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The Tim Ferriss Show Transcripts: Dr. Kevin Tracey — Stimulating the Vagus Nerve to Tame Inflammation, Alleviate Depression, Treat Autoimmune Disorders (e.g., Rheumatoid Arthritis), and Much More (#824)

2025-08-29 14:38:33

Please enjoy this transcript of my interview with Dr. Kevin Tracey (@KevinJTraceyMD), president and CEO of the Feinstein Institutes for Medical Research at Northwell Health, a pioneer of vagus-nerve research, and author of the recent book The Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes. 

His contributions include identifying the therapeutic action of monoclonal anti-TNF antibodies and discovering the specific reflex control of immunity by the nervous system, called the “inflammatory reflex.” These discoveries launched the new scientific field called bioelectronic medicine, which investigates the therapeutic applications of vagus-nerve stimulation to cure disease.

Dr. Tracey, a neurosurgeon, pursued studies of inflammation after the mysterious death, from sepsis, of a toddler who was in his care. His lab has since revealed molecular mechanisms of inflammation and identified the use of vagus-nerve stimulation to treat it. An inventor on more than 120 US patents and the author of more than 450 scientific publications, he is among the most highly cited scientists in the world. He co-founded the Global Sepsis Alliance, is the author of Fatal Sequence, and is a national and international lecturer.

Transcripts may contain a few typos. With many episodes lasting 2+ hours, it can be difficult to catch minor errors. Enjoy!

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Tim Ferriss: Dr. Tracey, good sir. Nice to see you again. Thanks so much for making the time to have this conversation.

Dr. Kevin Tracey: Thanks so much for having me on. I’m really looking forward to it, Tim.

Tim Ferriss: And I am really holding in my enthusiasm, which I’m not going to do for very long because we had a brief chat maybe a week or two ago, and I was bouncing around in my chair. I was overflowing with excitement to ask so many questions. And the reasons for that excitement will, I think, become very, very clear very quickly. But let me as context for people listening, and you know some of this already, explain why I never looked at vagus nerve stimulation seriously up until very recently. And primarily it’s because there’s so much crap and so many charlatans, whether it’s deliberate or not, floating around online touting the most ridiculous approaches, devices, at best innocuous, sometimes probably putting people at risk. And at the checkout they might be selling audio chakra cleanse soundtracks and just associated nonsense that shows that they wouldn’t be able to find a logical argument if it bit them in the ass.

And I thought, you know what? I’m just going to put this in the category of things that I should ignore. And also I’d been sent, and not to throw this under the bus, but maybe we’ll get to it, a book on Polyvagal Theory. And I looked at it and I know just enough evolutionary biology to be dangerous. And I thought, I’m not convinced this actually makes a whole lot of sense. And again, I came to the conclusion I should just put this to the side, at least for now. The reason that changed is that a friend of mine who is quite technical, he is one of the top performing investors in biotech and let’s just call it medicine writ large, when it comes to public equities and other types of investments. He has patents to his name. This is a very smart guy. And he reached out to me via text, this is a good friend of mine, and asked if I’d ever looked at vagus nerve stimulation. And I was like, “No, absolutely not. Is there something interesting there?”

And he said, “I think there is.” And he’d been digging into the literature, that he’s also a former tier one operator from the military. And he had been using — and we’ll get to this because a device is not a device, is not a device. There are a lot of differences. But he had been using something purchased off the internet and had tripled his heart rate variability. And I mentioned the military piece because he has, I’m not sure if this is the right term and I’m sure I’ll misspeak a lot, so feel free to give me a polite smack when I do, but sympathetic overdrive. He would lay down to try to go to sleep, his heart would be racing, his glucose would be spiking, and not from PTSD, but from a lot of other things. And he had tried meditation, and he’s diligent. He will do what he assigns himself to do. 

He had tried all these interventions to improve heart rate variability and maybe we’ll talk about that. But suffice to say, within the realm of, say, athletics and recovery and this, that, and the other thing, often higher HRV is a good thing. And all of these interventions he tried had bumped things maybe 10 percent, maybe 15 percent. And then he used a vagus nerve stimulator for a few weeks and tripled his HRV. And he’s setting personal records week after week. And I thought, okay, could be N of one and placebo, sure, but I should take a closer look. And he sent me an email with a bunch of citations and I started going, as I do, obsessively down this rabbit hole. And I listened to an interview, I want to give credit where credit is due on STEM-Talk.

And they interviewed you and I thought, okay, I should really, really reach out to Dr. Tracey. And then just coincidentally, I was walking through a bookstore, and right in front of my face was your book The Great Nerve. And I thought, okay, universe, not to get too woo-woo, but I got the message, message received, reached out, and also read the book. I recommend everybody read this book. It’s not only from a very credible source, but you are a good writer. It’s very compelling. 

So let’s skip my TED Talk, thank you everyone for coming to my TED Talk, and go straight to the big news. I guess this was literally you emailed me and now it’s big. So what is the big news that literally has just been announced?

Dr. Kevin Tracey: It was just announced that the company SetPoint Medical, which will now be marketing a device to stimulate the vagus nerve to treat rheumatoid arthritis, has received FDA approval. So there’ll be a product launch underway for everything we’re about to talk about in the context of using a medical device that activates an evolutionarily conserved and ancient reflex through which the brain can suppress inflammation when it’s running out of control. We’ve discovered that signals travel from the brain through the vagus nerve. We’ll talk about what the vagus nerve is, but these signals traveling in the vagus nerve are like the brakes on your car. And when you tap those brakes to slow your car barreling down the hill, when this device activates what we call the inflammatory reflex. So you talk about this being a current event, as you and I both know, it’s the front page story in The New York Times today celebrating the successes at SetPoint Medical and kudos to them, to Murthy the CEO, to Dave Chernoff the CMO.

But it’s based, as the article explains also, on 20 years of work by my colleagues and I at the Feinstein Institute at Northwell in New York, and all of which has been essentially replicated by dozens if not hundreds of laboratories around the world. So it’s a rich story of science converging on how the vagus nerve can switch off inflammation that culminates — this morning, as you point out — in a story about patients who’ve already been treated, some of whom had rheumatoid arthritis for decades, couldn’t button their blouse, couldn’t pick up a pencil.

Tim Ferriss: If you don’t mind my interjecting.

Dr. Kevin Tracey: Yeah.

Tim Ferriss: Let’s — 

Dr. Kevin Tracey: I get excited too, Tim, I apologize.

Tim Ferriss: Oh, you get excited too, please, I don’t want you muted. I don’t want muted Kevin, I want excited Kevin, and let’s feed that fire a bit. Let’s talk about, specifically, one of your patients who shows up multiple times in the book, but most memorably to me in the coda, and could you just tell her story in brief? Doesn’t have to be super brief because I want people to understand just how drastic, and this is not going to be true for everybody with every condition, but just how significant the transformation can be.

Dr. Kevin Tracey: Kelly Owens is the patient you’re referring to. I know her story very well. I know her very well now. And when I think of her story as you just introduced it, I got goosebumps again as I do every time. Kelly was a teenager when she was playing sports in high school and developed one night after a trivial injury, a major swelling in her knee that cascaded to a very serious problem that ultimately was diagnosed as Crohn’s disease, an inflammatory bowel disease complication affecting her joints. Kelly spent her teenage years and most of her twenties in and out of hospitals, in and out of wheelchairs. Her father actually gave her a cane for one of her birthdays, I’m not sure which one. Now it’s really important, I should point out, Tim, that these stories are so interesting and compelling because for much of her life Kelly always loved to write. She still loves to write, and she blogged many of these stories in the public domain for much of her life. So all this is out there for other people to read. 

Kelly ultimately became a school teacher, but could not be treated. Her condition couldn’t be fixed from New York to the Mayo Clinic to Hawaii and back. And it culminated when her physician told her and her husband Sean to plan on staying home without children because of all the medications she was on, childbearing would be too risky, and to get used to her life like that. Around that time she saw me on a Huffington Post live internet interview, live stream, and she contacted me and I don’t recall that contact, but I recommended she look into SetPoint Medical, the company that I had co-founded in 2007 to do these clinical trials.

Tim Ferriss: And Kevin, can I pause you for just one second? Don’t lose your train of thought, but also I recall, and fact-check me here, chronic fatigue, having to lay down, elevate her legs, I mean really just had trouble functioning on a day-to-day basis is my recollection.

Dr. Kevin Tracey: Absolutely. People think of — they hear the word arthritis, when they hear rheumatoid arthritis, they hear arthritis. This is not the trivial sports injury you had in high school and now it’s a rainy day and your knee or your elbow is sore. This is a serious condition that affects the whole body. It can affect the kidneys, it can affect the brain, it can affect your heart. Similarly, for inflammatory bowel disease, it’s not obviously bouts of diarrhea and abdominal pain and nausea and vomiting can be disabling, but the inflammation that affects the intestines in inflammatory bowel disease or in Crohn’s disease also affects other organs, the spine, the joints in Kelly’s case, in her arms and legs. And so these are serious disabling conditions. They can cause depression, they can cause anxiety disorders, they can cause chronic fatigue. So that’s exactly right.

Tim Ferriss: All right, so she reaches out to you, you recommend she investigate SetPoint Medical, then what happens?

Dr. Kevin Tracey: My hope was that although I wasn’t optimistic because she lived in New Jersey and the clinical trials were being done in Europe, but now that I know Kelly, I understand how she was able to talk her way into a clinical trial in Amsterdam. She and her husband Sean, sold all their earthly belongings, as she said, everything that wasn’t tied down. Their friends and family through a GoFundMe kind of operation, raised the money they needed to move there for six months. She enrolled in the trial and was one of the first patients to receive an implant. I call it a generation one implant. It was like a cardiac pacemaker under the collarbone, under the clavicle with a lead or a wire that is tunneled up into the left neck where the vagus nerve travels next to the carotid artery.

A couple of weeks later, they’re in Amsterdam still, and Kelly is running a little bit late for her follow-up appointment as part of the clinical trial to get checked out by the doctors in the trial. There’s elevated trains in Amsterdam and Kelly sees a train coming and runs up the stairs to hop on the train so she won’t be late for her appointment. She turns around like where the hell’s Sean? Sean’s at the bottom of the stairs with tears streaming down his face because Kelly, it was the first time he’d seen Kelly run up the stairs in years.

Tim Ferriss: Yeah, she had trouble walking on the cobblestones in Europe —

Dr. Kevin Tracey: She had trouble walking on the cobblestones. 

Tim Ferriss: — not long before.

Dr. Kevin Tracey: Her father gave her a cane for her birthday that she used for many, many years when she wasn’t in a wheelchair and now she’s running up those metal stairs in Amsterdam to catch a train. So she had a remarkable response to this therapy. So a few months go by, and I didn’t know any of this, a few months go by, I get an email. The subject line was, “Thank you for saving my life.” So it was wedged in between a lobbyist in Washington talking about research expenses and my own corporate controller talking to me about my laboratory’s research expenses. So I read Kelly’s email first and I learned her story and that she wanted to thank me in person.

And so I said, “Come on in.” But I also brought, on that first meeting, a couple of my physician colleagues, and we talked at length about Kelly. When she told me that she wanted to help us in the bioelectronic medicine universe, be a patient advocate for this idea, we spent a great deal of time with her explaining that there are risks and benefits to this. People resist change. The world is not ready for something truly new. The world’s not ready to talk about a one-inch device in your neck instead of taking pills and injections. This is going to change everything. And if you’re going to be a leading spokesperson on the patient side of this you may be — people are going to tell you you’re a placebo effect. Tim, all of those things happened.

Tim Ferriss: Oh, I’m sure. 

Dr. Kevin Tracey: The CEO of a major pharmaceutical company at a social event told Kelly, this was many years ago, “If you’re real — ” I mean, how do you say this to a patient? “If you’re real, then everything I’m doing is at risk and I could be out of a job.”

Tim Ferriss: And not with a smile on his face.

Dr. Kevin Tracey: That was a real important day in my life. She hugged me, I hugged her, she cried, I cried. And then she said she had a present for me. And I said, “What’s that?” And she gave me a gift-wrapped cane. It was clearly a cane the way she wrapped it, the handle was wrapped and the cane was wrapped with a big bow on it. I opened the card, which I of course still have attached to the cane. The cane is still wrapped, the bow is still on it, and it sits in the corner of my office. And every day, if I’m having a tough day in the lab or any of my colleagues are, we come down and we look at Kelly’s cane and it reminds us why we do what we do and what we hope can happen when you do science in the hopes and dreams of discovering things that might help people someday ’cause it can happen.

Tim Ferriss: So I want to add a few things to that. What a story. And like you said, some people at the time were like, “Ah, placebo,” but placebo effect, and I’m pulling directly from you here, rarely has durability passed a certain point.

Dr. Kevin Tracey: Right.

Tim Ferriss: But when you’re looking at six months out, 12 months out, and she furthermore — not to say this is more important than anything you just described, but certainly for a lot of people listening, and for me personally, having suffered from what I would describe as chronic fatigue for decades, and we might dig into some of that — she went from basically having a blinking battery empty for her day-to-day to having too much, almost too much energy, which doesn’t say it was a problem, but just kind of running up the stairs, bouncing off the walls, and my God, what a difference. The lives that are lived by the former and the latter, the magnitude of that difference just can’t really be overstated. It’s two different experiences of life. Now I’m going to get all excited and lose my train of thought, but I’m going to scatter shot here for a second.

So just to also lay out a few things for folks. So part of what has been so exciting about this and why I want to pay a lot of attention to it, there are a few things feeding into it for me personally. So one is having some exposure to, I suppose what you might call bioelectric medicine through early, early generation TMS, but then also later accelerated TMS with better hardware, better software, better targeting for things like treatment resistant depression. People can look at Nolan Williams out of Stanford, and just some incredible data there. Focused ultrasound and conversation with Nora Volkow for potentially hitting the nucleus accumbens for addiction. 

And the possibility, not just the possibility, but now a lot of compelling data, for instance, around SetPoint Medical and other forms of vagus nerve stimulation, but I know you might put some of them in quotation marks, to be an option, an alternative to biologics, let’s just say oral or intravenous or intramuscular medication that have a host of really non-trivial side effects.

And for myself, looking at past depressive episodes, looking at as I’ve tried to unwrap that for myself, which is very under control for the last, I’d say 10 years, but looking at the Lyme disease, which I’ve had twice. And by the way guys, that’s not an, oh, I just happened to be lethargic and I’m hunting for a diagnosis, going from quack to quack until I get Lyme disease. Eastern Long Island, look at the CDC map, it is as red as it gets. And thinking of, then, later neuro-inflammation, I have neurodegenerative disease in my family on both sides. So looking at all these things unfold and feeling like this is going to be a way overreach, but there seems like there might be, I don’t want to say unified theory, but there there’s some connective tissue tying this stuff together and started playing with the microbiome. Because changes in gut flora have been associated with, say, depression or animal models of depression or lack thereof.

Also looking at, say, the ketogenic diet or exogenous ketones as a way to reduce inflammation. And when you start looking at all this, and then when I read your book, the reason this ties into your book is, and we should probably define what the hell the vagus nerve is because it’s more like vagus nerves. And you’ll give a great description. I’ll just give a couple of quick samplers and then we can get back into them at any point. But GLP-1 agonists, in the news, Ozempic, Mounjaro, take your pick. But at least in animals, my understanding is if you sever the vagus nerve, those GLP-1 agonists, they cease to exert a lot of their effects that you would otherwise see.

And similarly, people may have heard these stories, which are based on research of microbiome transplants from, say, obese mice to normal/lean mice, let’s just say. And lo and behold, this amazing thing happens, which is the normal mice take on the attributes, the insulin and sensitivity, the weight gain of the obese mice. Fascinating. But if you cut the vagus nerve, that doesn’t happen. So what the hell is going on? And all of these things are interconnected in the most interesting ways. There’s so much left to learn. 

But let’s begin with a definition of basic terms, vagus nerve. How should people think about the vagus nerve?

Dr. Kevin Tracey: When you look online, you’ll find billions of web impressions of vagus nerve. So I’ll just describe it anatomically and functionally first, and then we can cherry-pick where to go. We also should define, if you agree, bioelectronic medicine, because you talked about the connective tissue in the story, and then we should define inflammation.

Tim Ferriss: Let’s do it.

Dr. Kevin Tracey: So the vagus nerve, we call it the vagus nerve, and that’s what it’s called, but you have two of them. So there’s two vagus nerves, like two thumbs, one on each side. Each one arises at about the level of your ear at the base of your brain, travels down both sides of your neck with the carotid artery, and then across the chest into the abdomen. And along the way, it sends out countless branches to all the organs in the chest and abdomen that you don’t think about all day long. Now, within each of those two vagus nerves left and right, you have a hundred thousand fibers. Each fiber is a unique nerve. That’s the part that’s lost almost immediately by 99 percent of the casual readers of vagus nerve stuff.

200,000 fibers, each fiber has an origin in either the body or the brain. 80 percent of them actually originate in the body. They carry information about the organs and your body up into your brain, and then obviously the other 20 percent originate in the brain and they carry information back down to your organs. So again, we’ll try to clear up some misnomers along the way. The biggest misnomer is that you have one vagus nerve, like a solid copper wire. You don’t. You have 200,000 vagus nerves if you treated each one as a wire.

Tim Ferriss: So let me ask if this is a fair visual to paint for people. So imagine that from the base of the ear, roughly, look, this is Tim, the lay person talking. But you have these two thick cables coming down on either side, kind of tracing the carotid artery, and they’re like transatlantic cables just full of a hundred thousand fibers on either side. And they go down and then they kind of branch out like the Mississippi Delta or something like that. And innervate and touch, I don’t want to say just about everything imaginable, but there are 200,000 of these, right? And is that a fair visual to paint for people, or would you modify that?

Dr. Kevin Tracey: No, I wouldn’t modify it at all. In fact, if you go one step further, each nerve ends on either a cell in an organ or on another nerve. So if you put in and those other nerves, those secondary nerves that the vagus nerve ends on, those branch out further. Here’s how I like to visualize it. I think we chatted about this a couple of weeks ago. If I had a solution, if I had a vat of liquid that could magically dissolve all the cells in your body and I submerged you in it for five minutes and pulled you back out again, you would still look like Tim, because every cell in your body is essentially touched by or surrounded by nerves. You’re a walking nerve net. And so, one way of thinking of the vagus nerve, if your body is a walking nerve net, all your organs in your body are encased in a nerve net. Well, then the cable that pulls the nerve net out of the sea is like the vagus nerve. Because it’s connected to the brain, the brain would be like the fisherman operating.

Now, all the signals traveling in these electric networks are traveling up and down the transatlantic cable, the cable connecting the nerve net in your body to the nerve networks in your brain. And we know the identity of 200,000 individual fibers. What we don’t know, Tim, is we don’t know completely, we don’t completely understand the code of the information that’s being transmitted in each of those fibers, right? People talk about the action potentials, which are the spikes of voltage change that travel up and down a nerve fiber. Yes, we can study those. Yes, those are very important. The question is that all the information that’s being transmitted, that’s an area of active research, now that’s very interesting to me. Because on one hand, 200,000 fibers is a lot, but on the other hand, 200,000 fibers isn’t that many. And for instance, we know you can transmit, on the same fiber optic cable, lots of TV shows and lots of radio shows at the same time. So there’s a lot of interesting questions embedded there.

Tim Ferriss: And let’s just say, of those 200,000 fibers, do we know roughly how many affects HRV and cardiac function?

Dr. Kevin Tracey: It’s a much smaller number than people think. We don’t know exactly for sure. We know in mice, in some beautiful work out of Harvard Medical School by Steve Liberles and his colleagues, we know in mice that somewhere around a 100 or 150 fibers are sufficient to control breathing. Now, a mouse vagus nerve has 5,000 fibers, not a hundred thousand, but it’s still a really small fraction of the total number. And so for instance, a few dozen of those fibers control when the mouse gets a full inhaled breath, and another few dozen of those fibers control the process of holding the breath and on down, exhaling the breath. In human beings, for instance, and we’ll come back to this some more, but I estimate somewhere between a 1,000, give or take, maybe 1,500, maybe 2,000 fibers control the amount of inflammation cytokines being produced in the spleen. We can map the identity of the number of fibers going to the heart. Again, it’s a few thousand. So the open question is say we can assign the action of 10,000 fibers on each side. What — 

Tim Ferriss: Yeah, the 90,000 — 

Dr. Kevin Tracey: — are the other 90,000 doing? Yeah, exactly.

Tim Ferriss: I want to keep giving people Scooby Snacks here just because I’m so excited. I want to keep reiterating the potential payoff of doing this the right way. And you mentioned cytokine. I want to double click on that for a second. We don’t need to get immediately into the technical definition of that. I’m sure we will. But people may know that word from, what, COVID-19, cytokine storm, boom, can lead to fatality in some patients. And I suppose I’m curious to know, and just in short form, what happens to cytokine production when you stimulate the vagus nerve correctly?

Dr. Kevin Tracey: It gets turned off. If you stimulate the fibers we were just talking about, it turns off cytokine production quite effectively. And we discovered this by accident actually, 27 years or so ago in the laboratory. We were working on an experimental anti-inflammatory drug that we had developed, and we put it in the brains of animals with a stroke. And the idea was this anti-inflammatory drug in the brain would stop inflammation. And that did happen. And the stroke in the animals was smaller, and we were very happy. But surprisingly and unexpectedly, when we looked at inflammation in the body of those animals with the drug in the brain, they also had less inflammation. And this was a head scratcher. This made no sense whatsoever.

Tim Ferriss: And that’s a head scratcher because the effect should have been sequestered to the brain because of the blood-brain barrier, or what is the reason?

Dr. Kevin Tracey: Either the blood-brain barrier, but also because we had put such small amounts of drug into the brain, there wasn’t sufficient amounts to account for the saturating and stopping inflammation in the body. Well, we discovered years later was that the drug in the brain was actually turning on the vagus nerve. At the time we discovered the signals were in the vagus nerve, it sort of became obvious to me as a neurosurgeon working on cytokines in the lab, it became obvious that if the vagus nerve is turning off inflammation, then it should be possible to stimulate those fibers in the vagus nerve with electrodes and treat inflammation with a device instead of drugs. And so that’s what we wrote on the back of a napkin 27 years ago that led to where we are today. At the end of the day, we understand using techniques like optogenetics where you can make neurons in the mouse brain sensitive to laser light and other sophisticated molecular biology and genetic tools. I can explain to you how the brain through the vagus nerve turns off cytokines and inflammation. 

Tim Ferriss: I’m sorry, Kevin, can I pause you for one second before we get there? And this is something I do not — I mean, I’m going to ask a lot of questions I don’t know the answers to, otherwise the interviews are pretty boring for me. So does this mean that you could use as an acute intervention, vagus nerve stimulation, say, hypothetically in the ER to stop anaphylaxis or to address asthma attacks or sepsis or anything like that?

Dr. Kevin Tracey: Once you understand the basic signals that flow in the vagus nerve to control one aspect of the immune system, in this case, how vagus nerve fibers can turn off cytokine production? You can ask new questions. And let me answer your question by adding a definition because I think it’s a perfect segue. So in order to understand the answer to your question, how to use vagus nerve stimulation and other conditions like asthma and other conditions, you have to back up a bit. You have to say, “Okay, what condition are we talking about?” Let’s look at how the pharmaceutical industry does this. Pharmaceutical industry starts by picking a disease, a condition. Let’s do rheumatoid arthritis first as it’ll become obvious why in a minute. We’re going to look at rheumatoid arthritis, the condition. What’s the molecular mechanism?

Well, the early research with using monoclonal antibodies against TNF show that that helps about half the patients, so that’s the mechanism. So now we can make monoclonal antibodies that hit the molecular target TNF to treat the disease. And now you sell your monoclonal antibodies and after they’re approved for safety and efficacy by the FDA, great, that’s what the pharma industry does. We proposed some years ago, 15 years ago or so now, the idea of bioelectronic medicine as an approach to develop therapies. You begin in the same way, you pick your condition. It’s rheumatoid arthritis. Then you say, rather than screen for antibodies or other molecules to stop TNF, which is the target in rheumatoid arthritis, let’s see if we can find nerves that control TNF production in the body in situ.

If we can find such nerves, then we can build devices to control the nerves, and the devices become the therapy. The bioelectronic medicine story works as long as you know the molecular mechanism, and that’s where people have to be really careful with vagus nerve stimulation. So there are many conditions today that are treated with anti-cytokine therapy, anti-TNF, anti-IL-1, anti-IL-6. Those conditions include things like rheumatoid arthritis, inflammatory bowel disease, Crohn’s disease, psoriatic arthritis, and some other conditions. Most of them are autoimmune conditions. 

When you ask about asthma, and you mentioned earlier, also, depression and some other conditions, I go back to the basic starting point. What is the disease? Asthma. What is the mechanism? Tim, no one knows. That’s a full stop.

Tim Ferriss: Therein lies the rub.

Dr. Kevin Tracey: That’s a full stop for me before saying vagus nerve stimulation will or will not work. I remember one of my mentors and friends, rest his soul, Frank Austen, was one of the leading experts on asthma research for decades, and a few years before he died, I said, “Frank, I think I’m going to do some asthma research.” He said, “Okay, what are you going to do?” I said, “Well, I’ve got this mouse model.” He goes, “Kevin, the last article I wrote in asthma was entitled ‘Mice Don’t Wheeze.'”

Tim Ferriss: I like that. ‘Mice Don’t Wheeze.’ Well, you know what that makes me think of, and we’re going to digress for a second here. But look, we need the animal research and there’s a lot you can do in a metaphorical Petri dish now with synthetic biology and stuff, there’s a lot coming down the pike, but still animal models are super important. But some of the, since I’ve funded so much early research and some later stage stuff with respect to psychedelics since 2015 and psychedelic-assisted therapy, but also basic science, some of the animal models are pretty hilarious, where they’re looking at the head twitching and paw licking. In the case of Barry Jacobs giving LSD to cats way back in the day, decades ago at Princeton. And they’re using, let’s just say, the anti-depression animal models might involve swim to exhaustion.

And then you’re like, “Okay, well, I guess methamphetamine is going to be one of the best antidepressants you could possibly give someone if we’re using that as the proxy.” And so a lot of it’s imperfect. And yes, mice don’t wheeze, right? So maybe, especially if you can’t identify, like you said, it’s the mechanism, you need to be able to at least hold onto some of the variables. 

So let me come to just depression for a second, and I know this is going to be all over the place. It’s like, Tim after too much caffeine and a couple of glasses of wine. Which is not where I am. I did have some pretty good ketone monoesters before our chat though. And I wanted to come back to depression because it’s a subject near and dear to my heart. It’s something that affects a lot of people. And when people experience depression, it can also feed on itself in the sense.

And I speak from experience, where you personalize it, like this is a me problem. This is a character flaw and it’s permanent. And it becomes this loop that can exacerbate the condition. But I’ve long had this suspicion, and this is part of the reason for a lot of the research involvement, is that anti-inflammation or inflammation is potentially at the core of a lot of this. Whether you look at, for instance, a very potent anti-inflammatory effects of certain psychedelics in the phenethylamine class, like 2C-B for instance. Very, very significant at very, very low doses. And when I’m looking at some of my highlights, I have a ton of Kindle highlights from your book, The Great Nerve. I’ll mention it again, pick it up guys. You’ll not be disappointed. But you can induce depression in animal models by causing inflammation.

Dr. Kevin Tracey: And people too, Tim.

Tim Ferriss: And people too. And I want to just read a little bit here. Because we’ve long had, and I think many, many doctors still ascribed to a chemical imbalance theory of say, depression or mental illness writ large, but depression. So this is directly from your book. If an SSRI has helped you or someone you know, that’s wonderful. Large randomized clinical trials of SSRIs indicate they confer some clinical benefit in some patients, which is true. I’ve seen lives changed. Now, whether it’s actually serotonin or not is a separate question, but back to your book. 

But these results, in your personal experience, do not prove causality or confirm that serotonin dysfunction is causing depression. For example, SSRIs may also inhibit inflammation. And then here’s the clutch paragraph that I highlighted. Interestingly, administering SSRIs to animals and patients with inflammation after receiving cytokines in the lab. So you’re deliberately trying to provoke inflammation. Administering SSRIs can alleviate depression caused by these cytokines.

This anti-inflammatory role of SSRIs is little studied and incompletely understood, and I sincerely hope that my colleagues are inspired to investigate it further. So this raises some very, very, very interesting questions. 

And since we last spoke, I have been toying around, and I use the word toy very deliberately, with some devices that I may not continue to use. But I have a variation that a friend recommended to me, very low cost that I’m going to be switching to because I don’t like the neck seizures very much. But nonetheless, I’ll say that the combination of the stimulation, plus, and I realize I’m fussing with a number of variables, intermittent fasting and exogenous ketones. So I am throwing a lot against the wall here. But the addition of the stimulation, which is just a few minutes a day, and we’ll definitely talk about your friend Ulf and his story, because that guy is not wearing a tinfoil hat, right?

Dr. Kevin Tracey: No.

Tim Ferriss: He’s credible. As credible as credible can be.

Dr. Kevin Tracey: Yes.

Tim Ferriss: The stability of my mood is remarkable. And again, I think there are people out there, just if I could throw some folks, not throw them under the bus, but just lay a criticism. There are some folks out there, well-educated but non-scientists, who worship at the altar of science with a capital S, or scientism, perhaps it is. And so they’ll criticize maybe a story like this or the story of your patient and say, “Ah, N of one placebo,” and they discard it that way. But a lot of very critical scientific investigations begin with case studies in the literature. I’m looking at that right now with respect to Alzheimer’s and exogenous ketones. There’s some very interesting stuff out there. 

So this is a very long-winded way of trying to set up inflammation. Inflammation is one of those terms that gets used like it’s specific, but it’s like saying business or sports or art. It’s a big umbrella term. So what is inflammation in the context of what you have studied and observed as a clinician and as a researcher and inventor for that matter?

Dr. Kevin Tracey: Yeah, we’re going to have to do a couple of shows, Tim. 

Tim Ferriss: Yeah.

Dr. Kevin Tracey: Simply put, inflammation was defined thousands of years ago, as the redness, the pain, the swelling and the heat that you feel when you sprain your ankle or get an infected wound on your body. Everybody’s seen it, everybody’s had it, and it’s a good thing. It runs its course and it’s the product of cytokines in part, in other molecules, TNF, IL-1, IL-6, but other molecules made by white blood cells and other tissues in your body. So it’s a good thing when it stops. It’s a good thing because it helps heal the wound, helps proliferate stem cells, helps fight off infection or bacteria that might settle in the wound. And it’s a good thing if it stops. The problem is, we’ll talk about why it stops, but the problem comes when it doesn’t stop. And when it starts spinning out of control, like in Kelly Owen’s case, then it becomes like the army showing up with howitzers to break up a peaceful demonstration or a picket line.

And you have these violent outbursts of inflammatory reactions that cause the problems in rheumatoid arthritis and inflammatory bowel disease and these other conditions. So that’s what inflammation is, that’s what the textbooks say. That’s what everybody knows. That’s what everybody’s taught. That’s what everybody talks about. That’s the anti-inflammatory drugs we have today. Modify the molecules we just talked about, the TNFs, the IL-1s, the prostaglandins. That’s how the ibuprofrens and other nonsteroidals work. And we go down the list on all this. The problem is, when you look in the brain of an Alzheimer’s patient, which everyone who studies Alzheimer’s agrees has some contribution role or cause or contributing factor from inflammation in the brain, neuroinflammation, you don’t see redness, you don’t see swelling. It certainly doesn’t, it’s not painful. 

And the same is true when you look in the adipocytes, the fat cells of an obese patient who has type two diabetes and has significant insulin resistance. They also, sometimes they have a few extra white blood cells in the fat, but it’s not rip-roaring inflammation that you see in an infected wound. They might have an upregulation of some of the cytokines. You might see the upregulated production of cytokines in the brains of Alzheimer’s patients. But it’s nothing like you see in an injured tissue or a rheumatoid arthritis. Some people have come up with new names, meta-inflammation, inflammaging it’s called sometimes when these kinds of changes occur.

Tim Ferriss: Inflammaging.

Dr. Kevin Tracey: Inflammaging. As tissues, age tissues from older people, from the elderly, they have higher levels of cytokines and more insulin resistance. They call it inflammaging. So we really, we do have an issue of semantics. But with that as a limitation, what’s so important about this conversation, in light of everything else we’ve been talking about is, you talked about a connective tissue in these stories and the connective tissue is in many ways inflammation. So let’s back up about what the problems facing the human race are. So 60 million people die on the planet Earth every year. And 40 million of them die from heart disease, stroke, neurodegeneration, Alzheimer’s, Parkinson’s, metabolic syndrome, diabetes, and cancer. So two thirds of the people that die every year on the planet Earth die of those conditions. And that’s according to the WHO. Those conditions all have one thing in common — they’re either caused by inflammation or made worse by inflammation. 

Now, if you look back at what happened in the last 80,000 years, 75,000 years since we came down from the trees and became talking monkeys, in that time period, almost everybody until a hundred years ago, 150 years ago, almost everybody died by the time they were 30. And what happened in the last 150 years can be summarized in a very simple sentence. The human race in the last 150 years removed infection as the leading cause of death. And by doing that, we added 40, 50 years to health span, to lifespan. So the question that wakes me up at 3:00 a.m. now is, “What if we could cure inflammation?” If we cured inflammation, what would that do to the death rate from cancer, heart disease, stroke, and all the conditions that kill two-thirds of the people on the planet earth every year? Look, there’s still people that die of infection. People died of COVID. People die every day of malaria and tuberculosis. I’m not being Pollyanna about this. But if you look at the cold hard numbers, the things that reduced death and increased survival of the human species, all affected the eradication of the threat of infection. Cleaner water, ample food supply, less starvation, all these things converged on better vaccinations, antibiotics, obviously. All these things converged on improving lifespan.

I think something similar will happen maybe in the next 20 years if we can really understand how to modify inflammation. And one way I think we’ll be able to do that is by continuing to dive deeper and deeper into understanding how evolution itself put the brakes on too much inflammation. I said that inflammation is bad when it’s not restrained, when it doesn’t resolve. Well, evolution knew that hundreds of millions of years ago. So from the very beginning of the evolution of inflammation, there’s been evolutionary mechanisms that evolved to suppress inflammation, to tame it, to put the brakes on it. And what we’ve now discovered in the last 20 years is that the brain does this by sending signals through the vagus nerve. So you ask if this idea may have an application and other conditions, I’m convinced it will. It’ll have to be worked through one condition at a time, one mechanism at a time, but I think it’s a really important new idea.

Tim Ferriss: Well, I guess once the devices are out in the wild, let’s say the implant, then docs may have some latitude to also experiment with patients. I mean, TBD. But let me ask. Let me do a few things. I’m going to allow us, if we want, just to abbreviate vagal nerve stimulation to VNS if we want to just make it a little easier on ourselves. Let me ask a question that I asked in our last conversation, and I’m sure is on the mind of a lot of folks, which is, along the lines of, wait a second, inflammation seems to serve presumably some important purpose. So just like some people might label cortisol bad, if you get rid of cortisol completely, you’re going to be in a world of trouble.

So if you are, say, decreasing cytokine production and release by 70, 90 percent with vagus nerve stimulation, could that not have downstream negative effects? How would you speak to that? And I was asking that broadly speaking in our last conversation, but also with respect to weight training and physical adaptations, where certain things — and I’m getting way over my skis here, but like interleukin-6, IL-6 and blah, blah, blah, blah, blah. Temporarily at least, or seem important for catalyzing some of these tissue adaptations. So are you at risk by suppressing cytokines with vagus nerve stimulation? Do we know anything about the side effect profile?

Dr. Kevin Tracey: We know a great deal about the side effect profile, but let me just first unpack the importance of what you’re talking about. So if we know for certain, if you take biologics like anti-TNF or anti-IL-1 or anti-IL-6 that you see advertised at the nightly news every night and on all the NFL football games every weekend. These biologics, the way they’re designed to work is they suppress 100 percent of the activity of the cytokine. So if you take an anti-TNF and your monoclonal antibody in your body bumps into your TNF in your body, it’s zero. And the antibody takes away a hundred percent. It’s yes or no. And because you take away a hundred percent of TNF or IL-1, depending on what drug you’re on, those drugs carry warnings. 

The most serious side effect warning the FDA can give is called the black box warning because they cause immunosuppression, which is exactly what you said. Immunosuppression means, now you no longer have enough immunological activity, or in this case inflammation activity, to fight off infections.

And so the risk is you’ll get things like sepsis or tuberculosis or other conditions, even cancer in some patients because your immune system is no longer fully armed to defend itself against these threats. You ask, does vagus nerve stimulation do that? The simple answer is no. And the reason we know this is because the FDA-approved vagus nerve stimulation to treat depression and epilepsy actually in the 1990s. So we have decades of experience implanting patients with vagus nerve stimulators. 

Now, there have been peer-reviewed studies with 30 years of longitudinal follow-up in a quarter of a million patients. I estimate that millions of patients have actually been implanted with these devices. So we know that there is always a surgical risk of any surgery. The surgical risks of an incision are small, and the surgical risks of nerve damage are actually quite small. Especially with the new SetPoint device, which is only one inch large, completely encased in it. But immunosuppression-wise, we also know that vagus nerve stimulators do not have black box warnings. There’s no evidence after decades of any immunosuppression. There’s no evidence of an increased risk of infection or cancer.

Why is that? Well, it’s because, and here we go back to laboratory studies, and even now in new human studies. When you stimulate the vagus nerve fibers that inhibit inflammation, the ones that travel from the brain to the spleen, for instance, to stop cytokine production, you inhibit, as you correctly said, about 70 percent of the cytokine production. You don’t inhibit a  hundred percent. So the best way I like to think of it is that, if you have an excessive or a dangerous cytokine response, you’re going to produce, call it a hundred units of TNF. And that’s going to be very bad for your tissues and for you. The normal range should be 10 or 20. The vagus nerve stimulation therapy and the SetPoint device is called actually the immunoregulation therapy because it’s only one minute a day. That drives the TNF from a hundred down to about 30 or so. So there’s plenty left to have an appropriate immune response, but it takes the TNF effects from the toxic range that cause rheumatoid arthritis and Crohn’s disease. 

The monoclonal antibodies only hit one target at a time, either TNF or IL-1. The vagus nerve is actually suppressing the whole system. So it’s taking the toxic levels of IL-1 down and the toxic levels of IL-6 down. Those things together, they act synergistically, so the effects are bigger than additives. So if you take them all from the toxic range to the healthy range, you’re going to be a lot better off. And the IL-6 response in skeletal muscle response in weight training, that’s that’s still going to be down in the healthy range. And who knows, Tim? We don’t know enough about it, but it may very well be that the vagus nerve signals that you activate during exercise, like on the sheep running on the treadmill in New Zealand, we could talk about that. Those vagus nerve signals may in fact be contributing to the IL-6 metabolism and turnover that’s going on. We don’t know.

Tim Ferriss: Maybe we’ll get to this, but who knows, because we’re going to bounce around a lot. But also, another aspect of your book that is very compelling is, it includes a discussion of meditation, it includes a discussion of cold exposure, and it includes a discussion of different breathing practices, and all of which seem to have applications to vagus nerve stimulation. And maybe it’s vis-a-vis the vagus nerve, but parasympathetic activation, which might be very counterintuitive to folks. And so for instance, reading your research and reading your book and chatting with you has led me to do something more than I already do, which is, yeah, that’s great, but why? And that’s interesting, but why? Yeah, that’s interesting, but why? Because for instance, I’ve noticed for decades, and I think a lot of athletes have noticed that if you do cold plunges, and I mean pretty much every division one soccer team, for instance, or you name it, is going to do some version of this.

If you do it not necessarily immediately after training, but say you wait an hour or two, and then you do cold exposure in a bath, that it seems to enhance recovery. Now you could say, “Well, ice decreases inflammation.” But then it’s like, is that true? Could there be another explanation? And what you point out in your book, which is something that again, intuitively now makes sense to me, is in the beginning when you’re exposed to cold, and there are studies demonstrating this, whether it’s in cold chambers for hours, which sounds like more misery than I can handle. But suffice to say, initially fight or flight response, sympathetic activation, adrenaline, noradrenaline cetera. And then at some point parasympathetic rest and digest activation. And could it be that the cold is affecting the vagus nerve, which is affecting parasympathetic, that helps with recovery? I don’t know. But I’ve, for instance, always wondered why it is that after a few minutes in a 45 degree bath, I start yawning. There’s a lot of yawning. And I don’t know if that’s direct. Interestingly, that’s also a very common onset symptom after say, ingesting psychedelics like ayahuasca, is yawning.

Yawning, lots of yawning, which is why all of these things seem to touch the hem of the same fabric. So anyway, now I guess that was more of a monologue than a question. 

But let me ask you something that has been also front of mind. Is it true, and I could speculate, but does it seem like within patient populations we’re dealing with more chronic inflammatory conditions? And is that because we have better diagnostics? For instance, you might say, “Oh, there’s an explosion of brain cancer.” Yeah, well, we also have much better tools and people are not dying of maybe things that are easily preventable by antibiotics, so who knows? And maybe it’s not that cellphone towers are causing an explosion of brain cancer. It’s very easily explained in other ways. But do we seem to be contending with population-level greater instances of chronic inflammatory diseases? And, question mark, can we even know that? And then if it appears to be the case, are there any plausible explanations for why that is?

Dr. Kevin Tracey: That is a billion-dollar question for which I’m not an epidemiologist, but I know there’s no easy answer to that one. There are epidemiological studies showing an increase of autoimmune diseases. There are studies suggesting some of these conditions are more common at higher latitudes, and some of them are more common at lower latitudes. 

Tim Ferriss: Interesting, the latitude. Wild.

Dr. Kevin Tracey: Yep. 

Tim Ferriss: I mean, correlation I guess doesn’t prove causation, but it’s interesting.

Dr. Kevin Tracey: It’s very interesting. It always comes down to two things pretty much in biology. It’s nature and nurture. It’s genes and environment. And environment is writ large. It’s the family you were brought up in, it’s your father’s income when you were six. It’s the germs, the pandemic outbreaks that were around your neighborhood when you were 10 and when you were 20, and on down the list. What you eat, what’s in the environment, in the air you breathe, how much microplastics did you consume, knowing it or not knowing it on. 

