Transcript for #1958 - Andrew Huberman

My vices in the food department are croissants. Thing is, you know, that hits the dopamine button and it's all about more. I mean, I can, I can sink. five of those things.

I don't adulterate my croissants. Really? No, maybe extra butter. For me, it's all the savory stuff. Savory salty. So it's croissants every once in a while.

I have.

I think the all butter for me justifies having, you know, three or four.

I like how in New York when you get a soda, even at a little, you know, at 7-11 type place, they offer you a straw. Yeah. It's one of the last civilized things in the life to be offered a straw.

I remember that the six pack container, those plastic things, he said, oh, yeah, that was the turtle.

I was gonna say Southeast, why would Southeast Asia have that issue?

I've seen those images of those giant like icebergs of plastic junk. Yeah. And I always hope that's not real.

Well, China's got no excuse because their GDP's way up there. They could actually manage it. But some of these other countries, as you mentioned, are definitely lower GDP relative to the United States. Right.

But China's got no excuse. That's incredible.

I remember for a while, There was a discussion about kids toys with the coloring, you know, and the toxins and plastics. Yeah. You know, I guess I don't know if we're going to go there because uh, it might as well, right? Okay. Well, you know, it's interesting for starting 2019. I started posting things on Instagram. That's how I got my stuff out. Then I was going on podcast and now we have the podcast, right? But I'd stayed off Twitter largely until this last year when I started putting a lot of stuff there. So you put stuff there. You start reading stuff there. Oh, no. And then, well, what's been really interesting to me is I followed this whole lab leak thing, right? Because early in the pandemic, people in my field started chattering about that. I was very, I love exotic animals, not to own them, but I'm really interested in animal conservation. And so, the Pangolan is an amazing animal. They pinned it on the Pangolan early on. And there were articles published in Good Journals, several of which I'm on the editorial board for. So, early in the pandemic, there were papers coming out really fast about the sequence of the virus in Pangolans, which were being sold in the Wuhan market, et cetera. And I was pretty disturbed by this, mostly because of the pictures of the Wuhan market that exotic animal trade is just, it's horrible, right? Yeah. Okay, close confinement, you know, these are beautiful animals that there's no justification for this stuff. But Bengal and meat is sold it. I forget what it is per pound, but it's a delicacy and it's considered very lucrative and to get Bengal and meat of all things. There's actually a female, Bengal and meat. influencer on YouTube and Instagram. Oh, yeah. No, it's like it. It starts to look like Pengol and meet ASMR. It's crazy and disgusting. So they're kind of mixing, you know, sexy women with exotic meats from these rare animals is just awful. So I was going deep down this rabbit hole of trying to understand this exotic animal trade. And then, um, and then there was chatter in my field about the fact that One of the members of the laboratory in Wuhan that was working with these, you know, very high restriction viruses had done her training in the United States, which is true. Had had has a master's degree, but was running a laboratory, which is unusual, right? Typically, the head of a laboratory is someone with a Ph.D. MD or both. Very rare for a so-called PI, a principal investigator, like mere, you know, another matwalker, for instance, principal investigator to have less than a Ph.D. The fact that she ran a lab or was important in running this lab as a masters with only a masters is unusual. And then there was a lot of chatter in my field about the idea that it might have something to do with the fact that her significant other was a member of the Chinese Communist Party. And so that laboratory had deep ties to the government and vice versa. And that's true of all laboratories in China, all laboratories. So the whole notion of the lab leak hypothesis was not foreign to scientists like me. You know, my laboratory works with rabies viruses, adenoviruses, sinbysviruses. None of these are as biohazardis as something like the coronavirus. But you work with these viruses and you have to use lab coats, gloves, bleached sterilization, you're careful, you know, hoods of prop, you know, but human error happens. So I'm not at all convinced one way or the other that it was a deliberate leak, but the idea that it would leak from a laboratory to a scientist like me who has what's called a wet lab where you, you know, with solutions and beakers and things that sort, things happen all the time. Not in my laboratory, we're very careful and everyone's checked up on often. The idea that human error could cause us is like, it was in, of course, to all scientists.

