← The Human Upgrade: Biohacking for Longevity & Performance
The Human Upgrade: Biohacking for Longevity & Performance
The Tiny Implant Replacing Life-Changing Drugs | Biohacking Tools : 1365
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- [00:00]
Kevin Tracey
When we look at the vagus nerve, there are 100,000 fibers on each side. There's controversy about how it actually works. We have a positive clinical trial where the patients in the US studied at 40 centers, 242 patients had significant benefit by having a vagus nerve stimulator the size of a multivitamin implanted in their neck at about the level of their Adam's apple. So once it's implanted, it's gone, it's invisible to the outside world.
- [00:28]
Dave Asprey
And then they try them and go, oh my God. Life changing.
- [00:30]
Kevin Tracey
It's been done since the late 90s, 1980s to treat epilepsy and depression. And I estimate more than a million people have had successful vagus nerve surgery without immunosuppression, without suffocating side effects. You can reduce inflammation markers in some patients. You can change heart rate variability in some patients. You can improve quality of life measures in some patients. This could actually be a new therapy for rheumatoid arthritis.
- [00:55]
Dave Asprey
You're listening to the Human Upgrade with Dave Asprey.
- [01:02]
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- [03:32]
Dave Asprey
After writing 450 peer reviewed papers, can we use electricity to replace drugs at least some of the time?
- [03:40]
Kevin Tracey
Let's begin with basics in semantics. Technically, electricity, yes, but actually not in the way people think about it. So if you want to invent a therapy for a disease, the first step would be to pick the disease. The second step. Now this is how the pharmaceutical industry has been doing it since Paul Ehrlich in 1912. Nothing's changed. You pick the disease, you find the molecular mechanism or the target, or the basic physiological or pathophysiological process, and then you screen molecules to hit the target, control the process, and in a way that the molecules have more benefit than toxicity. And then you sell them. There you go. Some years ago, my colleagues And I, maybe 15 now, proposed another way of thinking about that process. And what we proposed was what we call bioelectronic medicine. So you begin at the same place, you pick the condition or the disease, and you find the molecular mechanism. That's critical. We'll keep coming back to this, I suspect over and over in this chat. Knowing the molecular mechanism. Rather than screen for molecules that function lock and key, we proposed that you might be able to find neurotransmitters, products of nerve endings that could control the target in situ and restore the biology in a way that could be very precise. And if you can do that, if you can reveal a neurotransmitter to control your molecular target, then you can build devices and they are battery powered. That drive pulses of voltage difference into nerves and that actually causes the nerve to fire. It causes the nerve to propagate voltage gated spikes that are like dominoes traveling down the nerve. It's not electricity. Electricity travels in a copper wire. There's controversy about how it actually works, but suffice it to say, at the speed of light, whereas nerves propagate at a fraction of that speed. It's fast in biologic terms, but it's much slower. So the simple answer to your question is yes, you can use a battery powered device to target a neural pathway to treat rheumatoid arthritis. And the good news is, just about 10 days ago now, the FDA approved this idea that you're asking about to be a clinical product from a company, Set Point Medical, that I Co founded 18 years ago.
- [06:05]
Dave Asprey
Gotta ask, if the body's using electricity, but it doesn't flow at the speed of light like it does over copper, wouldn't that make our nerve fibers superconductive according to the definition of superconductivity?
- [06:17]
Kevin Tracey
I think you're asking another question about what is the nature of the information that is being transmitted in nerves. And the textbook answer is, the one that I gave a brief citation of a minute ago is that nerves transmit information by converting electrical information into chemical information. The electrical information travels down the nerves by a sequential activation of voltage sensitive ion channels that cause a flux of ions to flow from outside the cell to in and from inside the cell to out. And it's these voltage spikes that go from one end of the nerve to fiber to the other. The arrival of these voltage spikes at the end of the nerve gives the signal for the nerve ending at what's called the synaptic bouton to release the neurotransmitters. That's the dogma. What you're asking is, could nerves be transmitting information in other ways? Is it possible that because there's sequential voltage spikes that travel along the fiber, there must also be electromagnetic fields that are traveling around outside that fiber? Do those fields carry specific information? The answer is it's plausible. Maybe, but it's not in the neuroscience textbooks. And you're not going to find.
- [07:44]
Dave Asprey
A.
- [07:45]
Kevin Tracey
Card carrying neuroscientist to say that that's how they work? There are card carrying neuroscientists studying that question.
- [07:52]
Dave Asprey
As you know, it's so fascinating. I interviewed a physicist guy a long time ago and said, well, given that nerves are subject to something called the hall effect, which is a classical sign of that they are superconductive and superconductors basically carry electricity slower than the speed of light with they kind of seem like they meet the definition, but that would mean our bodies had room temperature superconductors, which should be kind of weird. And it's probably semantics and it's all above my pay grade anyway. But what we're saying is there's a system and it looks like it ought to be hackable in many different ways because if we're looking at voltage spikes, we're looking at cell membranes, we're looking at ionic gradients, you could play around drugs, but you could also just use electrical currents and maybe some lights and who knows what else. So have you successfully taken something that would have required a drug and used electrical current from an external device so that they didn't need the drug anymore?
