells for 80, 90, 100 years. In fact, I tell people, on the day that you die, your microglial cells will continue to roam around your brain for 8 hours trying to figure out how to fix the problem. So these— and these are the very same cells, you can watch them for years on end, it's the same cell. They're like, they're like our chaperones through life. And that's true in every organ in your body.

Yeah, we just have different names for them. These are the tissue-resident macrophages that are present. So they're the Kupffer cells in your liver, they're the the gastrointestinal macrophages in the gut, the alveolar in the lungs. We've got the Langerhans cells in the skin. They're doing the same thing. They're maintaining optimal functionality.

They're maintaining homeostasis. They're signaling to the brain through the vagus nerve, through other nerves as well, to the brain as to what's happening, giving it status updates in the brain as to what's happening in those organs.

The brain is then doing its processing and then signaling down through the 15% of those efferent vagus nerve fibers to the immune cells that are present again to say, yeah, okay, let's do it this way. Let's do it that way. Let's adjust accordingly. But that central control is the brain, but the immune system is directly connected through. And the big thing here is this takeaway that when vagus nerve function is decreased, when vagus nerve function goes down, inflammatory control decreases. What that means is these immune cells are pushed into a state where they're hyperactive, where they're hyper-inflammatory. They're going to produce more inflammatory cytokines and they're going to trigger more of a chronic inflammatory issue.

As we improve vagus nerve function, we improve the control mechanism. We can, we improve decreasing the inflammation that's going to be created by those immune cells. Because we're creating inflammatory control. And we do so through this cholinergic anti-inflammatory pathway that is run through the vagus nerve. It's this reflex of inflammatory control. And I think it's— this is kind of where the crux of vagus nerve functionality comes down to, is can you actually control inflammation within the body? Because inflammation isn't a disease, it's a process. It's necessary process in acute scenarios, but when it becomes uncontrolled and chronic and longstanding, that's where disease takes place. Inflammatory control is key.

So, if modulation of inflammation and nerve function, gut function, a lot of these downstream mechanisms related to the vagus nerve are so important, I read in your book that one of the ways that the vagus nerve communicates, I believe it's like released from the axons or something like that, is with acetylcholine. Is acetylcholine kind of like something that people can make themselves? Is that something that we should be supplementing with or eating high dietary food sources of in order to support vagal nerve function?

Acetylcholine is the only neurotransmitter that's utilized by the vagus nerve and we produce it ourselves and it's very easy to do so. We need two different components to this, acetyl-CoA and choline. So choline comes from natural sources. Most often runny egg yolks are one of the top sources. Organ meats are a top source. For people that are on the vegan vegetarian side of things, soy does have some.

And— Walnuts, I think. Aren't walnuts pretty high?

Walnuts are also quite high in choline.

Wait, wait, quick, quick. You said runny egg yolks. Does it actually matter It's preferential.

It's more bioavailable in runny egg yolk form than it is in cooked. So runny egg yolks are ideal. And when you then get that choline in, then you have one very important missing piece. There was a really cool research study, I believe it came out last year, talking about choline supplementation on its own decreased Alzheimer's symptoms by 30%, just like immediate, just with choline. So that was one piece. The second piece is the acetyl-CoA, which is the acetyl component of acetylcholine. Acetyl-CoA is produced from pyruvate and, uh, you know, mitochondria and the carb metabolism side of things.

It's mitochondria or the, uh, the Krebs cycle, right?

Exactly. So initiating or going into the Krebs cycle, we have pyruvate lactate. The carbs are broken down into acetyl-CoA. Acetyl-CoA then enters the Krebs cycle, but acetyl-CoA can also can also then be utilized. And if we're not producing enough of this because our metabolic machinery and our mitochondrial function are decreased, we don't have enough of the acetyl-CoA, then we're not producing acetylcholine as well as not supporting our mitochondrial function. So getting this in and getting that functionality up is really key. B vitamins are a huge piece to this puzzle. Making sure that you have particularly B1, B3, and B6 are the biggest ones to make sure that producing enough acetyl-CoA specifically.