I mean, all it takes is, you know, people might not be familiar with the pipetting is, but it's basically taking a little straw that sucks up, you know, press a button that sucks up some fluid. You move things, you know, between little tiny vials, can be done by robots too, but typically it's done by humans. And that's how I'm going to put in a center for your spin. It take off a little piece of that or take the pellet out of the bottom that spun down this kind of thing. All it takes is one loose thumb. And it's on a lab coat all takes that lab coat going on a rack all takes a somebody leaving work putting their lab coat on there and touching that I'm putting it's out in the world like it's not that complicated so it doesn't have to be that somebody had a plan to let this out. It could be, I don't have any knowledge of that. But the idea that it would come from a lab to me is far more plausible than the idea that it came from some pengolin sequence in the Wuhan market. So we were going down the wrong path on this for a long time. And I thought this is kind of bananas. And now everyone's so shocked. And it's like, I think to people who work in biomedical research, like, of course, this sort of thing could happen, of course. Because human error is the cause of most of these kinds of things.

Yeah, if you're had it, it's the luak coffee.

Yeah, when I was a postdoc, there was it. So this is it. That's the raccoon dog.

And it was March 2020 when everything kind of blasted, right?

Yeah. I think the Labley Kai-Pothethus is far more plausible.

Yeah, there are two, you know, we hear about gain of function, research, and now everyone associates gain of function with gain of function of this particular virus. gain a function research happens all the time in essentially every laboratory in the US and abroad that does mouse genetics. You knock out a gene and you ask what happens to this animal in the absence of a gene and then you knock it in and you see if it replaces that because in humans human genetics is only loss of function you don't have the option yet CRISPR will allow this to put things back in that are missing. And so gain of functional research is extremely common. We're no longer working on animals to be clear. We only do human studies now. But this is something that you're trained to do as a postdoc. Everyone learns loss of function gain of function. You need to do both. The gain of function actually, there is that one CRISPR experiments being of interesting science out of China. A guy, he actually was a postdoc at Stanford, worked for a guy named Steve Quake, and then separately on his own without permission or anything from Stanford went off and started his own laboratory in China. And stood up at a meeting a few years ago and said he had done CRISPR in human babies. This has been done. Yeah, he mutated the HIV receptor, which everyone thinks, OK, that was designed to prevent these babies from getting HIV. It turns out that that mutation is thought to perhaps enhance memory by parallel mechanisms. And then it was very unclear for a short while whether or not this guy was either going to get a Nobel Prize or that they were going to throw them in jail. And so everyone is very tense in waiting in my community thinking, okay, because when somebody's kind of up for a big discovery like this, everyone kind of circles maybe wanting that maybe they should be involved in getting the accolades. But as the moment that the international community, I think rightfully so, said, this is horrible. You can't do this. There's no ethics committee. You need to think about what you're doing. Everyone knows this. I had nothing to do with this guy. I had nothing to do with this guy. It was pretty interesting. Then China said, oh, we're going to punish him. But I'd be willing to bet both hands that he's his punishment consists of a jail cell that is pretty luxurious with a laboratory. There's no question that CRISPR is going on there. CRISPR is going on in certain regions of other locations on the globe where things aren't as regulated because think about the potential payoff for being able to. rescue a Huntington's mutation, right? Huntington's Korean mutation, it has somebody at some point in their life, you know, unable to control their arms. Hemi-balissimus of the arms. If what is it? Huntington's disease, it's a deterioration of the parts of the brain that control motor function. The parts of the brain that control motor function have two main pathways, one is a go pathway, like reach for this coffee mug, and the other one is a no-go pathway resisting movement. And the no-go pathway degenerate substantially, other things too. And people with Huntington's Korea end up with these writhing ballistic movements. And it's an inherited disease. So you know what gene is. The Huntington gene. And if you know that your, for instance, parent has it, you can get tested for it. A lot of people don't want to get tested. They don't want the answer. Because it's laid on set. So you mean normal, certain portion of your life and then get it. It's a tragic disease. But if you test positive for this gene, you know you're going to get hunting tens. In which case with CRISPR, you could just put the gene back in and rescue the function.