- [08:49]
Kevin Tracey
Yes, that's the FDA approval we just alluded to. Actually made the front page of the New York Times a week ago last Friday. The story is as follows. So we'll go back to our first principal approach with what is the condition of the disease? In this case, it's rheumatoid arthritis. What is the current therapy, the pharmacological or standard drug therapy for rheumatoid arthritis? Or what is rheumatoid arthritis? Sorry, some of your listeners. Rheumatoid arthritis is an autoimmune condition where the immune system attacks the joints in the body. It's serious damage can result from this. If you've seen pictures of people with deformed hands and knuckles, that's sort of a classic picture of rheumatoid arthritis. It's not your grand uncle or grandfather talking about his sore knee on rainy days from a football injury in high school. This is a serious condition. The inflammation that occurs can actually go and attack other organs like the kidneys and the brain and the heart. So many of these patients are seriously affected by this pain, swelling, inability to use their hands. Sometimes when it's treated, the treatment can sometimes, if you believe it, actually add new problems to the story. So the treatment is to immunosuppress. The treatment is to take powerful medications like steroids and what are called biologics, which block molecules called cytokines. These are proteins made by white blood cells that drive inflammation forward. The biologics are very powerful. They can eradicate important cytokines with names like TNF and IL1. They're monoclonal antibodies, the drugs, and they bind the cytokines and they take them out of the picture. The problem is at that point becomes several fold. First they only work about half the time. Second, because they are eradicating the immune system, parts of the immune system, they have complications of what's called immunosuppression. That means secondary infections can occur, even cancers, wound healing can be impaired. So these are not great drugs. And oh by the way, they have black box warnings, which is the most serious warning label the FDA issues. And they have to be injected and they can cost between 50,000 and $100,000 a year. So suffice it to say there are in the United States today about a million and a half patients with severe rheumatoid arthritis who are looking for other options. They don't want to keep taking these medications or they can't afford them. Along comes the story we're talking about. Some 25 years ago, my colleagues and I here at the Feinstein Institute in discovered that nerve signals traveling in the vagus nerve can actually turn off inflammation. This was really important back in the 1990s because vagus nerve stimulation as a therapy had already been developed to treat epilepsy and then later depression. So we knew you could safely implant a device, a battery powered device to stimulate the vagus nerve. We can talk about at length later perhaps about all the molecular details of how it works. But for now, suffice it to say that the vagus nerve we discovered, functions like the brakes in your car and it slows down inflammation. So on the back of a napkin in 1998, give or take, I wrote, I wrote a little, I drew a little picture of a vagus nerve stimulator implanted on a vagus nerve in the neck of a patient with rheumatoid arthritis to block the TNF being made by their immune system. And I said, I wonder if this could actually be a new therapy for rheumatoid arthritis. Started the company Setpoint Medical with my colleague Shaw Warren at Harvard. And here we are today, 18 years after the company was co founded, we have a positive clinical trial where the patients in the US studied at 40 centers, 242 patients had significant benefit by having a vagus nerve stimulator the size of a multivitamin implanted in their neck at about the level of their Adam's apple under the sternocleidomastoid muscle. So once it's implanted, it's gone. It's invisible to the outside world. It delivers the pulses of stimulating current 400 microamps for one minute a day. Many of the patients slept through it. Many of the programs were set to go off at 4:30 in the morning, some patients woke up. I met a patient named dawn. And I said, you know, I'm sure the engineers can reprogram it for you at set point and have it come so you doesn't wake you. She goes, doc, I don't mind. I'm a schoolteacher, and for years I couldn't. I could hardly work because I had so much pain and my alarm would go off and I would be so upset with my pain and having to go to work in pain. Now the little buzz for one minute, a little tingle in my throat wakes me up, and I smile because I don't have any pain. And I go to work happy. Wow.
- [14:00]
Dave Asprey
Why are people getting this vagus nerve dysfunction in the first place?
- [14:04]
Kevin Tracey
Well, we don't know. So you framed it as a statement of fact, but it's actually still a research question. When we look at the vagus nerve, there are 100,000 fibers on each side. Each of them was honed by millions, hundreds of millions, probably years of evolutionary pressure to have a specific origin, a specific destination, and a specific job description or function. You can walk and chew gum at the same time because individual nerve fibers do individual tasks. We have looked at the fibers that function like the brakes on your car and the immune system. We've looked at mice, because you can't really do this in people yet. We don't have the technology. But in mice, we estimate it's a teeny percentage of the fibers in the mouse in the vagus nerve that control. That are sufficient to stop inflammation. If it were a similar number in humans, which we suspect it is, it's probably a few hundred fibers out of the 200,000, maybe 1,000 fibers. So when someone says vagus nerve dysfunction, we have to break it down. Which fibers are dysfunctional and which ones are functional. We saw in careful physiology studies done in, actually in New Zealand a couple of years back by a group that studied the vagus nerve functioning in sheep when they were running on a treadmill. It's like a Far side cartoon in your, in your mind's eye. The sheep are running on a treadmill, and they're all wired up in a laboratory. I mean, it's, it's, it's a great visual. What they found is, as you'd expect, the sympathetic nerves going to the heart during the sheep exercise were increased because you've got increased heart rate and increased cardiac output, increased cardiac contractility. But guess what they found also. They also found increased activity in the fibers, in the vagus nerve fibers going to the heart and it was not acting in opposition to the fight or flight sympathetic because when they blocked those vagus nerve signals, cardiac function was impaired a little bit. In other words, sometimes in biology when you have opposing forces, you get actually a synergistic benefit. Back to your question. What do we know about vagus nerve function or dysfunction in autoimmune disease? We know very little about the fibers that go to the immune system because we can't study those in people. But we do know a little bit about the vagus nerve fibers that control heart rate variability. They seem to be impaired. They seem to be less, less well functioning. That doesn't prove that the other vagus nerve fibers to other organs are also impaired. Nobody knows that. So these, these are the kinds of questions I think that will, will be answered as we get more powerful tools that we can apply to human clinical studies looking at the function of individual nerve fibers. But we're a little ways off from that still.