Ben Greenfield: Kind of interesting where my fringe biohacking mind goes is that mitochondrial transplants are kind of an up-and-coming longevity-enhancing tactic. I'd be very curious to see what happens to vagal nerve function and HRV if one were to do something like that from a healthy donor paired with high choline intake as sort of a way to cure chronic low HRV issues.

Ben Greenfield, MD: Ben, I, I just published last month a paper in Nature Aging that explains how the coordination of all of the aging processes, all the hallmarks of aging, are actually controlled by your autonomic nervous system. And that when you're in a sympathetic, chronically sympathetically active state, every single one of the hallmarks of aging, every symptom progresses more quickly telomeres shorten, epigenetic drift is faster, you lose the control over autophagy, you're inflammaging. All of this is accelerating. And when you get back into parasympathetic recovery mode, it slows them down and in some cases reverses them. So you're absolutely right. But one of the things that I think most people, when they think of the, the nervous system, they think of a reflex is like, okay, if I hit the right spot on my knee, my foot, my foot's gonna jerk. But what they don't realize is that your autonomic nervous system is controlling your immune system. But even more interestingly, because it does that through the cholinergic anti-inflammatory pathway, acetylcholine is binding to a receptor, and the receptor is called the alpha-7 nicotinic acetylcholine receptor, which is why nicotine has that calming effect on you. Nicotine also reduces inflammation.

I don't think a lot of people would describe nicotine's effect as calming, though.

You know, you're— but, but think about it, you know, what do they give you before you get about to get shot on a firing squad? They give you a cigarette.

Okay, I did not know that.

Okay, so no, but, but literally nicotine is actually calming it. Try, try withdrawing from it, you'll see how anxious people get. But the, the other thing is that this receptor that is controlling this pathway is also present not only on immune cells, but it's present on the outer membrane of mitochondria. And think about that for a second. You've got an extracellular receptor that's controlling inflammation. It's also present on mitochondria. So to get to your point about mitochondrial transplant, what cells are responsible for transferring mitochondria into cells, other cells that need it. It's your tissue resident macrophages. I'll give you a perfect example. This is so exciting. Your heart, your heart is built, uh, it's a muscle. It's got cardiomyocytes in there. Those cardiomyocytes are incredibly energy intensive. They've gotta beat forever for your entire life. They're beating. There's never a break. Okay? They need lots of energy. They've got lots and lots of mitochondria generating ATP all the time. Well, sometimes some of those mitochondria burn out, but you can't replace cardiomyocytes. So you can't just, oh, say, oh, well that, now that that mitochondria's not working properly, we're just gonna get rid of that cell. No, can't do that. So what do cardiomyocytes do when they get a bad mitochondria? They spit it out. They literally eject it from the cell. Well, who takes up that mitochondria? The tissue resident macrophages that are sitting in that tissue take up that bad mitochondria and either digest it away or they spit it into the bloodstream so it gets ejected through your kidneys. Okay? And then what does that cardiomyocyte that says, well, I just lost one of my mitochondria, I need more. Your, my, your tissue resident macrophages will transfer a mitochondria back in to replace a good one, a new one, a fully functional one into that cardiomyocyte. That same process happens in your brain. That same process happens throughout your body. But what happens when after a while those tissue resident macrophages start to get inflamed? Because we have this process of chronically increasing our inflammation. We're eating the wrong foods, we're not exercising, we're not getting enough sleep, we're doing all these bad things. These tissue-resident macrophages start to lose the ability to replace those mitochondria. So you end up with atherosclerosis, you end up with, with a loss of, of muscle tone, you end up with a loss of neurons, all of this, you end up aging. So there are ways to, to replace those mitochondria. There are ways to suppress the inflammation. There are ways to slow the aging process down. And one of those really, really effective ways of doing it is through the vagus nerve.

Ben Greenfield: That's super interesting. You have almost like these Pac-Man pulling little red trailers full of baby mitochondria around the body. That's super quiet. I've never really heard it described that way, the link between the macrophages, the mitochondria, and aging. Obviously, I think lowering inflammation and living in such a way that supports proper mitochondrial health and having good dietary sources of choline probably for most people trumps the logistics of a mitochondrial transplant. But, I think the message is sound for sure. You guys, I would probably be remiss, especially with JP on, not to ask this question back to the whole biohacking world, I suppose. All these medical gadgets like Dr. Abib, you were talking about the auricular nerve. I know some headphones or handheld devices will kind of stimulate with electricity that part of the vagus nerve or that extension of it. Others will use light. It seems an increasing number of devices now that promise to somehow restore or improve vagal nerve function. JP, I know you've been involved with some companies that have developed certain things. What's your take on those? How effective are they? Which ones work? But what's your, what's your take on this?