Yeah, so it's not just deterioration of those particular neurons. deterioration of the neurons that control those neurons. Everything's working in a kind of a top-down suppression all the time. In fact, the head neurosurgeon at neural link, who somebody I know quite well named Matthew McDougall, he came up through my laboratory, Elon made a great choice in hiring him. Tell me recently, the best way to think about the frontal cortex is that basically it's main job besides picking context and strategy for a given situation is to tell certain parts of your brain that really want to do things. That's the best description I've ever heard of prefrontal cortex. You know, it's what's keeping Jamie from doing things that he shouldn't right now and me doing things that I shouldn't right now and every time you have a crazy idea, like maybe I should jump off this bridge. Why would I think that? I'm not that's a healthy operation of your brain saying I want to because I'm kind of curious, but I don't want to, so I'm not going to. With Huntington's what happens is just slow deterioration of those neurons, but there's a lot of deterioration of these neurons that control motor function. And eventually what happens is the deeper neurons that control motor function start shutting down the autonomic functions like breathing. heart rate and so eventually people just succumb to some basic you know we call them housekeeping functions you know so they'll have to be on a respirator and they they have to you know they have to use a catheter tube and you know they have to defigate into a bag and you know at some point they just become a deteriorated mess of neurons. So, what's first to go there, however, is the control of motor function, and it goes first in the direction of too much activity, because of all these breaks and accelerators that we have in the brain. So, in any case, CRISPR, gene manipulation of the sort that this guy did in this laboratory in China. Again, I think an ethics committee needs to tell the world or decide for the world what people should be allowed to do and not do. But you can imagine for something like Huntington's. It would be tremendously advantageous. Like if you had a child who knew what someday going to get Huntington's, you'd want to do a CRISPR mutation and put the healthy gene back.

There, I'm not so versed. It's a little bit like MS, another neurodegenerative disease, multiple sclerosis, where certain things exacerbate it, like inflammation of any kind. And those things can be almost random in some ways. Like some people who have MS will salad dressing with mustard and have a huge inflammatory response and have a flare up. blurry vision and get worse and then it returns faster. Things like mustard is mustard in flammatory? Well mustard isn't necessarily whole body inflammatory, but if it's spicy mustard it binds to what's called the substance P receptor or the cap-sacin receptor. We have receptors for anything that's kind of hot and spicy. And those are the same receptors that respond to hot liquid. Heat and spicy obviously very, very closely linked and pain, all three of those very close. Whereas Pain relief very closely related to men fall and cool not just the taste but the actual physical sensation of cool So heat pain and inflammation over cousins in this in the sense and cool men fall and lack of inflammation are also cousins in terms of receptors, neural circuits, this kind of thing.

Sure, yeah, really. Yeah, but I think one of the best ways to think about inflammation, and here I, you know, I definitely had tip to Lane Norton who we both know and Andy Alpin, who really, both really impressed upon me the fact that if we were to measure somebody's blood pressure inflammatory markers, heart rate, and court is all, during a hard workout, and you didn't know they were doing a hard workout. I just handed you the data and your medical doctor, you'd say, this person's dying.

So inflammation is robust during during a hard exercise. But I think what's so incredible about the human body is that the increase in blood pressure, inflammation, et cetera, is what triggers the adaptation so that blood pressure and inflammation, et cetera, are all much lower the other 23 hours of the day. And so there's something special about our system whereby, yeah, maybe if you had really hot peppers, like the most famous of these is the Carolina Reaper. The Carolina Reaper. I have some of my hot sauce.

There's there's a there's a is that a person or a brand's in your Latuga. It's a brand. Okay.

I'm not gonna, I'm gonna, I'm in Texas, I'll embarrass myself.

Well, the Carolina Reaper in small amounts, I'm sure you couldn't spice it just right. They're these pepper eating contests that people actually know.

So a few years back, somebody ate a Carolina Reaper and ended up with what's called thunder clap headache. Thunderclap headache is a massive inflammation of the meninges of the brain. So you got your brain at sitting in fluid, everyone knows that, and then there's some thick, durus stuff around it. There's thick, thick fibers tissue, like, you're a hunter. So when you get wanting to take the brain out, people think, oh, you just kind of pop the brain out. You have to, you need a sharp raise or really sharp scissors to get through a sharp knife. The swelling of the meninges is what happened to this person. They got an unbelievable headache and it's actually inflammation induced brain damage. Now that's only eating an extremely hot pepper in huge quantities. How many peppers did this guy eat? I don't know. I think