- [17:13]
Dave Asprey
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- [17:36]
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- [17:37]
Dave Asprey
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- [19:48]
Kevin Tracey
Well, I'm not sure that you have stimulated your vagus nerve device. Okay, so there's, there's two. If you, if we're going to talk about specific scientific mechanisms, cause and effect, which is, I presume, the angle that you want to start with. Because after that we can go into what we don't know and what may or may not be true. Sure. There's two ways to stimulate the vagus nerve, specifically. One is to implant an electrode on it. And this applies to humans and animal studies. We know that you can safely implant a vagus nerve stimulator in the neck of humans because it's been done since the late 1980s to treat epilepsy and depression. And I estimate more than a million people have had successful vagus nerve surgery without immunosuppression, without suffocating side effects. We can do it safely, you can do it systematically. That's one way to do it is with surgery. We also know now with the new SetPoint device that you can do it through a one and a half inch incision as sort of an outpatient surgery. And in the morning, home at night containing a battery, a computer, asic, a lead, an electrode, and the battery is fully rechargeable through the skin. The patient puts a collar on once a week. So that technology is there and it's specific. And we know the amount of current to be applied to the nerve. We know that 400 microamps is sufficient to stimulate the anti inflammatory fibers, which are. It's nowhere near sufficient to stimulate many of the other fibers. You don't see changes in heart rate, for instance, which requires a much higher. So that's all very. This is what we know, this is what's specific, this is what we can study the mechanism either in the laboratory and now in the clinic as well. Second way to specifically do almost all those things is with focused ultrasound. Focused ultrasound takes the energy in the sound waves and as the name implies, focuses them on a small point. You can use the ultrasound itself on the imaging mode to find various things like the vagus nerve or the splenic nerve or the glucose sensitive neurons in the porta hepatis of the liver. And this has all been done. In fact, my colleagues here, Sangeeta Siobhan and Stavros Zanos at the Feinstein reported a couple years ago now a study, their study of using focus ultrasound as an anti inflammatory therapy. And they. They focus the ultrasound on the spleen where the. I described the vagus as the brakes to your car, the destination of those signals in the immune system. One of the destinations is the spleen. And so they skipped the vagus nerve step and they actually activated the nerves in the spleen directly to prove that they could reduce inflammation in the bloodstream of human volunteers. So those are the only two ways to specifically stimulate the vagus nerve. All of the other modalities that go on the skin are electrically stimulating the skin.
- [22:58]
Dave Asprey
Couldn't you use pulsed electromagnetic frequencies to generate voltage to activate the voltage gated calcium channel in cell membranes and induce a current on the vagus nerve just using focus magnets?
- [23:12]
Kevin Tracey
There are several groups working on that. I'm aware of one group in Stockholm developing technology like that. There are patents out of MIT and other places that describe what you could think of as overlapping currents or current steering and. Yes, but that is not available yet for clinical studies or for. This would be highly experimental use in animals only. That would be a third way. I didn't put that in because it's not broadly available yet. It's a research project.
- [23:40]
Dave Asprey
Okay.
- [23:41]
Kevin Tracey
When you apply electricity to the neck, for instance, because the vagus nerve goes with the carotid artery, you can feel your carotid pulse. The vagus nerve must be in there somewhere. There's no evidence that putting the electric current on the skin stimulates the vagus nerve specifically or not?
- [23:59]
Dave Asprey
Because we don't know how to get it in. You're saying you could.
- [24:02]
Kevin Tracey
We just talked about current steering. That would be a way to do it. You could put multiple current sources in an array configuration and you could have. And you could map it so that the currents would cancel each other out. And the only place that got a current would be, you know, a few inches deep. But that's where the vagus nerve is. In order to get to the vagus nerve from the skin, you have to go through the skin, the subcutaneous fascia and fat, the platysma muscle. Then you go deeper through the strap muscles, you come across another layer or two of fascia. Then you come to the carotid sheath, which is actually a fairly thick structure. Then you come to the carotid artery and the jugular vein and the vagus nerve down there somewhere.
- [24:42]
Dave Asprey
Got it. I have an entirely not relevant, but hilarious story about the platysma. When my son was 5, we would do like a massage and I would name every muscle in his body. So we learned about the muscles. And then I would ask him to say it back, and I'm getting to his throat area. And I said, okay, what's the name of that? And he couldn't remember. Platysma. And neither could I. And I thought about it really hard and I said, that's your scrotum. So of course he laughs his little five year old butt off and runs out. Mommy, mommy, look at my scrotum. So now I know where the platysma is. It's on your neck. And so, guys, there you go. There's my dad. Joke. Sense of humor. But yeah, you're saying that the vagus nerve is really, really deep in there. Is there a spot I don't like the left ear, where it comes closest to the surface? Isn't there somewhere we can kind of get to as consumers? And I've seen people put lidocaine in their ears and claim it does something. And is all that just hocus pocus or is there something possible there?