So genes and environment, and sorting that out in real time is exceedingly difficult, especially when you think about the possibility that some of these things, after decades of study, turn out to be caused by previously unknown infections. One of my favorites is — stories about this, of course, is peptic ulcer disease. Everyone, when I was a kid, and in medical school, we all knew that peptic ulcer disease was type A personalities and — 

Tim Ferriss: Stress.

Dr. Kevin Tracey: — stress. And it’s the patient’s fault. I mean, I love to say, and then it turns out that there’s a bacteria that causes peptic ulcer disease. And when you treat these people with — 

Tim Ferriss: What is that? Not H. pylori.

Dr. Kevin Tracey: H. pylori. Yeah. And when you treat people with antibiotics to eradicate that infection, a large percentage of them get better. When I was a surgery resident, which wasn’t that long ago, I’m not that old. I mean, it was one of the commonest operations in the hospital.

Tim Ferriss: I thought you said communist for a second.

Dr. Kevin Tracey: No, no.

Tim Ferriss: I was like, “Oh, I didn’t see that coming.”

Dr. Kevin Tracey: No, no. One of the most common operations on the OR schedule was gastrectomy for peptic ulcer disease. You never see that. It doesn’t happen anymore because you take antibiotics. So my adage for this thing is, when you don’t understand a disease, think of epilepsy. You start off, you blame God. So they did exorcisms, and that doesn’t work. So if it’s not God’s fault, the next thing you do is you blame the patient. And when you realize it’s not the patient’s fault, in today’s era, oftentimes we find out it’s actually caused, there’s some infectious cause of this thing. And so autoimmune disease may have an infectious cause, it may have an environmental cause. People talk about genetic causes. You inherit some level of risk for autoimmune diseases, but very few of these conditions do you actually inherit the condition. It’s like the old story of the two guys playing golf and get hit by lightning. I’ll ask you a question, Tim. Is that environment or genes?

Tim Ferriss: Well — 

Dr. Kevin Tracey: It’s environment, right?

Tim Ferriss: Good question.

Dr. Kevin Tracey: It’s environment, unless — 

Tim Ferriss: Well, I’m also thinking genetic predisposition to risk taking when they’re like, “Ah, it’ll be fine.”

Dr. Kevin Tracey: Well, it’s easier than that. It’s easier than that. It’s father and son, and they play golf every afternoon in the summer in Florida. It’s like, those kinds of analyses with two people are hard to do the statistics on. When you scale it up to a population, it’s very, very, very difficult to give a simple answer to your question.

Tim Ferriss: Well, to make it even more difficult when we’re talking about H. Pylori, or pylori. I’m not sure how to pronounce it, I’ve only read it. But it seems like, tell me if I’m wading too deep into the deep end of my ignorance pool here. From your book, and this is not a counter argument from your book, but I’ll just read a paragraph that I highlighted. Which, it’s like I’d known this, but it was put very well. “Stress responses also activate your adrenal glands to release glucocorticoids, hormones that stimulate gluconeogenesis, the production of glucose in the liver.” Anyway that could explain, for instance, my friend’s sympathetic overdrive and having glucose spikes at night when he’s trying to go to sleep.

Going back to the book, “This in turn increases your blood glucose levels, elevated glucocorticoid levels as occurs in depressed patients, accelerates lipolysis.” Am I saying that correctly? “The breakdown of fats into fatty acids while suppressing digestion, muscle growth, and reproduction. Glucocorticoids also inhibit the action of insulin, meaning that your cells are less responsive to insulin. This further increases blood glucose, sometimes even to dangerous levels.”

The reason that I’m bringing this up is that if someone is type A, and if they’re subjecting themselves to situations that produce chronic stress response, could maybe all of the things I just mentioned and more make them predisposed to certain types of infections? So that they’re actually, just to complicate the picture further. Where, yes, it’s an infection, but there are certain behaviors or genetic predisposition, or who knows, even jobs that make it more likely that you would be susceptible to such an infection. I don’t know. I don’t know.

Dr. Kevin Tracey: Those kinds of studies are out there, and I think they tip both ways. Some suggest there is an increased risk and some suggest there isn’t. But I think the whole — last time I read about this, I’m not a psychologist, but the last time I probed this literature a little bit, the whole nomenclature of type A and type B personality actually broke down. What was retained is hostility. Most of the things that tracked with the classic type A personality, tracked or correlated to how much hostility. Now you’re back in the psychological domain of the top-down driving. That’s not me.

Tim Ferriss: Yeah. Which is understandable. 

Dr. Kevin Tracey: But it’s interesting. I was at a scientific meeting once when that data was being discussed, and somebody stood up in the front row and said, “Well, how hostile is hostile? How hostile do I have to be to be type A versus type B?” And everybody stared at him like, “Do you hear yourself, man? Relax.”

Tim Ferriss: Let’s talk about — because people are listening. And the SetPoint device, it’s maybe slightly larger than an Omega 3 capsule, or something that’s implanted in the neck, has a number of huge benefits. But then I’m going to ask you about other tools, potentially. I’d say probably the greatest benefit is patient compliance. If you have to remember to take something or do something every day, there’s going to be a lot of breakage in terms of patient compliance. From a purely practical perspective, there are some great benefits to an implant. But could you tell the story of your friend, Ulf, and just describe who he is, and lead into his story? If you’re open to it.

Dr. Kevin Tracey: Sure. On the SetPoint device, the one the size of a fish oil pill, I think we have to talk about that in the context of people who are really sick. These are people who have spent decades, sometimes, disabled. Oftentimes, as you said, chronically fatigued or depressed, or in pain. And these are people who are injecting themselves with drugs. Many of them can’t afford any more of the drugs they have to take, the ones with these serious side effects. There’s a tendency, not by you, but there’s a tendency by some in the short form conversation of these kinds of things to say, “Well, it’s a surgery, and they should do more push-ups or try to do more things to help themselves.” Well, I’ve got to be really, really outspoken on this, because when you meet people that have these conditions, if it was as easy as doing a couple of push-ups or taking a yoga class or breathing differently, they would do it. And if it made them better, they would do it.

These are serious medical conditions. And I think for those kinds of patients, there’s always going to be a need. Because compliance is so difficult, there’s compliance with remembering, there’s compliance with going to the doctors every month. There’s compliance with going to the infusion center, there’s compliance with injecting yourself. Compliance can break down at so many different places. People with serious illnesses, you’re absolutely right. The availability, not for all, but for those that are going to be able to go down that path, to have a small immunoregulator implanted in the neck, that’s going to be very interesting to see what happens. But for people who are essentially mostly well, like you seem to be, and I seem like — 

Tim Ferriss: What an effective mask I’ve created. Yeah. No, I’m generally well, yes.

Dr. Kevin Tracey: And me too, and I feel very fortunate for that. I try to do things that align with what people would call vagus nerve stimulation. Eat right, sleep right, try to get some regular exercise in, try to stay cognitively busy, try to enjoy my hobbies and my family, try to alleviate the stress from my life as much as possible. All the things that we all know we should be doing, and your GP or your primary care provider should be telling you to do every day. All those things, in one way or another that we’ve been talking about, can be said to stimulate directly or indirectly the vagus nerve. But there’s other modalities that people also talk about using electrical devices to stimulate the vagus nerve by applying these electrical devices or TENS units, transcutaneous electrical nerve stimulators, to the skin.

Before I go any further, let me be 1,000 percent clear. These are not vagus nerve stimulators. There’s only two ways to stimulate the vagus nerve directly and specifically. One is to implant an electrode on the nerve, and that’s either with the devices for epilepsy or depression. Or there’s another one now also to increase the rehabilitation outcomes from patients who have strokes. That’s a third one. Or the immunoregulator device from SetPoint. That’s the only FDA-approved way to stimulate your vagus nerve that directly specifically stimulates your vagus nerve. Full stop.

Experimentally, you can do it using focused ultrasound, and we’ve done that in the lab. My colleagues Sangeeta Chavan and Stavros Zanos, we’ve published on this in the peer-reviewed journals. It’s a special ultrasound. It’s very similar to the one that you visualize to see the baby in the womb or the gallstones, but you have a different lens on the probe, and you can focus the energy to target nerves in the body. And we’ve done this in humans to reduce the inflammatory markers in the blood of healthy volunteers by focusing the ultrasound on the splenic nerve, where the vagus nerve controls it. And we’ve done it in animal models of diabetes and obesity, and seen some very interesting effects. Everything else, the transcutaneous electrical nerve stimulation strategy to the neck, to the ear, to side of the head or the face, those are all non-invasive and non-specific, and really shouldn’t be called vagus nerve stimulators.

Tim Ferriss: Nonetheless, some interesting stuff seems to happen.

Dr. Kevin Tracey: Okay.

Tim Ferriss: Everything you said, it’s so true. So on point. I’m also tempted to go to the hockey puck for electric GLP-1 administration, but I’m going to call that a temptation and not an opportunity for the moment. And let’s talk about your friend Ulf, and what happened to him.

Dr. Kevin Tracey: I apologize for the digression, but I had to get that as you — 

Tim Ferriss: No. You’ve got to do it.

Dr. Kevin Tracey: — understand on the record.

Tim Ferriss: You’ve got to do it.

Dr. Kevin Tracey: Now, what about other stuff like a TENS unit? Let’s give a little background there. Anybody interested in auricular therapy, meaning auricle as ear. A-U-R, auricular therapy. And/or auricular acupuncture. Knows that the ancient Chinese acupuncture maps date back tens of thousands of years, and that there are points on the ear that map to various organs in the body. And if you stimulate them with a small needle, a probe, or a small electric current, that you’re supposedly able to affect the metabolism or the diseases of those organs. Everybody knows that’s 10,000 — 

Well it turns out, when I was writing the book, which I discovered that those ancient acupuncture maps of the ear originated in France in 1957 by a doctor named Dr. Paul Nogier, who had a patient who was being treated by a specialist, I think in Corsica. And the specialist was grounded in ancient medicine and was cauterizing a piece of this patient’s ear to treat the patient’s sciatica, the pain going down their leg.

Tim Ferriss: Burning their ear?

Dr. Kevin Tracey: Yeah, burning or cutting a piece of it off. I’m not exactly sure what they did. It wasn’t clear, but there was a little hole on the edge of this patient’s ear. And then he saw another one. And in both times the two patients claim that their sciatica got better. Dr. Nogier was a very clever guy, and curious and careful, and he took a ballpoint pen and he took the ink out of it, and he started probing all of his patient’s ears. And he aligned various conditions in the patient with the parts of the ear that he determined were most closely aligned with the symptoms and signs of the illness. And he made a map. Well, he did this for many, many years in many, many patients, and ultimately published this. And he had presented it at an acupuncture meeting that was being held somewhere in the Mediterranean, and it led to this overwhelming acclaim for him.

And the work was republished in China, which created the current textbooks of Chinese auricular acupuncture therapy based on a Frenchman’s work in the 1950s. That’s where the maps come from. They’re fun to look at. They really are. And especially in light of the story I am going to tell. If you look, you can see where the spleen is and where the bladder is and where the stomach is. They’re very clever.

We were reading, Sangeeta Chavan and I, my lab co-head and I, many years ago. 15, 20 years ago. We were reading about vagus nerve biology and physiology, and we discovered that there was a branch of the vagus nerve that goes to the cartilage of the ear. And when I say the ear, it goes to the cartilaginous part, the part outside the ear canal where you put your finger in your ear, and what looks like a seashell. It’s called the cymba concha. That’s where it gets its name, concha, like shell. Now, this branch of the vagus nerve that goes from that cartilage is very, very special. It’s the only place that the vagus nerve endings go to the surface of the skin, and they are sensory.

That means that when you stimulate the cartilage of the cymba concha, you can activate the fibers that go carrying information into the brain. And they go to the place in the brain called the nucleus tractus solitarius, which is the place where all the other sensory fibers of the vagus nerve go from your stomach and from your pancreas and from your liver. All the sensory input goes to the same place. You can think of it like the router in your house, everything goes into one spot and then it goes back out again. Well, why? Well, it turns out that fish — you like evolution, I heard you say at the beginning. Fish gills are cartilaginous and they’re innervated. And what became our human vagus nerve was one of the branches of the fish’s vagus nerve. And what became our cartilage of our ear used to be the cartilage of the fish gills. So it dragged it with it.

Tim Ferriss: Wow. Wild.

Dr. Kevin Tracey: It’s wild.

Tim Ferriss: I’ll be honest, as a non-biologist, long ago when I was shown these maps, I thought to myself, this makes absolutely no evolutionary sense. Because why would you, if in battle you get nicked by an ax and your spleen explodes? That doesn’t seem to have any adaptive purpose for natural selection. But lo and behold, fish gills. Well — 

Dr. Kevin Tracey: It’s fish gills. But I didn’t say it makes sense, Tim. You said that. I didn’t say it makes sense.

Tim Ferriss: Well, no, I shouldn’t say it makes sense. It’s just like a vestigial architecture.

Dr. Kevin Tracey: It’s definitely vestigial. How much of the architecture, that’s another area that I can’t say for sure we’ve— I actually can say for sure. Nobody to my knowledge has completely mapped out Dr. Nogier’s ear maps to the human body in any convincing neuroanatomical function or neurophysiological way. But it’s still interesting.

With that information, you could think of the cartilage of the ear as a way to drive signals into the brainstem through a branch of the vagus nerve. Immediately people start calling that vagus nerve stimulation. It’s kind of true, because it’s a sensory branch of the vagus nerve. And if you put a TENS unit or your finger on the cartilage of the ear, you are technically stimulating the receptors in the skin that activate the sensory fibers that carry the signals into the NTS. But it’s not the same as — I said it before, I don’t have to say it again. It’s not the same as electrostimulant — 

Tim Ferriss: Hitting the big cable.

Dr. Kevin Tracey: Right. Now, what happens? Now it gets really interesting. A long time ago, an early Russian investigator published a study where he took, essentially, an acupuncture needle and put it in the cymba concha, and put in a little electric current, and showed that he could get changes in heart rate variability, essentially. And this goes back, again, to the ’50s or ’60s. That exact study, to my knowledge, has never actually been replicated the way he did it.

This is the problem. You talked about clinical trials and proving. I agree with you, the case studies are often the most important ways to start, but you still have to do the big clinical trials, randomized controls with the appropriate control population. We’ll come back to that. Now you say, okay, what happens using other technology? Well, it turns out now, I can’t count all the publications that have been done by applying various forms of electric current into the ear and measuring.

Tim Ferriss: There’s a lot.

Dr. Kevin Tracey: You can’t count them all.

Tim Ferriss: There’s a lot.

Dr. Kevin Tracey: You can’t count them all. They come out every day now. And people have done some very sophisticated studies, usually with about 10 or 20 people per study. Usually. But you can look at and you can find brain imaging studies, FMRI. You can find pet studies. You can find far field evoked responses, which looks at the inputs and outputs into various brainstem regions and how the brain is processing the higher network signals. You can see some really interesting stuff. And what comes out of it is lots of different information. That’s the first problem. There’s no single consensus that if you put this kind of electrode in your ear at this time for this many minutes at this much current, you get this effect and this part of your brain in the morning and this part of your brain at noon, and this part of your brain — no one knows.

Put that aside for a second. And I put it in the book, I hope it was clear. What I find striking and interesting, and needing further study, is that if you compare people with electrical inputs to their ear, to people with electrical devices surgically implanted in their neck, there is some overlap in the brain centers that are activated. You see centers like the locus coeruleus, which is the top of the fight or flight chain. It’s the top of the sympathetic chain. You see regions in the basal forebrain, the cholinergic regions, which are linked up to the hippocampus and to other areas that are really important for learning and memory. 

And there is clinical data that patients with implanted vagus nerve stimulators have enhanced neuroplasticity, enhanced learning, and enhanced cognition, alertness.

Tim Ferriss: In another episode of STEM-Talk, which has become one of my favorite new podcasts. There was one of the hosts, I think it’s Dr. Ken Ford, who has served on a number of defense and intelligence-related advisory boards, including advisory roles at DARPA.

Dr. Kevin Tracey: He has a great voice too, Tim.

Tim Ferriss: Oh, his voice is amazing. The Defense Advanced Research Projects Agency is incredible. A lot of the technologies we use every day now originally came out of DARPA, ARPANET, et cetera. He was in conversation, and they were discussing neuroplasticity and learning with respect to vagus nerve stimulation. And I haven’t looked into this yet, but I’ve spent time at the Defense Language Institute in Monterey, and they were talking about using vagus nerve stimulation to enhance language acquisition, and that the effects seem to be durable for months after stimulation. Which, also in your book, just a quick note. Stimulation for two weeks, having an effect on insomnia for two or three months. What could be more interesting? Now it’s just so endlessly fascinating. 

Dr. Kevin Tracey: I have to respond to the DARPA.

Tim Ferriss: Yeah, please.

Dr. Kevin Tracey: I wouldn’t be talking to you right now if it wasn’t for DARPA’s support on this idea in the 1990s, when it was a freaking crazy idea that I’m going to target, with an electrode, the vagus nerve to stop sepsis and cytokine storm. And they said, “Okay, try it. What if it’s yes?”

Tim Ferriss: Yeah, people think of the “government” as just this big, monolithic, slow moving, stupid, inefficient thing. DARPA is an exception. You’ve got to check out DARPA. The brilliance and the innovation that comes out of that, and their willingness to throw a lot against the wall. And it’s science fiction, some of the stuff that comes out of DARPA.

Dr. Kevin Tracey: One of my heroes is actually a national hero. Geoff Ling. Dr. Geoff Ling, retired colonel, founded the biology technology office at DARPA. He used to instruct his team at DARPA, when the guys and gals would come in with the most crazy-ass ideas anyone could ever imagine. “You see that airplane out there? I can make it disappear. I can make it invisible.” And then everybody leaves and they go into Geoff’s office and he says to his team, “What do you think?” And they all say to Geoff, “He’s nuts. It’s crazy. You can’t make an airplane disappear.” And Geoff looked at his team and says, “What if it’s yes?” And that’s where stealth technology came from.

Tim Ferriss: Yeah. That’s so cool.

Dr. Kevin Tracey: And then you say, “Oh, I can still see the airplane.” And then Geoff slams his hand on the desk and goes, “If you can see it, it’s too late.”

Tim Ferriss: Technology to be able to see figures around corners, and that was years ago when I saw a rough description of that. In any case, they are doing lots of really interesting things. I took us off track for a second.

Dr. Kevin Tracey: One more thing. You said another thing; I’ve got to respond. The cognition part of vagus nerve stimulation is also a fascinating story that would require a full long form conversation. But in brief, patients who had epilepsy were implanted with vagus nerve stimulators. This was years ago. This goes back 20 years, or maybe 30. And a bunch of these folks did not get any significant benefit from the therapy, so the device was switched off.

Well, a very clever researcher brought them into his lab and gave them a — I’m not a psychologist, I already gave that disclaimer once. But gave them a cognitive learning test of some form, very simple. And then turned the device on and repeated it, and all their scores went up. It was very dramatic. And when they image these folks in subsequent studies, this is one of the studies that I mentioned before that pointed to the enhancement of activity in the regions of the brain that are really important for intention, learning, and memory. There’s a deep conversation there about neurocognition and vagus nerve inputs to the brain.

Tim Ferriss: I’m fidgeting around in my chair because I get so excited about finally trying to — and I’m not there, obviously. Who am I? I’m a muggle. I have to depend on pros like you. But looking at, for instance, the few things that I have come across that really seem to have very impressive effect sizes on intractable or hard to treat psychiatric conditions that resist frontline treatments with biologics for 15, 20 years. Until, for instance, just a few, some psychedelic assisted therapies, some types of brain stimulation. There are many different types, but let’s just take accelerated TMS as one example for certain conditions. And then metabolic psychiatry or ketogenic diet generally in some variation.

And a friend of mine, I’m going to pull this up. Just yesterday, and it’s not necessarily a new study, but he sent me a link because I advised that he try the ketogenic diet for certain types of overwhelm and anxiety he was experiencing. Because the downside risk is so minimal, particularly if you’re only doing it for a few weeks and your lipid profile’s under control. And he sent me this study. And the title, this is from Cell. This is not from some random person’s blog. And the title is “The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet.” The ketogenic diet was used in the early, I want to say 1900s, for epileptic children. And they’d usually use heavy cream to make it easier for compliance. But had this — maybe it even predates that — this incredible effect on eliminating or reducing the frequency of seizures. And these are kids who might have hundreds of seizures a day.

And I’m looking at this study, and here is just a little excerpt. “Mice treated with antibiotics or reared germ-free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides,” If I’m saying that correctly. “restores seizure protection.”

I literally have probiotics downstairs that are akkermansia from a company called Pendulum, which is pretty legitimate. But, what? Okay, so it’s mediated partially through the gut microbiota. And it’s like, okay, well, then you have the interplay of microbiota with potentially the vagus nerve with this two-way communication channel. And then you look at, for instance, psychedelic assisted therapies. And there’s a lot that we can get into there. But also, and this is finally — and I’m not saying — there’s a lot of nonsense and a lot of navel gazing and crystal waving folks in the psychedelic world. No offense to anyone who falls in that demo. But there were some credible folks, including, for instance, Dr. Andrew Weill, who actually has an incredible history of ethnobotany and is very, very technical. And he lost his allergy to cats after a number of experiences with, I believe it was LSD.

And these anecdotes on the underground, at least, with facilitators who have thousands, maybe tens of thousands of repetitions with patient sessions, the losing of allergies comes up pretty constantly. And then I’m asking myself, well, maybe it’s not the content. Although, I happen to believe the content of these experience matters. But maybe it’s the anti-inflammatory effects. Okay, well, what does that mean? And then, okay, well, maybe it’s having some immunomodulating effect. Okay, well, is the vagus nerve involved? Maybe. It’s not beyond possibility. And then you look at neuroinflammation and the effects of whether it’s different types of brainstem or the effects on, say, inflamed microglia by psychedelics. Like reductions in TNF and all this stuff, TNF alpha have been tracked in the scientific literature. And I just get really, really excited because I can’t parse it all, but it seems like these things all, to use an awkward phrasing, are touching the hem of the same garment in some way.

Anyway, that was a whole bunch of word salad, but I don’t want to lose the story of Ulf, because we’re talking about the maps. We’re talking about the fact that, yes, you should maybe at best put it in quotation marks, “vagus nerve stimulation.” But could you tell the story of Ulf, if I’m saying his name correctly? And maybe comically, one of only a handful of Swedes I know is also named Ulf. It makes me think that maybe it’s the John of Sweden, I don’t know. But who is Ulf, and why does he tie into this ear mapping that we’re talking about?

Dr. Kevin Tracey: Ulf Andersson is a retired professor of pediatric rheumatology at the Karolinska Institute. He practiced there for many decades. And throughout that whole time he also ran a research laboratory that was focused primarily on cytokines, on inflammation and cytokines. As you said before, this is a guy who knows his stuff.

Tim Ferriss: Karolinska Institute is also top tier. They do some of the most fundamental, kind of seminal work related to a lot of stem cell applications, and so on, has also happened at the same institute.

Dr. Kevin Tracey: It’s arguably one of the best medical research institutes in the world, it’s one of the largest in Europe. It’s a major teaching center. It’s a fantastic place. I’ve been there many, many times. Ulf and I have been close friends and collaborators for many decades. And he was diagnosed with a condition that was thought to be a cancer in his bile ducts, in his liver, that required a major surgery called a Whipple procedure, where they remove most of the pancreas, if not all of it, and they remove part of the liver, and they remove part of the bile duct system.

This was a long time ago, but at the time it was a death sentence. The cancer that they thought he had, it turned out to be benign, which was a blessing in disguise, because he had to undergo this major surgery to have this. After the surgery he developed, for the first time in his life actually, he developed intermittent bouts of depression. Serious depression. Which he attributed to excessive inflammation in his GI tract. Which was, through unknown mechanisms, coming episodically and causing this depression. Which, as he talks about in the book, and he’s written about on his own, led to the end of his marriage and was really ruining his life. Well, this was around the time that Sangeeta and I had discovered these funny acupuncture maps of the ear and saw that some people were using TENS units. And we had published a series of papers at that point, understanding how vagus nerve signals could turn off inflammation. And so we said, “What the heck?”

We put TENS unit — an over-the-counter product you can get anywhere — with the electrodes on the cymba conchae, not the tragus, not the lump that sticks out on the side, not the pinna, not the earlobe, but on the cymba conchae. And then, we drew blood on ourselves and on other volunteers, healthy volunteers, and we measured cytokine production.

It’s a little complicated how we did that. It’s not just drawing blood and doing an assay. We actually measured the ability of the white blood cells traveling around our bloodstream to make new cytokines. And when we did those experiments, we could show very conclusively, and we published it all in peer-reviewed journals that in most volunteers, about 70 percent, seven or eight out of 10 people, 16 or 17 out of 20, you could reduce the amount of inflammation that the white blood cells would make if you put this probe in the ear for five minutes.

And at that point, Ulf said, “Well, I think I have an inflammation problem.” Vagus nerve stimulation stops inflammation. If you want to call this vagus nerves, you can also call it transauricular nerve stimulation, because there’s lots of other nerves to the ear, but that’s another matter. And Ulf said, he decided he would try it.

Now, I didn’t treat my friend, Ulf. He decided he would do this. He’s a bonafide physician. He could do what he wants. And I frankly was not very encouraging. I said, “Okay, whatever.” Well, as he writes, and I know this for a fact, I see him several times a year. It turned his whole life around. He added some antibiotic therapy also to treat the bacterial overgrowth in his intestines, which comes with the surgery that he had, the Whipple. But he also uses this TENS unit in his left ear religiously twice a day like brushing your teeth, he says. And he then subjected himself to a fascinating analysis. 

So you mentioned heart rate variability a while ago, and that’s really complicated. But — 

Tim Ferriss: Yeah, the more I try to learn about it, the more I’m like, “Wait a second.” Quantum mechanics or something, I’m like, “Wait, I thought I kind of knew what the hell you were talking about. Now, I don’t.

Dr. Kevin Tracey: Yeah, yeah, if you understand it, then you don’t understand. “If you think you understand it,” like Richard Feynman said, “you don’t understand it,” right? I think we don’t have to get into it now, but suffice it to say if you have a — it doesn’t matter what your wearable is, if it’s a Fitbit or an iWatch or 10 other things that measure heart rate variability, I think this is a hundred percent true. It might only be 90 percent true. They’re measuring different things.

Not because — they all start with measuring the distance between individual heartbeats, which is instantaneous heart rate. They all start with that. But what they do statistically after that can vary dramatically.

I’ve done this, Sangeet and I have done this for a while. We worked on heart rate variability and we made our own devices, and it gets incredibly complicated. And we dropped it because if you miss — if you get a PVC, if you get a periventricular contraction or you get two irregular beats in a five-minute recording, you’ve got hundreds and hundreds of heartbeats. It shouldn’t do much, right? It messes everything up. It changes all the statistics.

So we can’t get into that. Now, however, Ulf was contacted by a guy in Finland who sent him a watch he had invented that recorded heart rate variability as a function of respiratory sinus arrhythmia, which is what heart rate variability is actually, quote-unquote, controlled by.

So if you want to do the experiment, if your listeners want to do this, it’s very easy. Take a couple of big breaths in, two hard sniffs in through the nose, fill your lungs completely, and you’ll feel your heart rate speed up a little bit. And then, breathe out slowly for seven or eight seconds. 

That increase in heart rate during inspiration is partly due to the change in pressure in your chest cavity, your thorax. As your diaphragm drops and you increase the volume, the pressure has to decrease. And then, as you exhale slowly, you’re actually increasing the pressure in your chest, in your thorax because you compress the volume.

Those changes in pressure all activate sensory signals in the vagus nerve, which go into your brain, which accelerate or decelerate your heart. Why? Well, because when you inhale, you want to accelerate your heart and exhale, you want to decelerate your heart. That’s the optimal physiological linkage. That’s the optimal physiological mechanism to maximize the amount of oxygen in your blood.

Now, this guy in Finland invented a way from the EKG of looking at the changes in the size of the QRS wave as an indicator of the heart shifting left and right, which also happens when your diaphragm goes down and comes back up. And so he found a way to measure respirations from the EKG and link it to the instantaneous changes in heart rate.

And what his HRV indicator is, in this method, is actually a correlation between the overlap between respiratory sinus arrhythmia and the breathing cycle and heart rate variability in the cardiac cycle. And that’s how you optimize oxygen uptake and delivery. It’s really cool, right?

Tim Ferriss: Yeah, it’s cool.

Dr. Kevin Tracey: And it’s pretty sophisticated stuff.

Tim Ferriss: So he ships the watch over to Ulf? Or — not watch. Device? Yeah.

Dr. Kevin Tracey: So Ulf puts it on and he’s got a terrible correlation between his heart rate variability and his respiratory sinus arrhythmia until he does his vagus nerve stimulation, and then it got a lot better. Now, that’s a pretty good experiment. It is an N of one — 

Tim Ferriss: Yeah.

Dr. Kevin Tracey: And somebody, I’d love to see somebody repeat that on 50 people. But it’s still hard to explain because he does it over and over again on many different days and many different conditions. The real kicker is during COVID, my colleagues and I at Northwell did a clinical study. We heard of results out of China, out of Wuhan actually, where patients taking famotidine, the antacid, were significantly protected against some of the lethal complications of COVID.

We actually did clinical studies of this drug. You can buy it for pennies over-the-counter at Amazon and Costco and CVS and everywhere. It’s a safe antacid. And it turns out, we did the clinical studies in Northwell, and we did, then, laboratory studies in my lab. It’s a pharmacological vagus nerve stimulator.

Tim Ferriss: Really? What was it called again?

Dr. Kevin Tracey: Famotidine is the generic name. It’s got a bunch of brand names, including one of them is Pepcid.

Tim Ferriss: No kidding.

Dr. Kevin Tracey: Yeah, you read about it, it will blow your mind, actually.

Tim Ferriss: Wow. Okay.

Dr. Kevin Tracey: So, when Ulf combined, this is the end of the story. When Ulf combined the famotidine with the TENS unit in his ear, he gets 100 percent overlap. He looks like a 21-year-old kid with this overlap between respiratory, sinus arrhythmia and heart rate variability. He’s written about it. He’s published his own personal recordings. And it’s a remarkable story.

And it’s remarkable, not because it’s a story of one, but because let’s go back to what we said before. The FDA-approved vagus nerve stimulation for the treatment of depression decades ago, and it’s used a little bit more in Europe than it is in the US. In the US, it’s not routinely covered by insurance payment. So there’s been tremendous resistance to applying this. It helps about half the patients.

Now, once again, like we said with the rheumatoid arthritis, let’s be concrete about this. Let’s not be the standoff folks who say, “Well, it only works half the time. It shouldn’t be used.” Well, in some of the people that it’s worked in, they were suicidal and now they’re not.

Tim Ferriss: Yeah.

Dr. Kevin Tracey: What is that worth?

Tim Ferriss: Yeah.

Dr. Kevin Tracey: In some of the people it’s worked in, they’re back at work taking care of their kids, taking care of the family. I think that it shouldn’t be — we should be doing it or not doing it based on the data we know so far. There should be a screaming call that we should be diving down into. We don’t know the mechanism, Tim.

Tim Ferriss: Yeah.

Dr. Kevin Tracey: We don’t know why Ulf got better. We don’t know why half the patients with depression got better. I think somebody should do a really simple study. We should segregate the patients into some sort of inflammatory groups, risk groups or activity groups with depression, and treat the ones with the most inflammation with the vagus nerve stimulation and see if they get better because you’ve stopped their inflammation. And the other ones have depression from another etiology, another cause, another factor. These are the important questions.

Tim Ferriss: Don’t you work at a place with a bunch of scientists? What’s required for something like that to happen? Does it just require a Scrooge McDuck to fund the study? I mean — 

Dr. Kevin Tracey: I’m the president of a great organization with great scientists. And yes, I am, and there is and will be more great work coming out of our place. But one place can’t do it all alone.

Tim Ferriss: Yeah.

Dr. Kevin Tracey: This is a call for everybody to get interested.

Tim Ferriss: It’s also potentially a call for some interesting distributed, I guess we could call them studies. They’re not going to be RCTs. But hey, something is better than nothing if it has recognition of its limitations. For instance, the people who manufacture WHOOP bands, the people who make Oura Ring, I mean, they could potentially put out a call to customers to try to do some type of distributed study.

Of course, you might be dealing, well, actually, you’re not going to be dealing with self-reporting. You’d be dealing with self-reporting perhaps in documenting, using a “Vagus nerve stimulator.” But the data is going to be available to the company vis-à-vis. Maybe it’s anonymized in some fashion, but the patients could make their actual Oura or WHOOP band or Fitbit data available to the company if it’s not already available.

So, that could be pretty interesting. I recall actually, WHOOP, I believe doing something like that with veterans who were on a standardized dosing of, I think it was microdosing of psychedelics looking at impact on HRV or potential impact on HRV. HRV fluctuations associated, let’s put it that way. 

Dr. Kevin Tracey: You mentioned before depression, serotonin inflammation. Should we pick up on that for a second?

Tim Ferriss: Yeah, let’s do it.

Dr. Kevin Tracey: As you read the excerpt before, there is evidence that some patients with depression get better with SSRIs and some patients don’t. And there’s also evidence that SSRIs can even make people who have known inflammation or experimental inflammation gain some benefit.

There’s also information that SSRIs in experimental conditions, clinical studies and experimental studies in the lab, can actually reduce inflammation. What we have to agree on is we don’t know what causes depression. And if we knew what caused depression, I think our chances of fixing it in more people would be better.

Tim Ferriss: Well, also, depression is, I mean, in my mind, could be like “Inflammation,” right? There could be many different species of depression or many different causes. I don’t know.

Dr. Kevin Tracey: I think there are. I think you’re right. And I think that’s not been parsed out very well yet because the focus has been this sort of excessive focus on serotonin as the hypothesis that has to be dealt with. And there’s lots of reasons for that, that we won’t get into now. But what I do like to raise again as a call to action, if you will, and a message of hope is we know that inflammation produces depression in animals and in people. It’s to the point now, there are some inflammatory molecules that are used to treat some conditions, some forms of cancer, for instance.

And when patients are signed up and they’re going to receive these therapies, this administration of cytokines that as their therapy that are known to cause depression, they’re often given a prescription to go see the psychiatrist to go on the SSRIs before they go get their therapy.

So we know inflammation causes depression. We don’t know completely how. There’s overwhelming evidence from many labs, including my own, that the presence of inflammation in the body activates signals that travel up, you guessed it, the vagus nerve. And so you can take a mouse, for instance, and inject it with IL-1, and the mouse will run in the corner of its cage. It’ll huddle up, it will look like it doesn’t feel well, like when you have the flu. It will avoid eating. It will avoid sex. It will avoid playing with toys in the cage. It looks depressed.

If you cut the vagus nerve back to your topic before, if you cut the vagus nerve in those mice and give them IL-1, they don’t get sick. They don’t get depressed. And so it puts the question, and the mind body experts and the far east religious dogmas focus on what we said before, the brain networks and the body networks are connected. And what I said before is the vagus nerve is a principal connector.

So if you have disruption of inflammation in the body, which you’re not even, maybe nothing hurts in your body, but your brain knows the inflammation is there, we call that interoception. It’s the subconscious sense that your organs are sending information about their status to your brain. If you have inflammation in your body, does it cause depression? That’s an important question.

Tim Ferriss: Yeah.

Dr. Kevin Tracey: Because maybe that’s why those patients who do get better and go on YouTube and type in some videos of these depressed patients whose lives were turned around with vagus nerve stimulators, it will bring a tear to your eyes, some of their stories. And if you look at those people who have benefited — and Ulf with his TENS unit in the ear.

Tim Ferriss: Quick question, has Ulf published his setup? Is that something that people can find online if they wanted to experiment with five minutes twice a day of auricular stim?

Dr. Kevin Tracey: Yes, yes, he did. He published it in a peer-reviewed journal that I believe is open access. If you Google his name, Ulf Andersson, with two Ss, Andersson.

Tim Ferriss: Good, good old Swedish last name. I will link to that in show notes. We’ll find that and put that in the show notes for everybody.

Dr. Kevin Tracey: Oh, I can send it to you for the show notes.

Tim Ferriss: Okay, perfect, perfect. We’ll do that. And I interrupted your train of thought.

Dr. Kevin Tracey: No, that was the end. I just want to call the question out to my colleagues that we should study the influence of interoception, the presence of inflammation in the body being sensed by the brain in causing depression in some patients, and can we treat that with vagus nerve stimulation? Is that why it works in the 50 percent of the — why 50 percent? Isn’t that kind of a funny number? It works.

Tim Ferriss: That is. It’s too clean, right? It’s too clean. Yeah, I got scammed recently on my credit card at a gas station, and it was $175, and I was like, “That’s too clean. That’s absolutely a scam charge.” Plus, I know gas is expensive, but it’s not $175. But in any case, yeah, when the numbers are that clean, you’re like, “Wait a second here.”

Let me ask you, this is out of personal curiosity, and I was goofing around going all over PubMed, which is sometimes a dangerous business when you’re a muggle. But it seems like there are some interesting data around acupuncture in the ears and fertility or pregnancy. And I know you don’t like to speculate, but there may be people who have looked at this closely. Is it plausible that that is mediated by a vagus nerve stimulation?

Dr. Kevin Tracey: The simple answer is, yes, I don’t like to speculate.

Tim Ferriss: But I’m just saying mechanistically, would stimulating the vagus nerve have some downstream, possible downstream effect on the ability to conceive or anything like that?

Dr. Kevin Tracey: I don’t know the studies that you’re referring to. I really don’t.

Tim Ferriss: Yeah.

Dr. Kevin Tracey: And I don’t know if acupuncture in the ear would stimulate the vagus nerve to stop inflammation. I know that what I did with an electrical TENS unit can reduce inflammation in the bloodstream of healthy volunteers. I can answer the question in the context of, are there some conditions in the abdomen, whether in the ovaries or the uterus or the fallopian tubes where the presence of inflammation would be restrictive or would make getting pregnant more difficult?

The answer to that’s a simple, yes. I mean, now the question is, if we had ways of selectively reducing that inflammation in the context of getting pregnant, if you could specifically reduce that inflammation, would you increase the chances of getting pregnant? Well, yeah, it’s quite logical. It’s plausible. Can vagus nerve stimulation do that? To my knowledge, nobody knows.

Tim Ferriss: I was just, again curious. And you know what? The first time this kind of — I’m probably using this term incorrectly, but sort of the homunculus on the ear came up in this podcast was with Martine Rothblatt, who I think has a quote on your book. Am I making that up?

Dr. Kevin Tracey: Martine is a close friend and another — 

Tim Ferriss: Also, phenom, what a wild background and such a polymath.

Dr. Kevin Tracey: Martine’s another national hero. I mean, she’s a satellite launcher. She’s a satellite communications expert. She’s an accomplished pilot including flying her own battery powered helicopter and setting land speed records and distance records, and she’s a good friend, and the CEO of United Therapeutics. Yeah, Martine’s wonderful. We talk a lot about this stuff.

Tim Ferriss: All right. So I’ll leave a shout-out if people want to get to know Martine, definitely suggest my interview with her. And I wanted to come to something that you mentioned at the end of your STEM-Talk interview. And I really don’t have context on this, but it’s of interest to me because I have for the last few years had chronic low-back pain, which is if you want to wander into the Bermuda Triangle of hand-wavy imprecision in at least pain diagnoses or orthopedics, low-back is a good place to go.

And what I have figured out, there are certain things that help and putting aside the biomechanics and strength training and so on for a moment, I know that anti-inflammation helps. There seems to be an inflammatory component. So, whether it’s through applying cold or taking oral anti-inflammatories or injectables for that matter, it suppresses symptoms. I know that, and I’m reading a number of books, Lorimer Moseley and his co-author have, actually, a very interesting book called Explain Pain, and it relates to this piece that came up maybe, which is why I wanted to talk about it. Because sometimes, like you said, the response to the equivalent of a picket line in your body is the entire Navy showing up with rockets blazing and it’s a severe overreaction.

So this relates to Professor Rolls, and I guess I’m going to try to word this in a way that makes sense. But how specific molecules inform memories/engrams in the brain and the implications of that? Could you just unpack that for me because you guys didn’t really get into it in the STEM-Talk? But I was like, “Wait, wait, wait, wait,” I want to hold onto this because it seems very interesting and it might somehow be relevant to me. It might not be. But could you just explain what I’m very clumsily trying to evoke or I guess elicit from you?

Dr. Kevin Tracey: Yes, I would love to. So let’s start with the picket line. The picket line in the low back situation. And I’ve also had on-and-off sciatica from a herniated disc in my back with pain down my leg, so I can relate to this.

Tim Ferriss: Yeah.

Dr. Kevin Tracey: So, in those instances, you have something in one of the joints of your back or potentially a fragment of a disc that’s pushing on a nerve causing pressure on the nerve, which sets up a cycle, which would be the picket line, right? There’s some injury there. There’s some injury, injury to the nerve, or there’s some injury in the joint, and that’s the picket line. It shouldn’t be a big deal to the human body having evolved over hundreds of millions of years. But in some people, not all, if you look at MRI scans, right? Everybody else’s back looks just like yours, right?

Tim Ferriss: Yeah, they look all messed up.

Dr. Kevin Tracey: They all look the same.

Tim Ferriss: It’s just like you get wrinkles on your face, your spine starts to look pretty funky.

Dr. Kevin Tracey: Exactly.

Tim Ferriss: So, I’ve got arthropathy. I’ve got the right foraminal stenosis at blah, blah, blah, blah, blah. But — 

Dr. Kevin Tracey: So does everybody else.

Tim Ferriss: Yeah, you can look at hamburger meat on an MRI of a back, and they’re asymptomatic.

Dr. Kevin Tracey: Right. So why does your back hurt and somebody’s MRI scan would be indistinguishable from it doesn’t hurt? Well, if you could maybe pinpoint the position on your MRI scan. Now, the question is different, right? Now, the question is, why is your body sending the Navy with rockets blazing to the picket line in your back, but not the guy next door?

Tim Ferriss: Yeah.

Dr. Kevin Tracey: Well, that is the question. So how can we connect that to two things? One to — because Ulf’s back pain got better. Two, by the way, he had injured his neck in a sailing — he was a world-class sailing champion. I don’t know if that made the book or not.

Tim Ferriss: I don’t think that was in there. I love this guy.

Dr. Kevin Tracey: He and his brother Jan Andersson won the European World Championships in the J class.

Tim Ferriss: Of course they did. Of course they did.