Yeah, thunderclap headache. We know a couple other things about spice. And here I just, I always want to make sure I give proper attribution. The Nobel Prize was given a couple of years ago. to a guy down at the Scripps Institute in San Diego, Ardem Patapuchin and David, excuse me, oh gosh, David Julius at UCSF for the discovery of these receptors for pressure, cool, heat. And it's an amazing set of discoveries that just occurred really in the last 10 years. We know that all of those pathways go to areas of the brain that are involved in, of course, like behavior, like if you touch something really hot, you taste something really hot for most people, they're going to resist that. But also to the hypothalamus, which houses all these hormone control areas, et cetera, people who can tolerate stronger spice, men and women, we know it's correlated with higher levels of circulating testosterone. That I think is interesting. What we're really talking about is higher pin threshold. And you and I've talked before about if there's one clear effect of testosterone, it's that it makes effort feel good. That that pain starts to have a little bit of a come-hither kind of thing to it. It feels a little bit enticing when testosterone levels are elevated. When testosterone levels are lower or people have lower levels of testosterone, effort feels more overwhelming. How's that? And the other thing is that ingestion of spicy peppers resets your calibration for what spicy. I think we know that too. And in a way that also adjust people's pain threshold. So if people get better eating hot peppers, they're better dealing with all types of pain. And I find this fascinating because I know you and I are both kind of obsessed with ice baths and cold cold dishes. And I've been going deep into that literature around cold and what's really known about cold thermogenesis and not known. And it seems like these acute adrenaline, acute pain pathways. They do exactly what exercise does, which is in the moment if you were to measure somebody's inflammation, et cetera. You'd say this person is dying. They are in a terrible state. They might as well be getting, you know, open heart surgery with no anesthesia, the way some people react to the ice bath. It's kind of silly. To us, but for people that don't like the cold, they're like, you gotta be kidding me. I'd never go near it. They try to disparage it. They try to poke every hole in the data. They're just scared, right? They're just scared. We know this. But they are actually the people that benefit the most because that really acute adrenaline spike, that pain that you feel creates a higher pain threshold later. higher threshold for work output all the things that most people seek and so to me it's always interesting that you have to look what's happening during and you have to look at what's happening afterward and for some reason as humans we like these creature comforts of massages which are great you know the sauna which is great although if you crank it up really hot it's work at some level

Yeah, and there's something about the burning in the nose for me, at least my heart rate starts like I want to get that one.

I'm, you know, it's always hard to know how hot it is right at the point least where it reaches your body. I've been crank it way, way up. Like what? 10%. Like 260. What? 260. But I cover. But I cover my head. So what do you a brisket? No, fuck are you doing? Well, so that what I found is, why are you doing that? Oh, so what's interesting is your desire to get out of the of the hot tub or the that too hot hot tub is because of burning on the skin, right? But desire to get out of the sauna. is usually a brain thing. You'll notice this because if you go to a Russian body they all wear the wool hats. That's to insulate their brain against the heat so they can stay in hotter temperatures on their body. So I'm in it to 60 but I've got my head covered with a wool cap. So it doesn't feel as stressful. but I'm doing it because I like to say.

Okay, so this is great because what you're starting to do is tease out the variables. So this is where I think it gets interesting. You can get better at sweating. I know fighters do this in preparation, you know, dropping weight. You can get better by doing more sauna. You get it to be a better sweater, which means that you can drop, you can cool more easily, even in clothes or if you're out running or hunting or doing anything. So there's some advantage to being a better at sweating. And sweating itself is a whole interesting story. You actually have nerves that control the sweat glands. That's actually controlled by little nerve endings. And those pathways can grow very, very quickly in the presence of heat. So what I've been trying to do is learn how to dump heat better. And if I don't use the, you know, the hat, what happened was I was getting up to 220 and I'd sit in there for like 45 minutes on something and this is not doing anything for me anymore. I want to increase my sweating.

if you're not trusting the two 60s. No. So what I did is I had the, no, I haven't. So it makes your sauna. This is Dundulk. But so what I had the guy do who had installed it for me is put the thermometer down low because it's a trigger, right? It's going to shut it off when it hits a certain temperature. So what I'm really trying to do is get, get it really, really hot down near the floor because then I, you know, when I stand up, when it's that hot, I'm just ready to pass out no chance. Yeah, but you know, I think layered I don't want to get this wrong on the numbers, but you know, I know layered brings his airdine bike in there.