- [25:42]
Kevin Tracey
Well, I think that's the theme of the billions of web impressions on social media and on the Internet. The theme being not the specific point you're making, but the theme being that's recited over and over and over and over again, is there's a vagus nerve function, vagus nerve anatomy, that does this. I can do that. Therefore it must be cause and effect. So let's break it down again. So your cartilage of your external Ear is actually embryologically derived from the cartilage of the gills of ancient fish. Nice. And obviously fish breathe with gills. They have to monitor oxygen and carbon dioxide and air pressure and all that. And you need nerves to do that. And the nerves in the fish, the nerve endings that innervated the cartilaginous gills of the fish, you guessed it, they're the branches of the fish's vagus nerve. Now, over the millennia, over the eons, literally, that piece of cartilage moved lateral ward and became the cartilage of part of your external ear called the cymbacantia. So where the opening to your ear is. And remember my grandfather, the pediatrician from Yale, his great advice was don't to your listeners. Don't put anything in your ear larger than the elbow of the. Of your opposite arm. So don't. Don't put anything in your ear, however, where you. Where you clean your ear with a Q tip or something. That opening to your ear, the cartilage around that which if you look in the mirror or look at a picture of someone else's ear, look at someone looks almost like a seashell, that's called the simba concha. And that cartilage is innervated by that sensory branch of the vagus nerve in humans as well as other mammals. Now, what's the significance of a sensory branch? Sensory nerves carry information from the body to the nervous system to the brain. In this particular case, you're absolutely right what you said. This branch of the vagus nerve, which is sensory, carries signals about the status, the pressure, the temperature, the sensations that arise in that cartilage, and it carries it directly into the brain stem, which is very unusual. Most bodily sensations itch and pain, and most bodily sensations travel up the spinal column and go into higher brain regions like the thalamus. But in this case, because it's a vestigial, meaning an ancient branch of an organ function, the lungs of the fish or the gills of the fish, this, what you have, is an interesting appearance of a visceral sensory branch of the vagus nerve that is near the surface of the skin. So when you put a tens unit or electrical stimulator on the simba concha, the cartilage of your ear, you are technically sending signals in to a sensory branch of the vagus nerve. Does that mean you've stimulated your vagus nerve? Once again, I go back to my old quip with my friends and colleagues when they say they want to stimulate their vagus nerve. I say you have 200,000 fibers, which ones do you want to stimulate? Once those signals arrive in the brainstem, in the area called the nucleus tractus solitarius, that's when things get interesting, because all neural inputs activate neural outputs. When you sit on the exam table and the doctor thumps your knee and you watch your leg fly up and you say, who did that? That's a reflex. And it happens because of a sensory input activated by the reflex hammer and a motor output activated as a reflex response to the input. So here's what we know. We know there's a sensory branch of the vagus nerve that goes to the ear. We know you can stimulate it all kinds of different ways, with a Q tip or with a electrode or with a TENS unit. And we know that the information goes into the brain. And the brain can send out its responses any old way it wants to. 100 billion different neuron ways. It can send signals back down the vagus nerve. Maybe it can send signals back down the autonomic sympathetic flight or fight response. Maybe it can send signals to through the pituitary access. Maybe it can send signals back down the vagus nerve to your heart or your immune system. So now it becomes a different question. Now the question isn't how it works, because you can't prove or disprove it. We don't have the technology, not yet, someday. But we can do clinical trials. And this is where it gets really interesting, because some of the clinical trials suggest that you can reduce. Most of them are pretty healthy people, so take that as a grain of salt. But you can reduce inflammation markers in some patients. You can change heart rate variability in some patients. You can improve quality of life measures in some patients. But one size doesn't fit all. And I think caution is warranted. Before we take a simple thing, stick this in your ear and say it's going to be some sort of panacea because you've stimulated your vagus nerve. There's five other nerves or four other major nerves to your ear. We don't even know in a specific patient with a specific method that we've specifically stimulated their vagus nerve. You could be stimulating two or three nerves at the same time. Or maybe you are just stimulating the vagus nerve.
- [31:16]
Dave Asprey
That is so scientific. And if I, I look for evidence of what you're saying to be true. I've played around with five or six different types of consumer grade vagus nerve stimulators. Some of them appear to have a great effect on me. My heart rate variability goes up. I feel calm, like Something happened there. Others I don't feel anything. Right. And it appears to be different by people because I know others who take the ones that don't do anything to me and then they try them and go, oh my God, life changing. So you're saying we may be getting the vagus nerve and we are, we don't know what it's going to do, whether it's the same in each person and we may be getting other nerves instead of or also. So it's kind of a crapshoot. Is it likely to be dangerous if someone tries it and it seems to raise their heart rate variability? Can we say well at least it worked on something good and just move forward?
- [32:04]
Kevin Tracey
I think for all, for all of these kinds of discussions. Look, you're a very smart, savvy person and you like to self experiment. That's all fine. You have the resources to buy these devices. That's all fine. I think we have to start with some ground rules for your listeners, for everybody, frankly. First make sure whatever you're doing is safe. You know, if you're buying electronic devices and they don't have the UL label on it, and if you're using them for a medical thing and it doesn't have an FDA label on it, you might want to be careful, at least check with your own healthcare provider. So safety first. The second thing is there is risk to devices that promise things and, and, and either, and nobody knows how they work there. The risk there is creating false hope. Having people spend their hard earned money when they may, may not be able to afford it. And, and on down the list. The risk, the thing I take, Umbridge, is the risk that it does to the good science that's out there. So you have scientific programs that have been done over 20, 25 years mapping in exquisite detail the molecular and neurophysiological mechanisms based on vagus nerve stimulation, either with direct vagus nerve stimulation or focus ultrasound. And then someone comes, we shouldn't even call the ear units, we shouldn't call them vagus nerve stimulators. They should be called transauricular through the ear electrical nerve stimulation in keeping with the nomenclature of a TENS unit. Now the naming of these devices is not something the FDA has worried, concerned itself with, frankly. So, so a lot of TENS units, which is an FDA approved class, a lot of TENS units are being used on the skin to stimulate the nerves of the ear and the neck and the back of the head and all different places. And then they slap a label on it and says vagus Nerve stimulator. So I think that's where caution is warranted. And what it does is it creates the environment you just described. Why? You tell me you have a device that makes you feel better. Great, let's subject it to a clinical trial and see if it's unique to you. That's an interesting question, right? Or does it work in 9 out of 10 people or 2 out of 10? And if it's 2 out of 10, what do those people have in common? These are fair scientific questions that haven't been addressed because people are marketing their devices, they're putting a rubber stamp on calling it a vagus nerve stimulator. I don't think that's, I don't think that's fair. I don't think that's good.