Dr. Kevin Tracey: In the 1960s. And, of course, ABBA sent them to the World Championships when they were in New Zealand or Australia or something, and they competed in the Olympics at UCLA at the L.A. Olympics.

Tim Ferriss: Wow. Wow.

Dr. Kevin Tracey: Anyways, his back got better. And so, the question is, why did his back get better? Because the signals from the ear to the brainstem went down the vagus nerve to the spleen and reduced the turnover of the inflammatory cells. Well, that’s a definite maybe. And what we know from very careful experiments in animals and some experiments in humans is that when those vagus nerve signals end up in the spleen, they switch the white blood cells.

Now, the spleen gets 20 percent of cardiac output. So all your white blood cells are racing through the spleen all day long. And when they pass through and pick up this nerve signal, they switch from a state called M1 to M2. M1 macrophages and monocytes, white blood cells, they’re the Navy shooting guns full blazing that you said. M2 are the doctors and nurses in the ambulances who race to the scene to heal.

Tim Ferriss: Mm-hmm.

Dr. Kevin Tracey: And so that’s an important area that a lot of people are chasing. And that’s in the context of therapy that we’ve been talking about. That’s probably how it works in rheumatoid arthritis actually, is the signals are switching the white blood cells as they pass through the spleen. So, when they go to the elbow or the knee or the hand, they tend to heal the cartilage of the joint.

Tim Ferriss: That’s M2 instead of M1?

Dr. Kevin Tracey: It’s M2 is better than M1. Exactly right. So, yeah, M1 to M2. So, that’s a take home point. That’s a simple way to think of how you get a nerve, the vagus nerve stimulation, which doesn’t go to your elbow and it doesn’t go to your wrist or your — but that’s why, they probably get better is because it changes the white blood cells that are going to the scene.

So what else is happening? Well, when that inflammation settles in, say, the colon, Asya Rolls, in a brilliant, I think one of the most important scientific papers in the field of what we call neuroimmunology, and maybe in the last 25 years, she discovered that what’s happening in the inflamed tissues in the colon in this case is actually forming a neural network in your brain, which you can think of as a memory. It’s called — neuroscientists call it an engram.

Tim Ferriss: So, that also be like a phantom limb. Would that be a, or is that a different thing? I don’t want to take us off track.

Dr. Kevin Tracey: No, it would be similar to a phantom limb, but it’s more concrete. And I’ll tell you why. And this is what’s so amazing about it. So, neuroscience has studied memories and engrams for many years and using a method that we call trapping technology. And so what you do is you have a genetically engineered mouse, a mouse with special genes that you can put in when it’s an embryo, and the mouse grows up with these genes.

And now, when you do something to the mouse, if you co-administer, say you give the mouse a drug, or you give the mouse inflammation, when you do that, at the same time, you give the mouse a drug that activates these special genes that turn the neurons red, for instance. But only the active neurons.

So, the neurons that get activated by the presence of, say, colitis inflammation in the bowel, they turn red and they stay red. So you can study them later, even weeks and months later. And that’s exactly what Professor Rolls did. She used another very sophisticated trick to take what’s called stereotactic injections, injecting virus particles into specific parts of the brain that she had mapped from looking at the red neurons. So she knew these are the neurons that get activated by colitis.

So she’d had the mice and she let them recover from colitis, and then she injected the virus into those neurons and reactivated. Now, just the neurons, not all the neurons in the brain, just the ones that remembered the place of the colitis, and they got colitis again.

The changes in the brain neurons. I call it a neural network. She does too. I mean, we all call it an engram or a neural network. There’s lots of neuroscientists have talked about this on lots of podcasts, but they call it the Jennifer Aniston neuron or the Santa Claus neuron. I’m a recovering neurosurgeon, right, Tim?

So you can do brain surgery under local anesthesia, and this is done a lot of times for epilepsy surgery, for instance, when you want to make sure that you don’t injure any part of the brain involved in speech. So, you can be talking to the patient during brain surgery. Now, you can put electrodes in various parts of the brain and ask the patient what’s happening. And there’s a famous story of a patient, “Well, I just saw Santa Claus,” or “I see Jennifer Aniston.”

And so it’s euphemistically, people call that, “Well, you have a Jennifer Aniston neuron.” Well, you actually don’t have a Jennifer Aniston neuron because you could put an electrode in another part of the brain and you say, “Well, Friends, the TV show,” and Jennifer Aniston’s neuron will light up in that because they’re part of a network.

Tim Ferriss: Right. It’s a constellation that is recognizable by the brain as — 

Dr. Kevin Tracey: It’s a constellation. Exactly right. Well, nobody before Asya’s studies, nobody thought that a constellation in the brain would recognize inflammation in a way that would not only remember the effects of it, but could then reactivate it.

Tim Ferriss: Not to interrupt, but since every podcast I do is self-interested in some way, is there a way to delete, control Z, those constellations so that you don’t have this hair trigger response to triggering colitis or low back pain response, right? And in this book that I was mentioning, Explain Pain, they talk about how surfers in instances, sometimes when they get their leg bitten off by a great white, they report it as a thump. It wasn’t painful. Whereas you get a paper cut and it’s excruciating, and there’s so much variability.

So is there a way to deactivate a constellation or overwrite it, or I guess fix my fucking low back pain is the short answer, without taking bottles and bottles of Aleve?

Dr. Kevin Tracey: This is about the third time in this chat we’ve had that I wanted to offer you a job in my lab. You ask all the right questions. We could do the experiments if you come in.

Tim Ferriss: Well, you’re not that far away. I mean, don’t threaten me with a good time.

Dr. Kevin Tracey: The simple answer is that’s what we want to do. So you might not have to remove the whole network. You might just have to disrupt a little bit of it.

And the question is, can you disrupt it with a molecule that targets selective neurons? That’s tricky, but not impossible. You have to figure out what the neurons are, figure out what the receptors are, figure out what’s unique. Then you have to design a drug to do that. That would be one approach.

But the approach I like, and again, I’m a recovering neurosurgeon, so call me what you want, but there are millions of people walking around with deep brain electrodes, millions. And it sounds like this horrendous, terrible thing, but it’s not. The electrodes that people are putting in now, whether it’s Neuralink or somebody else, I mean, they’re smaller than a human hair. And they go in and they don’t injure blood vessels and sometimes they don’t even injure neurons. They go next to the neuron. You could imagine a time in our lifetimes, I hope, when, if we knew how to target those neurons or map them in advance, that you could put these electrodes in and inhibit them. And yeah, that is the right question. I’m dead serious.

Now Asya’s paper has been out a couple years. I said before, I think it’s one of the most important studies that I’ve read in many years, and we have, of course, pursued it. We’ve been asking questions, my colleagues and I, Sangeeta Chavan and Okito Hashimoto and Eric Chang, we’re asking a very simple question. Can we make engrams, memories, neural networks in mouse brains, of specific cytokines?

And we’re writing the manuscript as I speak, and the answer is yes. We can show that when you give a mouse TNF, which causes a sickness behavior, it looks like it has the flu, and then a bunch of other metabolic things that are specific to TNF and map an engram, we can see where the neurons in the brain are and see what they do, when we do the same experiment with IL-1, which also gives a sickness response, but has a very different sort of metabolic physiologic, you can separate them. They’re unique. TNF and IL-1 are different. The physiology is different. We see a different neural network.

So now it’s complicated because how many cytokines are there and how many physiological states? I think the brain, a human brain has what a hundred billion neurons give or take, and trillions of synapses. So it’s more complicated than we think it is, but I think it’s accessing, processing, and potentially storing all the information that we haven’t even begun to imagine yet. And that’s what this data tells me.

Tim Ferriss: What are the possible implications of identifying the constellations? I just keep thinking about stars. It doesn’t take much to screw up Orion’s belt, right? If you move one or two things around, you could disrupt that engram, so to speak. What are the implications of identifying the engram signature of TNF-α IL-1, et cetera?

Dr. Kevin Tracey: What are the implications of it?

Tim Ferriss: Yeah, well, how would that translate or might it translate to some type of clinical practice?

Dr. Kevin Tracey: Well, I think you could literally, if you knew where to put the electrodes into the brain, you could have an electrode in the brain that communicates with an app on your iPhone, and you could dial it to up regulate or down regulate your inflammatory response to a specific cytokine or condition in a specific part of your body. Yeah.

Tim Ferriss: Yeah. That’s wild.

Dr. Kevin Tracey: It is. You said it right. I mean, people used to think it was impossible to track an incoming missile from the moon, but now they know how to do that. And the best example I like, and you’re better at this than I am, but someone explained the analogy I like the most. If you look at a TV screen with all the pixels and you see a picture of the Alps, you can’t possibly pick out the black square or the altered colored square. But if you swap that one square and make it a really bright color or a really black color, you actually can see it. It’s about subtracting, right? It’s about subtracting to pick out what you don’t know.

In order to do that in humans, there’s been all this rush to do brain imaging and brain anatomy. We still have a long ways to go because to my satisfaction, as someone who thinks about systems interacting and biology, we haven’t put enough emphasis on function.

Tim Ferriss: Yeah. 

Dr. Kevin Tracey: And I think even for heart rate variability, you and I can’t talk about heart rate variability ’cause we don’t know enough about the individual functions of the individual wiring diagrams.

Tim Ferriss: Yeah. And also, we can talk about science and studies and so on, maybe separately over a glass of wine or something, but sometimes the imaging tail wags the dog also for a host of reasons.

Dr. Kevin Tracey: Yes, yes.

Tim Ferriss: You get these beautiful pictures and there’s maybe some status associated with getting a bunch of money to play with the latest toys, and then you can slice and dice the data to create all these different publications. There’s an allure that I think can sometimes lead to an overemphasis on the imaging, which is not to negate some really, really incredible applications of the imaging, but I think what you said carries a lot of weight.

Let me ask, because there will be people listening who are curious about this. Cervical TENS units. So we talked about the transcutaneous auricular stimulation. There are devices, including some that are FDA-approved for, say, I believe cluster headaches and/or migraines, I can’t recall exactly, that are neck-based and could be applied to one side, could be applied to both sides, but effectively, supposedly, tracking or stimulating the vagus nerve where it would correspond to your pulse, let’s just, say carotid artery or arteries.

And there are a number of, you can find a number of publications on PubMed that talk about the data, but what might be the, if in fact they are doing something that is beyond placebo effect, what might the mechanism of action be? And you can start wherever you like. I’m just curious about the cervical devices because they’re floating around out there, and I’ve seen at least a few studies and I’m like, “Huh, okay, well, what the hell is going on here if in fact there is a signal instead of just noise?”

Dr. Kevin Tracey: I think it’s important to say that when you dive into these kinds of questions, there’s lots of factors. So the first is, can you afford to buy lots of devices and try lots of different things? That’s one approach. And second, do you like self-experimentation? That’s another approach. A third is, well, always check with your doctor first ’cause there are some things you probably shouldn’t do around the area of your neck. If you have carotid stenosis, you don’t want to put any pressure on your carotid artery. If you have cervical stenosis, you don’t want to turn your head certain ways.

Tim Ferriss: For sure.

Dr. Kevin Tracey: Check with your doctor. So those are actually important disclaimers. That’s not a joke. People should check with their doctor before they do these things, unless of course what they’re doing is FDA-approved. And some of these devices, most of them not, but some of these devices have been subjected to FDA approval.

In the context of putting electrodes on your neck, there are some FDA-approved devices that are called vagus nerve stimulators, and they are essentially TENS units. They deliver pulses of electric current, spikes of electric current, usually between 20, 30 hertz, usually on the order of milliamps. And you know it’s working because you feel a buzzing or a tingling. And when you put it on your neck, usually you know that the current is spreading around through the skin and through the nerves of your neck, because your platysma muscle, the muscles of facial expression in your neck will twitch, or your lip will twitch.

Tim Ferriss: Pull your lip down. You can make some goofy faces.

Dr. Kevin Tracey: That’s happened to you, right?

Tim Ferriss: Yes.

Dr. Kevin Tracey: Yeah. So that’s evidence that the electric current is activating lots of nerves and lots of muscles. Now, time for a slight digression. The carotid artery is encased in a sheath with the vagus nerve. So to get to the vagus nerve, you have to go through the skin, through the platysma muscle, through the layer of subcutaneous fascia, through the sternocleidomastoid muscle, which is that big thick strap muscle in your neck, thicker in some than others, but it’s there, down to the carotid sheath, maybe through another layer of fascia, through the carotid sheath, and then somehow either around or through the carotid artery.

Tim Ferriss: Right. So it seems like the TENS unit is not going to hit the vagus nerve.

Dr. Kevin Tracey: Engineers I’ve spoken to at length about this say, and I said it very politely and clearly in the beginning of the show, the only way to directly stimulate the vagus nerve is to put an electrode on the vagus nerve. That’s not this. You’re putting an electrode on the skin. Or to use focused ultrasound, which would penetrate all those tissues and could be focused to the vagus nerve in the neck. But those devices are not available for us to use at home. So your question was, could it work anyways? It’s FDA-approved to treat migraine, and the answer is — 

Tim Ferriss: Well, my question was what the hell might the mechanism be if it’s not actually getting through all that stuff to hit the vagus nerve?

Dr. Kevin Tracey: I have a very good answer for you.

Tim Ferriss: All right. Collective delusion and placebo — 

Dr. Kevin Tracey: No, no, no.

Tim Ferriss: Mass placebo? No?

Dr. Kevin Tracey: No, no. To defend the manufacturers and the FDA patients who put this on their neck and use it according to the FDA label and have severe migraines, a significant percentage of them do better than for patients who don’t use the device. So this is an example that we talked about before where you have a device, we don’t necessarily know how it works. It might work through some other mechanisms, but it seems to work in a statistical way in FDA-approved, randomized clinical trials.

Put that aside. How could it work? We’re talking now science here. Well, Charles Sherrington, one of the two fathers of neuroscience with Ramon Y Cajal back in the early 1900s, he wrote a famous book which I recommend to anyone, even casual readers of neuroscience should read Charles Sherrington’s book, The Integrative Action of the Nervous System. The title alone is brilliant, The Integrative Actions of the Nervous System.

He taught us this. It’s so simple, you’ll never forget it. You have to understand a simple reflex because there’s an input and then some sort of connection or process and an output. And that’s what happens when the doctor taps your knee. That’s what happens when inflammation happens in your body, and the signal goes in. Well, in the knee case, the rubber hammer stretches the tendon. The tendon sends a signal up your sensory nerves to the spinal cord. The spinal cord sends the signal back down to your quadriceps, femoris, your leg pops up, and you said, “Shit, who did that?” That’s a reflex.

In the context of inflammation, there’s inflammation in your body, the signal goes up your vagus nerve, signals come back down, stop the inflammation. That’s the inflammatory reflex.

“Got it. Okay, Charles, we got that. What’s next?” Then he said, “If you assemble a couple of reflexes, you could start to build a nervous system.” This is, again, this is your field more than mine is neural networking. You can assemble things. You can build up complex systems by just adding one more reflex, right? One more input, one more output, and then they start to connect. And then he goes, “End of the day, there’s no such thing as a simple reflex ’cause every nerve in your body is connected.”

So you put electricity on your neck. Some of it’s going to end up stimulating nerves that go into your brain or your spinal cord. Once it gets in the brain or the spinal cord, there’s the big router. The brain can decide how to send it out. In some patients, does it relax the muscles of the neck to interfere with a headache pathogenesis? Maybe. In some patients, does the brain send signals down the vagus nerve to stop inflammation contributing to migraine? Maybe. In some patients, does the brain send signals up to the resistance arteries that are controlling blood flow in and out of your brain that can give you a tension headache? Maybe. We don’t know. Nobody knows.

Tim Ferriss: I mean, it’s exciting to me that there are so many open questions. So just these like, just enough of a teaser and a taste test of something to make it really tantalizing to investigate further.

And my friend, he’s using a cervical device, the one who tripled his HRV. So who the hell knows, right? And ultimately, he and I were talking ’cause after our first chat, I was like, “Hey, man, I might have some good news, bad news.” And I was like, “Seems like your device is working for you, and I don’t want to burst the placebo effect. But also, it doesn’t seem to be a vagus nerve stimulator.” But we were joking, and I think one of us is probably me ’cause I’m a goofy ass a lot of the time, but I said, “I guess at the end of the day, ultimately you don’t really care if you’re somehow summoning Odin to come down with a magic unicorn and pierce you through your forehead with the spike like a narwhal to fix your low back pain or increase your HRV. You just want the output.”

So whatever is happening, it would be great to understand what’s happening under the hood, but it’s like you might like driving your Tesla. You don’t — how many people actually know how it works? Or the microwave or the refrigerator. Which is not to say that you want the larger scale RCTs and mechanisms of action. So I’m not trying to dismiss the importance of all of that or the power of placebo.

Dr. Kevin Tracey: Well, I don’t know if it’s placebo. You said it’s the power — It could be the power of one. And it could be that if a hundred patients were subjected to this and 75 percent of them have the effect your friend has, now that’s really interesting. Why? You know? This is where some people like to reach too far when they’re hawking their wares. 

Tim Ferriss: Some of the websites selling these things are so bad, I mean, so bad. You expect them to be selling boner pills and kratom and some sketchy, shitty cryptocurrency at the same time in the checkout process, they’re so bad.

Dr. Kevin Tracey: Yeah. People say, “Oh, well, is it safe?” Well, that’s important. But then you raise people’s hopes and then you take their money and you don’t know what you’re doing. I mean, there’s real questions there. I’m not saying it’s easy. Look, the simplest, what people would say is the simplest, stupidest clinical trial of one of these devices might cost $5 million or more.

Tim Ferriss: Yes, science is expensive. Good science is expensive.

Dr. Kevin Tracey: Yes. Yes.

Tim Ferriss: Yeah. All right. So we’ve covered a lot of ground. I highly, highly, highly recommend people check out The Great Nerve if you want, not just things we’ve talked about. We could do three rounds of the podcast. I didn’t even get through a small portion of my notes. And also in your book, I want to point out, because this is important, you have an entire section dedicated to different types of tools with some really remarkable results, whether that’s breath work, cold exposure, meditation.

You know what? Maybe just as a fun way to bookend this, could you please tell the story? You’ve got some amazing stories in the book. Could you please tell the story of the Dalai Lama? You got it. I mean, people are like, “What, the Dalai Lama? How the hell. It’s a good fit into this. Yeah. All right, so please, please tell that because it’s just fun. I mean, it’s so fun. It’s also fascinating, but it’s fun.

Dr. Kevin Tracey: Back in the day, was it about 2007, give or take? I can’t remember the year. It’s in the book. Maybe 2010. I got a call from the Dalai Lama’s New York office, would I like to go to a conference? Now the call came from a gentleman named Bill Bushell, who is a scientist in his own right who was working full time in the Dalai Lama’s organization. And he had been following my work. Because of these questions on the role of the vagus nerve and meditation, the Dalai Lama, of course, famously has participated and supported many, some very sophisticated brain imaging studies and meditation studies. And the Dalai Lama is on the record of saying that he’s convinced that the major tenets of his religion are true in a quantum mechanical way, as you alluded to before, from any perspective. His tenets are like the speed of light. They don’t change.

And he said, to the point that in fact, if Western science or new world science could disprove any of his tenets, then he would change the tenets. He has a deep interest in science. He hosted a meeting here in Phoenicia, New York on the top of a mountain where they own a compound, right outside of Woodstock where the rock concert was. I drove up there. Not all the funny stories made the book, Tim, but one I have to tell is when I’m checking in, I got there late, so it was dark, and I’m in the middle of the woods. And I like the woods. I like to camp. I like to be outside.

Tim Ferriss: I’ve driven by this place. It is in the middle, I mean middle of all of the woods, yeah.

Dr. Kevin Tracey: They own the whole mountain, right? So it’s dark, it’s nighttime. And they give me keys to a cabin in the middle of the woods. And as I’m going out the door, the woman says, “Don’t mind the bears.” And I’m like, “Fine, I’m going to walk in the dark.” It was through the bears to my cabin. And I said, “Well,” I’ll make a joke. And I said, “Well, I know they were here first, right? Ha ha.” And she looks at me with steely eyes. It’s like, “Okay, welcome to Woodstock.” I’m like, “This isn’t like the concert.” So the next day — 

Tim Ferriss: “Good evening, sir.”

Dr. Kevin Tracey: Exactly. The next day I’m on stage. The next day was two days of scientific talks, a whole series of times — I gave one. I remember Liz Blackburn was there, and when she was there was the time, it was during the meeting it was announced that she’d won the Lasker Prize. I think a year or two later, she won the Nobel Prize. So Liz and I were there and a bunch of other scientists. And the last day, the organizers came up to us and asked Liz and I if we would summarize the meeting for His Holiness the Dalai Lama on stage in front of all the attendees. So we said, “Sure.”

So Liz gave a talk, and then I gave a talk. I’ll never forget, I was on stage with the Dalai Lama with Bob Thurman who was sitting to his side. And that’s Uma Thurman’s dad. And he’s a professor of Tibetan studies and other studies at Columbia at the time, Columbia University. And a translator sat between us.

And I explained the vagus nerve and I said the vagus nerve. And he asked the question you did, “Where is this vagus nerve?” And I said, “It travels down your neck, across your chest, into your abdomen.” He goes, “Oh.” And then he said, through Bob, he said, “Is it in the front or the back?” I said, “Well, it’s in the front.” And then he said, “Is there one or two?” And I said, “Well, there’s two.” And then he smiled at me and that was that.

And then afterwards he left and a few monks came up to me, and In their long, flowing orange robes, as Bill Murray would say, striking, and they said to me, “His Holiness asked you those questions. Do you know why he asked you those questions?” I said, “No, I haven’t a clue.” And they said, “Well, we like to practice. One form of Tibetan meditation is we like to practice a cloud of blue energy over our heads that we channel in two waves down each side of the neck, across both sides of the chest, down into the abdomen.” And I said, “Cool.” And the monk said, “Yeah, it’s very cool.”

Tim Ferriss: Not everybody gets a Dalai Lama story. Yeah, that is a good one.

Well, people can find The Great Nerve, which includes so much more anywhere that you find your books. Dr. Kevin Tracey, T-R-A-C-E-Y. Is there anything else you’d like to say as we wind to a close, anything you’d like to add, point people to, requests, reminders, public complaints, anything you’d like to say before we land the plane?

Dr. Kevin Tracey: One thing. These things in the book and that a lot of people talk about for self-help, they’re good. I do them. Meditation is good. Exercise is good. Watching your weight is good. Getting enough sleep is good. All of these things I think are good to reduce the inflammation in your body. And they are good to probably to give your vagus nerve some exercise and improve your heart rate variability. It’s all good.

I just don’t like to say that it’s the cure for some of these serious medical conditions. And the fact that we now have a path to connect literally decades of science to now 15 years, 12 years of clinical trials on this science that gives hope to some patients with serious inflammatory conditions that stimulating their vagus nerve with this immunoregulator is what we really call it, this is an exciting time. And I really appreciate you having me on the show. And there’s more questions we could talk about next time maybe.

Tim Ferriss: Yeah, maybe round two of cognitive enhancement with vagus nerve stimulation. I mean, I could keep going, keep going for many, many hours, but I’ll call it here for now.

And everybody listening, we will provide links in the show notes to many different studies to Ulf Andersson’s protocol for the five minutes, twice a day, of course, to SetPoint to the New York Times piece as well, and to the book, The Great Nerve. And you’ll be able to find all of that at tim.blog/podcast. For the show notes, just search. My friend Kevin Rose will pop up a lot if you search Kevin, so search Tracey, T-R-A-C-E-Y, or vagus or vagus nerve, and this will pop right up. And until next time, folks, be just a bit kinder than is necessary not just to others but also to yourself. And as always, thanks for tuning in.

The post The Tim Ferriss Show Transcripts: Dr. Kevin Tracey — Stimulating the Vagus Nerve to Tame Inflammation, Alleviate Depression, Treat Autoimmune Disorders (e.g., Rheumatoid Arthritis), and Much More (#824) appeared first on The Blog of Author Tim Ferriss.

Dr. Kevin Tracey — Stimulating the Vagus Nerve to Tame Inflammation, Alleviate Depression, Treat Autoimmune Disorders (e.g., Rheumatoid Arthritis), and Much More (#824)

2025-08-28 01:28:58

Kevin J. Tracey, MD (@KevinJTraceyMD), is president and CEO of the Feinstein Institutes for Medical Research at Northwell Health, a pioneer of vagus-nerve research, and author of the recent book The Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes. 

His contributions include identifying the therapeutic action of monoclonal anti-TNF antibodies and discovering the specific reflex control of immunity by the nervous system, called the “inflammatory reflex.” These discoveries launched the new scientific field called bioelectronic medicine, which investigates the therapeutic applications of vagus-nerve stimulation to cure disease.

Dr. Tracey, a neurosurgeon, pursued studies of inflammation after the mysterious death, from sepsis, of a toddler who was in his care. His lab has since revealed molecular mechanisms of inflammation and identified the use of vagus-nerve stimulation to treat it. An inventor on more than 120 US patents and the author of more than 450 scientific publications, he is among the most highly cited scientists in the world. He co-founded the Global Sepsis Alliance, is the author of Fatal Sequence, and is a national and international lecturer.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube. The transcript of this episode can be found here. Transcripts of all episodes can be found here.

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SELECTED LINKS FROM THE EPISODE

• Connect with Dr. Kevin Tracey:

X | The Feinstein Institutes of Northwell Health | SetPoint Medical | LinkedIn

The transcript of this episode can be found here. Transcripts of all episodes can be found here.

Publications & Media

• The Great Nerve: The New Science of the Vagus Nerve and How to Harness Its Healing Reflexes by Kevin J. Tracey: A groundbreaking book exploring the potential of the vagus nerve to regulate the body’s vital systems and heal medical conditions without drugs.
• The Polyvagal Theory: Neurophysiological Foundations of Emotions, Attachment, Communication, and Self-regulation by Stephen W. Porges: A comprehensive compilation of decades of research on the polyvagal theory and its implications for understanding the autonomic nervous system.
• STEM-Talk: A bi-weekly interview podcast produced by the Florida Institute for Human and Machine Cognition featuring conversations with groundbreaking scientists, engineers, and technologists.
• The New York Times: A major American daily newspaper that featured coverage on SetPoint Medical and other medical developments.
• HuffPost: An American progressive news and opinion website where Dr. Tracey was interviewed about his research.
• Cell: A prestigious peer-reviewed scientific journal that published research on topics including gut microbiota and the ketogenic diet.
• Explain Pain by David Butler and G. Lorimer Moseley: An evidence-based book designed for therapists, patients, and students that explains the science behind pain and recovery strategies.
• The Integrative Action of the Nervous System by Charles Sherrington: A classic 1906 work in neuroscience that established fundamental concepts about how the nervous system functions as an integrated whole.

Medical Conditions

• Rheumatoid Arthritis: An autoimmune disease that causes inflammation in the joints.
• Crohn’s Disease: A type of inflammatory bowel disease that affects the digestive tract.
• PTSD (Post-Traumatic Stress Disorder): A mental health condition triggered by experiencing or witnessing a traumatic event.
• Chronic Fatigue Syndrome: A long-term illness characterized by extreme fatigue that doesn’t improve with rest and may worsen with physical or mental activity.
• Depression: A mood disorder that causes persistent feelings of sadness, hopelessness, and loss of interest in activities.
• Lyme Disease: An infectious disease caused by bacteria transmitted through the bite of infected ticks.
• Neurodegenerative Disease: A range of conditions that primarily affect the neurons in the human brain, leading to progressive deterioration of function.
• Anaphylaxis: A severe, potentially life-threatening allergic reaction that can occur rapidly after exposure to an allergen.
• Asthma: A respiratory condition in which airways become inflamed, narrow, and produce excess mucus, making breathing difficult.
• Sepsis: A life-threatening condition that arises when the body’s response to infection causes widespread inflammation and organ dysfunction.
• Psoriatic Arthritis: A form of inflammatory arthritis that affects some people who have the skin condition psoriasis.
• Autoimmune Conditions: Disorders in which the immune system mistakenly attacks the body’s own healthy tissues and organs.
• COVID-19: A contagious respiratory illness caused by the SARS-CoV-2 virus that can range from mild to severe symptoms.
• Alzheimer’s Disease: A progressive neurodegenerative disease that destroys memory and other important mental functions.
• Parkinson’s Disease: A progressive disorder of the central nervous system that affects movement, often causing tremors, stiffness, and difficulty with balance.
• Metabolic Syndrome: A cluster of conditions including high blood pressure, high blood sugar, excess abdominal fat, and abnormal cholesterol levels that increase the risk of heart disease, stroke, and diabetes.
• Diabetes: A chronic disease that occurs when the body cannot properly produce or use insulin, leading to elevated blood sugar levels.
• Cancer: A group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body.
• Malaria: A life-threatening disease caused by parasites transmitted through the bites of infected female Anopheles mosquitoes.
• Tuberculosis: A serious infectious bacterial disease that primarily affects the lungs but can spread to other parts of the body.
• Peptic Ulcer Disease: A condition characterized by painful sores or ulcers that develop in the lining of the stomach or the first part of the small intestine.
• Epilepsy: A neurological disorder in which brain activity becomes abnormal, causing seizures, unusual behavior, sensations, and sometimes loss of consciousness.
• Cluster Headaches: A series of extremely painful headaches that occur in cyclical patterns or clusters, often at the same time each day for weeks or months.
• Migraines: Intense headaches that cause severe throbbing or pulsing pain, typically on one side of the head, often accompanied by nausea and sensitivity to light and sound.
• Sciatica: Pain that radiates along the sciatic nerve pathway from the lower back through the hips and down one or both legs.

Treatments & Therapies

• Vagus Nerve Stimulation (VNS): A medical treatment that involves delivering electrical impulses to the vagus nerve.
• Audio Chakra Cleanse Soundtracks: A type of alternative therapy mentioned as an example of “nonsense.”
• Biologics: Medications made from living organisms or their components.
• Ketogenic Diet: A very low-carb, high-fat diet.
• Exogenous Ketones: Ketones that are ingested through a nutritional supplement.
• GLP-1 Agonists (e.g., Ozempic, Mounjaro): A class of medications used to treat type 2 diabetes and obesity.
• Microbiome Transplants: The transfer of fecal matter from a healthy donor to a recipient to restore a healthy gut microbiome.
• TMS (Transcranial Magnetic Stimulation): A noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression.
• Focused Ultrasound: A non-invasive therapeutic technology that uses focused sound waves to target and treat a variety of medical conditions.
• Psychedelics (e.g., LSD, 2C-B, Ayahuasca): A class of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness.
• TENS (Transcutaneous Electrical Nerve Stimulation) units: A non-invasive method of pain relief that uses a mild electrical current.
• Auricular Therapy: A form of alternative medicine based on the idea that the ear is a microsystem which reflects the entire body.
• Famotidine (Pepcid): An over-the-counter antacid that Dr. Tracey describes as a pharmacological vagus nerve stimulator.
• Antibiotics: Medications that fight bacterial infections.
• SSRIs (Selective Serotonin Reuptake Inhibitors): A class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
• Ibuprofen: A nonsteroidal anti-inflammatory drug (NSAID).
• Monoclonal Antibodies: Laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses.
• Optogenetics: A biological technique that involves the use of light to control cells in living tissue, typically neurons, that have been genetically modified to express light-sensitive ion channels.

Key Concepts & Theories

• Polyvagal Theory: A theory that links the evolution of the autonomic nervous system to social behavior and emphasizes the importance of physiological state in the expression of behavioral problems and psychiatric disorders.
• Heart Rate Variability (HRV): The variation in the time interval between consecutive heartbeats.
• Sympathetic Overdrive: A condition where the sympathetic nervous system is overactive.
• Inflammatory Reflex: A physiological reflex that controls the inflammatory response.
• Bioelectronic Medicine: A field of medicine that uses electronic devices to treat diseases and injuries.
• Blood-Brain Barrier: A highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from non-selectively crossing into the extracellular fluid of the central nervous system where neurons reside.
• Cytokines (e.g., TNF, IL-1, IL-6): A broad and loose category of small proteins that are important in cell signaling.
• Cytokine Storm: A severe immune reaction in which the body releases too many cytokines into the blood too quickly.
• Inflammaging: Chronic, low-grade inflammation that develops with advanced age.
• Neuroinflammation: Inflammation of the nervous tissue.
• Neuroplasticity: The ability of the brain to form and reorganize synaptic connections, especially in response to learning or experience or following injury.
• Interoception: The sense of the internal state of the body.
• Engram: A physical trace of memory in the brain.
• M1 and M2 Macrophages: Two different types of white blood cells with different functions in the inflammatory response.

People

• Kelly Owens: A patient of Dr. Tracey’s who suffered from Crohn’s disease and rheumatoid arthritis and was successfully treated with a vagus nerve stimulation device.
• Murthy Simhambhatla: The CEO of SetPoint Medical, a bioelectronic medicine company developing vagus nerve stimulation therapies.
• Dave Chernoff: The Chief Medical Officer of SetPoint Medical, overseeing clinical development of bioelectronic therapies.
• Nolan Williams: A psychiatry professor and director of the Stanford Brain Stimulation Lab who pioneered Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an FDA-approved treatment for treatment-resistant depression using accelerated TMS.
• Nora Volkow: Director of the National Institute on Drug Abuse (NIDA) who pioneered the use of brain imaging to investigate addiction as a brain disorder and is researching focused ultrasound therapies for addiction treatment.
• Steve Liberles: A professor of cell biology at Harvard Medical School and Howard Hughes Medical Institute investigator who studies the molecular neuroscience of vagus nerve sensory systems and identified specific vagal neuron subtypes that control breathing and digestion in mice.
• K. Frank Austen: A leading expert on asthma research and respiratory medicine.
• Barry Jacobs: A researcher at Princeton University who studied the effects of LSD on cats and contributed to early psychedelic research.
• Andrew Weil: A physician and author with a background in ethnobotany who has written about his experiences with psychedelics including LSD and integrative medicine approaches.
• Ulf Andersson: A retired professor of pediatric rheumatology at the Karolinska Institute and friend of Dr. Tracey’s who used a TENS unit to treat his own inflammation-related depression.
• Paul Nogier: A French physician who created the first auricular acupuncture maps in 1957, pioneering modern ear acupuncture techniques.
• Kenneth M. Ford: Founder and CEO Emeritus of the Florida Institute for Human and Machine Cognition (IHMC), and co-host of the STEM-Talk podcast.
• Geoff Ling: Retired colonel who founded the biology technology office at DARPA.
• Richard Feynman: Nobel Prize-winning American theoretical physicist known for his work in quantum mechanics, quantum electrodynamics, and superfluidity.
• Charles Sherrington: One of the founders of modern neuroscience, known for his groundbreaking work on neural reflexes and The Integrative Action of the Nervous System, for which he won the Nobel Prize in Physiology or Medicine in 1932.
• Santiago Ramón y Cajal: The other founding father of modern neuroscience, known for his pioneering studies of the structure of the nervous system and the neuron doctrine, Nobel Prize winner in Physiology or Medicine in 1906.
• Asya Rolls: A professor who discovered that inflammation in the colon can form a neural network connection to the brain, advancing our understanding of the gut-brain axis.
• Sangeeta Chavan: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, contributing to bioelectronic medicine research.
• Stavros Zanos: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, specializing in neural engineering and bioelectronics.
• Okito Hashimoto: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, working in the field of bioelectronic medicine.
• Eric Chang: A colleague of Dr. Tracey’s at the Feinstein Institute for Medical Research, contributing to neuroscience and bioelectronics research.
• Martine Rothblatt: A friend of Dr. Tracey’s and CEO of United Therapeutics, she is a renowned polymath who founded SiriusXM satellite radio before entering biotechnology to develop treatments for her daughter’s pulmonary hypertension, becoming the highest-paid female CEO in America.
• Lorimer Moseley: Co-author with David Butler of the book Explain Pain and a leading researcher in pain neuroscience and clinical neurosciences at the University of South Australia.
• William Bushell: A scientist who works with the Dalai Lama on studies involving meditation, consciousness, and human potential.
• Elizabeth Blackburn: A scientist who won both the Lasker Prize and the Nobel Prize in Physiology or Medicine in 2009 for her work on telomeres and telomerase.
• Bob Thurman: Uma Thurman’s father and a professor of Tibetan studies at Columbia University, known for his scholarship on Buddhist philosophy.
• The Dalai Lama: The spiritual leader of Tibet and global advocate for compassion, peace, and interfaith dialogue.
• Bill Murray: Formidably funny man and serial-striking bowler.
• Kevin Rose: Probably not the Kevin you’re looking for, but Kevin, by any other name, would smell as sweet.

Institutions & Companies

• SetPoint Medical: A commercial-stage medical technology company that developed the first FDA-approved neuroimmune modulation device to treat rheumatoid arthritis using vagus nerve stimulation.
• Feinstein Institutes for Medical Research: The research arm of Northwell Health and home to 50 research labs, 3,000 clinical research studies, and 5,000 researchers where Dr. Tracey and his colleagues work.
• Mayo Clinic: A world-renowned nonprofit American medical organization dedicated to integrated healthcare, education, and research.
• Stanford University: A prestigious private research university in California known for its groundbreaking research, including work on accelerated TMS and other medical innovations.
• Centers for Disease Control and Prevention (CDC): The national public health agency of the United States, responsible for protecting public health and safety through disease prevention and health promotion.
• Karolinska Institute: A prestigious medical research institute and university in Sweden, home to the Nobel Committee for Physiology or Medicine.
• Defense Advanced Research Projects Agency (DARPA): A research and development agency of the United States Department of Defense responsible for developing emerging technologies for military use.
• Defense Language Institute: A United States Department of Defense educational and research institution that provides language training to military personnel and federal employees.
• United Therapeutics: A biotechnology company focused on creating innovative products to address the medical needs of patients with chronic and life-threatening conditions, including pulmonary arterial hypertension and organ transplantation technologies.
• World Health Organization (WHO): A specialized agency of the United Nations responsible for international public health, setting global health standards, and coordinating international health responses.
• Columbia University: A prestigious private Ivy League research university in New York City, renowned for its contributions to medicine, science, and other fields of study.
• Pendulum: A science-backed biotechnology company founded by doctors and scientists that produces next-generation probiotics, including the only commercially available live Akkermansia supplement.
• WHOOP: 24/7 monitoring across sleep, strain, stress, and heart health.
• Oura Ring: A smart ring that monitors over 20 biometrics that directly impact how you feel.
• Fitbit: Wearables designed to “keep you close to your goals, boost your motivation, and show your progress throughout your health and fitness journey.”