With oven mitts on. So he's got he's got to be putting himself at at least 260, right?

Yeah, that's psycho, but he's a different kind of human being. Yeah, but I'm contrasting this with cold. Yeah, and so that's a difference. Are you going cold and then to 60? I'm a wimp. I start in the cold for a minute, then I go into the sauna, then back into the cold for two minutes, back into the sauna, then three minutes.

Well, listen, if I were tougher, I'd go five minutes in the cold straight off. Yeah. But I just had Susanna Soberg out for a podcast. And she taught me some really interesting things. First of all, this is really helped. I did this.

Susanna Soberg did her PhD in Denmark, because I think one of the best scientists in terms of deliberate cold exposure in its benefits, because she actually did something that's remarkable, not just in that field, but overall, which is that she employed real world type experiences and exercise of deliberate cold and sauna and turned it into a very rigorous study of brown fat thermogenesis which is this sort of think of it as sort of like the oil into the candle of your body increases mitochondrial function and thermogenesis heat to up metabolism, subjective well-being, sleep, et cetera. She did all of that, and publishes and so reports medicine, and I realize it's just one study, but to do that studies on humans is hard, to do it with multiple variables is even harder, and to do it in a real world context is even harder. So what she showed was that if people get 11 minutes of deliberate cold exposure per week total, and this has divided up into sessions of one to three minutes or four minutes, even So it's not 11 minutes all at once. They fundamentally change the amount of brown fact that they have, which means they fundamentally change the number of mitochondria and the brown fact, which means they fundamentally change their thermogenic properties of their body and increase their metabolism. Now, the people who don't like cold say, well, they increase in metabolism, wasn't enough to offset more than a few bites of a bagel or something. But that's not the point, really. What she also showed was that this increase in thermogenesis allowed people to be more comfortable in cold environments, even when they're not in the cold. And then people say, well, who cares, right? I'll throw on a jacket. But what she was able to show is that the ability to be comfortable in the cold correlates with a bunch of other important immune functions and metabolic functions and insulin sensitivity, which is a good thing. And the inability to do that is likely to not be healthy for us. She also showed that 57 minutes per week is the threshold for sauna. So if people get 57 minutes per week of uncomfortably warm but safe sauna exposure, they can get very similar effects. And then that gave rise to the question I always said, do you end with cold or do you end with heat? And she said, end with cold because then your body's forced to warm itself back up. And that's what's now called the sober principle, which is when you end with cold, your body has to use its natural machinery to heat back up. In talking to a recently, I learned some really interesting things that I've been incorporating. First of all, I've always avoided putting my head under until the very end in the cold. Turns out that if you put your face in the water right as you go in, you activate the mammalian dive reflex. And this reflex increases the so called parasympathetic activity of the autonomic nervous system, which is just as nerd speak for it lowers your heart rate. It makes you calmer and it makes you better able to tolerate stress. So try this next time. You could even just put your face in before. I go right under. You go right under.

So I didn't know this. A lot of people that do deliberate cold get headaches. They don't feel good and a lot of times it's because they slowly immerse themselves up to the neck and then write it that interface of cold and hot. It creates change, these are constriction right below a little bit. These are dilation above the get headaches. They don't feel good. The heart rate is way too high. Putting your face under.

Well, it's psychological and it's physiological. So you're physiological because of psychological. Absolutely. Absolutely. So here's what we know for sure for the first 20 to 30 seconds of cold shock when you get in just how it's described. That prefrontal cortex that normally has the job of handling context and says, to the reflexes of the brain and the impulses of the brain is not active for 20 to 30 seconds. So your reflex to get the hell out of there is very there's a clear and logical reason for that. After that 20 or 30 seconds the forebrain starts coming online again. That's your opportunity to start negotiating with yourself. Oh, this is actually good for me. This, this is, I can handle this. I got through that so I can get through the next one. What I've been doing recently is trying to not go for time, but going for the only way I can describe this would be walls. Like sometimes just getting in the thing that is a wall for me. So I go, okay, I got over one wall just getting in the damn thing. Then, like, oh, God, here it comes. For a brain shutting down, I'm panicking. I'm going to get through this. And then I'm watching for when I have the impulse to get out. And when I start to notice, is that the gaps between those walls start getting longer and longer. The more you do it. The more you do it. You do it. I do it. Yeah. And then pretty soon, what's happened? Oh, cold is it? Ah, that's hard. I suppose it's probably in the low 50s. What? Low 50s are, why is it so warm? I don't know, I low 50s high 40s. Why do you do that staying there longer? I don't know. Well, we have two. I confess we have the morosco one, which is that one's really cold. And that one is. You avoid that one. Sometimes. I like to go in the sauna. I don't like when I'm here. Well, here's the thing. I've been doing longer exposure in the warmer one.