- [34:30]
Dave Asprey
I appreciate accuracy in marketing and I, I do some things in the EEG field and, and I know of one company that's not doing electrical measurement off the scalp that calls their stuff neurofeedback and like, pretty sure that's a marketing term. And, and so I, I dislike misuse of science and marketing. And at the same time, if 25 years ago I could have bought something that would have had a 10 chance of working, I'd have bought it. And if it worked, I'd have been really thankful and it would save me a million dollars. And if it didn't work, I'd have given it someone else who needed it or sent it back. So I like the right to experiment as we figure out the science. Seems like the FDA hates that. Right. And that I think it's a fundamental human right and all the risk you just said are real. Right?
- [35:16]
Kevin Tracey
Right. Well, it's, it's interesting now. Full disclaimer. And it's in my book the Great Nerve. I put a TENS unit in my ear twice a day, every morning for five minutes and every night for five minutes. And why do I do that? Well, because we've done enough clinical projects, clinical research projects here. My colleague Sangeeta Shivan and I, my colleague Ben San, a pediatric gastroenterologist. My colleague Christina Sefna, a pediatric nephrologist. We've published these studies in peer reviewed journals. They tend to be between 15 and 25 patients, which is when you're asking a new question. In clinical research, you start with, you don't start with a thousand patients, you start with 10 or 20. And that's what we did. And we got very interesting results with these TENS units placed in the sympaconsha. We saw decreased inflammatory markers in our own, my, my blood and my colleagues.
- [36:06]
Dave Asprey
So you're saying that may not be, they may not be vagus nerve, but at least the sima concha stimulation is good enough to drop inflammation. So you're down?
- [36:13]
Kevin Tracey
Yes, I mean I think, I think if you're, if you're a healthy male and, and, and you're trying to reduce the inflammatory burden in your body because you don't want to accumulate inflammation in your coronary arteries and in your cerebral vasculature and you have a evidence that simba conscious stimulation, let's call it that, or trans auricular nerve stimulation reduces the inflammatory burden in your white blood cells. We proved that, we published it, it's peer reviewed, it's been done several times and you don't mind doing it and you can afford to buy a cheap tens unit online somewhere then? Yeah, I think it's interesting. I think it's fundamentally interesting.
- [36:53]
Dave Asprey
But you're the rare hardcore scientist who's willing to go that way. I interviewed Dr. Nicotine from Vanderbilt University, Dr. Newhall, who published the first study in 1986 showing that pharmaceutical nicotine can actually treat Alzheimer's. And you know, this is a long time ago. I'm like so what kind of nicotine do you use, doctor? He goes I've never tried it. I'm like ah. So thank you for being willing to go out on an electrode and try it on yourself.
- [37:23]
Kevin Tracey
Back in the early 2000s I, you have to Google it. I forget the year, I think it was 2003 we published a paper which explains probably that benefit the benefits of nicotine. And we published it in Nature and what we discovered and proved was that the neurotransmitter from the vagus nerve is called acetylcholine and it interacts with nicotinic receptors which are called alpha 7 nicotine acetylcholine receptors. Nicotinic acetylcholine receptors. It turns out that in human white blood cells the alpha 7 nicotinic receptor, which is very sensitive to nicotine, is necessary and sufficient to stop cytokine production. It's anti inflammatory. And so to the. Yeah, oh yeah. To the extent that inflammation contributes to Alzheimer's, I'm not saying it causes it, I don't think it does. But to the extent that inflammation makes Alzheimer's worse, which it almost certainly does, the nicotine therapy may have been down regulating inflammation through this alpha 7 nicotine like acetylcholine receptor. In fact, I bet, I'd bet, I'd bet it did. But you Know, back to these clinical recommendations for transauricular nerve stimulation. I think at the end of the day, the clinical studies are there in many small cohorts. And when you move to the necessity of doing carefully, some of many of our, many of them aren't randomized. We've done some randomized, but it's hard to randomize if you feel the buzzer in your ear. But suffice it to say that to move this into any sort of a clinical recommendation. I mean, I'm a neurosurgeon and I study inflammation. I can't make a clinical recommendation without large, well controlled clinical trials that are randomized and have appropriate statistics and have been replicated. And that's not because people are trying to be difficult at advancing medical progress in this space. It's because that's what's required to have a sufficient understanding of who, who to recommend the theory therapy to. I mean, back to your story. It's great that this helped you, but why did one of the devices help and the other three didn't? You know, we don't know enough and we need, we need to do more work.
- [39:47]
Dave Asprey
Do you think nerve stimulation will treat Alzheimer's someday?
- [39:51]
Kevin Tracey
Yes, I do. And I mean nerve stimulation writ large. I mean there's a very interesting company called Cognito Therapeutics that was co founded by my friends at mit, Lee Wei Tsai and Ed Boyden. And what they're doing is they're using 40Hz gamma entrainment through light signals and auditory signals to slow the progression of Alzheimer's disease. And they've published some of their first clinical trials. This is based on a decade or more of basic science research in the lab, in mice published in journals like Cell and Science and Nature and, and that is technically a nerve stimulating modality. When you are in training neural networks at 40 hertz, you're stimulating the brain's nervous system to do a specific thing. The interesting thing now is to see these clinical results coming out and then some people are gaining benefit. It's really interesting.
- [40:49]
Dave Asprey
I love the way you're seeing this. I mean, you've been in the field for so long and you're right, there's probably tens of millions of people who could benefit from the type of implant you already have manufactured for uses we don't even know about. And meanwhile there's going to be a whole bunch of other stuff that comes out. And when you get into longevity, it's probably worse. I mean, I've had gene therapy that for the average person reduces your Measured age with your DNA methylation by about nine years. But it's like what gene therapy.
- [41:20]
Kevin Tracey
Ah.
- [41:21]
Dave Asprey
And people go nuts. I'm like, well I don't know. The science was good enough for me, but maybe you want to wait a little while.
- [41:26]
Kevin Tracey
Can I comment on that?