Relevant Research & Resources

• Kevin Tracey on Neuro-Immunology and the Treatment of Inflammatory Diseases | STEM-Talk
• Kevin Tracey, MD, Reveals Vagus Nerve’s Power in New Book | Northwell Health
• SetPoint Medical Receives FDA Approval for Novel Neuroimmune Modulation Therapy for Rheumatoid Arthritis | SetPoint Medical
• New Implant Offers Hope for Easing Rheumatoid Arthritis | The New York Times
• I Tried 22 Different Medications Before an Electrical Implant Healed My Crohn’s Disease | Prevention
• Nolan Williams — A Glimpse of the Future: Electroceuticals for 70%–90% Remission of Depression, Brain Stimulation for Sports Performance, and De-Risking Ibogaine for TBI/PTSD | The Tim Ferriss Show
• Dr. Nora Volkow — Director of the National Institute on Drug Abuse (NIDA) | The Tim Ferriss Show
• Reappraising the Role of the Vagus Nerve in GLP-1-Mediated Regulation of Eating | British Journal of Pharmacology
• Role of Vagus Nerve Signaling in CNI-1493-Mediated Suppression of Acute Inflammation | Autonomic Neuroscience
• Good-bye to Drugs? Kevin Tracey, MD on the Bioelectronics Revolution at the Dysautonomia International Conference | Health Rising
• No Audible Wheezing: Nuggets and Conundrums from Mouse Asthma Models | Journal of Experimental Medicine
• Here’s What Happens When Animals Eat LSD | DoubleBlind
• Some Practical Thoughts on Suicide | Tim Ferriss
• The Evolution of Inflammation | Pfizer
• FDA Black Box Warning Raises Awareness of Medication Risk | GoodRx
• Effects of Anti-Inflammatory Vagus Nerve Stimulation in Endotoxemic Rats on Blood and Spleen Lymphocyte Subsets | Inflammation Research
• Vagus Nerve Stimulation for Epilepsy and Depression | Neurotherapeutics
• Vagus Nerve Active during Exercise, Research Finds | The University of Auckland
• Jumping into the Ice Bath Trend! Mental Health Benefits of Cold Water Immersion | Stanford Lifestyle Medicine
• The Thermoregulatory Theory of Yawning: What We Know from over Five Years of Research | Frontiers in Neuroscience
• Prevalence of Autoimmune Diseases Is Strongly Associated with Average Annual Temperatures: Systematic Review and Linear Regression Analysis | BMC Rheumatology
• Nobel Prize Is Awarded to Doctors Who Discovered H Pylori | The British Medical Journal
• What Happens to Your Blood Sugar While You Sleep? | WebMD
• Type A Personality Traits vs. Type B | Simply Psychology
• Focused Ultrasound Neuromodulation of the Spleen Activates an Anti-Inflammatory Response in Humans | Brain Stimulation
• History of Auriculotherapy: Additional Information and New Developments | Medical Acupuncture
• The Medial Surface of the Auricle: Historical and Recent Maps. What Are the Possible Expectations of the “Thumb-Index Technique” | Medicines
• Our Ears Share a Common Ancestry with Fish Gills | Scientific American
• JP Errico Explains How Vagus-Nerve Stimulation Reduces Inflammation and Chronic Diseases | STEM-Talk
• Vagus Nerve Stimulation May Enhance Language Learning, DoD Study Reports | Practical Neurology
• Geoffrey Ling: From DARPA to Life | Twin Global
• Vagus Nerve Stimulation (VNS) Therapy | Epilepsy Society
• The Gut Microbiota Mediates the Anti-seizure Effects of the Ketogenic Diet | Cell
• Dr. Andrew Weil — Optimal Health, Plant Medicine, and More | The Tim Ferriss Show
• The Hidden Flaws of HRV Tracking | The Unlazy Way
• Breathe to Directly Control Heart Rate via Huberman Lab | Instagram
• Famotidine Activates the Vagus Nerve Inflammatory Reflex to Attenuate Cytokine Storm | Molecular Medicine
• WHOOP Adds Psychedelics Tracking | Fitt Insider
• Why Don’t We Know How Antidepressants Work Yet? | Chemistry World
• Ulf’s Case Study: VAGUS Smartwatch ECG Test | VAGUS Health Ltd.
• Study of the Transcutaneous Auricular Vagus Nerve Stimulation May Advance Outcome in Chronic Pediatric Inflammatory Diseases | Medical Research Archives
• Acupuncture Enhances Chances of Pregnancy in Unexplained Infertile Patients Who Undergo a Blastocyst Transfer in a Fresh-Cycle | Chinese Journal of Integrative Medicine
• Acupuncture as Treatment for Female Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | Evidence-Based Complementary and Alternative Medicine
• Dr. Martine Rothblatt — A Masterclass on Asking Better Questions and Peering into the Future | The Tim Ferriss Show
• Immunoception: The Insular Cortex Perspective | Cellular & Molecular Immunology
• New Science Shows Immune “Memory” in the Brain | Quanta Magazine
• Jennifer Aniston Strikes a Nerve | Nature
• Quantum Physics — His Holiness the Dalai Lama Participates in the 26th Mind & Life Meeting at Drepung | The Office of His Holiness The Dalai Lama

SHOW NOTES

• [00:00:00] Start.
• [00:06:34] Factors alleviating my skepticism about vagus nerve stimulation.
• [00:11:12] SetPoint Medical receives FDA approval for vagus nerve stimulation device to treat rheumatoid arthritis.
• [00:13:24] How Crohn’s disease sufferer Kelly Owens went from a wheelchair to running up stairs in Amsterdam.
• [00:20:36] Placebo effect concerns and the conditions driving my interest in bioelectric medicine.
• [00:25:31] Vagus nerve anatomy 101.
• [00:32:53] Cytokines and inflammation: What happens when the vagus nerve is stimulated.
• [00:33:45] Discovery story: Accidental finding of brain-body inflammation connection.
• [00:35:39] Bioelectronic medicine approach vs. pharmaceutical approach.
• [00:38:18] Mice don’t wheeze.
• [00:40:13] Depression and inflammation connection: SSRIs may work through anti-inflammatory effects.
• [00:42:46] My personal experience with vagus nerve stimulation and mood stability.
• [00:44:22] The pros and cons of inflammation, and how controlling it may lead to even longer lifespans.
• [00:50:56] Weighing the safety of VNS vs. biologics in cytokine suppression.
• [00:56:27] Cold exposure, meditation, and breathing practices affecting the vagus nerve.
• [00:59:01] A population-level increase in chronic inflammatory diseases: Nature vs. nurture.
• [01:00:48] H. pylori: For when you can’t blame stress, God, or the patient for that nagging ulcer.
• [01:03:13] Stress, cortisol, and inflammation connections.
• [01:05:42] SetPoint device vs. non-invasive alternatives for different patient populations.
• [01:11:09] Auricular therapy’s curious French origins.
• [01:13:28] There’s something fishy about this vestigial vagus nerve pathway.
• [01:16:03] Overlapping activation patterns from brain imaging studies of ear stimulation.
• [01:19:01] DARPA support and Geoff Ling’s “What if it’s yes?” attitude.
• [01:21:58] Neurocognition and vagus nerve inputs.
• [01:27:20] How Ulf Andersson turned his depression around with a TENS unit.
• [01:31:55] Heart rate variability complexity and measurement challenges.
• [01:33:05] A breathing exercise for directly controlling heart rate.
• [01:35:30] Using a common antacid as a pharmacological vagus nerve stimulator during COVID.
• [01:36:23] A call for more inflammation-based depression research and patient stratification.
• [01:39:52] SSRIs and anti-inflammatory mechanisms in depression treatment.
• [01:42:20] Interoception: The body’s inflammatory signals reaching the brain via vagus nerve.
• [01:43:22] Ulf’s published protocol for TENS unit ear stimulation.
• [01:44:37] VNS, acupuncture, fertility, and Martine Rothblatt.
• [01:47:16] Chronic low back pain and an inflammatory overreaction analogy.
• [01:48:35] Implications of Asya Rolls’ engram research and inflammation memories in the brain.
• [02:02:35] Cervical TENS vs. true VNS.
• [02:07:12] Charles Sherrington’s reflex theory and nervous system integration.
• [02:12:15] Blue energy meditation and vagus nerve pathways with the Dalai Lama.
• [02:16:47] Parting thoughts: Serious medical conditions vs. self-help approaches.

DR. KEVIN TRACEY QUOTES FROM THE INTERVIEW

“60 million people die on the planet Earth every year. And 40 million of them die from heart disease, stroke, neurodegeneration, Alzheimer’s, Parkinson’s, metabolic syndrome, diabetes, and cancer. So two thirds of the people that die every year on the planet Earth die of those conditions. And that’s according to the WHO. Those conditions all have one thing in common: they’re either caused by inflammation or made worse by inflammation.”

— Dr. Kevin Tracey

“It was just announced that the company SetPoint Medical, which will now be marketing a device to stimulate the vagus nerve to treat rheumatoid arthritis, has received FDA approval. So there’ll be a product launch underway for everything we’re about to talk about in the context of using a medical device that activates an evolutionarily conserved and ancient reflex through which the brain can suppress inflammation when it’s running out of control.”

— Dr. Kevin Tracey

“We’ve discovered that signals travel from the brain through the vagus nerve. … These signals traveling in the vagus nerve are like the brakes on your car. And when you tap those brakes to slow your car barreling down the hill, this device activates what we call the inflammatory reflex.”

— Dr. Kevin Tracey

“If we can find such nerves, then we can build devices to control the nerves, and the devices become the therapy. The bioelectronic medicine story works as long as you know the molecular mechanism, and that’s where people have to be really careful with vagus-nerve stimulation.”

— Dr. Kevin Tracey

“Almost everybody until a hundred years ago, 150 years ago, almost everybody died by the time they were 30. And what happened in the last 150 years can be summarized in a very simple sentence. The human race in the last 150 years removed infection as the leading cause of death. … I think something similar will happen maybe in the next 20 years if we can really understand how to modify inflammation.”

— Dr. Kevin Tracey

“My adage for this thing is, when you don’t understand a disease, think of epilepsy. You start off, you blame God. So they did exorcisms, and that doesn’t work. So if it’s not God’s fault, the next thing you do is you blame the patient. And when you realize it’s not the patient’s fault, in today’s era, oftentimes we find out it’s actually caused, there’s some infectious cause of this thing. And so autoimmune disease may have an infectious cause, it may have an environmental cause. People talk about genetic causes. You inherit some level of risk for autoimmune diseases, but in very few of these conditions do you actually inherit the condition.”

— Dr. Kevin Tracey

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Want to hear another episode about the future of electroceuticals and brain stimulation? Listen to my conversation with Stanford’s Dr. Nolan Williams, in which we discussed 70%–90% remission rates for treatment-resistant depression, brain stimulation for sports performance, accelerated TMS protocols, de-risking ibogaine for TBI/PTSD, the future of “electroceuticals,” and much more.

The post Dr. Kevin Tracey — Stimulating the Vagus Nerve to Tame Inflammation, Alleviate Depression, Treat Autoimmune Disorders (e.g., Rheumatoid Arthritis), and Much More (#824) appeared first on The Blog of Author Tim Ferriss.

The Tim Ferriss Show Transcripts: Dr. Jeffrey Goldberg — Creating Supranormal Vision, Cutting-Edge Science for Eye Health, Supplements, Red Light Therapy, and The Future of Eyesight Restoration (#823)

2025-08-22 03:23:48

Please enjoy this transcript of my interview with Dr. Jeffrey Goldberg, chair of the Department of Ophthalmology and director of the Byers Eye Institute at Stanford University. He is a leading scientist in the development and degeneration of the visual system from eye to brain and a professor, practicing ophthalmologist, and surgeon.

Dr. Goldberg is a member of the National Academy of Medicine and has won a number of prestigious awards, including Scientist of the Year by the Hope for Vision foundation and the Cogan award from the Association for Research in Vision and Ophthalmology. Dr. Goldberg received his BS magna cum laude from Yale University and his MD and PhD from Stanford University, where he made significant discoveries about the failure of optic nerve regeneration. 

Dr. Goldberg’s research is directed at vision restoration, including neuroprotection and regeneration of the retina and optic nerve, a major unmet need in glaucoma and other eye diseases. His laboratory is developing novel molecular, stem-cell, and nanotherapeutics approaches for eye repair, and he is widely recognized for translating advances in the lab into clinical trials for patients. 

A number of his innovations have spun out into startups and clinical-stage companies, and he serves as medical and scientific advisor to a number of ophthalmic start-up, pharma, and device companies. His goal is to translate scientific discoveries to patient therapies.

Transcripts may contain a few typos. With many episodes lasting 2+ hours, it can be difficult to catch minor errors. Enjoy!

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Tim Ferriss: Dr. Jeffrey Goldberg. So nice to meet you. Thanks for making the time.

Dr. Jeffrey Goldberg: Absolutely. Thanks for having me on. I’m really looking forward to it.

Tim Ferriss: I have so many questions for you. And as usual, I’m scratching my own itch. This is going to be a selfish conversation for yours truly, in some respects, because the way this whole thing came about is I put up a post on social media asking for cutting edge technologies or treatments related to presbyopia. Which for those who don’t recognize the term is a very fancy way of saying age-related visual decline. If you’re a word nerd like I am, presbyterian, similar etymology. Leadership of the elders.

And I have noticed in the last year that my near work, my near vision has started to falter looking at books, looking at my iPhone, looking at supplement bottles. And this has led to somewhat of a crisis of meaning for me because I have had my identity based on, in some respects, very, very good eyesight and visual acuity for my entire life.

And Andrew Huberman, a mutual friend of ours, texted me and said, “I’ve got the guy. I know the guy.” And, “Listen to our interview.” Which I did. And for that reason, we’re going to go all over the place, but I thought we would start where I had to start, which is supranormal visual performance. And these is the notes I scribbled down from your conversation with Andrew, I recommend everyone listen to it, goggles that reduce frame rate for basketball.

And that was sort of left hanging a little bit. You guys didn’t do a deep dive on it. So I want to start right there. Because of course there’s preventing decline, there’s maybe restoring function, and then there’s going further and taking things as far as you can. And nowhere are the stakes higher and the rewards greater perhaps than in professional sports. So could you take that and run with it in any way that makes sense?

Dr. Jeffrey Goldberg: Yeah, sure, sure, sure. And yeah, presbyopia, vision of the old. So I’ll tell you just a funny side note. We all get that. I, like you, have gone my whole life without needing glasses until I hit around age 40. And when everyone hits around age 40, our lens inside the eye won’t compress and reshape to focus up close. So your distance vision might still be great, but you just can’t bring that focus in as tight. And I discovered it accidentally in myself, because I was actually in my house and I found a pair of glasses in a closet, somebody must’ve just left them there.

Tim Ferriss: I see where this is going.

Dr. Jeffrey Goldberg: And it turned out they were readers and we couldn’t figure out whose they were. We’re calling around, friends and family. Fine, nobody’s claiming. And then one day I just put them on. “Let’s see how I look in glasses.” And I look down at my phone and I’m like, “Oh, my God, wait a second. I can see a lot better with these readers on.” And then once you do it, you’re addicted because good vision is pretty addicting, right?

Tim Ferriss: Yeah, for sure.

Dr. Jeffrey Goldberg: So now I’m in them too and I’m pretending to look so young with you not wearing them right now, but here they are, just in case. Yeah.

Tim Ferriss: Yeah, very common. Yeah, very, very common.

Dr. Jeffrey Goldberg: So it raises a really cool question that you’re raising, which is as an eye doctor I spent a lot of time, and as a researcher spend a lot of time — we could come back to talking about how do we prevent the sick from losing vision on all these big eye diseases? We could come back to that. But there’s a much bigger world of people who have pretty good vision. Maybe they need glasses, but they’ve got good vision.

And how do we think about the difference, not from sick to normal, but how do we think about the difference from normal to supranormal? And we know they’re supranormal because when, for example, as you bring up, professional athletes get studied, they have better vision. They have better reflex time, they have sharper vision. We talk about 20/20 vision. That means I can see at 20 feet what a “normal” person can see at 20 feet, so I have normal vision. But you can have 20/12 vision, which means you can see at 20 feet what normal people can see at 12 feet. You’ve got better than normal. And it turns out a lot of pro athletes have that.

And then the next question becomes, and you just kind of hinted at it right there, can we train to supranormal vision? Can we induce supra — ? And almost no one studies that. But there are some really cool tools and toys that actually might have that effect. And so you brought up one of them. So we see, like our cones inside of our eyes, we’ve got rods and cones, the cones, they’ve got a refresh rate around 30 to 60 frames per second, kind of like our computer screens do.

And so if you actually subtract out a couple of frames, so if you put on some glasses that dim one out of every 30th of a second, or they dim two out of every 30th, or push it, three, and now you’re giving up visual data, and I throw a basketball at you, if you’ve got your regular vision, you’ll catch it. But if I’m only giving you 90 percent of your vision, or 80 percent or 70 percent or 60 percent of that vision, you might miss the ball. Right?

Tim Ferriss: Yeah.

Dr. Jeffrey Goldberg: But if we practiced and trained in those goggles, where you’ve got to play basketball, throwing and catch, shoot, whatever, throw a baseball back and forth at 70 percent vision, and then we put you in the game back with 100 percent vision. You’re going to be better, faster reflex time, all of that. Hand-eye coordination. So it’s actually like some of these supranormal visual tactics are actually trainable and there’s tools that athletes are using, but they’re accessible to all of us, yeah.

Tim Ferriss: All right, so I — 

Dr. Jeffrey Goldberg: You can grab one of those, Tim.

Tim Ferriss: Yeah, let’s dig into this a little bit. I have a number of friends who have engineering chops and have played with sensory substitution experiments and all sorts of wild stuff. And in fact, I think there’s some folks at Stanford, David Eagleman comes to mind, who’ve developed tools along these lines. We won’t go down that route. 

Let me stick with vision for a second and just note that there are, for instance, indigenous groups in various parts of the Amazon, I’ve seen them in Brazil and in Peru as well, which use eye drops of various types. Could be from a plant, could be from a toad, for improving not near work but distance work. Most of them use shotguns these days, but some still use blow guns and bow and arrows for hunting, say, monkeys.

So there seems to be something to it. Now you could say, “Ah, that’s a bunch of voodoo hoodoo nonsense.” But then you have eye drops for, as I understand it, temporarily inducing more, this isn’t going to be the right term, but flexibility in the lens. Is it pilocarpine? 

Dr. Jeffrey Goldberg: It’s actually the iris. Yeah, yeah.

Tim Ferriss: The iris. There we go.

Dr. Jeffrey Goldberg: So I don’t know what they’re using in the plants, but we now have FDA approved eye drops, and what they actually do is they bring your pupil size down by having your iris constrict to a smaller circle. And it turns out that if you have refractive error, so you need glasses, the shape of the front of your eye, the shape of your lens isn’t perfect, you have a little bit of glasses or contacts, or whatever to correct that, including if it’s not focusing up to close, you can have reading glasses that change that refractive, that light coming into your eye so that you’re focusing up at close. If you come down to a pinhole, you actually kind of normalize the light so that it’s as if it’s all coming from infinity and you actually kind of correct refractive error.

One of the ways we can tell if someone needs glasses is we have you read the eye chart, and then we have you read the eye chart through a little pinhole, a little device you stick in front of that eye, and read through a pinhole. And if you can read better through the pinhole, you actually have better vision and could correct it with glasses. So now we could just give an eye drop that kind of makes your pupil closer to a pinhole and then it allows you to see without glasses, near or far. In fact, people are using it now for near vision, for that presbyopia you were talking about in the beginning.

Tim Ferriss: So for people listening, and also for me frankly, could you just give a vision 101, and in this case, let’s focus on the eye, just so people understand the basic components of the eye.

Dr. Jeffrey Goldberg: Yeah.

Tim Ferriss: And part of the reason I want to explore this is there are different levers you might be able to pull on to improve vision, some of which might be structurally related, but not all, at least to the eye. But could you just lay out the basic anatomy of the eye, the architecture?

Dr. Jeffrey Goldberg: Yeah, absolutely. So light comes in the front, goes through the clear window in the front of our eye called the cornea. You can have corneal diseases obviously that block that light from coming through clearly, but if it’s healthy, that light comes through clearly. The cornea is curved on the front, and that curvature is actually responsible for curving most of the light into the back of the eye.

Then the light goes through your pupil. So that’s the iris, which it’s brown in me, but brown, blue, hazel. So that’s our iris. And the iris can open and close like we were talking about a minute ago. Comes through the middle of that, the open middle part of that, goes through the lens. The lens does fine focusing, a little focusing from far to near, that kind of thing. And that’s what we were saying, stiffens as we age. So we can’t go far to near as well as we get older, you’re passing 40 years old, typically.

And then it goes through the gelatinous middle part of the eye. We call it the vitreous. After the lens is called the vitreous. That’s where floaters are. People who get floaters, they’re floating, it’s like little concretions of proteins and stuff floating in the vitreous. It’s a gel. As we get older, that gel turns to water, kind of shrinks up. Our eye doesn’t shrink because it fills in with salt water, but the gel shrinks up.

And then the light hits the retina. And our retinas are what we call inverted. So the light actually passes through almost all of the retina and then it hits the rods and the cones. And those are the photoreceptors. They absorb the light, like the photons of light. The rods are really, really only good for nighttime vision. They’re only good at very low light. If you go into normal daytime vision, sitting here in the room, whatever, those are getting bleached out, you’re not really using your rods too much.

And next to them, the cones. The cones are great for color vision, they’re great for bright lights. They’re what we use most of the day. That’s what you and I are using mainly right now. The rods and the cones collect all that light. They process it and transmogrify it into electrical signals. And those electrical signals are then propagated back forward through the retina. There’s some internal processing layers in the retina, so it’s not just a layer of film, you’re actually doing some computation right there in the retina.

And then they hit what are called retinal ganglion cells. And those are the cells that then send a process across the surface of the retina. It’s an axon, but it’s like a telephone wire. And that then goes back out the back of the eye into what we call the optic nerve. And that optic nerve connects the eye to the brain. So those retinal ganglion cells are collecting all the data and sending it all back through the optic nerve to the brain. And then of course all that rest of that processing is happening in the brain.

Tim Ferriss: All right, there we go. That was a great summary. Thank you very much. And I’ll tell folks, if you thought that is a lot to remember, it is a lot to remember. But the point of it is, as I, as my own N of one, am trying to consider different paths forward with presbyopia, whether it’s glasses, yes, my readers do fix the problem, they do fix the problem, but I am a little concerned of increased dependency and then increased magnification over time. I know there are arguments for and maybe some arguments against, but when I put up my social post, and I think people can identify with this, there was a lot of noise. There were some of the most harebrained, insane, certainly potentially dangerous suggestions you can imagine.

And then there were a few things that came up when I reached out to, and let me get this right, is it a vitreoretinal surgeon and researcher — 

Dr. Jeffrey Goldberg: Uh-huh.

Tim Ferriss: — who I happen to know, and he sent me a number of white papers, or I shouldn’t say white papers, more so studies and meta-analyses and so on that I read up on. And I thought to myself, “Look at that. Surprise of surprises.” A few of the things that came up repeatedly in the hundreds of responses to my post actually show up in the literature and there might be something to them. And we’ll definitely come to a number of those.

But it can be very overwhelming for people to try to figure out what to do next. And the reason I wanted you to do that recap, and then I’ll stop giving my second TED talk of our conversation, is that much like if someone complains of, say, brain fog and fatigue, a rose is a rose is a rose is not a rose, in the sense that there can be many different factors and independent variables that contribute to that. So one person might have insulin insensitivity and trouble with glucose disposal. Somebody else might have Lyme disease or some infectious disease that is contributing to metabolic dysfunction. I mean, there’s so many different contributing factors that it helps to, I think, get a little thinly sliced.

So in my case, I have the stiffening of the lens. Please correct my terminology. I also have a really pretty sizable, I’d never seen it before, I did some really impressive imaging on the eye, but a huge nevus on the back of my right eye that I need to keep an eye on. So I’ll be following up on that in three or four months. But I wanted to, I suppose start with, what are other ways to improve vision?

Now there’s certain things I’m always looking for: limited downside, potential upside. So for instance, I’m taking the AREDS 2 supplement with lutein and various other ingredients in it. I would say it’s probably not going to help, but within my patient cohort of the medical practices I work with, there are a few folks who claimed after six weeks that their vision really improved and they didn’t need their readers, even though technically, mechanistically, the AREDS 2 shouldn’t have helped them. So whether it’s placebo effect or not, interesting outcome. I know the plural of anecdote is not data, but I was like, “Ah, okay, sure, I’ll take the supplement.”

What are some other cutting-edge treatments or augmentations for improving vision? And I’ll shut up in a second, but I’ve been very excited to talk to you, so I’m chomping at the bit here. Because as you mentioned, there’s this sort of eye architecture, brain interface. And among professional athletes, just because I’ve funded a lot of science in this area, low dose psychedelics also seem to improve visual acuity. So everyone from Aaron Rodgers, to very, very high level athletes that I will not dox here, report measurable performance improvements that they attribute to increased visual acuity. Well, it’s probably not changing the anatomy of the eye, so what’s going on? So I would just love you to speak to any other means of supercharging visual perception.

Dr. Jeffrey Goldberg: There are some things that we have a pretty decent sense on. AREDS 2 and some of these supplements — first of all, eating a lot of carrots, it’s probably not going to actually do it. So great, childhood, get the kids to eat their vegetables. We definitely exercised that ourselves as parents. But AREDS 2 clinically proven, if you have moderate age-related macular degeneration, to slow down your vision loss. Does that mean it doesn’t work at all if you have mild age-related macular degeneration or if you have no age-related macular degeneration? It might just be like we haven’t done a study big enough to detect those effects. And as you say, that’s probably not going to hurt, so feel free if you want. We can’t prove it’s helping, but feel free.

There are other supplements that have received some study that maybe suggest there isn’t much going on there, that again, they’re probably not going to hurt. Some patients take CoQ10, some patients take ginkgo. There is actually, maybe the hottest topic in supplement vitamin space right now internationally, is actually vitamin B3, nicotinamide, which has really been linked to a number of good potential medical uses and is receiving a lot of study. There’s actually international clinical trials, including one here in the US, actually testing whether it could restore vision in certain eye diseases like glaucoma, which is my specialty. So definitely some hints in that direction.

We already talked about some device elements, and I think between vision training, like we talked about earlier, and also visual augmentation, we’re moving into augmented reality. And so training vision and visual reflex time almost certainly makes a difference in the activities you’re training in. If you’re training in basketball, will it also help you doing some weekend surfing? I don’t know. But definitely can help move you from normal to supranormal or help enhance and improve what you’re doing.

And then there’s all sorts of stuff that, I’m going to be honest, Tim, we don’t know. Because A, it’s really new, really hot right now, like microdosing certain psychedelics, things like that, that we know act on the nervous system, including the brain. But the retina, in the back of the eye, and the optic nerve that connects the retina to the brain, those are developmentally an outgrowth from the brain. They are part of the brain, they’re part of the central nervous system, and we barely know about how to influence the wiring, the plasticity.

Are there drugs that we can give? A lot of people have talked about gabapentin and drugs in that space. Obviously microdosing in LSD is a really hot area right now for inducing plasticity. There’s actually great science showing in animal models, and a little bit now in humans, that you can actually reopen brain plasticity by dosing some of these drugs at appropriate doses. Obviously we’ve got to be careful, we don’t know what the right dose is yet.

But it’s really worth looking at because there’s clear evidence that these are relevant and likely to have some effects. We’ve just got to figure out a little bit more like how, what’s the right dose? By the way, when you’re doing it, should you be doing some behavioral training, like visual training? But these things act on the brain, and about a third of our brain inside our skull is dedicated to processing vision.

Tim Ferriss: Yeah, there’s a lot there. All right. I have been so — I’m not just over-caffeinated because I’m actually not really caffeinated, I might be over-ketoned. I have quite a bit of ketone monoester in me at the moment. But putting that aside, so I am right now, and this could make me seem like I’m in the tinfoil-hat-wearing crowd, but I had a number of companies reach out to me, not surprising after I put up my social posts. Most of them didn’t make any sense. A few of them seemed to make sense, and the people involved seemed to have technical chops and also some pretty credible research backgrounds. And I’m not going to name the company X, I’m not done with my personal testing.

But I have been testing at about eight minutes a day, I don’t know the right descriptor to use, I would say maybe visual perception training. To distinguish it from, and we can talk about this, what I suppose some ophthalmologists or optometrists might call visual education. So trying to improve the ciliary muscle strength and so on around the eyes. Much like, if people want a visual, sort of the springs around a trampoline. But in this case it’s very quick flashes of blurry or not blurry circles, and you need to identify what is more blurred. And there are many permutations. It adapts to your successes and failures over time. And it could absolutely be placebo, but after about a month now of using it, I feel like my near vision has improved. Even the woman I’m dating has commented on this. And I am still waiting. The jury is out. But this is just to say that I’d love to know what you think of visual improvement that is not dependent on surgery or drops. Is there something to the various types of visual education? Is there something there or not? And then when we go maybe upstream a bit, if that’s the right phrasing to use, to the brain, are there interesting approaches like limiting the frame rate, or removing a number of frames, that you think are at least plausibly interesting for enhancing performance?

Dr. Jeffrey Goldberg: Yeah. First of all, absolutely. And it does get back to that idea of visual training, the reducing frame rate, training on visual perception. There’s actually a fair amount of data. Actually, there’s enough data to even say there’s elements that make it better. For example, if you do visual training where you’re just showing yourself, like being shown these different objects, maybe they’re getting smaller, dimmer, blurrier, etc., your ability to train off of that is significantly better if it demands a behavioral outcome, a motor action.

So for example, you’ve got to point at the right one or choose something. And it’s not just that you’re mentally thinking that was the sharper image, it’s actually the motor output of pushing a button, or pointing at something, or doing an activity that actually reinforces the visual perception training. So that’s one great example.

Another great example is after concussion. So concussion, traumatic brain injury, of course, very common in athletes because they’re more likely to get into the head bumps and things like that, but it happens all the time in kids.

Tim Ferriss: Military. Very big problem.

Dr. Jeffrey Goldberg: Military. A very, very big issue. And the line in between mild concussion, severe concussion, traumatic brain injury, that’s all on a spectrum, a continuum. And there’s actually decent data from that group of people, that if you get a concussion, actually visual symptoms are some of the more significant symptoms. Ability to focus, ability to sleep, and vision are three of the big symptoms that people get in that concussion through TBI spectrum. And those can be debilitating, right? And kids are out of school, they’re missing high school for weeks or longer. It can be really debilitating. 

Obviously, if you’re an older adult and you’re in your job situation, really tough. And it turns out though, that there are visual perception exercises that you can put patients through in those situations that, in the limited clinical studies that have been done, point to a positive effect of basically rehabbing, like neurorehabbing you back. Now, that of course is back from injured to normal, but the idea that that can also induce the same kind of plastic remodeling in our eye and brain, and particularly the eye-brain connection in patients who are starting from normal and trying to get themselves up to supranormal, try to improve performance, visual performance. We’ve set up here a whole human performance laboratory, really just to study these questions and the data rolling in make it look like, hey, there’s something here. This is definitely worth chasing. Yeah.

Tim Ferriss: What can someone search if they want to find something to read up on related to the concussion rehabilitation protocol? Because this type of visual training, because there’s a lot of nonsense floating around and charlatans out there. Any particular search terms or principle investigators or anything that people can search?

Dr. Jeffrey Goldberg: I would say, if you want to at least hit some of the science or science-adjacent web resources, you’re going to want to use a few technical terms in there, like concussion, neurorehab, neurorehabilitation, plasticity, and then some of the terms you’ve already been using, visual perception exercises. And then, look, in these situations, you’ve got to look not just at the content but of the source, right? And so, is this a dude on his blog, or is this coming from a foundation, or an institute, or one of the academic centers, or some of the choices like that?

Tim Ferriss: All right, Jeff, I would love to hop to another set of interventions, and this is in the device category. Red light in the morning for mitochondrial health, question mark? Violet light to reduce progression of nearsightedness in children. Is there an application of red light or violet light? To what extent do we have supporting data for using either of these? Do we have an idea of what best practices look like? Is it only for people with a disease state or can they be potentially used to preserve vision before vision loss?

Dr. Jeffrey Goldberg: Yeah, the disease state data is pretty good. And also the myopia control is pretty good data too.

Tim Ferriss: Just for a definition for folks, what’s myopia?

Dr. Jeffrey Goldberg: Myopia is nearsightedness and it’s an epidemic, more common in Asians or people of Asian heritage, but common in everyone. And kids can get nearsighted. If you’re a little nearsighted, it might be annoying to wear glasses. If you get more severely nearsighted, it actually can lead to all sorts of problems inside the eye, real severe vision loss, even early in life. So that’s a big one. And then what was really shocking was it turns out that a small dose of daily red light can slow down progression of myopia in young people. We’re talking about teens and younger even. So what’s even more shocking to me is that it also works with violet light. So how’s it work with light at the two ends of the visible spectrum? And definitely mitochondria are implicated.

Mitochondria are the little power houses, energy sources inside the cell. They are a big player in converting the sugar a cell takes in into energy that the cell can use for all of the cellular processes. So our bodies clearly need functioning mitochondria. In fact, one of the big features common across many neurodegenerative diseases of the eye and the brain is dysfunction of mitochondria. There’s an FDA-approved red light therapy for patients with macular degeneration, but there’s good data that it may also be supportive or protective in other eye diseases. And we’re talking in small doses. This is not overwhelmingly bright lights and we’re talking about minutes a day. You don’t have to sit in front of it for two hours a day, so minutes a day. So it’s exciting.

The data suggests that the mechanism of action is giving a little protective booster shot to our mitochondria so that they don’t get dysfunctional, whether that’s dysfunctional just from normal use throughout the day or dysfunctional because you happen to have a disease that’s getting in the way of those mitochondria. So now, we don’t know what the right dose is. We don’t know what the right brightness is. All we know is that in these initial things that have been tested, the initial brightness of how and how many minutes, three minutes a day, for example, there’s a signal there. There’s something working there. Should we have everybody buying one on the internet right now, hopping on Amazon, spending 25 bucks, spending three minutes a day? We don’t have the data to support that. Is it going to hurt? Probably not. So, Tim, it’s a problem because we’ve got so many things that are like, “Oh, that looks promising,” and we just, we need a little more science. We need a little more study.

Tim Ferriss: Yeah. Well, a friend of mine wanted me to write a blog post about — look, I’m not a doctor. I don’t play one on the internet, but the difference between getting into science versus getting out of suffering in the sense that you know and I know of just having been involved with the funding side, randomized controlled trials are expensive and they take a long time. But at the same time, if you take the advice of every wackadoodle running around on the internet, you’re going to have 600 different interventions, some of which could do a lot of damage. Or you’re going to get the wrong device. 

I’ve seen this all since I’ve talked about accelerated TMS and different types of brain stimulation for potentially addressing treatment-resistant depression. And Nolan Williams at Stanford has done a lot of great research related to that. And you see these people on YouTube with DIY TMS and they’ve got the polarities reversed, and I’m just like, “Oh, my God, what are you doing to your poor brain?” But I also want to preserve my vision as long as humanly possible, and maybe you can dispel a concern that I have, and this is based on the fact that I have a lot of Alzheimer’s and Parkinson’s in my family. And I’m APOE3/4, some 2.5 times or so more likely to develop Alzheimer’s, based on what we currently think we know, than someone who is, I guess, 3/3. And it scares the hell out of me. And I’ve had conversations with audiologists who point out the correlation, I don’t know how strong the signal is, between hearing loss and onset or progression of dementia. Is there something similar for visual loss?

Dr. Jeffrey Goldberg: Absolutely. Actually, one of our faculty here has done some of the really foundational research showing that correlation between vision loss and cognitive decline, and the loss of input. Again, vision is our biggest input sense. It’s driving, a third of our brain is dedicated, as I said, to processing and using that vision, and interfaces with every other thing that we do. It also is a really critical piece around depression and mental health. Anxiety is vision, the work that Andy Huberman had done on visual fear and how that plays into the fear and anxiety pathways as well as the depression pathways. And not only does visual decline accelerate cognitive decline, possibly because, in part, because of how depression then plays in with cognitive. These things are all clearly related to each other, but also remarkably, if you have low vision, let’s say from something as simple and correctable as cataracts, a blurring of the lens that happens with age.

If we all live to a hundred, we’re all going to need cataract surgery, some people younger, some people older. But if you do cataract surgery and restore vision in an older person who appears to be suffering, is suffering with cognitive decline and/or depression, you can reverse a significant amount of that decline in either of those domains. And so it just, again, it speaks to the interplay of vision with our mental health, our cognitive health, and this is long-term, important stuff.

Tim Ferriss: And this, tell me if I’m interpreting this the wrong way, but it seems like this would lead to a strong pro argument for wearing glasses instead of suffering in silence. I don’t know, but that’s what I hear when I’m trying to read between the lines.

Dr. Jeffrey Goldberg: There’s an important myth to dispel, especially when it comes to presbyopia and wearing reading glasses. Between age 40 and around 60 or so, that lens stiffens, and stiffens, and stiffens. And the first year you only need +1.25 glasses, and then three years later you’re like, “Ah, I need +1.5, +1.50s.” A few years after that, you’re moving up to the 2.0s. Eventually you’ll peak out at around 2.5 or 3.0s, because that’s the difference, basically. That’s the refractive, the glasses difference between viewing something at infinity, which from an optics perspective is actually just three feet away or further, and viewing something at 14 inches, comfortable reading distance, right in front of us. So 2.5 to 3 power of those readers is all you’re going to need, but you’re going to progress through those numbers whether you wear the readers or not. So wear the readers!

Tim Ferriss: I got it. Is it a mistake in causality then, where people believe?

Dr. Jeffrey Goldberg: Yeah.

Tim Ferriss: Because an optometrist said this to me a couple of weeks ago, and I was like, “Well, I assume you know what the hell you’re talking about,” which is always a stupid assumption, but that you develop increased dependence, but it’s actually just tracking along with the natural stiffening of the lens, in the case of presbyopia.

Dr. Jeffrey Goldberg: It is and it’s psychological dependence. It’s just like what I went through as soon as I started wearing those readers by accident. I didn’t think I needed them. I was still reading off my phone. It was fine, but as soon as I experienced that extra crisp vision, I was like, “Well, I like that.”

Tim Ferriss: Yeah.

Dr. Jeffrey Goldberg: So I got psychologically dependent because who doesn’t want their best vision?

Tim Ferriss: Yeah, for sure. And I’m going to keep saying this, it’s going to get annoying because I’m like a sweaty-palmed fanboy, jumping all over you, but I was very excited to chat with you also because the nose, the brain, these are direct paths into the brain in a sense. And for instance, I don’t know, I don’t expect you to track all things in all fields. That’d be impossible, but Cognito Therapeutics, it’s a headset that is used and they have a lot of good data. I think they’re either phase two or phase three. They’ve raised a ton of money, and it’s a headset, and they have these visors covering the eyes, and then earpieces. And it produces, I want to say, gamma waves in the brain. There’s more to it, but using flashing lights, and this appears to — I’m getting into the deep end of my ignorance pool here, pulling from memory, but it appears to assist in the breakdown of beta-amyloid plaque, maybe tau as well. I’m not really sure.

So using flashing light to help people with conditions like Alzheimer’s. It’s mind-boggling, I guess, literally and metaphorically. And that does come from credible researchers. I wish I could cite them offhand, but it’s going to take me too much time to find the scientists involved. But that is one that appears to be — Ed Boyden and Li-Huei Tsai out of MIT.

Dr. Jeffrey Goldberg: Yeah. Yep, I know them both. Ed was a graduate student here at Stanford when I was at Stanford.

Tim Ferriss: Oh, amazing.

Dr. Jeffrey Goldberg: Yep, yep.

Tim Ferriss: Yeah, so there you go.

Dr. Jeffrey Goldberg: Yeah.

Tim Ferriss: Are we going to see more of these devices and how far away are they? Because I’m seeing decline in my near relatives. I’m currently taking care of two relatives with severe cognitive decline. It scares the hell out of me. And some of them are 3/3, by the way, and I’m 3/4, so I’m like, “Good God. Okay, if there’s anything I can do,” and I’m already doing quite a few things, but are there other devices that are on the cusp of being available that you find interesting?

Dr. Jeffrey Goldberg: Yeah, I think so, and input through the visual system and output through the visual system are both looking really interesting these days. So you’re talking about input. What can we stick in through the visual system to influence the rest of our brain, brainwave activity, plasticity, like we were talking about before, help preventing cognitive decline? We actually, there is very strong data, for example, that if you give the right amount of electrical activity of our neurons in the eye and the brain — so the neurons in the brain talk to each other through electrical activity, like little wires and too much activity is bad. Really too much activity is epilepsy, for example, Too little’s clearly bad too. If you have a stroke, then you’ve got no electrical activity in that area of your brain and it’s just not working anymore. But providing that sweet spot in the middle of electrical activity, in addition to it participating in the processing of whatever that area of the brain does. In the retina, it’s your vision, obviously.

It also stimulates pathways like plasticity and responsiveness to the survival and growth factors. And we and others have shown that very clearly in animal research over the years, that you need not just the right growth factors circulating around in the brain, but you also need the right levels of electrical activity so that the neurons are maximally responsive.

Tim Ferriss: Yeah, it’s like weightlifting. You can have all the protein in the world.

Dr. Jeffrey Goldberg: Right.

Tim Ferriss: You need the stimulus.

Dr. Jeffrey Goldberg: You’ve got to have the right amount, right? You’ve got to match that up, and so it’s really cool. We actually know in the eye the visual — you were talking about flashes of light, but it turns out different cells in our eye respond differentially to different stimuli. We have some cells that fire when the lights go on. We call those, very creatively, ON cells. We have some cells that fire when the lights go off, called OFF cells. We have some cells that are firing between blue and yellow, others that are differentiating between red and green. We have some cells that are in charge of motion detection in the eye, and all that data has got to get back to the brain. But if we stimulate, for example, the motion-direction-sensitive retinal ganglion cells in our retinas in headsets where we devise cues — 

Basically imagine you’re flying through that Star Trek field of stars, like you’re going into hyperspace, right? To engage, and you’re going into — and all those stars speed up by you. Those are great stimuli for some of our direction-sensitive cells in the eye. And could those actually stimulate those cells to then perform better or not degenerate in disease? And so we’ve been studying those kinds of questions. Cognito’s engaged in that kind of work. And then how does that affect what’s going on in the brain? Very reasonable that that’s going to actually lead to specific patterns of activity, flexibility, plasticity that are going to change our brains. And the idea that some of that work can not happen only in the academic world, but that people are excited about it, and are funding the startup companies, and taking that science into that either health domain, healthspan domain or consumer domain. How do we get the normals protected against the future? There’s a lot going on there. That’s on the input side.

Tim Ferriss: Yeah. Okay. I am going to just bookmark that for a second, and I’m going to highlight a few things that I thought were of interest and I’d like you to expand on from your conversation with Andy. So glaucoma, could you have a normal reading during the day, but higher at night? And then the potential place of cannabis edibles.

And my question there was do we know what compounds are responsible? People are listening to me and they’re like, “What the hell are you talking about?” So if that’s enough of a cue, would you mind just discussing that? Because a big challenge with people who are trying to do the right thing. They’re trying to get check-ups. They’re trying to get assessed/ they’re getting their blood work done, but maybe it’s once a year and they had their blood draws, the last one was at 8:00 a.m. and the next one was at 11:00 a.m., and lo and behold, their testosterone is really different and they freak out, and this, that and the other thing. So timing matters among other things. Could you just speak to glaucoma in that respect?

Dr. Jeffrey Goldberg: Absolutely. So let me just back up one step. Glaucoma, after Alzheimer’s disease, glaucoma is the most common neurodegenerative disease. It’s the number one cause of irreversible vision loss in the world. It’s a degeneration of that optic nerve connection from the eye to the brain. So those retinal ganglion cells that are collecting the data in the retina and their axon fibers, those telephone wires running down the optic nerve, carrying that, all the vision from the eye to the brain, they degenerate in glaucoma. If you take all comers, it’s around two percent of people in an aging population that will have developed glaucoma. If you have a primary family member, a parent, a sibling, a child with glaucoma, your risk probably goes up to about 20 percent. So it runs in families, but just because your parent has it doesn’t mean a hundred percent you’ll have it.

There are two main risk factors for glaucoma. One is increasing age, and we’re all working desperately on correcting that one, but we don’t have a slam dunk treatment for that yet. 

The other main risk factor for glaucoma is actually increasing eye pressure. If you have real high pressure, you’re going to get glaucoma. But a lot of people with normal looking eye pressure can also develop glaucoma. It’s just like they were more susceptible, and the eye pressure isn’t just the same number. We’ve got short-term variability and long-term variability. So long-term is, this month, it might be whatever number, next year, it might be a little higher, a little lower. You can vary through your life. But there’s also this short-term variability. It actually varies in our diurnal cycle. So everybody has a diurnal cycle where you — your circadian rhythm, and some of us, like myself, are night people, and we love to be up at night, and getting up in the morning isn’t our favorite thing, and other people are the opposite. And all this stuff relates to our diurnal cycle, our circadian rhythm.

You can try to take melatonin and affect that, but your eye pressure also varies by that. And as you say, if I take your eye pressure in the morning and then the next week I take it in the afternoon and I say, “Oh, my God, your pressure’s gone up. I’ve got to take you to surgery.” Well, wait a second. It might just be because I’m measuring at different times. 

Now, you brought up the most common question that I get asked. I’ll tell you the most common question that I get asked by patients with glaucoma is, “Hey, can I take cannabis?” And by the way, it’s like legal for medical use in many states and frankly, recreational use also in many states, and certainly accessible in every state. Can I take cannabis? Cannabis, whether you smoke it, or eat it in the brownie, or take the chewy, it lowers your eye pressure, if you’re using the version which are available where you feel a little high from it, you get that good feeling. The problem is that it only really lowers the eye pressure during that time that you’re getting high. So I tell patients, it works but you’d have to be high 24/7, so maybe you should just use this eye drop instead, right?

Tim Ferriss: Do we know which compounds within cannabis are responsible for the lowering of the eye pressure?