I listen well 34 34. Yeah, you and Camhaines.

I just got one of the things and floats the top. Yeah, you realize I just uninvited myself on the, the Camhaines hunting trip because he was like, you should come hunting. I've never gone, but I think I'd, he'll probably just say I'm a little excited until I get down to the 30s on these cold flunkers. No, I didn't work out with him. I went up there. I was sore for two weeks. Those high rep weight workouts.

Yeah, like I'm a slow lazy bear in the gym. Like I like to lift heavy West kind of look at those kind of thing.

Well, I'll do the long runs. I do a long run on Sunday. I did two hours yesterday around. They called a lake, but it looks like more like a river.

So I kept going around that thing until I couldn't go around anymore. But yeah, I need to go colder. I will get in the ice one. What does this will need to go? Why don't you just do it? Well, there are mornings. I'll just jump in the cold one for 30 seconds.

There's no negotiation.

I'm not saying I don't go in every day. I'm saying I don't always go into that one first. I go first thing in the morning. Okay. Well, you're a better man.

Well, I'm going to get thermometers a second thermometer for the sauna. Verify. I'm going to verify the data, second independent measurement, and the cold. I may have to imagine that the Mirasco one because it has pieces of ice floating in it. It's got to be colder than 50.

Okay. So I've been doing shorter exposures there, and then longer exposures in the 51.

I mean, they're a while. So that one, when I go in there, I'm staying, you know, 10, 20 minutes. And here's the reason the study that was published in the European Journal of Physiology that showed these huge increases in dopamine, that was the first of these sorts of studies. I don't know if I've mentioned this, but when you go in the cold for a very brief period of time, one to three minutes, and it's shockingly cold. You have to catch your breath, stabilize your mind. That evokes adopamine, epinephrine, and nor epinephrine release. These three things together are called the catacolamines. Those normally would increase from a cup of coffee and a heart sprint for 10 to 30 minutes, maybe an hour. When you do the cold exposure, the way you're doing it, or longer exposures in about 50 degrees or so, You're seeing increases in dopamine, nor up in effort and in an effort. That are two to three acts above baseline. This is huge. Wow. This is huge. This is only order of many drugs, but the difference is most drugs spike dopamine in the drop it below baseline. that increases in this case are lasting many hours, two to four to even six hours. There are very, you know, whenever people criticize deliberate cold exposure, they go, it's not leaning to that much fat loss, granted. But to my knowledge, there is no drug. Nor is there any form of exercise, conventional forms of exercise that increase the catacolymines to that level for that long. And with dopamine, it's all about The amplitude and the duration, how fast it rises, how fast it stays up there. There's nothing quite like it. And I did three plunges here. I'm staying in a place that actually has a plunger. I don't know the temperature, but it felt cold to me. So I did three minutes, three minutes, three minutes, and then a hot tub. So I bounced back and forth for a minute and between. And as you know, you feel better much of the day. If you get the entire day, that is not a coincidence. Your system is circulating much higher levels of the catacolymines. And this is shown in that paper. It's now been shown in a series of other papers. My colleague Craig Heller at Stanford has known this for a long time. And this is why. And for other reasons, the athletes at Stanford who use cold do it before their workout. Yeah. Everyone now knows that it blocks hypertrophy if you do it after.

Yeah, absolutely. I mean, I think that it, you know, I think of health and performance, so mental health and performance along, you know, fundamentals, you talk about these all the time. I think the five pillars, if you will, or sunlight, if I may, getting light in your eyes, avoiding too frequent bright light exposure in your eyes at night, unless you're doing something you really enjoy. Okay, so you're doing comedy. You're out past 10 p.m., right? You're not going to wear sunglasses or something necessarily. But it'll be ridiculous, right?