- [41:27]
Dave Asprey
Yeah.
- [41:28]
Kevin Tracey
So I think the same thing's going to happen with vagus nerve stimulation in the coming years. Yeah, I think, I think there's overwhelming evidence that a higher vagal tone, which I define in the book, but call it whatever you want. Call it a slower resting heart rate. Call it a, a more active set of brakes on your immune system to keep your inflammatory burden low. Keep it a, call it a better glucose insulin feedback system. I would call all those things improve vagal tone. The only thing we measure right now is heart rate variability. But the other things are there too. Let's just say that vagus nerve stimulation with a device was a way to strengthen the activity of the signals in the vagus nerve. We don't even know that, that that's possible. But let's just say that's a science project. If you could do that, what would happen to the, all the diseases caused by inflammation? There would be less of them or they would be less severe. If you could do that, what would happen to health span? It would, it would be prolonged. If those things are, if those things are true, even on the, on the surface, my prediction is that high net worth individuals and people interested in, in, in self experimentation like you're describing are going to start looking for, to have their own vagus nerve. People are already putting magnets under the skin of their hands so they can see which way north is when they walk home from work. I mean it's going to be very interesting times. It's going to be very interesting.
- [42:50]
Dave Asprey
It's like you read my mind on that one. My next question was going to be if I want to get a set point device because I know about inflammation, I write books about this and, and I know the mitochondrial effects and I've been playing around with stimulating pretty much every nerve I can reach with the electricity for 20 years because I know what myelin does for me. So okay, I want to get one. Like what country can I go to and how much is it going to cost?
- [43:15]
Kevin Tracey
Well, that's, I'm not full disclosure. I co founded Set Point and as I said a couple times and I, I'm not employed there. I can make introductions to you offline to some of the folks at Set Point. You can ask them, I think right now we're in a very special place where the FDA has approved the device for specific indications in the US which will be for rheumatoid arthritis patients who are either unable to afford or tolerate their current drugs and or the current drugs are not giving them sufficient benefit. So that's about a million and a half patients today in the US how.
- [43:51]
Dave Asprey
Much are they paying for at ballpark? I know you're not working for the company anymore, but is this like a thousand dollar problem or a $10,000 or 100,000 DOL?
- [43:58]
Kevin Tracey
The device will probably be marketed similar to other vagus nerve implants for depression and epilepsy. I am guessing, and this is me talking, not the company, I'm guessing in the $50,000 range.
- [44:08]
Dave Asprey
Okay, so it's expensive.
- [44:10]
Kevin Tracey
Yeah. The reason that makes sense is because first of all, there's some precedent for that. Second of all, the drugs people are taking today for rheumatoid arthritis are between 50 and $100,000 a year every year for life. So in one year you have a cost return, you have a cost savings, you know, return on investment. So I think that's what's going to happen. I think the company will have a product rollout that will be starting a few centers. If you're rolling out a new product that requires surgery, you're going to want to make darn certain that it's done by people who are totally checked out and rheumatologists to totally understand the indications and the patient criteria to be implanted. But eventually, over the next year or so, I think you're going to see a, a nationwide rollout of this product. You asked specifically about going somewhere else. Well, you got to ask the company that. But my understanding is it's going to be a US based product launch and obviously you have to see what happens after that for the rest of the world.
- [45:07]
Dave Asprey
Okay, that's a fair answer. And the reason I ask is a lot of the most innovative things. I have to go to Costa Rica or Abu Dhabi where regulatory. There's just a little bit more medical freedom to do the things that for me, I don't care much about Health span. Of course, everyone wants that. I want health span and twice the lifespan. Actually. I just want 50% more lifespan. I don't, I'm not greedy.
- [45:30]
Kevin Tracey
Right.
- [45:30]
Dave Asprey
So if that's my goal, I'm going to treat things more aggressively. And I do probably micro doses on intermittent dosing of eight different pharmaceuticals that attack longevity pathways that I cannot get with natural supplements or lifestyle. And I Have no problem doing that because risk, reward. But if I can get some implanted electrical stuff. Now, some people are going to get really offended here because, you know, the whole cyborg thing, I'm open to it, but I would want to make sure that I had full control of anything that was under my skin. How do we handle hackers controlling your medical implants? That's a little scary.
- [46:07]
Kevin Tracey
Yes. That is not what I know about. I'm not in that space. It is. I mean, it goes back to when Dick Cheney was vice president. Right. And he had to have a cardiac pacemaker implanted. And the devices that are, that are being built now are obviously very encrypted. And you're much more of an expert on hack, on hacking, thanks to.
- [46:31]
Dave Asprey
I was a computer hacker and that's why I have some concerns about it. You know, the idea that you're going to get a neuralink brain implant or something and you know, It'll be about 20 minutes before some law firm figures out a way to insert spam into your visual field that you can't turn off. And I just don't want that. So security matters. Is there any risk? If I have a device that can stimulate my nerves that, you know, I'm going to, I'm making this up. I'm going to lick a battery and go for a swim and suddenly I'm going to get overstimulated.
- [47:04]
Kevin Tracey
I'm not sure what that would, what that would mean in the context of the vagus nerve stimulator for treating inflammation.
- [47:12]
Dave Asprey
What if you get it? What if it gets stuck on? Like if I, if I ran that 400 milliamps and didn't turn off after a minute, it just.
- [47:19]
Kevin Tracey
Microamps. I was going to say that seemed.
- [47:21]
Dave Asprey
Like a lot of power as I said that. Okay, thank you. Microamps. Yes. Yeah, that's a little bit more appropriate.