Dr. Jeffrey Goldberg: Yeah. There’s actually data that both the THCs that do get you high and the others also that don’t can have that effect. And there’s some cool startup companies that have been working on trying to isolate and now test in human patients the, you don’t get high versions of those compounds or chemically modifying them, and by the way, turning them into an eye drop so that it’s really just treating the eye and make that really accessible. You don’t want to be on your glaucoma treatment and not able to drive, so — 

Tim Ferriss: Yeah, that’d be a bummer. Trade-offs.

Dr. Jeffrey Goldberg: — it’s got to be compatible with daily life for most patients, right? Yeah, so that does work. That does work.

Tim Ferriss: Mm-hmm, so — 

Dr. Jeffrey Goldberg: The second most common question I get asked is, “Well, can’t you just fix my eye, or give me stem cells?” Or that kind of thing, but number one is cannabis.

Tim Ferriss: Well, what’s your answer to the stem cells, the magic stem cells?

Dr. Jeffrey Goldberg: We’re getting there on stem cells. So if you’ve lost your retinal ganglion cell connection to the brain through the optic nerve, we are actually getting pretty good at growing retinal ganglion cells out of human stem cells, in the laboratory cell culture dish. And we’re actually starting to make real progress, in animal models to start, showing that you can transplant them in. But I still tell patients, don’t go to some clinic that’s telling you they’ll give you stem cells and pay $18,000 of your hard-earned money. It is not ready for that yet.

Tim Ferriss: Go to Tijuana and get a new pair of eyes.

Dr. Jeffrey Goldberg: Exactly. Don’t waste your money.

Tim Ferriss: Well, yeah, that’ll be the least of your problems, will be the money part. So let me circle back to the cannabis for a second. So I don’t consume much cannabis, but I have experimented with cannabis for chronic pain and specifically a number of back issues that I have and some of it’s congenital. I have a transitional segment and a bunch of orthopathy and blah, blah, blah, blah, blah. And interestingly, a lot of folks, including people who are sort of credible and familiar with the literature, recommended CBD, but I did not find it to have a pain-relieving effect that was sufficient for sleep until adding a little bit of THC, which I thought was actually pretty interesting.

And I’m wondering if this actually cycles back to our very short discussion of psychedelic compounds also because why might psychedelics, say, improve visual acuity? You can come up with a dozen sort of plausible explanations, but when you look at, say, the depression outcomes with psychedelics, people on many different parties in terms of arguing why or how they exert their effect, one that I think is under emphasized is the anti-inflammatory effects, which can be potent in some psychedelics. And you can find studies where they look at anti-inflammatory, just standard off the shelf anti-inflammatory effects on depression, which can be substantial. Do we have any data to suggest that anti-inflammatories have any effect on vision or can in any subpopulation improve vision?

Dr. Jeffrey Goldberg: Yeah, absolutely. So decades ago there was a pretty hot focus on to what degree the immune system might be playing a role, particularly in eye diseases including the common ones, macular degeneration, glaucoma, and then it was hard to pull that together in part I think because we didn’t know as much about the immune system 20, 30 years ago as we do today. And now we know a lot about what we call the innate immune system, which is not the part that learns about the flu virus and makes you immune the next time you get the flu virus. But just how our immune system interacts with our body normally and how it also might interact with our gut bacteria and then cross-react with our own body, things like that. And so it turns out now that we’ve got this much deeper appreciation from the whole immunology crowd about how the immune system and in particular the innate immune system works, we’re now revisiting in neurodegenerative diseases, including glaucoma macular degeneration, and it turns out it is just packed with evidence that the immune system and innate immunity really play a role.

Let me give you one example that is shocking. If you raise the eye pressure in a mouse, the retinal ganglion cells and the optic nerve will degenerate just like in human glaucoma, but in a really beautiful set of experiments that came from a woman, a professor at Harvard, Dongfeng Chen, she showed that if you raised the eye pressure in a mouse that was raised itself, grew up in a germ-free environment and doesn’t have all the normal mouse dirty gut bacteria and therefore its immune system is at some level fundamentally different, you can raise the eye pressure in that mouse, but the optic nerve won’t degenerate, they won’t get glaucoma damage. And then if you take the immune cells out of the first mouse and just put them back into the bloodstream of the second mouse, then the optic nerve will regenerate.

Tim Ferriss: Wow.

Dr. Jeffrey Goldberg: So the immune system is playing a huge role that was previously totally underappreciated and they’re amazing drug therapy candidates that are now moving up through the pipeline towards human testing to test, hey, if we could suppress the immune system. Not totally suppress it because by the way, we still want to be attacking bacteria and viruses but just suppress the little leg of that immune system that’s attacking our body and leading to neurodegenerative disease, that’s going to be off the charts.

Tim Ferriss: As you’re talking about the microbiome and so on, I was doing a bunch of reading for another interview I’ll be doing shortly with the scientist and one of the stories, and this is in animal models of course, but looked at how — and some people have heard through the grapevine one way or another how you could take the microbiome just for simplicity’s sake of say obese mice and transplant that to lean mice and they get fat or vice versa. And I might be getting some of the details wrong, but roughly you see some very interesting effects. However, if you sever the vagus nerve in those recipient mice, they do not exhibit those changes.

And so then some of the questions that are kind of outstanding is, well, if that indicates that you could instead of using ablation or severing something stimulation to achieve a similar effect, then what can you start to do? And then you have hockey puck size things that you put next to the liver that can via some technological wizardry affect these things. But God, I suppose that the more I look at a lot of these things also with family with Alzheimer’s and they might take something like Theracurmin, which has, on some level, inflammatory effects. I’m like, okay, well, and I don’t want to be a one trick pony with the one thing I keep beating over the head, but it’s like, okay, well, if we know that inflamed like microglia have all of these hosts, or at least they’re associated with a host of different neurodegenerative diseases and inflammations associated with depression, to what extent can we mitigate these things and we’re sort of hitting a bunch of birds with one stone.

Does that make any sense? Which is why I’m so interested in the possibility of using devices. I’m so interested in the ketogenic nutritional ketosis, but also exogenous ketones. Brain loves this stuff also, the beta hydroxybutyrate, very potent anti-inflammatory. I’m just wondering, do you think that I am just too clever by half and I’m missing the plot here? 

I feel like chronic inflammation, which is kind of like saying business or the arts, right? I mean there are a million different facets to inflammation. You need inflammation for a lot of reasons, but when it is pathological and chronic, it turns into a big issue. With rapid decline in eyesight, let’s just say in glaucoma, how often is that comorbid with metabolic syndrome or something like that when the decline is faster than, say, average?

Dr. Jeffrey Goldberg: The earliest data looking at, let’s say diabetes as a marker of a lot of patients with type two diabetes, it’s associated with what we call metabolic syndrome, which is this cluster of high lipids, high blood pressure, insulin resistance. And so there was initial data suggesting that a little bit of diabetes might actually be a little protective in glaucoma.

And then some of the follow up next set of studies suggested like, no, no, no. Maybe it’s a little bit bad for your glaucoma. And so the net is it’s probably not metabolic syndrome as a whole is probably not a huge difference. But I’ll tell you the place where those two are converging is one of the hottest topics in medical science today, which is these GLP-1 receptor agonists, which are going to have a huge effect on human health by reducing metabolic syndrome, overweight, obesity, et cetera. But also are looking very promising for neuroprotective.

And I think it actually gets to that point. You’re trying to tease yourself, are you just getting ahead of it? But actually you’re touching on, I think where we’re actually coming to as an understanding is where the science is going in the field, which is this axis between the brain, which you think of, well, isn’t that mostly inside my head, but also the peripheral nerves that are going out to the whole rest of our body and the immune system and those two are talking to each other all the time and now we’ve got the microbiome and that gut axis is like a third leg of that stool because that’s clearly also interacting with both the nervous system and the immune system in very specific ways.

So we’re going to see a lot more of that really, I think, come together and understand more mechanisms. Is it going to be one day that we’re all just kind of taking that purified poop pill that we just swallow down and it changes our microbiome for the day and it protects us from Alzheimer’s or glaucoma in the future? We’re all hoping that’s going to happen. We’d love that protection one day. Should you buy the poop pill off the internet just yet? I’m not sure. Yeah, I don’t think so.

Tim Ferriss: Yeah, Sri Lankan poop pills from rural children. I’m in. Yeah, be careful with what’s out there on the internet, guys. And I’m not supporting a company, I might have to bleep this out, but called Holobiome and they’re actually creating the most comprehensive library currently of gut microbiota because it’s like what you can buy currently off the shelf. First of all, most of it’s dead. It’s inert by the time you consume it. A lot of it doesn’t actually get through your metabolism to where you want it to be. And it only represents maybe in a few dozen, I don’t know what the right term is, strains of bacteria. Whereas there’s like thousands upon thousands. So there’s so much to explore, which is also very exciting.

Dr. Jeffrey Goldberg: Let me give you one more idea of what might be that ideal world on the way to that.

Tim Ferriss: Yeah.

Dr. Jeffrey Goldberg: We share microbiomes between us. Actually we had our at Stanford Med School years ago when I was there, we had a microbiology professor and he used to kind of tease the world is covered with a thin layer of poop because no matter how well you wash your hands after going to the bathroom, there’s a couple bacteria that got on your hands or your belt buckle and then you shake hands or pat someone on the back. I don’t want to increase anyone’s anxiety, but the world is covered — 

Tim Ferriss: This episode is brought to you by Purell.

Dr. Jeffrey Goldberg: There’s a thin layer of poop. “What we call clean and dirty,” he used to say, “is really just how thick that layer is.” Okay, so that joking aside, if you just shack up with someone who’s got great longevity and a great microbiome, good chance you’re going to absorb their microbiome, maybe that’ll be good for you.

Tim Ferriss: Look at that.

Dr. Jeffrey Goldberg: They’ve got to put that on the dating websites. Get your microbiome on that profile.

Tim Ferriss: Right? Craigslist, microbiome casual encounters. So this is going to be a bit of a hard left, but preservative-free strips of tears for dry eye. Why? That was one of my notes from the conversation that you had with Andrew because I’m also looking for just low-hanging fruit for people who are contending as we all do with aging eyes. Maybe you could speak to that. And then I do have to ask about the blood serum for eye drops. Maybe you can hit that too.

Dr. Jeffrey Goldberg: Sure, sure. So look, actually the most common eye disease as we get older is actually dry eye. As we get older, we make fewer tears. We also make lower quality tears. Our tears at high quality have a liquid phase, like a water, salt water phase. There’s also like an oily component to good, high-quality tears. And that oily component also kind of dissipates a little bit as we get older, gets less as we get older. So we make fewer tears and lower quality tears. And a real simple over-the-counter solution for so many people is just put in some artificial tear drops.

The thing is that those little bottles come with preservatives so that when you use it all month, by the end of the month, it’s not growing bacteria. And if you’re just using a drop or two a day, fine, that’s getting you by, fine. Just buy those bottles. They’re the cheapest. But if you’re getting to the point where it’s three, four, five, six times a day, maybe you work on the computer a lot so you blink less and your eyes get drier, you want to use more of those, then we usually recommend at that stage switch over to preservative-free artificial tears because it turns out that preservative in those bottles of drops at a drop or two a day, fine. But if you’re getting up to a lot of drops a day, the preservative is actually irritating and kind of inflammatory to the ocular surface. It actually kind of breaks down some of the cells on the surface of our eyes.

So at that point, we like to switch people to recommending the preservative-free. They’re the ones that come — like usually they come in a little strip of tiny little plastic. You break one off, it’s got its own little cap on it. It’s got this tiny little bubble of fluid that you can squeeze. It really tests if you’ve got bad fingers or bad — by the way, if we’ve got bad vision, you’re poking yourself in the eye with it. So anyway, that’s what we recommend. Switch to preservative-free. And then people who need more than that, we actually have drugs that, for example, reduce on the ocular surface to help the tear quality and quantity come bounce back a little bit.

And then we also have drugs that contain growth factors, things like nerve growth factor that are almost certainly also good for the surface. And when our eyes get dry, the surface, the reason it feels irritating is not just because it feels dry, it’s actually because the surface starts to break down a little bit. And when you go to sleep every night and your eyelids are closed and nothing can evaporate, it bounces back a little bit by morning. So it kind of regenerates or rejuvenates. The ocular surface can regenerate pretty well every day, but at some point your eyes are getting dry enough that you’re having much more chronic problems.

And that’s where sometimes we can use what are called serum tears. So our blood serum, if you take out a blood, like a tube of blood, you’re getting your blood drawn. That tube of blood has your red blood cells carrying all your oxygen, your white blood cells, which is like your immune system, and then all just the liquid with the proteins in it. That’s what we call the serum. That’s the serum. So you could take that tube, you spin the cells out — 

Tim Ferriss: Let me ask a dumb question. Is that different from plasma or are we talking — 

Dr. Jeffrey Goldberg: Serum and plasma. Yeah, depending how you treat some of those proteins, that’s serum and plasma. Let’s just say you’re spinning out the cells and then you can take that serum. Maybe you dilute it a little bit in some of that preservative free artificial tears. Maybe you just use it straight. Usually we dilute it a little bit and we can give patients their own serum as artificial tear drops. And that serum is filled with really good juicy growth factors that help the surface rejuvenate. And that’s the principle of, in some patients, using serum tears.

Tim Ferriss: Maybe this is just a difference in terminology, but it makes me think of a platelet-rich plasma or platelet-poor plasma. Are there experiments with different, I’m not sure, concentrations or cocktails?

Dr. Jeffrey Goldberg: Different cocktails. That’s a great way to put it. Yeah. And platelet-rich plasma, again, one of the reasons that that looks so rejuvenating for our bodies is again, it’s just like chock-a-block full of growth factors. And so I don’t know, I’m sure somebody’s testing this as another way to treat really severe dry eye, or if your dry eye is so bad, you’re actually getting kind of ulcers on the surface of your eyes. Some of the most severe cases might really benefit from like serum tears. Maybe platelet-rich plasma would work too. So that’s a hot area right now. And again, filled with growth factors.

Tim Ferriss: So we talked about the importance of timing with, say, glaucoma exams, things of that type. What are some other recommendations for perhaps avoiding common mistakes or filling gaps that are commonly unfilled? Any recommendations to folks?

Dr. Jeffrey Goldberg: Yeah, there’s a bunch of things. First of all, get an exam and if you have a family member, a blood relative with eye disease, maybe get that exam even sooner. Take glaucoma as an example. If you got an exam and you’re 40 and you don’t have a family history and your exam was normal, you don’t have to come do that full exam every year. You could come back in five or 10 years, try it again. But especially as we get older now, half the people in the world need glasses, half the people in the US need glasses. So you might be going in to your local eye care provider, optometrist, getting your glasses checked each year or two anyway, just to see if you’re still in the right prescription and they can do the full exam, check for everything else, make sure nothing else looks suspicious, leave you in great shape.

So getting that periodic eye exam, especially as we get older and more of those age related diseases like macular degeneration, glaucoma, et cetera. Obviously if you have diabetes, you’re supposed to get an eye exam every year just to make sure, because if you’ve got diabetes and it’s starting to affect the retina inside your eye, we could get ahead of that. We’ve got good treatments that can prevent you from losing vision. So we want to stay ahead on these diseases. That’s the main thing. Other things, everyone’s going to get cataracts eventually, but what can we do to slow down the development of cataracts? Well, one real easy one is reducing UV light exposure. So you’re out in the sun a lot, wear sunglasses. All sunglasses made today have UV protection. By the way, all regular glasses that don’t have darkened tinted shades, they also block the UV light from going through.

So even if you’re wearing your regular glasses outside because you need glasses, that works too. So wear sunglasses or some sort of eyewear protection. And then eyewear protection is another big one. Depending on what industry you’re in, you’re gardening, you’re in steelworks, you’ve got anything where you’ve got eye injury risk, wear a protective eyewear. It costs like a buck 50 at Home Depot to get those really attractive plastic glasses that are wraparound, but wear them when you’re in those work situations. That’s a big one too. You see a lot of athletes now wear eyewear and sometimes it’s for sun protection, but you’ll see a lot of them when it’s not that sunny day or they’re even playing inside and they might be wearing it for prescription, but also just for eye protection.

Tim Ferriss: Eye protection. Is there anyone out there, and I don’t have a dog in the fight, it’s just that this conversation around sunlight and exposure, it’s like a religious war online. Is there anyone you would consider scientifically credible who has any counter-argument with respect to UV light, why it is important to also get natural exposure or could be important to get exposure to UV light? Or does that just not exist? Is there a strongman argument for that or does it just not exist?

Dr. Jeffrey Goldberg: I don’t ever want to say something doesn’t exist because someone on the internet — 

Tim Ferriss: Which is why I say scientifically credible.

Dr. Jeffrey Goldberg: But no, full-spectrum light, white light that goes from violet through red, full-spectrum light. There’s a lot of decent evidence that that’s good and important. By the way, let’s come back to the development of nearsightedness. We used to say like, oh, maybe people are getting nearsighted as kids because they’re spending too much [of their time] indoor reading. And so it’s just like too much near work is leading to nearsightedness. There’s now pretty good data actually that it’s not the near work, it’s the being inside part of reading inside. And if you just send your kid outside and let them read outside in full-spectrum lighting, they could still be doing their near work or doing their homework, whatever it is, but it’s the full-spectrum lighting that will actually slow down their development of nearsightedness.

So you can get full-spectrum white light, but skip the UV by either having full-spectrum lighting indoors or through the window and you’ve got a nice sunny window. The sun that comes through the window, the glass actually filters UV light, so that’s fine. Your car window filters UV light. So even if you’re not wearing sunglasses inside the car, you’re getting that full-spectrum sunlight. Go outside in the morning, fine, get that first sunlight if you want. But there’s no data that suggests that part of that full-spectrum light has to include UV light.

Tim Ferriss: Okay, got it.I know that this might be asking a lot, but what do you think we might be getting wrong currently in any paradigm of how we think about vision or eye health? Right? I mean, I have a lot of doctor friends, a lot of researcher friends, and I guess it’s especially common among MDs, but they’ll say, yeah, 50 percent of what we know is wrong. We just don’t know which 50 percent. Which doesn’t mean science isn’t important, guys. By the way, it is incredibly critical for not fooling ourselves. And anyway, I don’t think I need to preach that to you, but what would you not be surprised to see overturned in the next five years if you were like, you know what? We’ve always thought X and it turns out, nope, it’s different.

Dr. Jeffrey Goldberg: I’m going to pull one out of my personal favorites list here.

Tim Ferriss: Yeah, great.

Dr. Jeffrey Goldberg: And it comes back to these big ticket eye diseases like glaucoma, macular degeneration, even diabetic retinopathy and other less common versions of these degenerations, let’s say, of the retina, the optic nerve. And we have always said, I even said earlier in the podcast with you, Tim, that glaucoma is the number one cause of irreversible blindness in the world. That I think is going to be the piece that we overturn. We have always said, “Hey, we’ve got to prevent you from losing vision. We’ve got to slow down the disease because once you’ve lost whatever vision you’ve lost, I can’t get that back for you.” And I think that is about to topple.

We are about to get into vision restoration at a level that has been totally unexpected and totally unprecedented, and the science supporting these directions in these diseases is getting really, really juicy. We have discovered so many molecular pathways, approaches to cell therapy. Some of the things we even talked about earlier, like inducing plasticity in the brain. If I stick a stem cell into the adult retina and I say, “Hey, I need you to turn into a retinal cell, hook up with your partners and start doing vision.” Well, during development, the retina, those cells are all developing. They learn to wire up together, do it right.

How do we get a cell that we’re going to put into an adult person to say like, “Hey, I know all you other retina cells are already neighbors with each other, but I’m moving into the neighborhood and I want you to accept me.” But we’re figuring out how to induce that plasticity, like open up the neighborhood, let that cell get into the network, start to participate in the network and restore vision. So it is moving really quickly right now and it is starting to translate, this laboratory science is starting to really move quickly into appropriate, safe human clinical trials. And so I think that is going to be the biggest topple is going to be that we can restore vision. And I will not be surprised if our colleagues in the brain follow suit quickly. We like to tease who’s going to come first, the eye or the brain. I will not be surprised if our colleagues in the brain follow quickly and maybe we could restore cognition in people with severe cognitive disease, Alzheimer’s and these others. So I think this kind of restoring the central nervous system, including the retina and optic nerve, spinal cord injury, I think this is all, we’re going to topple that in these next few years.

Tim Ferriss: That’s very exciting. When I talk to folks I’m like, look, I know it seems like one day, they’re like bananas will kill you and the next day bananas will help you live forever. And it’s like, first of all, a lot of that is fun house mirror warping by media coverage. And secondly, there are so many breakthroughs or breakthroughs that are on the cusp of making their way into clinical practice. I can’t help but be super optimistic about so many, at least the fields that I have a decent amount of exposure to. And I’m going to ask you a few follow up questions, but first, I’ll just say for people interested, if you are interested in looking at how, for instance, and there are multiple ways to induce greater plasticity in various ways, but if you’re interested in the reopening of critical periods, which we alluded to earlier, Gul Dolen, who was at Hopkins and is now at UC Berkeley, has done some wild work and has really rocked the boat and I think a very productive way looking at how MDMA but also potentially other compounds can potentially do that.

And she’s got wild experiments with octopuses and all this stuff that people should check out. But I believe that at some point, if she’s not already doing it, she’s going to look at, for instance, using these compounds to help stroke patients recover motor function. And there are also devices like DARPA and the defense language in Monterey have used for improving language acquisition. I mean, I really feel like there’s a lot of stuff that is not only happening but converging in interesting ways. What leads you to believe that we’re so close, the next five years is close, right? So is it just the publications you’re seeing, the types of science that is being done? Is it just new and novel ways to induce plasticity? Is it because the plasticity gang is finally playing nice with the eye people who are playing nice with the other brain people? What is actually happening?

Dr. Jeffrey Goldberg: Some of those things, like I was teasing before, but the truth is, we, eye people, love to work closely with our colleagues in brain because there’s so much shared science. I do think that there’s an increasing attention to, hey, let’s answer these questions properly, let’s do proper trials, let’s really study these things properly and let’s also move things out of the laboratory and into human testing and have it not just be the fantasy and the mice, but never move it to the person. And so I think that transition, that willingness to grow in that direction, we’ve had actually, to be honest, a remarkable two to three decades now of increasing support for science at the federal level, but also startups. Biotech has had an amazing age and that biotech, when you’ve got an amazing age cooking on the pharma side like big pharma, that then trickles down. So that means startups can say like, “Hey, let’s roll the dice and test this anti-aging formula because if it hits, there’s a market for it at the end of the day. This is important. These are big impact areas.”

So I think the investment that we make in science plays out and we’re sort of coming to a head a culmination. And I think that happens to be matching in time the advances we’ve been making in neuroscience. I think we made huge advances in immunology and cancer biology a couple decades ago, even just understanding what all the cells are. And I think that the analogy is the advances we’ve made even just in the last decade of being able to map the brain, not just even down to the cell level, but the cell-to-cell connections called synapses. We’re now mapping entire brains at that level and understanding how they talk to each other and recording and creating. We’ve got a colleague here who just had an amazing suite of papers, Andreas Tolias and his colleagues creating a digital twin of the entire brain.

And then you can do experiments on the digital twin of the brain. You don’t have to actually do them on an animal or a person to start. You could start there. So the advances in neuroscience and understanding of plasticity and all of these elements I think are converging with the advances that we’ve just been willing to make over the last couple of decades in healthcare, health-related research, discovery research, translational research, clinical trial research. And I think we’re just kind of seeing those two converge right now in an amazing way.

Tim Ferriss: If you don’t mind, let’s talk about mitochondria again for a second. So mitochondria, often referred to as the powerhouses of the cell, I won’t bore people with more ketone talk, but also read a piece recently from a very credible scientist, beautifully written also, about how they’re not just the powerhouses but maybe the motherboards of the cell. And there’s actually a lot of what you could view as social interaction between mitochondria and among mitochondria. Really just the deeper you go, the more interesting it becomes. And I’m wondering outside of the red light, if there are other interventions or technologies, biologics, anything, that you think are interesting for improving mitochondrial health within the visual system, however you want to take that.

Dr. Jeffrey Goldberg: Yeah, absolutely. And in fact, mitochondria, not only are they social with each other and they actually talk to each other, they actually fuse and then separate. They get trafficked up neurons. We talked about the ones that stretch from the eye to the brain. There are neurons of course that stretch from the top of our brain all the way down to the bottom of our spinal cord. There are neurons that stretch from our spinal cord all the way down to our toe tip. These are some long cells and they’re trafficking mitochondria all up and down. So they are social creatures for sure, but it turns out they’re yet a third thing. So they’re powerhouses, they’re social creatures, but they’re also scaffolds and they’re actually the foundation upon which a lot of other cellular signaling that’s regulating what a cell is supposed to do is happening on the surface of the mitochondria.

And so you’ve got metabolism, energy, scaffolding of signaling. And so no wonder half of our neurodegenerative diseases are associated with one or another defect that we can trace back to mitochondria. So that kind of adds up at the end of the day when you look at it that way. And some of the things we’ve already talked about, I mean you brought up red light therapy, that would be one for sure, but vitamin B3, nicotinamide, it’s directly affecting some of that metabolic signaling that is interfacing with the mitochondria metabolism biology. And so actually a lot of these supplements that are about metabolism end up having some link back to mitochondria.

Tim Ferriss: Yeah, I was going to say it’s kind of hard to dodge the mitochondria.

Dr. Jeffrey Goldberg: Yeah. Yeah. And look, it’s cool. Look, I mean I just read that they’re now doing successful mitochondrial transplants, for example, into an embryo. So you can have inherited diseases where the disease is inherited because your mitochondria are bad. Mitochondria get most of their proteins and lipids and all of that that make up a mitochondria. They got most of that built from the nucleus, the regular DNA of the cell. But they have a little bit of DNA themselves that make some of the proteins inside the mitochondria. And so you can inherit that mitochondrial DNA that has mutations and have real serious diseases. It’s now been shown you can transplant mitochondria so that that baby will not have an inherited mitochondrial disease. Is it that far off to think that we could transplant mitochondria into the retina of your eye and stave off another decade of glaucoma? These things are on the table, so definitely interesting.

Tim Ferriss: Okay, so I saw some news about, I think you can’t trust the headlines, but basically babies with three parents, so to speak, out of the UK now. So you mentioned the embryo. So this is a case where you’d be taking third-party mitochondria — 

Dr. Jeffrey Goldberg: You’re hitting it. That’s exactly what I was talking about. So you’ve got DNA from the mom in the egg cell. You’ve got DNA from the dad in the sperm. But you could take a third party’s mitochondria outside of their cell, inject it into that egg just like the sperm went into the egg, and now that egg with Mom and Dad’s DNA and a third person’s mitochondria, including their mitochondrial DNA, will propagate and form the whole embryo. And it’s kind of, I mean it’s an amazing headline. Does that mean there’s three parents involved?

Tim Ferriss: I mean, it’s equally fascinating when you just understand what you’re describing. And part of the reason I’ve been reading and really trying to do a deep dive, always dangerous when you are only half scientifically literate. But on my mom’s side of the family, a lot of Alzheimer’s and my mom’s had some deterioration as well, but she’s APOE 3/3. And I’m looking at it, I’m like, I wonder if there — and also just word to the wise, again, not a doctor, talk to your medical professional, but if you’re trying to evaluate your metabolic health, don’t just get fasting glucose taken because you can get lucky with fasting glucose and you might even do hemoglobin A1C, which is a running three-month average of your fasting glucose is maybe a simple way to think about it, something like that. But also get your insulin measured because that was missed by my mom’s local doc for many, many years.

And her fasting glucose, even her hemoglobin A1C was kind of within tolerable levels. Then her insulin was, it was so out of range as to just jump off the page. And so then I was looking at it, and there of course could be a million different contributing factors, but I was like, I wonder if there’s some type of issue in her mitochondria, in which case, my understanding is you do inherit the mitochondria from your mom’s side is my understanding. And I was like, okay, well if that’s the case, I’d like to — I don’t know if there’s anything to be done about it at this point, frankly, but if there is even a small possibility that you could do something about it, I’m like, well, I’d like to kind of know what I’m dealing with. So that’s the genesis of me asking about also the mitochondrial health side of things.

Dr. Jeffrey Goldberg: We don’t have a great blood test for your mitochondria. Obviously, you could get it sequenced. We don’t know how much your fidelity to mom’s mitochondria might play a role in your future cognitive health. I would add to your list though, to other standard screening tests — 

Tim Ferriss: Yeah, please.

Dr. Jeffrey Goldberg: — that certainly are likely to impact your cognitive health as you age. And with that, again, the eye’s part of the brain, your visual health too, and that’s going to be your lipids, your fasting lipids, and your blood pressure. And every bit of science points to, yes, you can inherit it, your ApoE genes that can change your risk. But a very big contributor is going to be your lipids and your blood pressure because those are going to contribute to what we call microvascular disease and ultimately, brain atrophy as we get older and ultimately, cognitive function. And if you could be really ahead of the curve and be really clean with your lipids, whether that’s with diet and exercise or upgrading to some of the medicines that help with that and really clean with your blood pressure, again, diet and exercise or there are medicines we can give to help with that, staying ahead of the curve on those is almost certainly a huge contributor to your later cognitive health.

Tim Ferriss: Yeah, I’ve got those suspects under control and very well-dialed. I’m just like, are the mitochondria the boogeyman in the closet that I’m not contending with? But yeah, I’m trying to do all the stuff you would expect to also help support mitochondrial health and I don’t think this is immediately obvious, people think of exercise as body exercise. But if you want to increase the brain-derived neurotrophic factor release and Klotho release, which hopefully someday soon we will have, it’s an injectable therapy for humans, exercise, you’ve got to do it, do some weight training, do some Zone 2, do VO2 max every once in a while. It’s incredibly valuable.

Dr. Jeffrey Goldberg: And I think the important thing for listeners is that, and when I say listeners, I include myself because I intellectually know I need to do more exercise and I’ve still got to figure out how to get around to actually doing that more exercise. So I’m in the listener crowd here of what I need to say, but the important thing to remember is that the biggest gain comes from going from none to some.

Tim Ferriss: Yes.

Dr. Jeffrey Goldberg: If you go from some to twice as much, yeah, there’s an improvement there too, but not as big as the value proposition of going from none to some.

Tim Ferriss: Yeah, yeah. Just scale it down, guys, if you have to, but don’t do nothing.

Dr. Jeffrey Goldberg: Don’t do nothing because you feel like “I can’t do a million hours, so I’m throwing in the towel and I won’t do any.” Half an hour, four or five days a week, brisk walk, get that heart rate up, have it count, easy. Make it easy on yourself. If you want to then go nuts and do hardcore weight training, hit your Peloton, have your trainer, train for a marathon, okay, fine. But that biggest difference in your life was going from none to some.

Tim Ferriss: Can I give you the greatest non sequitur in the history of my podcast? It’s just because you mentioned that your number one most common question was, “Can I have cannabis?” So I’m lucky to know a bunch of very amazing docs and blah, blah, blah. I interview people, so I get to meet a lot of fascinating folks and one of these super high-end, really sophisticated docs, he was telling me the most, can you guess? I’ll give you a shot. I’ll give you a shot on the three-pointer. What do you think his — I’ll be astonished if you guessed this. Even if you believed it, you probably wouldn’t say it. But what do you think one of his most common questions is that he still refuses to answer publicly? I’ve wanted him to do it.

Dr. Jeffrey Goldberg: Oh, my God, this is a guess what you’re thinking. When we’re in training for medicine, we get asked questions like this all the time, and some of them are like, “Okay, I want you to guess what I’m thinking. Go ahead. Three trials.”

Tim Ferriss: No, no. All right, let me save you the trouble.

Dr. Jeffrey Goldberg: All right, lay it on. Lay it on. What did he say?

Tim Ferriss: This is the question he gets all the time, which is from male patients. “How can I shave my balls safely?” This is the question he gets more than any other. He’s like, “Really? I’ve done all this training, I’ve done all this. And that’s the question that I get more often than not.” Anyway, I don’t know why I felt compelled to share that. Sorry.

Dr. Jeffrey Goldberg: I’m going to trust that he’s not an eye doctor because I never get that question.

Tim Ferriss: Yeah, that’s right. He’s like, “What are you talking about?”

Dr. Jeffrey Goldberg: Tim, you interview a lot of people. What did Matt McConaughey say to that question?

Tim Ferriss: Maybe this should be one of my rapid fire questions that I finish with.

Dr. Jeffrey Goldberg: I’ll pick a path on that one. I don’t have enough experience to talk about that.

Tim Ferriss: Yeah, yeah. No, we can both pass on that one. But is there anything else that we haven’t covered that you would like to mention? Any treatment or research or researchers that you think people should take a look at? I mean, we talked a bit about mitochondria, certainly talked about the lens, we talked about glaucoma and hopefully within the next five years, as you said, being able to potentially restore function or stave it off to a much greater extent. We didn’t really get into treating nerves. I have a note about treating nerves, but I’m not sure we need to cover that. Is there anything else that you’d like to mention that we didn’t have a chance to discuss?

Dr. Jeffrey Goldberg: Look, I want people to understand that first of all, these are all amazing questions. You’ve hit a wide range and we can’t answer them without doing the science behind it. So first of all, as They Might Be Giants said, “Science is real.” So first of all, science is real. And second of all, I would just encourage people, ask your, in this case, eye care provider, “What’s going on with me? Are there clinical trials?” Volunteering to be in clinical trials, I’ll tell you, I know patients are so grateful when they get into our clinics here and they get into a clinical trial because they’re accessing a treatment before it is publicly available to see if it’s going to work. We don’t know if it’s going to work, but they’re taking a swing at that and they’re so grateful to get into these trials.

But I always say, “We are so grateful. We can’t do the trials and therefore, decide whether you should take the supplement or use this virtual reality device or go in front of red lights every day or microdose LSD or change your microbiome. We can’t figure that out if we don’t have the patients come be in the clinical trials and volunteer their time and energy, the extra trips to the office to get their eyes measured or special pictures taken or all that kind of stuff.” So I say, “I know you’re grateful to be in this trial, but I’m grateful to you too.” We are grateful to the patients. So I think we’ve all got to participate in science as a community so we can do these trials and figure out how we’re going to fix ourselves and go from disease to normal. And by the way, go from normal to supranormal. Right? We’ve got to prove it, right?

Tim Ferriss: Yeah. Where would you suggest people search for or find clinical trials around them? And I’ll just reiterate what you said. I have seen so many studies that I’ve been involved with hit a wall with subject or patient recruitment. They just hit a wall.

Dr. Jeffrey Goldberg: That’s a tough one, right?

Tim Ferriss: They really, really benefit from people who are proactive. But if someone’s listening, they’re like, “That sounds amazing. I’d love to actually see what this looks like in practice and maybe figure or help people figure out something in the process for others or myself,” where do they even look? Where would they begin?

Dr. Jeffrey Goldberg: One really good place in the US to look is a website called clinicaltrials.gov. So it’s got it right there in the name, and you go on the front page for clinicaltrials.gov and you type in your disease. So you could type in glaucoma, diabetes, whatever it is. It’ll give you a list of, here’s trials that are recruiting right now actively. And then you can click on any of those and say like, “Oh, that one’s in my city,” or “It’s not in my city, but I’m going to call or send an email to them anyway and say like, ‘Hey, could I be eligible for that?'” So that’s probably one great resource. And then the other would be, again, for diseases would be in the case of research for specific diseases, almost every disease has one or more foundations or patient support sites that bring people together.

And I think of one in our backyard, here in San Francisco called The Glaucoma Research Foundation. There’s another one in New York City called The Glaucoma Foundation, dozens more of course, but they also maintain websites that have a lot of patient-directed information, patient-facing, what to learn about your disease. You were asking before, where’s a reliable source to learn about stuff? That’s one. But they’ll also sometimes talk through what’s happening in clinical trial space or where is that happening or where some hot spots for clinical trials. So I think those are a couple good resources. Of course, nowadays, Google, just any web search engine, it’ll get you started in the right direction.

Tim Ferriss: Yeah, perfect. And if people are wondering, “Well, Tim, have you done any of this yourself?” Yeah, actually, I’ve been a subject in all sorts of different studies from undergrad all the way up to a few years ago for various things, including at Stanford, way back in the day, just a few years after college. So it’s fascinating also just to see what it looks like in real life. What does scientific study look like when it’s implemented? Well, thank you so much, Jeff. This has been a fantastic wide-ranging romp. It’s still and will continue to be intensely personal. So I will keep people listening posted. I promise not to sell you any kratom eye masks through some MLM scheme. And I will be continuing to investigate all of this. This has been super helpful. I took a ton of notes. Is there anywhere you would point people to find you online or learn more about you?

Dr. Jeffrey Goldberg: Yeah, absolutely, Tim, and you joked in the beginning that this podcast is yours and certainly allowed to be self-serving. But I’ll throw one plug in here at the end, the Stanford Ophthalmology website. We actually maintain a list of clinical trials. And again, if we want to tap this whole team here on the back, our faculty, our clinical research staff, everyone involved in it, stem to stern is fantastic. And I’d like to point out a lot of the clinical trials of trying to pull things out of the lab and test them in patients for the first time, a lot of work on vision restoration, vision protection and restoration. Clinical trials going on right here. My work and some of the work of our amazing faculty and staff here.

So you can actually go to Google Stanford Ophthalmology Clinical Trials. We have a web page on our Stanford Ophthalmology site that goes disease by disease and has contact info in how you plug right into the trials here. And we have people in our community participating, but we have people who fly in from everywhere to participate in these clinical trials. So we’re happy to see if we can fit you in too.

Tim Ferriss: Beautiful. And for people listening, I will link to that in the show notes at tim.blog/podcast. So that’ll be easy to find. If you just search Jeffrey Goldberg or Goldberg, I think you might be the only Goldberg. There might be one other. Search Jeffrey Goldberg, and it’ll pop right up and you’ll be able to find the links. Jeffrey, thanks so much. I really appreciate the time. And to everybody listening, as mentioned, show notes, tim.blog/podcast, you’ll be able to find links to everything we discussed and more. And until next time, be just a bit kinder than as necessary to others, but also to yourself. And thanks for tuning in.

The post The Tim Ferriss Show Transcripts: Dr. Jeffrey Goldberg — Creating Supranormal Vision, Cutting-Edge Science for Eye Health, Supplements, Red Light Therapy, and The Future of Eyesight Restoration (#823) appeared first on The Blog of Author Tim Ferriss.

Dr. Jeffrey Goldberg — Creating Supranormal Vision, Cutting-Edge Science for Eye Health, Supplements, Red Light Therapy, and The Future of Eyesight Restoration (#823)

2025-08-21 05:34:02

Dr. Jeffrey Goldberg is chair of the Department of Ophthalmology and director of the Byers Eye Institute at Stanford University. He is a leading scientist in the development and degeneration of the visual system from eye to brain and a professor, practicing ophthalmologist, and surgeon.

Dr. Goldberg is a member of the National Academy of Medicine and has won a number of prestigious awards, including Scientist of the Year by the Hope for Vision foundation and the Cogan award from the Association for Research in Vision and Ophthalmology. Dr. Goldberg received his BS magna cum laude from Yale University and his MD and PhD from Stanford University, where he made significant discoveries about the failure of optic nerve regeneration. 

Dr. Goldberg’s research is directed at vision restoration, including neuroprotection and regeneration of the retina and optic nerve, a major unmet need in glaucoma and other eye diseases. His laboratory is developing novel molecular, stem-cell, and nanotherapeutics approaches for eye repair, and he is widely recognized for translating advances in the lab into clinical trials for patients. 

A number of his innovations have spun out into startups and clinical-stage companies, and he serves as medical and scientific advisor to a number of ophthalmic start-up, pharma, and device companies. His goal is to translate scientific discoveries to patient therapies.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube. The transcript of this episode can be found here. Transcripts of all episodes can be found here.

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Want to hear another podcast episode with a Stanford neuroscientist who won awards for vision research? Listen to my conversation with Dr. Andrew Huberman, in which we discussed the foundations of physical and mental performance, core supplements, sleep optimization, psychedelics, neural plasticity, and much more.

SELECTED LINKS FROM THE EPISODE

• Connect with Dr. Jeffrey Goldberg:

Faculty Profile | Stanford Ophthalmology | Clinical Trials

The transcript of this episode can be found here. Transcripts of all episodes can be found here.

Conditions and Key Concepts

• Presbyopia: Age-related decline in near vision due to the stiffening of the lens.
• Myopia: Nearsightedness; an epidemic condition, especially in children, that can be slowed with red or violet light.
• Glaucoma: A neurodegenerative disease and the leading cause of irreversible blindness, characterized by damage to the optic nerve, often associated with high eye pressure.
• Age-Related Macular Degeneration (AMD): An eye disease that can cause blurred or no vision in the center of the visual field.
• Cataracts: A clouding of the lens in the eye that leads to a decrease in vision.
• Dry Eye: A common condition where the eyes don’t produce enough quality tears.
• Neuroplasticity: The brain’s ability to reorganize itself by forming new neural connections, a key concept for vision training and restoration.
• Supranormal Vision: Vision that is better than the “normal” 20/20 standard, such as 20/12.
• Mitochondrial Health: The proper functioning of mitochondria, the “powerhouses” of the cell, which is crucial for the health of neurons in the eye and brain.
• Metabolic Syndrome: A cluster of conditions (high blood pressure, high blood sugar, etc.) that increase the risk of heart disease, stroke, and type 2 diabetes.
• APOE3/4: A genetic variant that increases the risk of developing Alzheimer’s disease.
• Three-Parent Technique: An IVF method that cleverly avoids passing along mitochondrial disease to the offspring by incorporating DNA from three parents.

Anatomy of the Eye

• Cornea: The clear front window of the eye that does most of the light bending.
• Iris: The colored part of the eye (brown, blue, etc.) that controls the size of the pupil.
• Pupil: The opening in the center of the iris that light passes through.
• Lens: The structure behind the iris that performs fine-focusing; it stiffens with age, causing presbyopia.
• Vitreous: The gel-like substance that fills the middle of the eye.
• Retina: The light-sensitive tissue at the back of the eye that contains photoreceptors.
• Rods and Cones: The two types of photoreceptor cells in the retina. Rods are for low-light vision, and cones are for daytime color vision.
• Retinal Ganglion Cells: The neurons that collect visual information from the retina and send it to the brain.
• Optic Nerve: The bundle of nerve fibers (axons) from the retinal ganglion cells that connects the eye to the brain.