Yeah, so the very first vagus nerve stimulators to come to market were almost like pacemakers. They had to be implanted into the body. They were planted into the chest wall with an electrode that wrapped up into the neck and around the vagus nerve directly. And those were approved originally for treating epilepsy. They were found to be effective for depression. They tried to get an approval for obesity, although I think it probably has more to do with metabolic function we just talked about. As opposed to obesity itself. And those devices have been approved and are on the market. We stepped into the fray and said, "Boy, wouldn't it be great if instead of having to have an implant with a lead literally surgically wrapped around the vagus nerve, which involves literally cutting through your carotid sheath in order to get there, and you're exposing the carotid artery there." We said, "Wouldn't it be great if we could do it noninvasively? Give somebody a handheld device that could deliver electrical stimulation through the skin whenever they need it. And so, we did come up with a number of devices. I think I showed you one before. This is one that's been on the market since 2000. I think we got approval in 2017.

Oh, yeah, the gammaCore. Yeah, yeah. Just a quick question. Is that one marketed for headaches too? For some reason, I think somebody had mentioned to my wife to use one of those for migraines.

Yes, it has multiple FDA clearances for for the treatment of migraine. More recently, we've done two things. One is we've done work with, uh, the people at DARPA, the Defense Advanced Research Projects Agency, because they were looking to see whether or not any of the various different neuromodulation technologies that are out there could actually make people smarter. I know that sounds very Star Trek-y, etc., but, but they did a $100 million study to look to see whether or not any of these devices could literally make people's brains work more focused, better memory, better cognitive function, better recall. And out of that study, which again was probably a 5-year project starting in 2000— I think 2016— they came to the conclusion that our device, our non-invasive vagus nerve stimulation devices, had the ability to do that and did it pretty remarkably. So, we've been in the military now for a while with a device called TacStim, and that product is used for performance enhancement on healthy adults.

What'd you say, TacStim?

TacStim, T-A-C. Like T-A-K?

Yes.

T-A-C. Oh, like tactical stim? Yeah, tactical stim.

Is that something people can buy?

Well, you can't buy it because it's sold only through the military channels, but the thing that the military wanted us to do was they said, listen, we've got a bad history of telling healthy people that they have to use medications or medical products. Can you create a version of this that is not a medical product, that's a wellness product? And so we decided to do that. And as Dr. Habib, I think, is about to hold up, we have a device called the TrueVega. And the TrueVega is—

Oh yeah, I've seen that one. Yeah, I have that one. It's under my bed.

Yeah, there you go.

It's—

Okay.

Effectively the same thing, it's just not labeled for a medical treatment. It's for stress management, it's for better sleep, it's for all the things that you want, and cognitive enhancement. There was a study that was done at the Defense Language Institute, which is the equivalent of, the military's equivalent of like the CIA Foreign Language School, where highly intelligent people go to learn a language very quickly. And we did a study there, And that study was published in Nature Communications. And what we, what we found was that when people were tested and used this device regularly, they were able to maintain focus for 50% longer. They were able to learn 40% faster, and their recall months later was 50% better on what they had learned. So, I mean, we're not talking about small percentages here. We're talking about a significant a significant improvement in cognitive function.

Yeah. And, that one you hold up to either side of the neck, right?

Yeah, just like this. It takes a couple minutes.

2 minutes bilateral each side?

You don't even need to do bilateral. One side works totally fine because you're getting the 80% plus afferent fibers going up, you're signaling and you're stimulating the nucleus tractus solitarius where all the vagus nerve fibers are coming into.. And once you get that stimulation occurring, you're going to get it bilaterally functioning anyway.

Great. You just saved me 2 minutes. Check's in the mail. Time is money.

Exactly.