- [47:25]
Kevin Tracey
Well, that, that experiment's already been done. So as it turns out, as it turns out, the epilepsy and depression devices operate at between three and five milliamps for five minutes at a time, five minutes on, five minutes off, 24 hours a day, year after year after year after year. So the answer is you might feel some buzzing around the corner of your mouth if you're speaking when it's firing. Obviously if it's 4:30 in the morning and you're sleeping, you're not talking. But if you're speaking and some of the current travels back up through the recurrent laryngeal nerve to the voice box, to the Adam's Apple, the larynx, then you might have a buzzing or vibrato in your voice and patients do notice that.
- [48:10]
Dave Asprey
But it's like built in auto tune really. So people might pay for that.
- [48:15]
Kevin Tracey
Well, that would be a future, that could be a future invention that you could work on. It's very, very interesting question. The, the reality is that there haven't been problems from, from literally 10 times more continuous on, from stimulating the vagus nerve. Now I think what happens is at those high current flows and at that large duty cycle, I actually think that that may be why there's only a 50% response rate in depression and epilepsy. Because there's a very good chance that that frequent duty cycle and that large current load is actually inducing tachyphylaxis or tolerance. And so you may actually be desensitizing, desensitizing the nerves. But it didn't cause serious problems. So I'm not worried about side effects of this vagus nerve device. I'm also not worried that the electronics are going to go haywire. They've been subjected to rigorous testing. And again, you and I are sitting here talking in this particular case about you as a healthy individual trying this. And if I did it, what would be the downside? That's not what the patients are dealing with. Right. The patients are, are miserable. Many of them, they lose weeks or months of sick time every year because they're in too much pain to go to work or can't get dressed or can't drive. And they're taking these drugs that frankly scare them. And if it's parents with children, they don't want to see their kids on the drugs. They don't want to get pregnant when they're on some of these drugs. So it's that versus putting this one hour procedure, maybe hour and a half, inch and a half in the hospital in the morning, home in the afternoon. Turn it on and see if it works. And by the way, in the, in the clinical trial of 242 patients, 75% of them, this is remarkable, actually, 75% of them were no longer taking biologics or Janus kinase inhibitors. 75%. It hit the primary endpoint at three months. That was a randomized cohort of either treated, turned on or not turned on. And they hit the primary endpoint.
- [50:19]
Dave Asprey
So that's remarkable. And if it doesn't work, you can take it out, right?
- [50:24]
Kevin Tracey
You can. The device is, like I said, about the size of a multivitamin. It sits in like a silastic pea pod. That wraps around the device and holds it on the vagus nerve if it had to be removed or if the patients wanted it removed. You go in and cut one stitch that holds the silastic pea pod together. It pops open and you take it out. It's.
- [50:48]
Dave Asprey
Or you could just get in an mri. It'll take it out for you, right?
- [50:51]
Kevin Tracey
No, no, it's MRI compatible. Nice try.
- [50:53]
Dave Asprey
That was my next question. Okay, guys, listening. If there's too much metal, MRI will pull things out of your body. Don't do that.
- [50:59]
Kevin Tracey
But. But. But you'll. You'll love this story. The device was developed to treat epilepsy based on research in Pisa, Italy, right after. Right after World War II. They were still rebuilding the city when. When the researchers there discovered that an electric current applied to the vagus nerve of cats would stop epileptic fits in the cats. Well, skip forward 40 years to the 1980s. And they implanted vagus nerve stimulators to treat epilepsy patients. And as I said, about half of them got significantly better. Now, I mean, these are people who might be having hundreds of seizures a day.
- [51:34]
Dave Asprey
My mom has epilepsy. I grew up with her having it, so I get that.
- [51:38]
Kevin Tracey
Yeah, well, if you go from having many seizures a day to none or one, then the risk of surgery seems pretty small, right?
- [51:46]
Dave Asprey
It's a small risk if it's. If it's clean.
- [51:48]
Kevin Tracey
Right? Exactly. Exactly. So then. But anyways, half the patients did not gain benefit from this. And so the surgeon said, well, we'll take it out. And the patient said, no, you're not taking mine out. And they said, why? Because I feel better. I have a better outlook on life. That's what led to the clinical studies of. Of using vagus nerve stimulation to treat depression.
- [52:12]
Dave Asprey
All right, I. I actually do want you to hook me up with. With the company. After the episode, I will talk to them about experimenting with getting one of these things. I can. I can have chat GPT help me define all the symptoms of rheumatoid arthritis I can report so I get access to it. Would that work? I'm kidding. I'm kidding. But I do want to. I do, actually. I would try this, and people are saying, what, Dave? What are you talking. Yes, I'm willing to try it. And like I said, if it improves my quality of life, my longevity markers, my hiv, if everything goes through the roof, it worked. I'm okay with that. And if we learn more about it later, the downside seems pretty small. What could we see? Overstimulation of the nerve, maybe mitochondrial and happiness or something. But these are small amounts of current, right?
- [52:52]
Kevin Tracey
I'll tell you. Yeah, very small amounts of current. I'll tell you a funny story. This was way back in the early days, the late 90s, early 2000s, we had written a couple of papers proposing what we called the inflammatory reflex, which is that inflammation occurs in your body from an injury or an infection or unknown causes, like in rheumatoid arthritis. And that sends molecules like cytokines and prostaglandins and eicosanoids and other things into a furor. The presence of those molecules activates nerve signals that travel up the vagus nerve to the nucleus tractus solitarius, gets relayed over as a reflex output to the dorsal motor nucleus of the vagus. We proved all this 10 ways to Sunday. In animals, the motor signals travel back down the vagus nerve to the spleen, and they put a damper on the white blood cells as they pass through the spleen. So we mapped all this out and I got a call from a journal, the Journal of Clinical Investigation. They asked if I would write a review article that explained this in more depth. I said, sure. So I'm doing my research and I remember there was no chatgpt. There was no. None of the modern tools, but there was Google, and I typed in Google. Vagus nerve stimulation. And other than the epilepsy and depression, which was just coming out, I got. This is what I got. I got regular aerobic exercise, eating a balanced diet, taking safflower oil and olive oil, meditation, prayer, cognitive behavioral therapy, engagement in social activities, being in the zone. All the things that are good for you have been associated one way or another, directly or indirectly, with, quote, unquote, stimulating the vagus nerve as defined by slowing heart rate and increasing heart rate variability.