Supplements, Treatments, and Technologies

• AREDS 2: An over-the-counter supplement formulation clinically proven to slow vision loss in moderate age-related macular degeneration.
• Vitamin B3 (Nicotinamide): A vitamin supplement being studied for its potential to restore vision in diseases like glaucoma.
• CoQ10 and Ginkgo: Other supplements mentioned as having been studied for vision, with less conclusive evidence.
• Pilocarpine: The active ingredient in some FDA-approved eye drops that constricts the pupil to improve focus and treat presbyopia temporarily.
• Red Light and Violet Light Therapy: The use of specific wavelengths of light for minutes a day, shown to slow myopia progression in children and potentially support mitochondrial health.
• Strobe Goggles: Eyewear that reduces the visual frame rate (e.g., by strobing or flickering) to train an athlete’s reflexes and hand-eye coordination.
• Visual Perception Training: Computer-based exercises that aim to improve vision by training the brain’s processing abilities.
• Cannabis (THC/CBD): Mentioned for its ability to temporarily lower eye pressure in glaucoma patients, though continuous use is impractical.
• Low-Dose Psychedelics: Compounds like LSD mentioned for their potential to increase visual acuity and induce neuroplasticity.
• Stem Cells: Mentioned as a future, but not yet ready, therapy for replacing damaged retinal cells.
• Serum Tears: Custom eye drops made from a patient’s own blood serum, rich in growth factors to treat severe dry eye.
• Preservative-Free Artificial Tears: Recommended for frequent use to treat dry eye, as preservatives in standard drops can be irritating.

Media and Resources

• Andrew Huberman’s Podcast: Where I first heard Dr. Goldberg speak.
• Clinicaltrials.gov: A US government website for finding and learning about clinical trials for various conditions.
• Stanford Ophthalmology Website: Mentioned by Dr. Goldberg as a resource for finding clinical trials related to vision.
• Science is Real: A song by They Might Be Giants.

Institutions, Companies, and Foundations

• Stanford University: The institution where Dr. Goldberg, Dr. Huberman, Dr. Eagleman, and Dr. Williams work or have worked.
• FDA (Food and Drug Administration): The US agency responsible for approving medical treatments, mentioned in relation to eye drops and red light therapy.
• Cognito Therapeutics: A company developing a headset using light and sound to treat Alzheimer’s disease.
• MIT (Massachusetts Institute of Technology): The university where Ed Boyden and Li-Huei Tsai conducted foundational research.
• Harvard University: The institution where researcher Dongfeng Chen works.
• Holobiome: A company mentioned for creating a comprehensive library of gut microbiota.
• Glaucoma Research Foundation: A San Francisco-based non-profit organization.
• The Glaucoma Foundation: A New York City-based non-profit organization.
• DARPA (Defense Advanced Research Projects Agency): Mentioned for using devices to improve language acquisition.

People

• Andrew Huberman: A neuroscientist at Stanford and a mutual friend.
• David Eagleman: A neuroscientist at Stanford mentioned in the context of sensory substitution tools.
• Aaron Rodgers: A professional athlete mentioned in connection with using low-dose psychedelics for performance.
• Nolan Williams: A researcher at Stanford known for work on accelerated TMS for depression.
• Ed Boyden: A neuroscientist at MIT who co-developed the technology behind Cognito Therapeutics.
• Li-Huei Tsai: A neuroscientist at MIT who co-developed the technology behind Cognito Therapeutics.
• Dongfeng Chen: A professor at Harvard whose research linked the immune system and gut bacteria to glaucoma in mice.
• Gul Dolen: A researcher, formerly at Johns Hopkins and now at UC Berkeley, known for work on reopening critical periods of brain plasticity with psychedelics.
• Andreas Tolias: A researcher mentioned for creating a “digital twin” of the brain.
• Matthew McConaughey: American actor, author, and producer.

SHOW NOTES

• [00:00:00] Start.
• [00:05:30] How do you solve a problem like presbyopia?
• [00:08:34] The athletic benefits of training supranormal (better than 20/20) vision.
• [00:11:49] Indigenous eye drops and FDA-approved pilocarpine for presbyopia.
• [00:14:05] Understanding basic eye anatomy.
• [00:17:27] Exploring AREDS 2, CoQ10, ginkgo, vitamin B3, and other supplements for vision.
• [00:23:00] Visual training devices and psychedelic-prompted brain plasticity.
• [00:25:12] Thoughts on visual training effectiveness and motor action requirements.
• [00:28:29] Concussion rehabilitation and visual perception exercises.
• [00:32:36] Red light and violet light therapy for myopia and mitochondrial health.
• [00:36:07] Vision loss correlation with cognitive decline and depression.
• [00:39:36] Presbyopia progression and psychological dependence on readers.
• [00:41:15] Cognito Therapeutics headset for Alzheimer’s treatment.
• [00:46:46] Glaucoma basics: neurodegenerative disease and risk factors.
• [00:48:53] Eye pressure variability and diurnal cycles.
• [00:50:02] Cannabis effects on eye pressure and compound isolation.
• [00:51:47] Stem cell research for vision restoration.
• [00:53:09] Anti-inflammatory effects and immune system role in eye diseases.
• [00:55:15] Gut microbiome connection to glaucoma in animal models.
• [00:58:43] Metabolic syndrome and GLP-1 receptor agonists.
• [01:00:50] Microbiome sharing and future therapeutic possibilities.
• [01:03:31] Dry eye treatment: preservative-free tears and serum drops.
• [01:08:43] Vision screening recommendations and UV protection.
• [01:11:22] Full-spectrum light benefits vs. UV exposure.
• [01:13:27] Paradigm shifts: irreversible vision loss becoming reversible.
• [01:17:18] Convergence of neuroscience advances and biotech investment.
• [01:21:58] Miraculous mitochondria: health, transplants, and three-parent babies.
• [01:26:24] My family history concerns and metabolic health screening.
• [01:29:26] Exercise’s biggest gain: going from none to some.
• [01:33:03] Clinical trial participation resources and parting thoughts.

DR. JEFFREY GOLDBERG QUOTES FROM THE INTERVIEW

“I have gone my whole life without needing glasses until I hit around age 40. And when everyone hits around age 40, our lens inside the eye won’t compress and reshape to focus up close.”

— Dr. Jeffrey Goldberg

“Professional athletes get studied. They have better vision. They have better reflex time. They have sharper vision. We talk about 20/20 vision. That means I can see at 20 feet what a ‘normal’ person can see at 20 feet, so I have normal vision. But you can have 20/12 vision, which means you can see at 20 feet what normal people can see at 12 feet.”

— Dr. Jeffrey Goldberg

“Glaucoma is the number one cause of irreversible blindness in the world. That, I think, is going to be the piece that we overturn. We have always said, ‘Hey, we’ve got to prevent you from losing vision. We’ve got to slow down the disease because, once you’ve lost whatever vision you’ve lost, I can’t get that back for you.’ And I think that is about to topple. We are about to get into vision restoration at a level that has been totally unexpected and totally unprecedented, and the science supporting these directions in these diseases is getting really, really juicy.”

— Dr. Jeffrey Goldberg

“Cannabis, whether you smoke it or eat it in the brownie or take the chewy, it lowers your eye pressure if you’re using the version … where you feel a little high from it, you get that good feeling. The problem is that it only really lowers the eye pressure during that time that you’re getting high. So I tell patients, ‘It works, but you’d have to be high 24/7, so maybe you should just use this eye drop instead.'”

— Dr. Jeffrey Goldberg

“A small dose of daily red light can slow down progression of myopia in young people. We’re talking about teens and younger, even. So what’s even more shocking to me is that it also works with violet light. So how’s it work with light at the two ends of the visible spectrum? And definitely mitochondria are implicated.”

— Dr. Jeffrey Goldberg

“There’s an important myth to dispel, especially when it comes to presbyopia and wearing reading glasses. Between age 40 and around 60 or so, that lens stiffens and stiffens and stiffens. That’s the refractive, the glasses difference between viewing something at infinity, which from an optics perspective is actually just three feet away or further, and viewing something at 14 inches, comfortable reading distance, right in front of us.”

— Dr. Jeffrey Goldberg

“If we all live to a hundred, we’re all going to need cataract surgery—some people younger, some people older. But if you do cataract surgery and restore vision in an older person who … is suffering with cognitive decline and/or depression, you can reverse a significant amount of that decline in either of those domains. It speaks to the interplay of vision with our mental health, our cognitive health, and this is long-term, important stuff.”

— Dr. Jeffrey Goldberg

“The important thing to remember [about exercise] is that the biggest gain comes from going from none to some.”

— Dr. Jeffrey Goldberg

The post Dr. Jeffrey Goldberg — Creating Supranormal Vision, Cutting-Edge Science for Eye Health, Supplements, Red Light Therapy, and The Future of Eyesight Restoration (#823) appeared first on The Blog of Author Tim Ferriss.

The Tim Ferriss Show Transcripts: The Random Show — Ketones for Cognition, Tim’s Best Lab Results in 10+ Years, How Kevin Hit 100 Days Sober, Home Defense, Vibe Coding Unleashed, and More (#822)

2025-08-14 04:25:49

Please enjoy this transcript of another wide-ranging “Random Show” episode I recorded with my close friend Kevin Rose (digg.com)!

We cover Kevin’s sobriety journey and marking 100 days without alcohol, my results with the ketogenic diet and intermittent fasting, GLP-1 agonists, home defense and security, the future of Venture Capital, authenticating yourself online, AI, the cultural shift toward human-to-human connection, Roblox, and more.

Transcripts may contain a few typos. With many episodes lasting 2+ hours, it can be difficult to catch minor errors. Enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube.

DUE TO SOME HEADACHES IN THE PAST, PLEASE NOTE LEGAL CONDITIONS:

Tim Ferriss owns the copyright in and to all content in and transcripts of The Tim Ferriss Show podcast, with all rights reserved, as well as his right of publicity.

WHAT YOU’RE WELCOME TO DO: You are welcome to share the below transcript (up to 500 words but not more) in media articles (e.g., The New York Times, LA Times, The Guardian), on your personal website, in a non-commercial article or blog post (e.g., Medium), and/or on a personal social media account for non-commercial purposes, provided that you include attribution to “The Tim Ferriss Show” and link back to the tim.blog/podcast URL. For the sake of clarity, media outlets with advertising models are permitted to use excerpts from the transcript per the above.

WHAT IS NOT ALLOWED: No one is authorized to copy any portion of the podcast content or use Tim Ferriss’ name, image or likeness for any commercial purpose or use, including without limitation inclusion in any books, e-books, book summaries or synopses, or on a commercial website or social media site (e.g., Facebook, Twitter, Instagram, etc.) that offers or promotes your or another’s products or services. For the sake of clarity, media outlets are permitted to use photos of Tim Ferriss from the media room on tim.blog or (obviously) license photos of Tim Ferriss from Getty Images, etc.

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Tim Ferriss: Hello, boys and girls, ladies and germs. KevKev. Random Show.

Kevin Rose: TimTim.

Tim Ferriss: Here we are again. Nice to see you here.

Kevin Rose: Here we are. Good to see you as well.

Tim Ferriss: And you crazy listeners and viewers out there, we have a lot to talk about. This is going to be an action-packed episode. Features all sorts of new biological hacks, psycho-emotional hacks, even includes some homeless people hiding in a closet. And that is not a metaphor. We’ll get to that eventually, but let’s kick off with a huge congrats, man. 100 days. Why is 100 days significant? What is the milestone?

Kevin Rose: The milestone is no alcohol for 100 days.

Tim Ferriss: Fucking A, man. Congratulations. That is huge.

Kevin Rose: Thank you.

Tim Ferriss: That is huge.

Kevin Rose: It is huge, especially given how much of an alcoholic I was.

Tim Ferriss: Well, let’s dive into it. Because I have, over the decades, I guess, at this point, right, seen you take a stab at sobriety many different times, and the success has varied, but nothing has approached 100 days. Nothing. Nothing.

Kevin Rose: Well, don’t make it seem like it’s that bad.

Tim Ferriss: When you were laying under those overpasses just taking hit after hit.

Kevin Rose: Hey, listen, you’ve also taken a stab at non-sobriety with me many times.

Tim Ferriss: I know, I know. Well, I was going to say 100 days sober, even for someone who does not consider themselves a drinker, but let’s just say for someone who drinks occasionally, socially, that’s a meaningful period of time. That’s a quarter of the year, more than a quarter of the year. So I’m sure we’ve talked about this, we’ve tracked it a little bit over time, but what made the difference this time around? Let’s reiterate that for folks and maybe your answer’s changed.

Kevin Rose: Yeah. I think that initially it was fear of death, which was largely driven by my doctor calling me up and saying, “Your liver enzymes are like,” whatever it was, “5X, 7X what they should be.”

Tim Ferriss: Oh, wow. Okay.

Kevin Rose: So that was number one. But just to give people a benchmark of where I was at drinking-wise. My journey with alcohol, it’s been one of a love affair. I’ve definitely enjoyed the drinks, but for me, it’s never been about drinking to blackout or drinking to even any type of illness or sickness. It’s just kind of consistency, meaning that when COVID happened, I was sober as could be for the first three weeks. And then I’m like, “Eh, what do we have to do? We should just drink a little bit. I think everybody’s going to be okay.” At first, I was like, “Got to get my immune system on point,” and then I just gave that up and there was a lot of loneliness. And I was out in the woods in the middle of nowhere in Oregon, and had some young kids, and was like, “Ah, let’s just crack a bottle of wine.” So it was a very common, very normal thing for us as a household — 

Tim Ferriss: Yeah, for a lot of people.

Kevin Rose: — to just crack a bottle and just finish the whole bottle between two people, and that became the norm. And then I just remembered that there — for me, I was always asking myself, “Can I take a day or two off per week?” Which I think would be a good, healthy thing. But then if you just add up the amount of drinks, even with taking a day or two off, if you’re doing three drinks a night, that’s a lot of drinks every month.

Tim Ferriss: It’s a lot. And just to put that also in a broader context, part of the reason I’ve never lived full-time in New York City, and part of the reason some of my friends have moved out of New York City is not because New York City is a bad place, but at least in the social circles by and large that I know, finishing a bottle of wine between two people, let’s call that two and a half drinks apiece, that would be a light night in New York City. And to do that minimum three nights, but three, four, five, six nights per week — and a lot of the groups I know at least, that is just par for the course.

Kevin Rose: Right. The issue is that when you get into your 40s and you have all that cumulative damage of decades, you realize, “Well, things start to shut down like your liver.” So I think that was the first sign, but then I just realized — 

Tim Ferriss: Only have one liver, so you want to take care of that baby.

Kevin Rose: Yeah, the nice thing obviously about the liver is that until you’re at that point of no return, it’s pretty damn good at healing itself. And my liver enzymes snapped back to normal ranges within four weeks, which was great to see. But when I think about: when have I truly given it a break? When have I truly taken more? And I’ve taken a month off here or there, there’s those dry Januaries, and I would have a dampish January where you have a drink or two, but it’s still kind of dry January. And so that was the norm, and then I just said, “If I can’t go three months, then —” And actually my therapist told me this, she said, “Kevin, it’s kind of a golf clap at one month, three months is where the magic happens in terms of how you feel, your energy, your mood, weight loss, glucose control, all of the things that you’ve said you want to have.”

But can you do it? And it is really challenging to go three months for someone like myself that it is a crutch around social situations. It is a crutch around, if I’m being honest, when you have a partner where you’re dealing with a couple little kids and it can be challenging with the kiddos and with the logistics of a household, and all of a sudden you’re just like, “Ah, I had a hard long day at work and I had a long day at home, and I have some good wine sitting right there.” It’s very easy to tap into that.

Tim Ferriss: So what would you say made the difference this time around? You had the health scare or at least the doctor saying, “Hey, hot shot —”

Kevin Rose: It was surrounding myself with people that had done this before. 

Tim Ferriss: How did you find them?

Kevin Rose: Well, I think we’re at the age that if you — I’m sure you probably can check this box as well, where I know right now three people that have successfully done 12-step programs.

Tim Ferriss: Sure. Yeah. Easily three.

Kevin Rose: In fact, we have a couple of friends in common that are now sober and have done these programs. And yeah, that’s exactly it. And you reach out to them and say, “Hey, what did you do? What about these 12 steps has worked for you?” I was always kind of put off by the religious aspect of — 

Tim Ferriss: Sure.

Kevin Rose: — some of the 12-step stuff. It just seemed to me like a little — I don’t know. I didn’t really think I had it that bad, but I knew that there were people that, and I had seen this, that had stuck to it with the help and support of these people. And they gather around you and really give you a kind of tool kit to lean into. And for me that has been really understanding that it’s not about the three months, it’s just about winning today. And so if you can reframe it as just not today. Yeah, I can have a drink tomorrow, but just not today.

Tim Ferriss: Not today, Satan. Not today, Satan.

Kevin Rose: Yeah, exactly. And it sounds so silly, but — 

Tim Ferriss: No, it doesn’t though.

Kevin Rose: — do these little tiny things

Tim Ferriss: Eternity — well, I guess we’re not going to live for all eternity unless you believe some people on the internet, but until you die is a long time, or at least you hope it’s a long time. But today or tomorrow, today, it’s very digestible, right?

Kevin Rose: Yes. Yeah, 100 percent. And so that was a big thing. And having those friends, and the first thing they did being — some of them are — one’s still in AA and two or ex-AA. They said that, “What we do here is we can just give you our numbers and you call anytime you’re having a craving or you think you’re getting close to not pulling this off because we want to see you succeed.” And I think that’s a powerful thing to be able to have a hotline to someone that is like, “I’ve been here. It sucks.” Yes, yes, you can get to two weeks, but do you want to white knuckle this all the entire way by yourself or do you want someone that’s going to go have a tea with you and sit with you for an evening on a day that’s particularly hard?

And so I think after you get to kind of six — well, I’m just speaking for myself, but when I got to six or ish weeks, the kind of the headache-y kind of desire of it all faded away a little bit. And then I found a bunch of shit that I really enjoyed doing that was not drinking. And I think that’s the other big thing you have to do, is you have to really figure out what is going to fill that space. Because if it’s just sitting there thinking about drinks — 

Tim Ferriss: Smoking. Copious amounts of weed. No, I’m kidding.

Kevin Rose: Yeah, I started cocaine and I just did a bunch of weed, but other than that — no. I wish I liked weed. I do not like weed for some reason. It just doesn’t — I like the way it —

Tim Ferriss: I think Sigmund Freud for a while was viewing cocaine as the solution to heroin. I’m not making that up. He’s a very famous psychoanalyst, but that’s not that. So, you didn’t go for snow blindness, you went for — 

Kevin Rose: No, but I did go for this. Look at this.

Tim Ferriss: Oh, okay. Now this looks like a Japanese LEGO-ish — those are Nanoblocks?

Kevin Rose: Yes. So this is called Nanoblocks, and it’s one of the things I wanted to talk about today. So, Nanoblocks are from Japan. And I did a little research and essentially they were able to find a way around a lot of the LEGO patents. And they created — look at how small this block is.

Tim Ferriss: Yeah, he’s holding it up.

Kevin Rose: If you listen to audio — 

Tim Ferriss: Yeah, it’s about the size of a baby aspirin. It’s tiny.

Kevin Rose: Right, exactly. And so they literally sell Nanoblock branded tweezers to put these things together.

Tim Ferriss: That’s the most Japanese thing I can imagine at this moment.

Kevin Rose: Exactly. And so the instructions are horrific, which actually makes it more fun. Look at this. Look at this bad boy.

Tim Ferriss: Oh, wow. Okay. So, he’s holding up a cherry blossom tree. It’s actually awesome. It’s kind of mesmerizing in that lo-fi kind of way. And it probably has, I’m just going to guess here, 857 pieces, something — 

Kevin Rose: No, this was 2,500, I think, pieces.

Tim Ferriss: Oh, my God. Here we go.

Kevin Rose: So, this’ll take you a good solid week.

Tim Ferriss: It’ll keep your hands — idle hands of the devil’s workshop, but not if you have Nanoblocks.

Kevin Rose: Yeah, exactly. So, I will say that little hobbies like this, especially ones that you can do with your kids — do I have my — yeah, so this one back here is also LEGO.

Tim Ferriss: Oh, that’s — I guess I’m blanking on the exact name. The Great Wave, Hokusai. Almost everyone will have seen this in some form or fashion. That’s cool. That’s very cool.

Kevin Rose: Yeah, so that actually is legit LEGO. This is not Nanoblocks, but this one is really cool. We talked about that one once before, but I think these things are great to have. These little hobbies are great to have. And Nanoblocks, I will say, if you go on Amazon, they sell them on there, they have horrible reviews. And the reason why the reviews are so bad is because the instructions, like I said, are horrific. But once you understand the way that the Japanese want you to do it, there is a method to their madness, and they all work the same way. So, it takes you an hour and a half to be like, “Why are they telling me to put it like — what does that arrow mean?” And then you understand the arrow systems because there’s a lot of Japanese, a little bit of sprinkled English throughout the instructions.

Tim Ferriss: Probably doesn’t help very much.

Kevin Rose: Right, but look at this kit here. So they have these cute little kits.

Tim Ferriss: Oh, ramen. Yeah. Cup O’ Noodle, basically.

Kevin Rose: That little ramen.

Tim Ferriss: Yeah, 140 pieces, ages 12 plus. That’s fun.

Kevin Rose: Yeah. So, this ramen is going to be about the size of — 

Tim Ferriss: A shot glass.

Kevin Rose: — a little teacup. Like a shot glass. Exactly. But it’s super tiny, and it’ll take you eight hours to put that together. But they’re so fun. They’re so fun. And I have a massive Godzilla that’s cool.

Tim Ferriss: So, two things. Number one, if a video on YouTube doesn’t exist already, you should just create a video, which is like, “Let me explain how to use these fucking things.” That would be a great service to humanity.

Kevin Rose: You know what’s funny is I’m actually doing that. I’m going to do a live — there’s this whole movement right now where people go out — actually Craig Mod is quite good at this, where he’ll go out — you had him on your podcast, fantastic. All things Japan, Craig Mod is the best. He has gone out and he’s done these ambient recordings where he just goes to these rural parts of Japan.

Tim Ferriss: Oh, they’re so cool.

Kevin Rose: And he just sets up his mic and you listen to the street traffic, you listen to the people doing various tasks, and there’s something to be said about — they call this slow TV, this movement. There’s this whole thing where people watch people grooming and shearing sheep. Have you seen this.

Tim Ferriss: No, but I saw this guy who has a podcast that is sort of, I guess, interviewing thought leaders, and he didn’t disclose this in the tweet, but the tweet was like — there is an account of a Norwegian truck driver, this is on YouTube, just driving through different parts of the countryside in Norway, and it has 5,000,000 subscribers or something. And he said, “Meanwhile, there are other podcasts that do this on YouTube, and they only have 9,000 subscribers,” link. He didn’t disclose that it was actually his account. But yeah, the slow, I suppose, what’s the right word, sort of living vicariously as a fly on the wall with things that seem very day to day.

Craig Mod has actually a super relaxing — it’s hard for me to explain exactly what it is. Maybe it’s just a mild antidote to digital loneliness. Maybe that’s part of it. But he went to a Japanese jazz listening bar where people — or a jazz listening cafe, where it’s full of vinyl. People sit there in true Japanese fashion, practically dead silent, just listening to the owner who’s effectively the DJ, put on different vinyl. And he got all the — 

Kevin Rose: I’ve been to this bar.

Tim Ferriss: — all the ambient sounds. And Craig Mod, what a gem. Definitely look him up.

Kevin Rose: Yes.

Tim Ferriss: The name is M-O-D, as you heard.

Kevin Rose: Yeah. And I will say that I’ve talked to Craig about — I asked him, I said, “Hey, how do you get this? Why does it sound so amazing? What’s your secret here?” And he uses these binaural microphones that, essentially, they go into his ears. And so he plugs them into his ears and then into a solid state recording device. And so you’re listening as though you’re sitting in his ears because there’s a mic on each side. And so that’s the left and right audio channels, and it creates this illusion of a depth of audio as you’re listening, which is just brilliant, and it’s so much fun. But yeah, there is a massive movement, and I get it. 

Tim, we are so addicted to our devices that, I don’t know, maybe it’s because I’m getting in my late 40s, but I desperately crave more analog in my life.

Tim Ferriss: Yeah, more analog.

Kevin Rose: More so than I ever have.

Tim Ferriss: For sure.

Kevin Rose: Do you find that to be the case with yourself?

Tim Ferriss: Oh, 100 percent. Next week I’m going on this wilderness trek in Montana and Idaho that is going to be off grid and with a couple of close friends. And sure, you could bring, say, a solar charger and try to use your phone, but I’m just going to leave mine behind. I don’t need it. What am I going to do?

Kevin Rose: You just bring in your printed Playboys. You’re going all analog.

Tim Ferriss: I’m bringing the stash from the late ’80s. I kept those with my D&D from childhood when I packed them up. And analog, more and more analog. We are just evolved to thrive and feel at ease in analog environments, which isn’t to say all digital is bad, but certainly past a point, the self-soothing becomes a poison. And I don’t think we need to convince anyone of that. You see it everywhere. So, it makes sense that even in a digital sphere, this type of slow viewing cat — I was going to say cat-on-the-wall, not even sure what that would be. Maybe it — it sounds like a Japanese t-shirt, but fly-on-the-wall experience, it allows people to put something in the background. I used to do this when I was writing my books.

So 4-Hour Workweek — I don’t even know if you know this, so 4-Hour Workweek, 4-Hour Body, 4-Hour Chef, I would do most of my writing late at night. And a lot of authors I know who are productive, not saying I’m one of the most productive at all, but either write very early when everyone’s asleep or they write very late when everyone is asleep. The upside is you can focus, the downside is it can feel very, very isolating. So I would sit in my TV room and I would put on music, but I would always put on movies to watch, so I had people around on the screen.

And these were movies that I would just watch on repeat. So I’ve seen, for the first movie — or first set of movies for The 4-Hour Workweek. It was Shaun of the Dead and the first Jason Bourne. And then for The 4-Hour Body, it was Snatch, and it was the first movie I chose that popped up on Amazon Prime, which is Babe. Masterpiece of a movie. So, I watched Snatch and Babe like 5,000 times each. Absolutely high hundreds each. But it’s just to have something in the background that is comforting while I’m isolated and I’m listening to music and writing, so it makes sense to me.

Kevin Rose: You know The Naked Gun is coming back.

Tim Ferriss: Yes, I do. I saw the reviews and I’m like, “God, I hope it’s true,” because The Naked Gun was so good.

Kevin Rose: Yes.

Tim Ferriss: Liam Neeson is actually a fantastic actor, despite the fact that he’s made some version of Taken like 789 times, but the guy has chops. But in the same way Johnny Depp has chops, but when they did a remake of Willy Wonka and The Chocolate Factory, I was like, “Oh, I don’t do it. Gene Wilder is going to be really hard to top. That’s going to be really tough.” So I’m optimistic in a way I suppose with movies that I haven’t been in a long time. So, I’m excited to check out The Naked Gun.

Kevin Rose: I’m just curious to see if they’re going to keep up with the — because The Naked Gun you could not make today. Well, maybe you could.

Tim Ferriss: As it was.

Kevin Rose: Yeah.

Tim Ferriss: There’d have to be some script doctoring for sure. Let me — before we get to The Naked Gun, I want to make an observation, which is you and I text a lot, and we’re in one ridiculous small friend group thread. And since you cut alcohol out, the tone of your communication is completely different, in the sense that you basically don’t complain anymore, effectively gone as far as complaining. But I think that’s just related to the ups and downs that are maybe more noticeable when you’re drinking and all the effects on metabolism and insulin sensitivity and so on. But it’s like your general tone and existence and demeanor is so much more stable in its positivity since you stopped drinking. So I just wanted to mention that because it’s very noticeable.

Kevin Rose: That’s interesting.

Tim Ferriss: Not that you were bitching and moaning all the time before, but the change is very noticeable.

Kevin Rose: Yeah, because I feel like your bitching has gone up.

Tim Ferriss: Yeah.

Kevin Rose: As you get older, something’s happened.

Tim Ferriss: Something’s not right here.

Kevin Rose: No, I appreciate you saying that. I feel as though — well, I will say this — you never know how much you should share on podcasts and whatnot, but I’m going to just go out here. I know my wife’s going to listen to this, but I might as well say it anyway. You argue less when you’re both not drinking, it turns out.

Tim Ferriss: Yeah, for sure. For sure.

Kevin Rose: And you and I are always — we’ve been known to text each other various grievances with our partners and people we’ve been seeing.

Tim Ferriss: Yeah, you need to do it. Yeah, you need to do it.

Kevin Rose: You need an outlet, especially with your buddy.

Tim Ferriss: You need an outlet. It’s like you just need somebody to vent to. But I would say holistically, so if you even took the partner piece out of it, just in general, you’re much more upbeat and it’s noticeable. 

And again, I want to mention something that I’m pretty sure we haven’t. I didn’t want to repeat myself, so I used AI to summarize our last few Random Shows. And a few things that I’ve done I’m pretty sure since our last conversation were interventions for health also. And the primary drivers behind that were not any type of medical emergency, but I’m now caring for two family members who have rapidly deteriorating cognitive health. And this is very common in my family. Lots of Parkinson’s, lots of Alzheimer’s in particular.

And what I’ve noticed is that some of these people who seem hardest hit by Alzheimer’s are, say, APOE 3/3. They shouldn’t have a high predisposition to Alzheimer’s. And I’m APOE 3/4, so I’m like, “Fuck, if I am, as we understand it now, something like 2.5 times more likely than the population average to be predisposed to Alzheimer’s, this is something I want to look at very, very closely.” Because there are some interventions out there, and you and I have invested in hopefully some new interventions to come in the four coming years, but that’s going to take some time. By the time the symptoms are really obvious, it’s very, very hard to treat something like Alzheimer’s, which doesn’t mean that the interventions don’t work, it just means they might not work at that stage. So, I’m really trying to — and I’ve already been taking a lot of mental health and cognitive neuronal health thing seriously. So I started wondering, and this is just a hypothesis, but if it’s possible that I have inherited some mitochondrial dysfunction, and looked at ways to improve mitochondrial health, which would include increased Zone 2 training, for instance.

Kevin Rose: I hate Zone 2, but yeah.

Tim Ferriss: It’s so boring.

Kevin Rose: Just annoying.

Tim Ferriss: It’s like flossing. It’s just like the worst — it’s not fun, but it’s mild enough that you can throw on something on Netflix or listen to a podcast. So, Zone 2, it’s boring, but you’ve got to do it. And I’ve been finding more interesting ways to do that. But in addition to that, looking at some old friends that I thought were worth dusting off and revisiting like ketosis and the ketogenic diet. So I’ll give you the punchline and then I’ll back up. So, did my blood draw, and also an oral glucose tolerance test, which we should really talk about because that’s just such an important tool in the toolkit to see how sensitive you are with respect to insulin or insensitive glucose disposal, et cetera. Getting fasting glucose isn’t enough. You can get false good news if that’s timed luckily or well.

So I’ve had my best lab results, and I get three or four tests a year, probably my best lab results in the last decade, most recently. And I would attribute that to a few things. I used ketogenic diet, very straightforward. You have to figure out a few meals that work for you. For me, it was a big salad with ribeye cut on top with some cheese. You have to figure out something that doesn’t make you feel like a human cheesecloth every day because you really want to keep your protein moderate. You can’t have too much protein on the ketogenic diet if you want to stay in high levels of high millimolar concentration of ketones. And I test all this with a finger prick. I shifted naturally, like ketosis first, to initiate some adaptations. And for everything I read, it takes about — I knew I didn’t want to do it super. It’s just too boring and too disgusting, and plus, I really need to watch my lipid profile.

Kevin Rose: Yeah, that’s my problem.

Tim Ferriss: But based on the reading that I was doing, it seemed like three to four weeks of serious ketosis was enough to initiate some durable changes. And then maybe if you do that at least, and this is speculation, but once every six months, once every year, that you can keep the metabolic machinery where you want it. And so I did four weeks and I was like, “Enough,” but I started leaning into intermittent fasting towards the end of that, and experimenting with 16/8. So, what that means is 16 hours of fasting, eight hours of eating. Eight hours could be noon to eight o’clock, could be 2:00 p.m. to 10:00. And then continued with the ketogenic diet, but just two meals a day, typically like one at two o’clock, and then one at, say, 8:00 or 9:00.

And then shifted back to a non-ketogenic diet, and this is going somewhere, folks, because the ketogenic diet may have nothing to do with it, but the combination of doing three to four weeks of ketosis and then doing intermittent fasting for the last two months, but at the time of my blood test, it was only about four weeks in, my insulin sensitivity — which my family just as a team sucks at. Genetically, I am not predisposed to having great glucose disposal or insulin sensitivity. And that’s a huge driver for accelerated neurodegenerative disease. If you have high blood pressure, if you have chronically elevated glucose or insulin and/or insulin, all of these things drive degeneration cognitively.

And people can learn all sorts of stuff about 16/8 intermittent fasting from Rhonda Patrick, and she’s had a number of scientists on her podcast. There’s also a guy I recommend with some reservation, but Martin Berkhan, who really popularized, to his credit, 16/8, and worked with a lot of clients and his audience. So, he had very interesting data, but his editorial tone is not for everybody. He will not die from confidence deficiency, I’ll put it that way. Nonetheless, his recommendations around intermittent fasting plus resistance training are very compelling. So, I would suggest people check that out. A byproduct of this is that, and this was very unexpected, my mood is so elevated and stable now, it’s kind of hard for me to believe that I didn’t figure this out sooner.

And I think part of that was, as a competitive athlete, especially growing up when we grew up, it was like, “Okay, small meals every four hours,” something like that was the dogma. And I think that was a just enough smoke screen that I was able to cover up insulin insensitivity because if I didn’t eat frequently, I would start to crash and then get grumpy, and then I would boost it back up with granted a healthy meal, but I was still eating very, very consistently. And in doing this, my mood on average has just been so much higher, so much more stable for, I would say, the last eight weeks. I don’t have any intention of changing.

Kevin Rose: That’s amazing.

Tim Ferriss: I think I could do the intermittent fasting indefinitely. And on top of that, I’ll say one of my concerns, and part of the reason I didn’t try this sooner is that if you don’t incorporate resistance training and if you don’t get enough protein — 

Kevin Rose: I was just going to ask you that.

Tim Ferriss: — you can lose a lot of muscle mass. And I remember doing DEXA scans way back in the day. I started doing DEXA before The 4-Hour Body in 2010. And the owners of these DEXA facilities would tell me the vast majority of people who try intermittent fasting think they’re losing fat, but they’re losing muscle mass, and their body composition goes upside down effectively. And I judged it harshly and I judged it prematurely. So, in animal models, and also certainly if you look at what Martin and some of his clients have done, that need not be the case. And you’re not necessarily going to pack on tons of muscle, but you can lose fat while preserving or moderately gaining muscle. So, I’m still getting stronger in my workouts, and it’s interesting how fat loss works too. And Martin’s observed this. A lot of people have observed this, but it’s not caloric deficit, and you lose a predictable amount every week. Sure, if you were a closed system, blah, blah, blah, law of thermodynamics, yeah, it should just be pure math. But what seems to happen, at least with me, is that it’s not really seeing anything, not really seeing anything, not really seeing anything, and then all of a sudden in week four or five, you just seem to drop a lot of body fat. And I don’t have a great explanation for that, but I’m sure there is a good explanation.

Kevin Rose: It’s that MCT oil that you’re taking with the — you’re running into the bathroom.

Tim Ferriss: Just letting everything pass through.

Kevin Rose: Yeah.

Tim Ferriss: But what I will say is that I have used just about every diet imaginable, and I would say one criticism I would have of some of what Martin recommends is he advises people to consume somewhere along the lines, if they can tolerate it, like 400 to 800 milligrams of caffeine a day to aid in fat loss.

Kevin Rose: Wow.

Tim Ferriss: And yes, that will aid in fat loss, but — 

Kevin Rose: Yeah, and lack of sleep.

Tim Ferriss: — yeah, I don’t want the sleep architecture disruption. And also it’s like you can get away with a lot if you’re taking stimulants. And this is said as someone who for a long time — I was first introduced to pre-workout stimulants by an older student when I was wrestling in high school.

Kevin Rose: Let me guess, N.O.-Xplode.

Tim Ferriss: So, N.O.-Xplode, little reds, yeah. N.O.-Xplode is like a later iteration, but at that point, this guy was giving me the cobbled together, you can’t really do this anymore and I don’t recommend it. 

Kevin Rose: Fen-Phen and shit?

Tim Ferriss: No, not Fen-Phen. Ephedrine caffeine aspirin, the ECA stack, and that will rip body fat off of your body, but you are not getting a biological free lunch. You are really hammering yourself and your system. So I’ve — 

Kevin Rose: Did you ever hit Bronkaid?

Tim Ferriss: Bronkaid is probably ephedrine, I would guess.

Kevin Rose: Yeah, I know, but did you ever hit it when you were younger?

Tim Ferriss: Actually an inhaler, or what do you mean?

Kevin Rose: Yeah, because that’s what people would do.

Tim Ferriss: No.

Kevin Rose: The bodybuilders would hit Bronkaid and they would put on sweatshirts and go on the treadmill, just sweat their faces off — 

Tim Ferriss: No, no. No, I didn’t do that.

Kevin Rose: And just get six-pack abs.

Tim Ferriss: No. You would buy Primatene Mist tablets. And don’t do this, folks, it’s not good for you. Also, if you try to buy Primatene Mist tablets now, you have to show your driver’s license because I believe there are labs or probably trailers is a more accurate description. People will use that as a precursor to produce methamphetamine is my understanding, which is why it’s very tightly controlled. So suffice to say don’t do that and I’ve been very wary of any regimen that requires a lot of stimulants is, I guess, what I’m trying to say. And the only time that I have reliably — if you look at every single male in my family, it’s kind of comical. You can spot them from a mile away.

And abdominal fat, I know this isn’t unique to my family, but nobody in the history of my family on either side has ever had six-pack abs except for me when I was taking disgusting quantities of stimulants. But this time around doing the resistance training plus intermittent fasting and yes, some of it could be explained by reduced caloric intake, but I think there’s more to it, the abdominal fat’s finally coming off. And this is at 48. I’m no spring chicken. So I’ve been very impressed that I’m able to do that.

Kevin Rose: Anything else like joint pain? Some of the benefits of a ketogenic diet, people say joint pain goes away. They get some of these other things.

Tim Ferriss: Yeah. So another reason in addition to mitochondrial health that I want to ketosis is because of the potent anti-inflammatory effects and some of the chronic back pain that long-term listeners will be sick of hearing about. So that was another reason why I did the ketosis. I felt the anti-inflammatory effects of that much more so than just the intermittent fasting with a “regular diet” that’s higher in carbohydrates. 

I have also been adding in with my, let’s just call it normal diet, intermittent fasting, exogenous ketones. So supplemental ketones in the morning because I also — I want to give credit where credit is due. Rhonda Patrick and I have had a lot of texts back and forth. Rhonda Patrick, for people who don’t know, I think — God, maybe you introduced me to her. She was like podcast number 12 for me out of 800 and something, which I didn’t realize it was so early.

She’s a PhD, she is a scientist and researcher. She has published in very credible journals and it’s just a great resource for separating fact from fiction in so many different domains. And her dad, I believe it was, was diagnosed with Parkinson’s and she’s been public about this. And so we were trading notes on all different things and we were talking about ketosis and if you’re in ketosis, what about intermittent fasting? If you have a tablespoon of heavy cream in your coffee in the beginning, are you sacrificing autophagy, this kind of cellular self-eating/cleanup? And she sent me a case study of an Alzheimer’s patient. Pretty progressed Alzheimer’s, very impaired function, who was given a ketone monoester, so this is a liquid that is basically just a shot, two or three times a day.

And I recognize this is N of one, so take it with a huge grain of salt, but still a huge regain in function. I mean astonishing, astonishing recovery of function and mood and personality. So I figured, well, let me experiment with this because I might want to suggest it to people in my family, but I’m not going to do that until I understand exactly what I’m dealing with from a first-person perspective and adding in, for instance, one option a mutual friend of ours, I’m not going to dox him, but recommended Qitone, Q-I-T-O-N-E. And it’s a powder that you can add into your coffee and mix up as a creamer, which is what I do.

Kevin Rose: Wait, can we ask you one question, Tim, before you go on with this one? You and I were on a call, not a public call, but a phone call and you had mentioned that you found the best basically ketones on the market that you believed at the time and this was recently. So are these the ones?

Tim Ferriss: These are not those ones in part because, this is going to make me sound like a dick, I will share that one soon. They’re very expensive. I’ll tell you offline. The reason, and people are going to hate me for saying this, but I want this stuff for my family and this producer has very, very limited inventory. So I want to make sure that I can get this stuff. And Furthermore, I think it’s really premature to start just dosing your elderly parents or aunts and uncles with this. I still have some open questions about concerns and long-term health, etc. So I want to do some more digging. This is not that one.

Kevin Rose: Is this one palatable?

Tim Ferriss: This one is palatable.

Kevin Rose: Because you should tell people, the hardcore stuff is no joke, right? It’s cruel to be giving it to someone with dementia and that you’re asking them to chug gasoline.

Tim Ferriss: Yeah, I thought it was going to be worse than it is, but I also have a stomach of iron and have choked down so much disgusting shit over my life that I think — I’m dating a lovely girl right now and I made some salad and she tried to eat it and she’s like, “This is inedible. This is so disgusting. Why did you put so much vinegar on it?” And I did put way too much vinegar on it and she almost puked at the table and I was like, “What are you talking about?” I’m just shoving it down my maw. So I don’t know if I’m the best reference for palatable, but they’ve improved a lot.

They used to taste like jet fuel, I mean based on reports. I wasn’t even willing to do it. Because literally, I think he’s been public about this, Peter Attia, famous doc, trained at Hopkins, Stanford, etc, a lot of people will know him, he told me about the first time he tried the OG ketone monoesters and he took a shot and he basically had to run to the sink and white-knuckle the sides of the sink as he’s dry heaving for like 10 minutes. And I was like, no thanks, no thanks. But this Qitone, the Q-I-T-O-N-E, it is very palatable. You just mix it in with your coffee. What I will say to folks is just public service announcement, your GI distress may vary. So you might be fine, you might not be fine.