But just to get to the crux of your question, there are other ways to stimulate the vagus nerve. Obviously, we've talked about things like meditation and chanting and gargling and stretching, all of these things. Deep breathing, great way of doing it. We've known about these things for tens of thousands of years. I mean, Ayurvedic medicine, et cetera, is based on controlling the yin and the yang of your parasympathetic and sympathetic nervous systems. But the electrical stimulation is much, much more powerful. I think of it like telling a person who has a headache, well, you can go outside and find a willow tree and you can chew on the bark and you're going to get some acetylsalicylic acid, but you could just take an aspirin. And that's sort of the way I think about it. You can spend 2 hours meditating or 2 minutes using this. I mean, that's really the way, the way it works. But there are other paths to get to the electrical stimulation. You mentioned these earbuds that stimulate the auricular branch of the vagus nerve. Just in terms of scale, I just want people to understand on the right side of your neck, there's about 200,000 fibers. In the vagus nerve. On the left side, it's about 120,000. Okay? In the ear, there's about 300.

So, these ones you put on your neck are better than the ones that go in the ear?

Just based on scale, but one really important piece there is placement matters. And, where the actual vagus nerve fibers on the auricular branch go to is very particular. It's one particular area called the Simbha Konka, within the auricle of the ear, and it's just the skin component there. It's not these, like the tragus does have a bit of input from the vagus nerve, but it's not these, the ones that you clip on your earlobe. It's not the ones that you clip on the top of your ear or anything like that. They need to be placed in the exact right position to get the auricular stimulation to occur versus the neck. Once you find your pulse, you're in the right spot. And, as long as you're not engaging your sternocleidomastoid muscle, you're in the right spot. So, placement is key here. And then, one other big piece of the puzzle is based on the scale, how long does it take to get the same effect? And, this is the big thing is we live in a life that is like we're on the go, right? Everything is kind of rush, rush, rush. Time is money you mentioned earlier. So, what if you can get in 2 minutes of stimulation on the neck what it takes between 30 and 60 minutes to get in the ear. What's easier to plug into your daily life?

And so I'm not against any of the auricular devices by any means. If they're placed correctly, if they have good data behind them, if the electrical stimulation is actually effective, I'm more— I'm all for you using it. But what's easiest for you to plug into your daily life in a clinical or daily therapeutic pattern?

And when you're holding the thing on the side of your neck, it's not the auricular, is it? What is it like, the It's the actual cervical trunk of the vagus nerve. Okay, the cervical branch.

Cool.

The cervical trunk, and you're like super deep to the cervical branch.

No, no, you just hold it up against the skin. I mean, it's really— the, the signal that we've generated with this is, is relatively painless. I mean, it's honestly, it's, it's the first time you do it, you're going to go, wow, that's weird, I haven't done that before. But once you get used to it, it's something— I'll tell you, the, the animal models dogs especially love it. We have a— we had a vet, a vet version for canine epilepsy and canine anxiety, and within 24 hours animals will, you know, you pull it out and they'll roll over and show you, show you their neck. They love it.

Wow, super cool. Um, JP, what's the name of your book again?

Uh, The Vagus Immune Connection.

The Vagus Immune Connection. Cool. That one I haven't read. This one I have, Activate Your Vagus Nerve. This is kind of along with meeting Dr. Habib at that conference, what inspired me to interview you guys. I want to read yours too, JP. I might have to give you my address off air. I got to literally maybe 30% of the questions I wanted to ask you guys and we're kind of out of time. But, what I'm going to do is if you're listening and you go to BenGreenfieldLife.com/VagusPodcast, V-A-G-U-S Podcast, I'll link to JP and Navaz's books. And then, I'll also link to some of these vagal nerve stimulators that we talked about and some other episodes I've done on the vagus nerve. And then, your podcast is— what is it, Health Upgrade?

The Health Upgrade Podcast.

Health Upgrade. Okay, cool. I'm going to have to tune into that one. Thanks so much for doing this, guys. This is really incredible information.

No, thanks for having us.

Yeah, this has been great. Thanks, Ben.

BenGreenfieldLife.com/VagusPodcast, V-A-G-U-S, not Las Vegas, V-A-G. @BenGreenfieldLife.us. And leave your questions and your comments, your feedback over there. I love to read what you guys think. And leave the show review wherever you're tuning in. Alright. Thanks, guys.

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