- [54:39]
Dave Asprey
I was going to ask you about some of the standard biohacking tools I've been teaching for a long time, like stimulating the mammalian dive reflex by sticking your face in ice water or just doing a cold plunge. Or certain kinds of breath work that seem to be vagal activating or even heart rate variability feedback training, which I've been doing since 2008. Any of those things doing something to the vagus nerve that's relevant for what we're talking about.
- [55:04]
Kevin Tracey
Yeah. Back to the 200,000 fibers. Right? You knew I was going to say that, of course. So let's do the simple one first, which is cold immersion. So don't do cold immersion on your own. Check with your doctor to make sure you have heart condition, make sure you do it safely. All, all that, all that's very, very important.
- [55:24]
Dave Asprey
Don't drown, don't freeze to death. Got it?
- [55:26]
Kevin Tracey
Exactly. Okay, good. When you go in cold water, the first thing that happens is a massive fight or flight response. And you know all the. If you feel like all the air has been sucked out of your body hurts. Even when you get used to it, you're still aware of the pain, right? Even after you've done it for a long time, you're still aware that if there's a painful sensation there, you just don't react to it the same. Your heart rate goes up, your blood pressure goes up. And you can measure all these things in laboratories and you can see the norepinephrine, epinephrine cortisol levels, they spike up. That's very, very quick. That's not vagus nerve stimulation. But maybe it is. Remember the sheep on the treadmill? It's not possible in a human to get an acute measure of vagus nerve activity as an electrical or neurotransmitter function. We don't have the technology. So it's possible that the vagus nerve is being stimulated with the sympathetic nervous system which goes along with the sheep. That's exactly what happens in the exercising sheep in New Zealand. However, let's say you stay in the cold for a while and you're, and you feel your heart rate slow down. You can check your pulse or you can just become aware of it. And when you, and it takes a few minutes and when your heart rate slows, you often will experience almost an emotional detachment or a feeling of calm or even enjoyability. It's like peace that is associated with slowing heart rate. And that would be evidence of, definite evidence of increasing vagus nerve activity of the fibers that go to your heart. Now why do I take, you know, cold showers a few times a week?
- [57:04]
Dave Asprey
Oh well, there we go.
- [57:05]
Kevin Tracey
Because I believe my data so.
- [57:07]
Dave Asprey
Oh no self experimenting.
- [57:11]
Kevin Tracey
The data are when you walk into that ice cold shower or cold bath or whatever it is you're doing, this massive fight or flight response is anti inflammatory. We've done this in, in the laboratory, in clinical studies we published 30 years ago when I was still at the New York Hospital Cornell Medical center, when I was still training actually to be a neurosurgeon. Massive fight or flight surges in epinephrine and norepinephrine are anti inflammatory. They suppress the white blood cell production of cytokine. Storm Wim Hof proved this with his colleagues, Peter Pickers ran the study in Amsterdam and they measured the cytokines. That was from his breathing, but it's direct cause and effect between elevating epinephrine and norepinephrine and decrease. So that's the first reason I do it. The second reason I do it is because when I do stay in the cold long enough to feel that slowing of heart rate, I know I've stimulated my vagus nerve because that's how heart rate slows. It's increasing signals in the vagus nerve that slow heart rate. And the third reason I do it is I like the experience of standing in the cold or sitting in the cold and thinking this. I'm aware of the pain. I know this hurts. But who's doing this? You know, who and what is paying attention. It's very, it's very interesting.
- [58:36]
Dave Asprey
What's something that most people misunderstand about the vagus nerve?
- [58:41]
Kevin Tracey
Most people completely misunderstand the vagus nerve because they don't realize it's 200,000 vagus nerves in your body, each with its own specific job description, anatomy and function. They actually treat their vagus nerve as if it was a copper wire, a solid copper wire. And they talk about do this, that or the other thing for your vagus nerve. And just in the example we just covered, you have when you get in the cold, you are technically, even in the first fight or flight phase, you are technically stimulating your vagus nerve because it's sending. Thousands and thousands of fibers are in your body, are being activated by changes in heart rate and blood pressure and carbon dioxide and oxygen and glucose. And all those signals are going in your sensory vagus nerve up into your brain. But it's nothing at all. It's nothing at all like most people mean when they say, stimulate my vagus nerve.
- [59:37]
Dave Asprey
There's something really beautiful when someone dedicates their life to becoming a master of knowledge about one system or one area of expertise and just goes in and goes in and goes in and then writes a book about it. And I, I want to thank you for writing the Great Nerve because there's very few, if any people on earth who've gone to that level to go, oh, yeah, there really are 200,000 parts and they're all different. And you're oversimplifying it. And you didn't just write it for other scientists. You know, it's meant so that we can all understand it.
- [60:09]
Kevin Tracey
So.
- [60:10]
Dave Asprey
So thanks for being so focused on this one thing for decades and decades to really master it. And then to share it and also to build stuff that we can use. And thank you for being on the show.
- [60:22]
Kevin Tracey
Thank you for having me on. It's really been a blast talking with you. I learned a lot today and I hope your listeners enjoyed our serious and fun conversation.
- [60:35]
Dave Asprey
See you next time on the Human Upgrade Podcast.
- [60:43]
Dave Asprey (Host Outro)
A Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of diagnosing, treating, curing, or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider carefully read all labels, and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place of a consult, consultation, or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by Bulletproof Media.