Kevin Rose: Just chase it with an Imodium, you’ll be fine.

Tim Ferriss: Yeah. And of particular danger is caffeine ketones and creatine, which is also great to take.

Kevin Rose: Well, and MCT.

Tim Ferriss: But yeah, if you take any two of those four, you’re in the danger zone. If you take three or four out of the four, there’s coin toss disaster pants. So just stay close to the bathroom. You do get used to it. But I just used this ketone this morning for instance because the stuff at some point that I hope to share when they get their production ramped up, number one, it does taste pretty awful. It’s pretty god-awful. And then second, it’s very expensive. I mean, it’s like 20 to $30 a dose.

Kevin Rose: Wow.

Tim Ferriss: Yeah. It’s very, very expensive. So if you’re going to be giving someone this particular exogenous ketone two or three times a day on an ongoing basis, we have to figure out a more economical solution because outside of the one percent of one percent, no one’s going to be able to afford that.

Kevin Rose: So Tim, for people that are listening and they’re hearing you talk about two different ketones here, it begs the question, if you are pricking yourself, doing blood work afterwards and finding out what your ketone levels are or peeing on a strip or however you’re doing it, obviously you can tell that these things work and I’ve done it myself because you take them and then you literally go do the test and a half hour later or five minutes later you see that your ketone bodies are elevated and you’re like, okay, it’s in my system, it’s working. Right?

Tim Ferriss: Yeah.

Kevin Rose: And I don’t know about you, but I can feel it. It’s like a light switch goes off.

Tim Ferriss: Yeah, you can absolutely feel it.

Kevin Rose: Cognitively your brain, also cardiac tissue, loves ketones.

Tim Ferriss: Yes, brain juice. It’s brain juice and — finish what you’re saying and then I’ll add something else.

Kevin Rose: My question for you is why would you even consider the more expensive 20 to $30 when there are so many other readily available, call it the five to $7 range ketones that are out there on market? What are the advantages of that $30 model?

Tim Ferriss: It’s hard for me not to dox a supplier by giving too much detail, but what I will say is this. Subjectively, and I’ve checked with a few people who have tested it, nothing feels like these ketones.

Kevin Rose: Really?

Tim Ferriss: Nothing. Not even close. It’s the Bugatti of exogenous ketones. You flip on the switch and for instance, I’m doing a lot of media interviews and stuff right now because of this Coyote game and we could talk about that at some point, I mean that’s very analog, as analog as it gets. I’m doing a lot of media and historically what would I have done? Because I want to be sharp, even in the afternoon I would have tea or coffee, but then that fucks up your sleep so badly and it turns into this vicious cycle. So now I just take the exogenous ketones in the afternoons and if anything, it’s going to help you sleep, which is something you observe with the ketogenic diet that’s really wild is that you are, at least personally, and this is true for a lot of people, your sleep requirements go down and when you wake up, I’m not a morning person historically, it doesn’t take me an hour to get up to speed. When I’m in ketosis, I wake up and I am ready to go nine or 10 out of 10.

So I would say for a lot of folks though, at least based on the reviews and reports that I’ve read, the diester, this Qitone, Q-I-T-O-N-E, it’s more than enough to get a taste test for whether or not you’re going to get any response. It’s hard for me to imagine anyone not getting a response because we’re evolved to produce and consume ketones. And I’ll just say also that I have found it very helpful to think of Alzheimer’s, and this is simplifying things and I’m not the first person to say this, as type three diabetes. Brain diabetes. And that is part of the reason why this is so interesting to me. Not only is it possible treatment or something that could reduce symptoms, maybe restore function, but also for preventative purposes.

If I can do, as I did for a long time, for many years I did a seven-day water only fast per year and then I would do a three-day water only fast once a quarter, I still think that’s a good idea, but for whatever reason in the last few years I became less tolerant of that. I would do a seven-day fast and I would get really dizzy if I stood up. I would have memory problems and I think it was increasing insulin insensitivity in part that caused that. And now that I’m doing this 16/8 intermittent fasting and I’ll occasionally just switch it up and — ketosis takes a little while to get into, so there’s a bit of an on-ramp. But now that I’m doing this, I’m also feeding my system with exogenous ketones. My working hypothesis is that I’m keeping that ketone machinery busy so that it doesn’t atrophy.

And my expectation is, and I’m going to test this again soon, is the next time I do, three days is pretty easy for me at this point, but a seven-day let’s just say water-only fast, by the way, you don’t need to lose much if any muscle mass doing that either but that’s a whole separate conversation, it’s kind of counterintuitive, I will be able to test this hypothesis. Did all this stuff help? I think doing 16/8 by itself probably helps you with an extended fast. So we’ll see. We’ll see. But my feeling is that I’m late to the party in a sense, but that intermittent fasting is very interesting and it’s compelling from a compliance perspective because for instance —

Well, I just think of my parents or anybody. I can get so many people to change their behavior on the planet and my parents will not listen to a thing I say. And it’s very hard to get people to change what they eat. I think it’s easier to change when people eat. And just from the perspective of trying to grease the wheels for behavioral change in people who are resistant, who have failed a lot before, this is very interesting, particularly — 

Kevin Rose: People really underestimate what snacking does to keep their glucose levels elevated. Because when you have that full eight hours plus of downtime of no eating and you really give your body a chance to — for me, I’m just like you where I did a glucose tolerance test and I stayed elevated for way too long.

Tim Ferriss: You want to explain what that is?

Kevin Rose: Yeah, so for people that don’t know, when you go to a fancy doc like Peter Attia or some of these other concierge doctors, and you can ask your normal GP to do this and some of them will if you have a cool one and they’re on top of it, but they’ll essentially sit down with you and they will give you a straight glucose drink. So think of a Gatorade syrup, like if it were just pure syrup, right? And you drink that and then they’re going to, one, draw your blood at baseline and then they’ll pick intervals, I can’t remember what it is. Tim, do you remember off the top of your head?

Tim Ferriss: Yeah, every 30 minutes for two hours.

Kevin Rose: Right. And then they’re testing for insulin response and also where is your glucose over time? And ideally you want to see a spike up, not too high, and then a rapid kind of — 

Tim Ferriss: Recovery.

Kevin Rose: Return to a normal baseline, right?

Tim Ferriss: Yeah.

Kevin Rose: And mine just stays elevated for 5X too long. It just hovers around that 135 forever. So that could be my muscles aren’t sensitized, they’re not taking up enough glucose, I have metabolic dysfunction. It could be a handful of different things. 

And so I’m actually taking a different approach than you in that I also have been talking to Rhonda a lot.

Tim Ferriss: Phone a friend. Poor Rhonda.

Kevin Rose: Yeah, exactly. Poor Rhonda. So she told me not too long ago, maybe this was like six months ago, she was like, “There are people —” and this is not an endorsement of this but, “There are people that are microdosing GLP-1 now.”

Tim Ferriss: Yeah. So I want to hear more about this.

Kevin Rose: So I started microdosing, basically about two months ago, tirzepatide.

Tim Ferriss: Yeah. Zepbound also.

Kevin Rose: Right, it goes by Zepbound or on the glucose side it’s Mounjaro for people who have glucose and diabetes issues. So there’s two brands for it. Zepbound is if you want the fat loss. It’s the same drug. So essentially the lowest dose you can get that in is two and a half milligrams, but they sell it in vials now. So if you grab yourself an insulin syringe, you can give yourself a little under one milliliter of it and — not milliliter. What am I thinking of?

Tim Ferriss: Milligram?

Kevin Rose: What is it the insulin syringe is? A little under one unit basically.

Tim Ferriss: IU, yeah, international unit.

Kevin Rose: Yeah. So a little under one unit of that compound. And I notice over the course of a week, because that’s how long you microdose it for, I have lower just standard resting glucose, and then also my spikes don’t get near as high. I probably trim 30 percent off the spikes and my return to baseline is so much better. And so I’m kind of repairing that through a little bit of a hack. And so there’s a bunch of people now that are starting to think of this as more of a longevity drug. And we’ve known this that people that take these drugs, they have fewer cardiovascular events. There are other benefits of GLP-1 other than just can I look good? Right? So obviously I’m not doing it for the weight loss, I need more for weight loss, but if I could see one ab, I’m not going to be pissed.

Tim Ferriss: I’ll take a two pack at this point.

Kevin Rose: Yeah, exactly.

Tim Ferriss: No, but try the 16/8, man. It’s been wild to watch.

Kevin Rose: Well, I mean, you’re talking to the guy that created zero, the intermittent fasting.

Tim Ferriss: Yeah, yeah.

Kevin Rose: I’ve definitely done my fair share of 16/8.

Tim Ferriss: It takes some time, just the long-term durable changes. And I don’t mean indefinite changes, but with the ketogenic diet it really took a few weeks and then there was a step function in terms of change.

Kevin Rose: Yeah.

Tim Ferriss: A few more things about GLP-1 agonists. So I have some of my relatives with neurodegenerative disease on tirzepatide, low-dose tirzepatide. And by the way, folks, talk to your doctors. We are fucking not doctors, we’re clowns on the internet.

Kevin Rose: This is bro science at best.

Tim Ferriss: At best. Yeah. Bro science B minus. But they’re on tirzepatide, that’s with supervision of very competent doctors, for the metabolic dysfunction primarily. So glucose control, etc. Some of these, and I’m not sure which in particular have been studied, but some of these GLP-1s appear to have neuroprotective effects also. So that is very interesting to me. And there’s actually, I think they’re called DORAs, a sleep medication, also appear to have some neuroprotective effects primarily or at least relevant to me related to Alzheimer’s. So I’ve also thought — 

Kevin Rose: What was the name of the one that — I can’t remember the name of it. The sleep medication.

Tim Ferriss: It’s a class, so let me get this — 

Kevin Rose: But there’s a name for that. I just got a prescription to one of these and I had to pay out of pocket for it because I didn’t qualify obviously for insurance and it was insane.

Tim Ferriss: Well, let me just finish my thought for a second here.

Kevin Rose: Yeah, go ahead.

Tim Ferriss: So I want to hear about this. So I said NORA or DORA, I’m mixing up my words here, but I’m pretty sure, and do your homework, folks, that DORA is dual orexin receptor antagonist. And I’ve been thinking, because you and I probably still use occasional or continuous trazodone for help with sleep for — 

Kevin Rose: I don’t use trazodone anymore.

Tim Ferriss: You don’t? Okay. I’ve been thinking of replacing that with a DORA, obviously with medical supervision, because now that I’m an adult and I can see what’s going on — because as a kid I had a grandmother who kind of disintegrated under the weight of Alzheimer’s, but I was too young to really know what was going on. Now that I’m an adult and I can see the personality changes, the anxiety, the depression, everything that comes with it, I am looking for a full stack of capped downside, ideally well-studied low risk, but potential upside interventions. So you tried some of these? What happened?

Kevin Rose: Yeah, I have one. I’m trying to find the name of it. I’ll have to go into my pharmacy and look.

Tim Ferriss: Into your pharmacy.

Kevin Rose: Well I have an online pharmacy. But it’s legit. It’s Amazon Pharmacy. I’ll just say it.

Tim Ferriss: Oh, all right. All right.

Kevin Rose: Amazon Pharmacy.

Tim Ferriss: I thought you just had next to your red room, you have a dedicated pharmacy.

Kevin Rose: You’re the one with the [Inaudible].

Tim Ferriss: Well yeah, that’s true. That’s true. 

Kevin Rose: Cut that out. 

Tim Ferriss: Tomato, tomato.

Kevin Rose: Yeah. Exactly.

Tim Ferriss: Whatever floats your boat.

Kevin Rose: Oh, so I tried Belsomra.

Tim Ferriss: No idea. Sounds like a Japan animation character.

Kevin Rose: Yeah, exactly. So Belsomra is the one that I tried and it was, I want to say about $600 off prescription, which was just insane.

Tim Ferriss: Yeah, that’s pricey.

Kevin Rose: But I just wanted to see what it would do. Yeah, it’s $600. So far I only tried it one time and it was great, but I don’t know, I’ve also been sleeping a lot better now that I’ve quit alcohol. And so I would say that I need to try it again. So it’s on my to-do list. It’s sitting in the cabinet. I’ll give you some next time you come, once you get your doctor to say that you’re allowed to have — 

Tim Ferriss: Yeah, yeah. Okay. Black market bro trades.

Kevin Rose: What could go wrong? Give me some of your ketones, your quality ketones.

Tim Ferriss: Yeah, exactly. Exactly. My off-the-back-of-a-truck Bugatti ketones. 

All right, so I want to give — not to make this the Rhonda show, but I want to give her two more nods. Two other changes I’ve made — 

Kevin Rose: 10 grams of creatine.

Tim Ferriss: No, I’ve been doing that for a long, long time, but I have upped the quantity and actually yeah, if I’m feeling deprived of sleep, like my HRV, my heart rate variability was really low this morning so I took 20 grams today to try to compensate for some of the effects of sleep deprivation. But the most important, maybe most important one is that I reduced the temperature of my sauna based on some conversations with Rhonda. So I’m no longer doing 194 plus throwing lots of water on the rocks, which is what I’ve been doing for many, many years.

Kevin Rose: Wow, that’s high.

Tim Ferriss: Yeah, it’s high, but I reduced it to 175, 180, and that’s based on some literature and studies that Rhonda cited out of Finland. Now I don’t know how well-designed these are. I haven’t read them myself, but I’m like, you know what? It kind of makes sense to me. I mean, I feel like I am cooking a steak and my head happens to be the steak at 194 plus, whereas at 180 it’s less microwave in my head and more of a full body thermic effect. Because too hot could be actually— Accelerates dementia. So it’s like, oh, good lord. Okay.

Kevin Rose: Well, she found a study that too hot is not good for you. There actually was a study that showed you get the inverse at too hot and that 174-ish, 5-ish is kind of the sweet spot for 20 minutes.

Tim Ferriss: Yeah.

Kevin Rose: Are you wearing a felt hat?

Tim Ferriss: I’m not wearing a felt hat. I probably should because — 

Kevin Rose: A hundred percent.

Tim Ferriss: Yeah, because I’ll get hot enough wearing the, I guess it’s a wool hat. Yeah, the — 

Kevin Rose: Wool, that’s what I meant.

Tim Ferriss: If you go to Coney Island or some of these Russian bath houses with people with lots of tattoos you shouldn’t fuck around with, then not only will they have the hat, have you ever seen them wearing the oven mitts, the wool mitts?

Kevin Rose: No.

Tim Ferriss: Yeah, they look like oven mitts. They’re these wool mittens that the super hardcore will wear and — 

Kevin Rose: Oh, damn, I’ve got to get that.

Tim Ferriss: They’ll just sit in there forever and people might think, wait, doesn’t wool keep you warm? It’s like, well, actually wool can do both because it’s an insulator. So it can keep the cold out, but it can also keep the hot out from what it’s covering. So that’s a good point. I should start wearing my little Keebler elf hat again. I do have one here. And then the other one that I’ll mention just because I’m sure there are people listening who have, if not chronic pain, then occasional pain. I mean, particularly as you just accumulate life, you get bumps and bruises along the way. 

I have begun to — and I really try not to take oral anti-inflammatories much at all. There was about a year and a half when I was on prescription anti-inflammatories and all this stuff, which is just systemically not great for you, but I needed it at the time for back pain.

Curcumin phytosome from Thorne, so really switching from NSAIDs like ibuprofen, aka Advil or naproxen sodium aka Aleve, just shifting away from that stuff to curcumin. 

Everybody should read the blog post I wrote called “No Biological Free Lunch,” but there is some trade off. And part of the reason I stopped using curcumin on a regular basis, which also seems to have some potential effects on slowing the onset of neurodegenerative disease like Alzheimer’s, so it seems to have a lot of applications, but if I used it daily for say a week or two and then I stopped, I would be incredibly sore for a few days afterwards and I was like, I don’t love that.

So I’ll probably cycle on and off, but I have shifted to Thorne brand and I have no dog in that fight. Nothing to gain from saying that. Curcumin phytosome. So those are a few. Now you’ve got a lot on your list. I haven’t gone too far into the Google Doc, but where should we start? Well, where should we start, we’ve already started.

One thing before we move on from this topic though I think it’s important to mention is that when I first started doing the ketogenic diet with Peter Attia as my physician, he was running my blood work. And I am one of the unique individuals that, because heart disease runs in my family, I have that genetic marker that essentially hates saturated fat. And so my ApoB shot up through the roof, so much so that he freaked out and he was like, “Okay, you can never do the ketogenic diet again.”

Tim Ferriss: Abort, abort, abort.

Kevin Rose: Yeah, abort. So if you’re going to do the ketogenic diet, definitely get your blood work done, check your ApoB, make sure you’re working with your doc. It’s not a free lunch for everyone.

Tim Ferriss: No, it’s not. And also I’ll say, so I’m a cholesterol hyper absorber, so I also have to be very careful with saturated fat intake. So if I’m not in ketosis, I really do watch any type of saturated fat intake. Also have to be careful around MCT oil to a certain extent. But since I am on medication already for controlling some of that, my body was actually able to tolerate the ketogenic quite well. But the point of all of this is you need a professional tracking this and helping you to understand what you’re working with. Because I mean, the number of people who got really into, back in the day, Bulletproof coffee — 

Kevin Rose: Oh, my God, I had so many of those.

Tim Ferriss: And then realized, oh, shit, my labs are so bad that it looks like I could have a heart attack tomorrow. You just have to know thyself. And that begins with measurement and professional guidance. So yeah, thanks for saying that.

Kevin Rose: Yeah. All right, let’s talk about people in your house. So one of the things I’ve been thinking about lately is how one approaches modern day home security in terms of how you protect yourself. So it was one of the things I wanted to ask you what you’re doing at home, because one of the things that I had recently was a homeless person in my closet.

Tim Ferriss: I thought you were screwing with me, but this is actually a real thing.

Kevin Rose: Yeah. So basically what happened is — I only say my closet because we ended up getting the place. So real quick for people that aren’t aware, I was part of those crazy fires that happened out in California. We lost our house, everybody was safe and sound, which is great, and we moved into an apartment and recently I found a new place to move into. We were touring the house and my wife is upstairs and she walks out of the room and she looks at the person that’s showing us the house and goes, “There’s somebody in the closet.” And I’m like, “What are you talking about?” It’s an empty house, like a brand new empty house. What are you talking about? And she goes, “Yeah, I opened the closet door. He was crunched down in the corner and he puts his finger up to his lips and goes, ‘Shh, don’t tell anybody.'” Nothing more creepy than that.

And he walks out and he’s like, “Hey.” And we’re like, “Who are you?” And he’s like, “Yeah, I just live in here.” And he ended up being a really nice guy. I was actually kind of impressed because he goes, “I make the bed every day. I wash my clothes here because there’s a washer and dryer here and I’m keeping the place nice.” But he goes, “This is what I do.” I felt really bad for him because he said he worked at a car wash, he makes $500 a month, he can’t afford a place to live, and this is what he does. He just crashes in homes that are under construction and are newly built homes. And then he started bragging. He’s like, “You won’t believe some of the mansions I’ve lived in. I’ve lived in crazy places.” And I was like, this is crazy.

And so he leaves and then he won’t leave. He’s standing in the driveway just standing out there and we’re like, “Hey, buddy, you kind of have to go.” And then he just stands there and we shut the door and we’re like, okay, clearly he’s not completely of sound mind, but he’s a nice enough guy. And eventually he knocks on the door again and he’s like, “I left all my stuff in the cupboards there.” And he had all this stuff in the cupboards, like peanut butter and all this stuff. And I was just like, ah, this poor guy. So we ended up sending him some — he had a cell phone, so the realtor was nice enough to send him some cash just to help him get a meal that night and whatnot. But it makes you think, especially — I mean, when I was younger, listen, I lived in some really shitty alleys and bad places in San Francisco, so I’m fine with that. But when you have kids, it’s — 

Tim Ferriss: It’s a different story.

Kevin Rose: It’s a different story, right? And so I immediately started thinking, what do you do? And so I went and did some research online and this is one of the pepper sprays that I found. Because all of the home defense stuff that I had before burned in the fire. And so I’m basically starting from scratch. And so I bought two pepper sprays and a taser. And I’m just wondering, what does Tim Ferriss do for home protection? I know what you do. You’ve got AR-15s and shit.

Tim Ferriss: Well, all right. This is not — let’s see —

Kevin Rose: It’s not weapon advice.

Tim Ferriss: No. Yeah, this is not professional weapons. Talk to your professional armorer.

Kevin Rose: Yeah, exactly.

Tim Ferriss: All right, so I would say a few things. There are a few things. We can say, “How do we get really good at pulling people out of the river?” But then there’s like, “Why are people falling in the river in the first place?” It’s actually a Desmond Tutu paraphrase, but the point of that is that there’s, “What do I do when someone’s in my house?” or, “Who comes to my house?” And then there’s, “How do we just prevent that from happening in the first place?” And there’s serendipitous accidental/unpredictable randomness and then there’s premeditated trying to find you.

So I would say, for me, step number one is choosing very carefully where you live, if you can, and secondly, just paying a lot of attention to privacy. So if you might have people who are going to seek you out, and this is going to become an increasingly relevant problem for anyone who even becomes micro famous for a second, you think it might not happen, who knows, you’re doing something funny, you end up with 3,000 followers on Instagram or TikTok or wherever, 3,000 people is a lot of people.

Kevin Rose: Yeah, all it takes is one crazy one.

Tim Ferriss: All it takes is one crazy one. And for that reason, there are lots of basics, and none of these are foolproof, but it’s like buying your home through an entity of some type, which doesn’t need to cost a lot of money, but simply to cut down on how easy it is for casual fair weather stalkers to find you, never having anything shipped to your home address. Always having a UPS store or some type of mailbox where everything is sent because if someone, for instance, sends anything to your house, maybe they’re trying to be really nice, it’s a friend of yours and they send you 1-800-FLOWERS, this is not a real example, I’m just making that up, but they send you flowers and those businesses rent and trade and maybe even sell mailing lists as part of their business — 

Kevin Rose: Or they get hacked.

Tim Ferriss: Or they get hacked. Before you know it, you’re doxed, your home address is everywhere. So I would say that thinking about privacy, and honestly, trying to red team yourself, that’s just to say, we won’t get into what that actually means, but the basics are have one of your friends who’s smart pretend to be a stalker and try to find you, preferably somebody who has some technical chops or is at least tech-savvy because just because someone’s crazy does not mean they’re stupid. There are actually a lot of unstable smart people out there. So that’s step number one for me. Since taking all of that stuff seriously, I’ve very rarely had to deal with any type of stalker issues.

Kevin Rose: People in your closet?

Tim Ferriss: Yeah, the people in the closet are a thing of the past.

Kevin Rose: The college years.

Tim Ferriss: Yeah. Then I would say I never thought that high-rises condos would be of any interest to me, but there are added layers of security. My place in Austin is way the hell off a ground floor. There are multiple, I don’t want to say security points, but you need a key and a fob to get through the elevators and to get past the front desk and to do these various things. So I would also consider that as a viable option if you currently have or expect to have any type of real public exposure.

And again, this seems like a problem for the one percent of the one percent of the top creators, that’s not going to be the case. And increasingly, this is a problem even for people who are micro famous to a few thousand people. That’s step number one. But you’re very savvy with a lot of that kind of stuff. On a home security level, and you mentioned the kids, look, you and I have shot firearms together. We did three-gun shooting training with Taran Tactical — 

Kevin Rose: Yeah, Taran Tactical.

Tim Ferriss: — way back in the day before he was everywhere.

Kevin Rose: Tim Ferriss Experiment.

Tim Ferriss: Yeah, good for him. So we did a lot with Taran over the span of a few days, a bunch of training, before he did the John Wick movies and everything else. That’s where Keanu Reeves trains. That’s an amazing spot. So we both know how to shoot guns and I have firearms and so on. I’m not recommending that for everybody. If I had kids, I would rethink that really, really strongly because kids are smart, and yes, you can have biometric safes and this, that, and the other thing. Jim Jeffries does a hilarious and tragically realistic reenactment of gun stuff in the US. He’s from Australia. He’s hilarious and very politically incorrect, if you want to check out his comedy. He’s been on the podcast too.

But basically, it’s like if you want your guns ready to go, you need to be able to get them quickly. But if you want them secure enough that your kids are insured against some type of horrible accident, which is sadly pretty common, then you need them really, really fail-safe in their protection. So you’re sort of moving in the right direction with a taser and so on. 

Some people obviously have physical security. I think physical security is often overrated compared to digital security, frankly. For instance, if you have physical security for a portion of the day or at your home and then you’re constantly posting where you are on social media in real time, or you’re putting your family on actually publicly accessible social media. I remember this friend of mine wasn’t really thinking about it because he doesn’t have a lot of exposure to crazy people, but has become better known in his niche sphere. And he was at the grocery store with his kids and somebody recognized his kid and was like, “Oh, that’s so-and-so.”

Kevin Rose: Oh, shit.

Tim Ferriss: Recognized his kid, not him.

Kevin Rose: Right.

Tim Ferriss: That’s spooky as fuck.

Kevin Rose: Yeah, people have done that with my dog.

Tim Ferriss: Yeah, definitely.

Kevin Rose: They actually see Toaster and they’re like, “Oh, there’s Toaster,” and I’m not even there. They see Toaster and they can recognize him, which is crazy.

Tim Ferriss: So I would say if you’re intending on having people familiar with how to use a taser or pepper spray or any of that stuff, first of all, even with firearms, most police officers in a pinch will not be able to hit someone under dark conditions at any decent distance. And that’s not to insult police officers. It’s very, very hard, which is why people use bear spray instead of firearms, oftentimes. With bears, it’s just easier to get the job done. So you might consider, because that little pepper spray that you just showed me, the effective range of that is probably going to be pretty low.

Kevin Rose: It’s 10 feet, yeah. But it is the highest concentration. This is the heat test. They have those ratings on them. This is the highest legal concentration you can get, which I think is 2.4 in heat or something.

Tim Ferriss: Just just get a bear spray that you can hit them at 25 feet, if you get to that point. And I’ve played around with tasers before. Amazing tool. But just like anything else, it takes a good amount of practice to be able to hit anything with that, particularly under duress. So when I’m training for, say bow hunting, which I’ve done for 10-plus years now, the way that I’ll train a lot of the time as I’m getting closer to the season is I’ll do a bunch of kettlebell swings outside until my heart rate is peaking, my hands are kind of shaking, and then I will grab the bow and I have the ability to shoot one arrow. That’s it. That’s a pass/fail.

And practicing under those heightened conditions I think is important if you’re going to take it seriously. But when I’ve talked to my military friends, I know this uncorking a lot here, but sure, they’re very good with handguns and they’re very good certainly with their primary weapon system. And I’ll talk to some of them about, say, hand-to-hand combat stuff. And yes, fundamentally, if they get to tier one operator, they’re kind of mutants and they’re physically very, very, very impressive and almost, I shouldn’t say almost, all of them can fight hand-to-hand, but the point they’ll make, because they’re not trying to become a black belt in jiu-jitsu necessarily, although some of them are, they’ll say, “If it gets to the point where I am having hand-to-hand combat, 17 things have gone wrong.”

You never want to get to that point. Sure, you want to know enough that you can cover the base, but if it ever got to the point where you’re tasing someone or your wife is having to use pepper spray, a lot of things preceding and preventing that would’ve had to have gone wrong, right? I don’t know if that’s a satisfying answer. I do think, and I’m saying this as someone who takes certain precautions for natural disaster, et cetera, but a lot of the prepper stuff misses the plot, I think, past a certain point. And as much as we would all like to think that we’re Steven Seagal, in the movies, not in real life, plus Jason Bourne plus American Sniper, we’re not, trust me. An ounce of prevention is worth a pound a cure, for sure. How are you thinking about it? Because you’re living in L.A. where it’s not exactly marauders in Mad Max, but there are some issues, right?

Kevin Rose: Yeah. It is certainly depending on the block you’re on, a roll of the dice on who’s going to confront you, and that becomes very clear at about 3:00 a.m. every night because you just hear the zombies in the street that are strung out, screaming their brains out, just going crazy. It’s less about someone’s going to rob me, it’s more who’s going to stumble into the yard or hop the fence or whatever it may be.

I’ve already put up those little spikies that will cut you wide open if you try and hop the fence. You get those on Amazon. I got those and I put those all around the perimeter. So that’s been good. I think about the pepper spray as more like I’m taking my kids out to the park or out to some place where you could bounce into someone. And for me, it’s just like I don’t want to engage. Could I take out a crazy person?

Tim Ferriss: No, you don’t want to engage.

Kevin Rose: Depends on what they’re on.

Tim Ferriss: You don’t want to engage.

Kevin Rose: You don’t want to engage. Exactly.

Tim Ferriss: Nobody’s going to win, everybody’s going to get hurt, and if they have a knife, you’re going to get stabbed or cut. There’s no way around it. Look, I’m sure there are some people out there who are master ninja disarmers, but here’s what you can do. I think Krav Maga has a lot to offer, but it sometimes instills a false sense of confidence in people.

If you think you can disarm someone with a knife, have somebody take a nice big highlighter, hold onto it, and be like, “I’ll give you 10 bucks for every mark you can leave on me,” and see what happens. You’re going to get covered in highlighter. Those are all cuts. So it’s not worth engaging. So I think if I had to bet, I’m sure other folks are going to have good ideas here, but I think spray is probably the way to go.

Kevin Rose: Spray is the way to go.

Tim Ferriss: It’s going to have the most margin for error and you’ll have more rounds per se than a taser if you miss fire or you miss the target.

Kevin Rose: Yeah. Fun times though, people in your closet. That was the weirdest house showing I’ve ever been to.

Tim Ferriss: I could also totally see your wife just going, “There’s a person in the closet.”

Kevin Rose: Right, exactly. Didn’t freak out at all. 

Tim Ferriss: Very calmly.

Kevin Rose: Yeah. It was very strange. I’m glad I kept my cool because I get very protective, especially if my kids are there. He ended up being a very nice guy, but still.

Tim Ferriss: When I was younger, growing up as a townie with a rat tail, working in the restaurants on Eastern Long Island where there are a lot of wealthy people, I would look at them with the hedges and all the protection and I would just think to myself, “What a bunch of assholes. They think they’re so important, blah, blah, blah.” And now I’m like, “Yeah, okay. I get it. You don’t want some weirdo just digesting everything you’re doing in the house, like someone watching TV.” There are a lot of unstable people out there, I hate to say it. And it’s not like they’re the majority of the population, but it just takes one.

Kevin Rose: It’s funny, I was walking through a grocery store the other day here in L.A. and it’s so strange because I had this flashback as when I was a kid and my dad would essentially just say like, “Okay, go have fun,” in the grocery store. So I’d just run around and go to the toy aisle and see what they had and try and grab some Twinkies and sneak them into the cart when he wasn’t seeing and stuff like that. That was my childhood. And I looked around and I was like, “I don’t want my kids out of my sight.”

It was just filled with, I would say, the potential for — there was a lot of people there that clearly either were on drugs or had just taken a step too far in that direction. And we just didn’t have that. I was standard lower middle class growing up. The drugs weren’t as hardcore. We would have alcoholics, that was it. If you saw somebody down on their luck, they were an alcoholic. And now you see people that sadly just don’t have the care and they’re talking to themselves. It’s brutal. It’s really brutal and it’s tough because there’s no easy fix.

Tim Ferriss: Yeah. So throwing stars and sharks with lasers, folks, I think that’s where we landed.

Kevin Rose: I had throwing stars as a kid.

Tim Ferriss: So dangerous.

Kevin Rose: I should bring that back.

Tim Ferriss: Another thing that I was allowed to do. Literally, I just threw out my throwing stars that I got from Asian World of Martial Arts magazine catalog. I think they shipped it from Philadelphia. And I’m just like, “I cannot believe I was allowed to play with these.” Because what happens, you throw a throwing star at a tree, it just bounces back and shoots right back at you.

Kevin Rose: No. Here’s what we did. So this was the hack. 100 percent they would just bounce back at you. My dad, for some unknown reason, let me go into the garage and use his metal grinder polisher to make it sharper. I made them sharp. So mine would stick in the tree. So you would go to our front yard and there were all these holes in our tree from me just throwing stars at it. And I think he kind of looked at it and was like, “Oh, that’s cool. Kids are throwing stars at the tree.”

Tim Ferriss: Different world. I’m just — 

Kevin Rose: Different world.

Tim Ferriss: — amazed that I’m alive, honestly, when I look back.

Kevin Rose: Well, that was the same era where he would just be like, “We’re going to the grocery store, jump in the back of the pickup and put your arms over the side.” And the word of advice was, “Lean up against the back so your backs are touching the back of the pickup.”

Tim Ferriss: So you’re protected.

Kevin Rose: Yes, so you’re protected. Exactly.

Tim Ferriss: That’s like the brace position in an airplane in case of impact, you’re like — 

Kevin Rose: Exactly.

Tim Ferriss: — “Yeah, that’s going to do a whole lot.” Sorry, I’ll shut up on the reminiscing, but it is kind of wild. I was into skateboarding. You were too. I was never terribly good at it, but I had confidence and enthusiasm way beyond my capabilities. And my parents, to their credit, were cool. They made a homemade quarter pipe, right? Now, that sounds cool and I loved it, but homemade quarter pipe, the angles aren’t quite right. And the way that we would use this, because there’s just grass and gravel around, is drag it out. And cars would go by and then you’d drag that quarter pipe out into the street — 

Kevin Rose: Yes, we did the same thing.

Tim Ferriss: — and start skateboarding and then try not to get hit by traffic and then pull it back over.

Kevin Rose: Oh, for sure. We would just leave a quarter pipe sitting in the street and then they’d be like, “Drag it back to the sidewalk,” and we’d drag it back. And I had a trampoline in my backyard. I was lucky enough, my dad eventually bought us a trampoline at Costco, and I used to climb on my roof and jump off the roof onto the trampoline. And he would hear me climbing on the roof and he’d come out and be like, “Get off the damn roof,” and that was it. And then he’d just watch me jump off the roof onto my back on the trampoline.

Tim Ferriss: Yeah. Wow. By a consequence of many miracles, we are still here today.

Kevin Rose: Exactly. Minus the back pain.

Tim Ferriss: Yeah. No, shit. Jesus. Yeah, it’s not exactly a total mystery. I want to hear about something that you texted me, and people might be, who knows? I think it’s interesting. Let’s hear about it. We’ve got book recommendations coming, we’ve got all sorts of stuff coming, so don’t skip out. Also, shameless plug, coyotegame.com, just in case it doesn’t come up later. It’s gone fucking bananas right now, which we should talk about, but it’s awesome.

Kevin Rose: You texted me — 

Tim Ferriss: And — 

Kevin Rose: Go gentle here on what I said exactly.

Tim Ferriss: Okay. All right. You know what? I’m not even going to say it because I don’t want to misstep and then put more work on my post-production. All right, what did you say to me and where do I go?

Kevin Rose: Well, we were talking about venture capital funds and investing.

Tim Ferriss: We were talking about venture capital and what did you say?

Kevin Rose: The way that I put it is, you had asked me about investing in certain funds and I said I would be careful because I believe that venture, they’re not necessarily on sound — 

Tim Ferriss: Footing.

Kevin Rose: — footing right now.

Tim Ferriss: This is the most doctored Kevin I’ve ever seen.

Kevin Rose: I know. Well, I work in venture capital, so that’s probably part of the reason why. So I have to be careful in what I say here.

Tim Ferriss: So is it fair to say that the gist of what you’re saying is venture capital is going to get a lot harder. Is that fair?

Kevin Rose: I believe it’s going to be a lot harder for early stage funds. Well, let’s first start with the problem and what’s changed. Essentially, what we’ve seen historically with venture capital is that venture capital can be a fantastic return for investors if done right because you get into early stage, predominantly, technology startups, if you’re doing a venture on the tech side.

And if you get into the next Uber or OpenAI or whatever you may pick your unicorn, the returns are just insane. And they outpace that of pretty much all public S&P or whatever it may be. It’s just a good asset class to be invested in. Not to have all of your eggs in that basket, but certainly a lot of professional investors would want some exposure to venture. Endowments want exposure, universities, that’s where a lot of the LPs or limited partners that invest in these funds come from.

Tim Ferriss: It’s also how the GPs make a lot of their management fees. Yum, yum, yum.

Kevin Rose: That’s right. Yes. So partners at firms both get management fees and they also get upside in the return on those funds.

Tim Ferriss: And also for people who have not enough context, and I would’ve said this in the intro somewhere, but you have a ridiculous track record with not just creating companies, but investing in super early stage companies. And, I’ve said this to a lot of people, you’re a rare breed because you are very good at investing in a whole lot of different asset classes at different stages of size and growth, and it’s very hard to do that. So I just want to understand that Kevin is speaking from a place of being a very good practitioner of this craft. Continue.

Kevin Rose: I appreciate you saying that. No, thank you. It’s kind of you to say. I’ve certainly enjoyed the journey. It’s a crazy journey when you get to see these things at a very early stage and watch them grow and have eventual outcomes. But the craziness that’s happening right now, it should come as no surprise for people listening, is that AI is the absolute darling of Silicon Valley right now. So everyone is talking about AI. All the funds are geared towards AI. I’m a partner over at True Ventures. I would say nine out of 10 deals that we do these days are all AI-focused in some regard.

There was a couple of decades of what Marc Andreessen famously kind of coined is software eating the world. And now we’ve kind of transitioned into this world of AI eating the software. So AI is doing a lot of both retooling of the software to make it more, I would say, AI dominant in that you’d need less employees. And AI does a lot more of the heavy shouldering of the burden and work. So it’s causing a lot of disruption all across multiple industries and multiple verticals, starting with customer service, eventually getting into coding and beyond, drug discovery, basically everything.

Tim Ferriss: And eventually, the next 12 months, it’s got to be. I would imagine law firms are already reading the writing on the wall for hiring of associates for rote tasks that can be done in 30 seconds by AI. I know actually a senior partner at a law firm, he is in charge of spearheading a huge AI initiative within the firm for cost-cutting and efficiency.

Kevin Rose: Absolutely. I have seen it on the legal side as well. Our mutual friend, Josh Cook, has talked to his junior associates and said, “Look to your left, look to your right, one of you is not going to be here in the next five years, and it’s most likely just going to be the AI.”

Tim Ferriss: Five years is generous.

Kevin Rose: Yeah, five years is very generous. The tea leaves that I’m reading right now, and where I think that venture is going to have a hard time, is I would say on non-capital intensive businesses, meaning that if you’re building something that is hardware-based, you’re building the next robotics company or whatever it may be, you need a lot of capital to get that off the ground. There’s no doubt that that’s still the case, so venture makes a lot of sense.

And I feel very fortunate that we’re quite good at that particular area in that we’ve done the Pelotons and the Rings and the Fitbits and all those companies that kind of go off and build on the hardware side. 

On the software side, what’s happened in the last, I call it 18 months, is that the barrier to entry for a new engineer, you don’t even have to be an engineer, they call it vibe coding now. So if you have an idea, you can spend the next 48 hours maybe, let’s just say double that, watch YouTube videos and be, I would call it a second year computer science student in terms of your efficiency — 

Tim Ferriss: What you can produce.

Kevin Rose: — your ability to deploy. Yes. Tim, even today, if we started today and we said, “Okay, listen, we’re going to make you watch these 10 videos on Cursor and AI and use Claude Code and insert the four or five most popular AI coding tools right now,” I would bet, without a doubt, within four days, you could dream up any app that you could imagine in terms of the Tim Ketone dosing regimen app, whatever it may be.

Tim Ferriss: Ketonesuppositories.ai.

Kevin Rose: Exactly. The Bugatti ketone suppositories get sued immediately.

Tim Ferriss: That’d be awesome.

Kevin Rose: There’s a co-branding deal there somewhere you’re missing out on. But I’m not even kidding. You could actually ship that to the app store and have it fully functioning. And how much is it going to cost you? Traditionally, you had gone out, you’d hired a designer, you’d have gone out, you would’ve found an engineer, you probably would’ve maybe needed a back end engineer, probably mostly front end. You’d picked your language, it would’ve been a whole, call it, 250k project.

Tim Ferriss: Side end, power top, all those,

Kevin Rose: Right. You know all the angles that you need to hit. You’re already speaking code, look at you. But imagine that’s 250k traditionally, right?

Tim Ferriss: Yeah.

Kevin Rose: That’s $50 now.

Tim Ferriss: It’s so nuts.

Kevin Rose: Because your Cursor account is going to be $50 a month and you can deploy that on Vercel for an extra 20 bucks a month.

Tim Ferriss: I don’t even know what Vercel is. But I want your help doing this because this is something I want to do, just to interrupt for a second, and then I want you to tell me what those names correspond to because I haven’t been tracking this very closely. I’ve been meaning and meaning and meaning to dig into vibe coding. And then in a team thread with my employees, just in a few hours a night for a couple of weeks, one of my part-time employees created an app, a website, everything he wanted, had to pay a little bit for a Getty image to use Canva Pro to make some graphics, but all in, I think $240 is what he said.

Kevin Rose: Exactly.

Tim Ferriss: And he was using Base44, which six-month-old solo-owned vibe coder Base44 sells to Wix for 80 million in cash. That was June of this year. And then Lovable, right? There’s a post, this was in the same thread, which is why it’s right here top of mind for me, vibe coding platform, Lovable, becomes fastest growing software startup ever. I love the Swedes, right? They’ve got some good stuff.

Kevin Rose: Yeah.

Tim Ferriss: Swedish AI startup, Lovable, says it has surpassed 100 million in annual recurring revenue, ARR, just eight months after launch. This makes it the fastest ever software company to reach the milestone, eclipsing the historically rapid growth rates of companies such as Cursor and Whizz. That’s bananas. Eight months.

Kevin Rose: Oh, my God.

Tim Ferriss: Yeah.

Kevin Rose: Yeah. Lovable, I think is probably my favorite hosted vibe coding platform that’s out there. If you’re really taking vibe coding seriously, as seriously as you want to take that statement because it’s still not coding, you’re vibing your way through code, you would be using Cursor, not Lovable, but Lovable is great. It’s a great place to start, actually.

Tim Ferriss: Yeah. Okay.

Kevin Rose: The point being is that venture capitalists, what they do at the seed stage in the early stages, it’s their job to go out, find entrepreneurs that are building exciting new products, write that first, call it one, two, $3 million check, get their ownership.

Tim Ferriss: I don’t need to get on bended knee for $240.

Kevin Rose: Well, exactly. So what’s going to happen is you’re going to have 10 x the amount of ideas hitting the market because anyone can code, and probably even greater than that, call it 50 x. So we’re going to try and fail a lot faster, which is great. And then you’re going to have, and I’ve already seen this, startups that are one or two people, full investment, call it, to their first million users, might be a couple few thousand dollars, and they’re already profitable and on their way to great things. And yes, it’s going to be buggy right now because the code is a little bit janky and a little bit half broken.

Tim Ferriss: That’s going to get fixed real fast.

Kevin Rose: It won’t be in six months. Exactly. If it’s a second year CS student right now, in a year, it’ll be full-on college grad, and you’re off to the races. And you don’t need to raise venture capital. Why would you?

Tim Ferriss: Why would you?

Kevin Rose: Why?

Tim Ferriss: And also, how would venture capitalists even begin to filter and sort the winners from the losers?

Kevin Rose: With that volume.

Tim Ferriss: There’s be so many. You can’t have coffee dates with even one-hundredth of those founders, nor would they necessarily take the coffee to begin with.

Kevin Rose: Exactly.

Tim Ferriss: Maybe if they just want to meet you, sure. And maybe at later stages, if they’re going to be really — 

Kevin Rose: That’s right.

Tim Ferriss: — fueling massive growth. Well, here’s a question for you. You’ve got kids, I don’t have any that I know of, hope to change that at some point soon, but how are you thinking about educating your girls?

Kevin Rose: Yeah. Well, I would say I don’t believe there’s a profession that is really immune to the AI wave. I believe it’s going to touch anything and everything that’s out there. And so at the end of the day, this is really tough because I think the answer is the lamest one, which is you should be doing what you’re most passionate about and where you can find your life’s work. It’s really artists and crafts, handmade goods, things of that nature that will stand out and still be desirable because of the human touch side of things.

Tim Ferriss: So you’re saying I should buy a lot of Etsy, is that what you’re saying?

Kevin Rose: I just going to say, but then you just turn into an Etsy wool hat maker for saunas.

Tim Ferriss: Oh, man, mitts, sauna mitts. I’m all about the sauna mitts.

Kevin Rose: Exactly. But it’s wild because for the last two decades of my career, I would’ve said computer science, computer science, it’s all about these tech jobs and the tech industry. That’s the future. And I think if someone was just going into college and they said, “Hey, should I study CS?” I don’t think I would say yes. I don’t know where to point people because everything is kind of f’ed, you know?

Tim Ferriss: I mean, there is, and this isn’t Schadenfreude on my side wanting to celebrate the misery of others, but there is kind of this poetic justice to techies creating tools — 

Kevin Rose: That are killing themselves?

Tim Ferriss: That people thought would take away kind of working class blue collar jobs. And nope, surprise, bitch, we’re taking all the coding jobs. We’re taking all of the white collar jobs. Those are going to get smashed. I mean, so many of those jobs that are basically occupied by people who have helped create these tools, they’re going to get obliterated.

Kevin Rose: Well, you know what’s really interesting about that, that’s a great insight. And one of the things that I have found, which is pretty exciting actually, is that a lot of technical people that I know that are very senior computer science, like hardcore, they’re like, “Screw AI. Yes, it can look at my code base and tell me where to look for something, but I am going to be the one that manually writes that code because ego, ego, ego,” that plays out. And then you have the scrappy designer that’s the creative that says, “I have never coded in my life, but I have a lot of ideas.” And all of a sudden that person is empowered, that creative mind is empowered in a way that they have never been empowered.

Tim Ferriss: Yes, that’s exciting.

Kevin Rose: It’s interesting because Andreessen Horowitz, I actually did a post about this, it was this LinkedIn post or something where they said, we’re looking for designers to be the next CEOs, where they were really brilliant in saying actually the next wave forever, we’ve always said technical, who’s your technical team? What’s the technical shops? That’s been the kind of lens at which we’ve evaluated the quality of a startup. I think that really shifts to more of the creative side.

And I think that, I don’t think VC is dead. I think what happens is that valuations go up, which is great. It means entrepreneurs give away less of their company and you fund them at a later stage. Because ultimately, if you’re going and you’ve really hit the ball out of the park and need to grow from two to 200 people for a variety of different things that you need, it turns out you need a lot of stuff as a startup, not just more engineers. You’re going to need some working capital and VCs, that’s what VCs will step in.

Tim Ferriss: And also to be clear, and correct me if I’m getting this wrong, but there are many sectors and many categories where venture capital or some source of financing is still inevitable. It’s like if you’re creating an Anduril, you need cash, right?

Kevin Rose: Right.

Tim Ferriss: If you’re producing something that has a hardware component, you’re going to need some cash, et cetera, et cetera, et cetera. And I’ve thought, and I don’t know if this is just a simplistic, primitive way to think about it, but I’m really wondering with everybody focusing on the hottest girl at the dance, which is AI and everything that has AI slapped on it, what are the neglected unsexy, really fast-growing sectors? And it makes me think of, I remember somebody showed me a chart, somebody could look this up, we’ll put it in the show notes, but if you just invested in Domino’s Pizza at the right time, it would’ve smashed every tech company, right?

I mean, the growth rate was just shocking to behold. And it’s like what’s the equivalent of Domino’s Pizza that has nothing to do, at least at its core AI. So in some sense, maybe it’s outside of the overbearing influence of that, so maybe there’s less likelihood of it getting completely disrupted. Although like you said, nothing is immune, but Coca-Cola is going to be Coca-Cola. I don’t want to invest in poison, so I’m not going to, no offense, Coke invest in that. But there are certain things that may be fast-growing and maybe more predictable. And I’m just wondering what those things are.

Kevin Rose: I think this too. So I have two that I think I’ve identified that I have no crystal ball. I have crystal balls, but I use them for myself. That didn’t sound right.

Tim Ferriss: Yep. Got to be careful. You can end up in the ER.

Kevin Rose: Exactly. They can be painful at times. So let’s rephrase that. This is my best guess at kind of where I see the puck going on a couple of different fronts. One is that I believe that, well, I know this to be certain actually, it’s kind of the same bet in just two slightly different ways, which is that the lifeblood of AI, it should come as no surprise, it’s human data. It is human generated, actual human created data in order for it to learn, to evolve, to understand where humanity is going. It has to drink from the blood of us humans to serve us.

Tim Ferriss: It is such a nice vampire manservant, so polite.

Kevin Rose: But this is why Reddit is getting 50 million a plus a year to train on their data is why the Tim Ferriss blog should be charging AI to train on all of the original content that you’ve written. So what I really liked was a move that Cloudflare did here just a few weeks ago where they said, okay, everyone in the world uses Cloudflare. That is their DNS, more or less. They have anti DDoS protection and all that good stuff, which is a fancy way of saying that your service stay up and they’re really good at — 

Tim Ferriss: Keep your site up.

Kevin Rose: Yes, they keep your site up. So what they’ve done if they said, if you own original content like a Tim Ferriss, we can block the AI bots. So we won’t let them train on your data.

Tim Ferriss: Oh, that’s clever.

Kevin Rose: But we’re also going to create a marketplace.

Tim Ferriss: Oh, that’s fucking brilliant.

Kevin Rose: If you want to sell to the AI companies, they can bid to actually license your data. Isn’t that brilliant?

Tim Ferriss: That is brilliant. The first thing that comes to mind is, I mean, there are a lot of smart people working in these AI companies because they just use Wayback Machine to scrape all your stuff anyway. But I imagine Cloudflare is thinking about it, but yes

Kevin Rose: Well, I mean that’s also, it’s always going to be the most recent stuff as well, right? There’s no doubt they could go get a copy of Wikipedia and train on what they have.

But they’re going to need, “What does Tim Ferriss think about the latest GLP-1s?” And that’s going to come out next month. So they always need to be training on the latest stuff. So that’s one. 

And part of the reason why, and I swear this isn’t a self plug, but part of the reason why we’re — Alexis Ohanian, the co-founder of Reddit and myself — are rebooting digg.com, is that we believe that human authenticated original content is going to be so important to safeguard. Because if all of these social sites are just flooded with bot content — 

Tim Ferriss: Oh, man, just looking at the comments on some of these platforms I’m like, 90 plus percent of this is all bot. It’s all bot.

Kevin Rose: But so here’s the crazy thing is that you can still tell a little bit that it’s bots, but in a few years, or not even that in a few months.

Tim Ferriss: Six months.

Kevin Rose: You won’t even know it’s bots. You’ll just be sitting there being like, wow, that was a really thoughtful review that person wrote about X headphones, and then you’ll buy them off Amazon and you’d be like, why the hell these headphones suck so bad?

It’s because there were 37 bots and they’re all championing these headphones about how they’re so amazing and it’s all BS, everything. Nothing is to be trusted. 

So there’s this whole theory called the dead internet theory, which is that eventually the internet is just going to be completely overrun by agents, AI agents that are infinitely patient that will write perfect, perfectly screwed up copy enough for you to believe it, right? Because it can’t be perfect.

Tim Ferriss: Yes, yes, yes.

Kevin Rose: And so this is just all going to come. And so for us, what we’re focused on is really creating a safe haven for humans to have real conversation, and that’s exciting. So those are the two kind of things that I believe that original content creators, as long as you can prove that you’re an actual human, are going to be rewarded ultimately, hopefully by the AIs that crawl you.

Tim Ferriss: How do you think that authentication is going to work? Because doing private and public keys and stuff, there’s too much of an education hurdle to make that work. I would think. I think maybe Sam Altman has yet another company that is focused on human authentication, but what do you think is going to actually make the cut and become the standard of the driver’s license for proving this is me, right? Because there’s so much AI deepfake stuff out there right now with just, I can speak personally and it’s so good and it’s within six months, like you said, it’s going to be indistinguishable or close to indistinguishable.

Kevin Rose: Yes, I mean, this is something that I’ve kind of spent a lot of time thinking pretty deeply about, and I went and met, I traded a couple notes with Sam, and I met with the CEO of the Retinal Scanner Company, Tools for Humanity. They’re making that orb that scans your eyeball and went and met with him, and I actually got my retina scanned and did that whole process. It is not for everyone. I think a lot of people will kind of freak out by that. It is anonymous.

They’ve done it in a way that shards your data. They can’t link it back to you, all that good stuff. But that’s too much explaining. Consumers are not just going to believe that. They’ll use it for their TSA pre-check or whatever it may be to skip the line. But I don’t think for everyday purchases or general internet trust, it is going to hit scale. They’re paying people to do it. And right now, which I think is probably a signal that you don’t quite have the right product if you have to pay people to use it. So I don’t know. It’ll certainly be an authentication method that a lot of sites will use and support. And I could see us doing that as well.

Tim Ferriss: I can see consumers not wanting to, users of the internet, let’s just say broadly speaking, not wanting to use it for, well, if they had to for a checkout purpose to pay for things, then they would, but having a lot of resistance for say, just logging into Facebook or Instagram. But as a creator, if I want to give my fans a way to confirm that something is mine, then I think you’re heavily incentivized to use something like that.

Kevin Rose: Right. And I think, so there’s two sides of the coin right?

Tim Ferriss: But the education part is so hard just to teach people what to look for. It’s got to be common, as common in the vernacular as driver’s license for people to just know what to look for. If I have to be like, okay, guys, I’m going to teach you the exact watermark and this and that and watch out for these fakes though, because they’re very similar, but it’s never going to work.

Kevin Rose: Right, and that’s where I think there’s going to be a couple things. Well, we’re talking about a handful of different things here, right? Because we’re talking about consumers. How do I trust another consumer that when they say these headphones are the best headphones, I can really believe that. And then you’re talking about how do I know that Tim Ferriss is Tim Ferriss, right? And so those are two different things.

Tim Ferriss: They’re different.

Kevin Rose: I think on the internet. And I’m actually writing an article for Wired right now about this, where the trust is moving from a binary thing where we had binary trust before, meaning that back in the day, and I don’t think this is any longer the case, but more or less you could go onto Twitter when it was called Twitter, and you would see a blue check box next to someone and say, “Oh, that person’s been verified or validated in some way.”

So it’s a very binary, I guess I trust this person because of said box and graphic. Trust is moving to a gradient. And I think it’s very much going to be score, a score or a level based trust system where trust will be defined by a collection of actions that you take online and a collection of proofs that you do online. So a hardcore proof would be “I got my retina scanned, I’m showing you that I got my retina scanned, and here’s my proof of that.” A gradient would be, “I’ve been a paying customer for this service for X number of months, I can prove it”, or “I have purchased these headphones. That’s what the Amazon verified purchase does.” And so there are going to be open standards for that, and it’s going to be messy, but it will work.

And that if you come on the future version of Digg, for example, if you come on there and you say, “Hey, I own an Oura Ring and I love it,” anyone can say that. And so how do I trust that?

And so one way to trust that is to, there’s these fancy technologies, I won’t get into it here, but they’re called ZK proofs where you can go in and I can authenticate basically with my Oura account and prove to you without exposing who I am, but I can do cryptographic proof that I have owned an Oura ring for five years and I have used it daily. And so those types of proofs, almost like the way that we see secure certificates when we check out now on an e-commerce site, and we trust them because they are cryptographically secure, we will have those types of proofs for almost anything and everything that exists online. And so when you engage with another user, you’ll be able to say, “Okay, I’m clicking on Tim. How do I know that these are the ketones that he trusts or whatever it may be?” And there will be multiple ways to cryptographically prove in a non-geeky way. That’s the key here. It can’t be something that my mom won’t understand.

Tim Ferriss: Read this white paper.

Kevin Rose: Right, exactly. It can’t be that. So it’s going to be a little rough for the next couple of years while we hammer this stuff out. We come up with standards, we figure out with very easy consumer ways to show this. But ultimately, at the end of the day, there needs to be this. And also the other thing I was going to tell you is I believe deeply that human connection matters and that we need to really encourage more of that to happen. So one of the things that we’re without trying to spill the beans too early and what we’re building at Digg is a lot of proof around — 

Tim Ferriss: I was still thinking about the crystal balls.

Kevin Rose: Go ahead.

Yes, we’re not going to spill the, crack the crystal balls on this yet, but I will say that in person means a lot. And so when you actually gather a location with other people proving with technology that you’ve actually met in person and had broken bread in person is going to create a trust network that is unlike anything that can be done online. And so that’s on us to build and figure out as well, which is going to be pretty exciting.

Tim Ferriss: Yes, I have, and this might seem like I’m still in my bags, but I’ve thought this for a long time, just launching a card game literally as we record this. But I am so long analog, and the reason that I’m long analog is that at least one of the silver linings, I think of this post-truth internet experience, at least for a while, it’s going to be messy AF for a while. Yes. And it’s also a cat and mouse game, right? It’s not like you create this authentication, there’s no response. It’s a cat and mouse kind of cloak and dagger situation. There’s so many incentives, financial and otherwise, to scam people that trust me, the scammers have great, some of them are really sophisticated.

And it’s an arms race. And I think speaking of someone who’s not an engineer, I’m not a computer scientist, but I would like to think of myself as pretty tech-savvy. I’ve taken social media apps off my phone for the last handful of years, and I have systems for trying to sort fact from fiction, but it has become so exhausting and it’s going to become a hundred x exhausting. I’m like, I’m done with it. I don’t want to walk into this house of fun house mirrors and watch things that are fake read things that are fake, have to decipher what’s true and what isn’t, and get misled. I just don’t, there’s so much downside that I really am optimistic, at least I hope that people are going to actually do what we’re evolved to do, just spend more time interacting with humans, IRL.

And we’re seeing that with running clubs and board game nights and these various offline activities that are exploding in popularity. Who knows if that’ll sustain, but you’re seeing it in every major city in the United States at least. And that gives me some hope because if there were nothing to offset the opiate addiction of short form video and perfectly tune algorithmic feeds, we’re entertained to death, we’re done.

Kevin Rose: No, this is exactly why I think a big portion of this social site that we’re building is going to be about in-person connection. It really has to be. And you actually, Tim, you were a big inspiration for this. One of the things that we talk about, remember when you had, you did those global meetups where people gathered in?

Tim Ferriss: Yes, yes. That was so fun.

Kevin Rose: Do you remember the name of the service that you use?

Tim Ferriss: It was, let me get it right, it’s River. I think it’s river.io, and let me just make sure I’m getting that right. …

It’s getriver.io. So getriver.io in-person event and social platform for communities. So I used this service to run the podcast 10th anniversary global meetups around the planet, and we had 157 cities, thousands of people meeting up in person who have already a bunch of common interests, or at least lived experience. They’ve listened to the podcast, so they have something automatically they can talk about meeting in person. And it was so much better than I could have ever hoped for. It was so much fun. Some of these meetups had hundreds of people, some had four or five, and what I hoped would happen, and what did happen, is a lot of these people have stayed in touch and they’re meeting up afterwards. It wasn’t just a one and done. So had a great experience and the team over there was awesome.

Kevin Rose: So I met with her because of you, and then she was amazing. And we’re going to use them for our Digg launch. In fact, we’re doing a meetup tonight, close to a hundred people in L.A., just randomly threw it out there last week.

Tim Ferriss: I love it.

Kevin Rose: It’s exactly this, where if we can build part of that functionality into the product itself and encourage people with these interests that when you figure out that your weird is not so weird, if you’re into Japanese woodworking or the Tim red rooms that you love, whatever you’re into —

Tim Ferriss: Kevin’s crystal balls.

Kevin Rose: Yes, exactly. You can find 10 other people that are, and you can go break bread with them and hang out. But I think that is the future because don’t get me wrong, I still want to launch that app and learn about those funky, weird things that I would only find online. And you and I trade so many ridiculous videos, I wouldn’t want that to go away, but I also need to go and get outside and actually breathe some fresh air and meet people. And so I think that has to be a big part of what we do at Digg. And a lot of it was inspired by your success there, which is great.

Tim Ferriss: Oh, that’s awesome. I didn’t know that. So I got to, since we’re so on topic, I’ve got to just flash this guy right here.

Kevin Rose: Yes

Tim Ferriss: So as you know, I’ve been so nervous about this and excited, but so, Coyote, this card game, it’s fast casual, a couple minutes to learn, 10 minutes to play. Kids love it. Turns out people who have had a few drinks or smoked a little weed also love it does not help performance, but does make it pretty hilarious to watch.

Kevin Rose: [BLEEPED]

Tim Ferriss: We will have to see if that’s okay to keep in.

Kevin Rose: Just called out a friend of ours that likes to play games. 

Tim Ferriss: And it’s finally launching everywhere. Walmart’s had the exclusive for a few months and they’ve been actually awesome. And it’s been a bestseller and it’s started to go kind of bananas and gameplay videos. We’ve texted about this a little bit, but gameplay videos online have more than 300 million views now.

Kevin Rose: Dude, that is so amazing.

Tim Ferriss: So crazy.

Kevin Rose: Dude, congratulations man.

Tim Ferriss: Thanks.

Kevin Rose: After the NFTs, I’m glad to see you actually doing something that works.

Tim Ferriss: Thanks. And I got to practice my art in a different way. And we’re not going to get into a mud wrestling match over NFTs. I am still going to do a bunch with that CØCKPUNCH/ Legends of Varlata universe. You wait and see. I’m actually going to do a bunch of it. But yes, it’s been going nuts. If people go to Amazon or wherever, Target, it’s all over the place and it’s 8,000 plus retail locations as of this week. It’s feeding into all the locations.

Kevin Rose: That’s amazing.

Tim Ferriss: And it’s actually giving me both flashbacks that are really pleasant and also a little bit PTSD with my first book because the inventory is not getting to the warehouses fast enough. So it’s actually it can be a little challenging to buy this thing.

Kevin Rose: But hey, soak it all in, man. Enjoy that moment though, right? Because you’re in a great place to even have that issue. It’s so awesome.

Tim Ferriss: And you know what’s also been super fun is I’ve played with friends. I’ve seen all the play testing with families. We tested it with a hundred plus families. We tested the hell out of this. I mean, so many iterations, and it’s ready, it’s going. But I had a chance to play with a group of strangers, two different groups of strangers at a game shop in Brooklyn last weekend, and we were recording it for an instructional video. And they’re not actors, they’re people who love games, but people I’d never met before and the amount of fun that we had, that was the real test for me.

It’s like if I have a bunch of my dumb friends and we’ve had two drinks each and we have so much fun anyway together, it’s a warm audience. The game still has to work. And it did. But with a group of strangers where it’s a little uncomfortable in the beginning and everyone’s a little stiff, and then by the end we’re slapping shoulders and high fiving and laughing our asses off. I was like, okay, I can finally exhale a bit with this thing. Like, okay, okay, okay, okay. It’s actually on the way.

Kevin Rose: Dude that is so awesome.

Tim Ferriss: Yes, I’m so excited.

Kevin Rose: You caused a micro fight in our house last night because of the game.

Tim Ferriss: Was it over whether somebody messed up or not?

Kevin Rose: No. So here’s what happened. I was playing Roblox with my kids, and then Daria had her headphones in, and so she couldn’t hear me, and the kids were asking questions and I was like, she’s listening to her podcast. And I’m like, “Can you take them out so that you can engage with the kids?” And she’s like, “Well, if we weren’t playing this and we could play something like Coyote, then we wouldn’t have this issue. We’d all play as a family.” And I’m like, “Oh, fuck.”

Tim Ferriss: Oh, man. Quick funny note on Roblox. I actually want to interview the founders of Roblox. It’s such an incredible, just such a wonder they’ve created, and they’ve also, actually, I’m sure you did not know this, maybe you did. They have funded a ton of research related to dietary interventions for various psychiatric conditions. So with —

Kevin Rose: I didn’t know that.

Tim Ferriss: The ketogenic interventions, so they’ve actually funded a lot of science related to that. So on a whole bunch of levels. But the reason that I brought up Roblox is because you sent me and Sacca this video, this screen capture of playing Roblox, which is honestly really relaxing. It’s so relaxing.

Kevin Rose: Yes, it’s the garden that I grew.

Tim Ferriss: Yes, the garden that you grew —

Kevin Rose: Grow a Garden.

Tim Ferriss: — with the cherry blossoms, very relaxing to watch, but there was this classical music playing and I was like, wait a fucking second. You stopped drinking and now Kevin’s listening to classical music. What is happening here?

Kevin Rose: It’s built into the game. It’s built into the game.

Tim Ferriss: It’s built into the game.

Kevin Rose: Grow a Garden has millions of users now, I have the beautiful cherry blossom bushes if anyone wants to come check out my garden. And I built little forts for my kids to play in there. I’ve got some great bamboo, and I just got a rare little red Zen dragon today, which is cool.

Tim Ferriss: Congratulations.

Kevin Rose: Thank you. It was one percent chance to get it on a roll. And so I —

Tim Ferriss: Oh, what’s that?

Kevin Rose: It’s 20 bucks per 10 rolls.

Tim Ferriss: Oh, wow. What a bunch of geniuses.

Kevin Rose: Yes, and I won’t even tell you what I’ve done there. I’m not proud.

Tim Ferriss: This is like when they’re doing their internal presentations, they’re like, okay, so Q2 has been great. They’re like, really, we’re hit? It all hinges on the one percent of overspenders. There’s an avatar. We call it Kevin Rose.

Kevin Rose: Right, exactly.

I don’t know who this user is, but yes.

Tim Ferriss: Oh, my God. Awesome, man. So nice to see you, always.

Kevin Rose: Yes, good to see you as well.

Tim Ferriss: Yes, we’ve got to hang. This is also, I’ll just talk about in person. I’m like, man, we’ve got to hang in person. I’m sorry, I mean, you’ve got family and lots of stuff. I didn’t give you a ton of heads up either on the wilderness trip, but we’ve got to do something. Got to do something in person.

Kevin Rose: A hundred percent, Japan trip or something.

Tim Ferriss: Japan trip, or I will be in L.A. actually next month. So I’ll let you know. Either next month or the following. So I’ll let you know. I’ll be in L.A.

Kevin Rose: Awesome. Let’s do a little meetup.

Tim Ferriss: Yes. I’m taking my note. 

Kevin Rose: Speaking of in-person stuff.

Tim Ferriss: KevKev. All right. Sweet man. Well, I think you’ve got anything to add for folks? Anything to mention?

Kevin Rose: Oh, I always tell people, yeah, so that crazy site that I was telling folks about.

Digg.com with two Gs is really —

Tim Ferriss: Digg.com.

Kevin Rose: Yes, from the old internets, if you remember it from way back in the day, it’s rebooting. Alexis and I and my CEO Justin are working hard at work on it. We want to give people an early invite. It’s in beta right now. If you want to check out Kevin Next Gen, crazy, fun social network that is all about news and craziness around the web, email, and we will put you on the early invite list.

Tim Ferriss: TimTim, it’s two Tims at digg.com, digg.com, and we will let you skip that list and get you on one of the early invite lists.

So timtim.

And just FYI, and I’m not going to disclose because I don’t know if it’s public, but that’s a long, there’s a long list. You’ll be —

Kevin Rose: Several hundred thousand people.

Tim Ferriss: The bouncer will be letting you skip and come through the velvet ropes.

Kevin Rose: We’ve only let 25,000 in so far and we have a couple of hundred thousand people waiting on the wait list. Yes, so far people are loving it and we’re just getting started, so we’ve got a lot to build.

Tim Ferriss: So fun. So fun. Well, you look great, man. You sound great. Congratulations on the hundred days. That’s a big, big, big, big deal.

Kevin Rose: It sucks that you feel so much better. I hate it because I feel better. I’m slimming up a little bit and it’s like —

Tim Ferriss: I assume you’re being sarcastic.

Kevin Rose: No, it does suck.

Tim Ferriss: It’s like everything seems better.

Kevin Rose: I want to have a couple drinks, but —

Tim Ferriss: You’re getting to spend money on Roblox instead. Instead of the vice that kills your liver, you got a vice that kills your bank account. You got to trade.

Kevin Rose: I will say I’ve definitely kind of just shifted that funnel of cash over straight to Roblox in Grow a Garden. That little freaking dragon guy cost me like two grand or something.

Tim Ferriss: That’s the Kevin I know and love. There you go. He is back. He’s back.

Kevin Rose: Let’s do some Nanoblocks together.

Tim Ferriss: Yeah, I’m down for some Nanoblocks. I think I need one that is sub 500 pieces to start with because —

Kevin Rose: I’ll save this little ramen for you and we’ll do it live on video. That’d be fun.

Tim Ferriss: Have Craig Mod set up the audio for us.

Kevin Rose: Yes, exactly.

Tim Ferriss: All right. Cool, man. I’ll send this to you, buddy.

Kevin Rose: All right, brother. Talk soon.Tim Ferriss: All and everybody listening, I guess we’ll probably have some show notes for this. So tim.blog/podcast Random Show and just look for the newest ones. All right everybody, be well. Be kind and thanks for tuning in.

The post The Tim Ferriss Show Transcripts: The Random Show — Ketones for Cognition, Tim’s Best Lab Results in 10+ Years, How Kevin Hit 100 Days Sober, Home Defense, Vibe Coding Unleashed, and More (#822) appeared first on The Blog of Author Tim Ferriss.

The Random Show — Ketones for Cognition, Tim’s Best Lab Results in 10+ Years, How Kevin Hit 100 Days Sober, Home Defense, Vibe Coding Unleashed, and More (#822)

2025-08-13 11:56:35

Welcome to another wide-ranging “Random Show” episode I recorded with my close friend Kevin Rose (digg.com)!

We cover Kevin’s sobriety journey and marking 100 days without alcohol, my results with the ketogenic diet and intermittent fasting, GLP-1 agonists, home defense and security, the future of Venture Capital, authenticating yourself online, AI, the cultural shift toward human-to-human connection, Roblox, and more.

Please enjoy!

Listen to the episode on Apple Podcasts, Spotify, Overcast, Podcast Addict, Pocket Casts, Castbox, YouTube Music, Amazon Music, Audible, or on your favorite podcast platform. Watch the conversation on YouTube. The transcript of this episode can be found here. Transcripts of all episodes can be found here.

This episode is brought to you by Momentous high-quality creatine for muscular and cognitive support; David Protein Bars with 28g of protein, 150 calories, and 0g of sugar; and AG1 all-in-one nutritional supplement.

This episode is brought to you by AG1! I get asked all the time, “If you could use only one supplement, what would it be?” My answer is usually AG1, my all-in-one nutritional insurance. I recommended it in The 4-Hour Body in 2010 and did not get paid to do so. Right now, you’ll get a 1-year supply of Vitamin D free with your first subscription purchase—a vital nutrient for a strong immune system and strong bones. Visit DrinkAG1.com/Tim to claim this special offer today and receive your 1-year supply of Vitamin D (and 5 free AG1 travel packs) with your first subscription purchase! 

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This episode is brought to you by Momentous high-quality creatine and more! Momentous offers high-quality supplements and products across a broad spectrum of categories, and I’ve been testing their products for months now. I’ve been using their magnesium threonate, apigenin, and L-theanine daily, all of which have helped me improve the onset, quality, and duration of my sleep. I’ve also been using Momentous creatine, and while it certainly helps physical performance, including poundage or wattage in sports, I use it primarily for mental performance (short-term memory, etc.). Use code TIM at checkout and enjoy 35% off your first subscription order or 14% off your first one-time purchase! 

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Want to hear the last time KevKev and I did one of these Random Shows? Listen to our conversation here in which we discussed maintaining sobriety with a partner who still drinks, Taiwanese tea, finding magic in the ordinary, the ups and downs of accelerated TMS, the intersection of AI and life sciences, deepfaked side hustlers, when meditation retreats go right (and wrong), and much more.

SELECTED LINKS FROM THE EPISODE

• Connect with Kevin Rose:

Website | Instagram | Twitter | Threads | Bluesky | Digg.com

The transcript of this episode can be found here. Transcripts of all episodes can be found here.

People

• Sigmund Freud: Austrian neurologist and founder of psychoanalysis who revolutionized our understanding of the human psyche.
• Hokusai: Japanese ukiyo-e artist of the Edo period, famous for “The Great Wave off Kanagawa” and influential woodblock prints.
• Craig Mod: Writer, photographer, and publisher known for his thoughtful explorations of Japan, walking, and digital publishing.
• Liam Neeson: Irish actor known for dramatic roles in films like Schindler’s List and action films like the Taken series.
• Johnny Depp: American actor known for eccentric characters including Captain Jack Sparrow and Willy Wonka in Tim Burton’s adaptation.
• Gene Wilder: American actor and comedian famous for his iconic portrayal of Willy Wonka in the 1971 classic film.
• Dr. Rhonda Patrick: PhD scientist and host of the FoundMyFitness podcast, specializing in nutrition, aging, and health optimization.
• Martin Berkhan: Fitness expert and founder of the Leangains intermittent fasting protocol that revolutionized flexible dieting.
• Dr. Peter Attia: Physician and longevity expert focusing on the science of healthspan and lifespan optimization.
• Desmond Tutu: South African Anglican archbishop and Nobel Peace Prize winner renowned for his anti-apartheid activism.
• Taran Butler: Competitive shooter and founder of Taran Tactical Innovations, known for custom firearm modifications.
• Keanu Reeves: Canadian actor beloved for roles in The Matrix trilogy and the John Wick action franchise.
• Jim Jefferies: Australian stand-up comedian and actor known for his provocative and observational comedy style.
• Steven Seagal: American actor, screenwriter, and martial artist known for action films in the 1980s and 1990s.
• Marc Andreessen: Co-founder of Andreessen Horowitz venture capital firm and co-creator of the Mosaic web browser.
• Josh Cook: Digital strategist and entrepreneur known for his work in technology and social media engagement.
• Sam Altman: CEO of OpenAI and prominent figure in artificial intelligence development and governance.
• Alexis Ohanian: Co-founder of Reddit and venture capitalist focused on early-stage technology investments.
• Justin Mezzell: Digg CEO, designer, and creative director known for his distinctive illustration style and branding work.

Movies, TV, and Media

• Shaun of the Dead: A 2004 British horror-comedy film that brilliantly parodies zombie movies while delivering genuine scares and laughs.
• Jason Bourne: An action-thriller film series following the amnesiac super-spy created by Robert Ludlum, starring Matt Damon.
• Snatch: A 2000 British crime-comedy film by Guy Ritchie featuring interconnected criminal plots and memorable characters.
• Babe: A 1995 family comedy-drama about a pig who learns to herd sheep, combining live-action with groundbreaking animatronics.
• The Naked Gun: A comedy film series starring Leslie Nielsen as the bumbling Detective Frank Drebin, known for its slapstick humor.
• Taken: An action-thriller film series starring Liam Neeson as a former CIA operative with “a very particular set of skills.”
• Willy Wonka & The Chocolate Factory: A 1971 musical fantasy film starring Gene Wilder as the eccentric chocolatier in Roald Dahl’s beloved story.
• John Wick: An action film series starring Keanu Reeves as a legendary assassin seeking vengeance, known for stylized fight choreography.
• Slow TV: A television genre featuring real-time, unedited coverage of lengthy events like train journeys or knitting marathons.
• Playboy: An American men’s lifestyle and entertainment magazine founded by Hugh Hefner in 1953.
• Wired: A monthly magazine covering how emerging technologies impact culture, the economy, and politics.

Books

• The 4-Hour Workweek by Timothy Ferriss: A step-by-step guide to escaping the 9-5 grind through lifestyle design, automation, and the principles of working smarter rather than harder.
• The 4-Hour Body by Timothy Ferriss: An uncommon guide to rapid fat-loss, incredible sex, and becoming superhuman through data-driven body hacking and minimally effective dose principles.
• The 4-Hour Chef by Timothy Ferriss: A meta-learning manual disguised as a cookbook that teaches how to master any skill quickly using cooking as the vehicle for accelerated learning principles.

Brands, Companies, and Products

• Nanoblocks: A micro-sized building block system from Japan that makes LEGO look like giant boulders.
• LEGO: A line of plastic construction toys that bare feet have been stepping on since 1958.
• Coyote: A card game I made for strategic thinking and decision-making.
• Qitone: A brand of ketone supplement powder for metabolic optimization.
• N.O.-Xplode: A pre-workout supplement that promises to turn your gym session into a controlled explosion.
• Bronkaid / Primatene Mist: Over-the-counter medications containing ephedrine for respiratory relief.
• Belsomra: A prescription sleep medication (a DORA) that helps quiet the brain’s wake signal.
• Mounjaro / Zepbound: Brand names for Tirzepatide, a GLP-1 agonist medication for diabetes and weight management.
• Thorne: A health and technology company that sells research-backed supplements.
• Taser: A brand of conducted energy weapon manufactured by Axon Enterprise.
• Ring: A home security and smart home company owned by Amazon.
• Taran Tactical: A firearms training company specializing in competitive shooting techniques.
• Anduril: A defense technology company building autonomous systems for military applications.
• Cloudflare: A web infrastructure and website security company that keeps the internet running smoothly.
• Tools for Humanity: The company behind Worldcoin and the retina-scanning Orb for global identity verification.
• Oura Ring: A smart ring that tracks sleep and physical activity with impressive accuracy.
• Peloton: An exercise equipment and media company that brought the boutique fitness experience home.
• Fitbit: A company producing activity trackers and smartwatches, now owned by Google.
• Domino’s Pizza: An American multinational pizza restaurant chain known for delivery innovation.
• Coca-Cola: A multinational beverage corporation that has been refreshing the world since 1886.
• Andreessen Horowitz (a16z): A venture capital firm that backs bold entrepreneurs building the future.
• True Ventures: A venture capital firm focused on early-stage technology companies.
• Roblox: An online game platform and game creation system where users build virtual worlds.
• Amazon / Amazon Prime / Amazon Pharmacy: E-commerce and technology company that started with books and now sells everything.
• Costco: A multinational corporation that operates a chain of membership-only big-box retail stores.
• Walmart / Target: Multinational retail corporations competing for America’s shopping dollars.
• UPS: A multinational shipping and receiving and supply chain management company in distinctive brown trucks.
• 1-800-FLOWERS: A floral and gourmet foods gift retailer that pioneered phone-based ordering.
• Etsy: An e-commerce website focused on handmade or vintage items and craft supplies.
• Bugatti: A luxury sports car manufacturer that creates automotive art for the ultra-wealthy.

Institutions and Organizations

• Alcoholics Anonymous (AA): An international fellowship of people who share their experience, strength and hope with each other that they may solve their common problem and help others to recover from alcoholism.
• Stanford University: A private research university in Stanford, California, founded in 1885 and consistently ranked among the world’s top academic institutions.
• Johns Hopkins University: A private research university in Baltimore, Maryland, founded in 1876 and widely considered America’s first research university.
• TSA (Transportation Security Administration): A federal agency within the US Department of Homeland Security responsible for protecting the nation’s transportation systems and ensuring freedom of movement for people and commerce.

Websites, Platforms, and Apps

• Leangains: Martin Berkhan’s website on intermittent fasting.
• YouTube: An online video sharing and social media platform.
• TikTok: A short-form video hosting service.
• Instagram: A photo and video sharing social networking service.
• Facebook: An online social media and social networking service.
• Reddit: A social news aggregation, content rating, and discussion website.
• Wikipedia: A free, multilingual online encyclopedia.
• Digg: A news aggregator with a curated front page.
• Coyote: The official website for the card game Coyote.
• River: An in-person event and social platform for communities.
• Cursor / Claude Code: AI-powered coding tools.
• Lovable / Base44: “Vibe coding” platforms for building apps.
• Vercel: A cloud platform for frontend frameworks and static sites.

Concepts and Terms

• 12-Step Programs: A set of guiding principles for recovery from addiction, most famously used by Alcoholics Anonymous and other recovery organizations worldwide.
• Ketogenic Diet (Keto): A high-fat, low-carbohydrate diet that forces the body to burn fat for fuel instead of glucose, originally developed to treat epilepsy.
• Intermittent Fasting (16/8): An eating pattern that cycles between periods of eating and fasting, with the 16/8 method involving 16 hours of fasting and an 8-hour eating window.
• Zone 2 Training: Low-intensity aerobic exercise performed at a specific heart rate zone that maximizes fat burning and mitochondrial efficiency.
• APoE (Apolipoprotein E) Gene: A gene associated with the risk of developing Alzheimer’s disease, with the APOE4 variant significantly increasing susceptibility to cognitive decline.
• Oral Glucose Tolerance Test (OGTT): A medical test to assess how the body processes glucose over time, commonly used to diagnose diabetes and prediabetes.
• ApoB (Apolipoprotein B): A primary protein component of LDL (“bad”) cholesterol particles, considered a more accurate marker for cardiovascular disease risk than traditional cholesterol tests.
• Autophagy: The body’s cellular “housekeeping” process of breaking down and recycling damaged proteins and organelles to maintain cellular health and longevity.
• Exogenous Ketones: Ketone supplements taken orally to rapidly induce ketosis without following a strict ketogenic diet, though their effectiveness remains debated.
• GLP-1 Agonists: A class of medications that mimic the hormone GLP-1, used for treating type 2 diabetes and obesity by regulating blood sugar and appetite.
• DORA (Dual Orexin Receptor Antagonist): A newer class of sleep medications that work by blocking orexin receptors in the brain to promote natural sleep patterns with fewer side effects than traditional sleep aids.
• ECA Stack: A controversial and now largely banned supplement combination of ephedrine, caffeine, and aspirin once popular among bodybuilders for fat loss but associated with serious health risks.
• Vibe Coding: A modern approach to programming that relies heavily on AI tools and intuitive problem-solving rather than traditional computer science fundamentals, enabled by advanced code generation AI.
• Dead Internet Theory: A conspiracy theory suggesting that the internet is now predominantly populated by bots and AI-generated content rather than authentic human interaction.
• ZK Proofs (Zero-Knowledge Proofs): A cryptographic method that allows one party to prove they know specific information without revealing the information itself, crucial for privacy-preserving blockchain applications.
• DEXA Scan: A low-radiation X-ray scan that precisely measures bone density, body fat percentage, and lean muscle mass, considered the gold standard for body composition analysis.
• Venture Capital: A form of private equity financing where investors provide capital to startups and early-stage companies with high growth potential in exchange for equity ownership.

SHOW NOTES

• [00:00:00] Start.
• [00:06:54] Kevin celebrates 100 days sober! Why and how?
• [00:15:16] Nanoblocks: Kevin’s new Japanese micro-building hobby.
• [00:18:16] The Slow TV movement and Craig Mod’s ambient recordings.
• [00:20:58] Craving analog experiences and wilderness trekking.
• [00:22:24] Writing with background movies.
• [00:23:42] High hopes for The Naked Gun reboot.
• [00:24:35] Kevin’s improved communication since quitting alcohol.
• [00:26:28] My health interventions for cognitive protection.
• [00:29:00] How ketogenic diet and 16/8 intermittent fasting led to my best lab results in 10+ years.
• [00:33:35] Weight control regimens we don’t recommend.
• [00:39:51] Exogenous ketones: Qitone vs. premium options.
• [00:50:32] How glucose tolerance tests work.
• [00:51:58] Microdosing GLP-1 (tirzepatide) for glucose control.
• [00:54:12] DORA sleep medications and neuroprotective effects.
• [00:56:55] Belsomra trial and cost considerations.
• [00:57:52] Sauna temperature optimization based on Rhonda Patrick’s research.
• [01:00:28] There are no biological free lunches.
• [01:03:27] The time Kevin found a homeless person in his closet.
• [01:06:11] Modern home security and privacy measures.
• [01:19:42] Pondering how we survived childhood.
• [01:24:23] AI-driven venture capital landscape changes.
• [01:28:59] Vibe coding revolution: $250k projects now cost $50.
• [01:34:28] Education advice for kids in the AI age.
• [01:36:27] Empowering creative minds vs. traditional technical roles.
• [01:38:29] What Kevin’s crystal balls say about Cloudflare’s data marketplace for content creators.
• [01:42:02] The Digg reboot with Alexis Ohanian: a focus on in-person connections.
• [01:42:59] Dead internet theory and bot content proliferation.
• [01:43:25] Verifying humanity: the trust gradient.
• [01:54:28] My relief at the successful launch of Coyote.
• [01:58:03] Kevin’s Roblox addiction and Grow a Garden expenses.
• [01:59:56] Future meetup plans and parting thoughts.

The post The Random Show — Ketones for Cognition, Tim’s Best Lab Results in 10+ Years, How Kevin Hit 100 Days Sober, Home Defense, Vibe Coding Unleashed, and More (#822) appeared first on The Blog of Author Tim Ferriss.