I've got friends that wear the red lights at night and dim all the lights, you know that whole thing. That's a little extreme. It's a little extreme. Don't speak about it. It's always weird. Yeah, but sunlight. So sunlight during the day, morning and day, and trying to limit bright light exposure at night, as much as is normally possible. Then I would say movement. So you got to move cardiovascular and resistance training. That's one of the beautiful things I think that's happened in the last couple of decades is that resistance training is no longer just considered the thing that football players and bodybuilders do. Everyone, old young female male women no longer I hope are concerned about getting quote unquote too big from weightlifting or something or training into it. I think that's kind of gone away. I like to think that's gone away.

They look way better in our friend Peter Tia and his has talked about one of the major causes of death later is, you know, falls due to stepping down off things. Inability to hang from a bar is, you know, correlated with lack of health, right, in the form. So being able to have some strength. So exercise, then nutrients, right, macronutrients, proteins, fats, and carbohydrates, people now think about it. So you need all that stuff, vitamins, minerals, and the other stuff. And then I think in addition to that sleep, right, I think Matt Walker, deserves a tremendous debt of gratitude from everybody because 10 years ago everyone was like they'll sleep when I'm dead now we know You're probably not going to dissolve into a puddle of your own tears from a couple of bad nights sleep every once in a while, but sleep makes you mentally physically better, you perform better. And then the last one is this whole not notion, it's social connection. You can't stay isolated constantly or people lose their mind. So when you look at people that get very depressed or they're suicidal, one or several of those five things is going to be diminished. And then what happens is people hear about deliberate cold exposure. And if they don't like it or they want to poke at it, they say, oh, rocks high-perrophy. Okay. Well, only if you do it in the four to six hours after a high-perrophy workout. I thought it was two. Well, they've looked immediately after, you know, immediately after is bad.

Yeah, I think that the, that's okay, right? Right. I mean, it blocks, it lowers inflammation, which is the, which is what you want from the resistance training. Right. Again, it goes back to this.

You know, it wasn't just these guys, but I, again, I point to Lane and to Andy Galpanu have been shouting from the rooftops for years. Blood pressure up, inflammation up is a good thing. So you have to be careful when someone says, oh, you're romantic. You eat the hornmatic effect. You eat this, you become inflamed. Well, how long and what's the hornmatic effect? And so in terms of, You know, deliberate cold exposure, people like to say, oh, it doesn't burn much fad. It blocks hypertrophy, but if you look at the mental benefits of having your catacolymes, dopamine or up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up and up. four to six hours after a 30-second to three-minute protocol, you're not gonna show me a drug or a form of exercise that can do that.

Why is that? It's really interesting. When you heat the surface of your body, you would think, oh, you know, my whole body temperature is getting really hot. But if I were to measure your core body temperature, what happens is your ideal pre-optic nucleus of the hypothalamus says, Oh, the surface of my body is really hot. I'm going to cool down my core temperature. And falling asleep at night, involve requires a one to three degree drop in bodily temperature. And when you wake up in the morning, You have a one to three degree increase in body temperature in the morning. That triggers a cortisol spike. That triggers nor up an effort. And then you start waking up. So body temperature and the ability to fall asleep and stay asleep and wake up are very tightly correlated. Now your holster-cating rhythm is temperature driven. And so, for instance, you probably have a best time of day for you to work out where you feel best. If I were to have you train it, you know, 2 a.m. when you went to bed at, you know, a couple hours before you'd feel miserable. You're not going to perform as well, grip strength in the middle of the night. I wake you up, I take your grip strength measurement. It's going to be strong but not as strong as it would be. your peak time during the day. If we look at your body temperature, we'd find that your grip strength is weakest when your body temperature is lowest. So you'd say, well, I'm asleep. That's why. But there's an easy experiment. This has been done. We just keep your wake for 24 hours. We measure your body temperature. It has a very regular circadian rhythm. That persists. And we measure grip strength. That's been done numerous times. People living in caves, they've done those experiments.

Ah, sauna's dropping your core body temperature.

So at some point, you won't be able to thermal regulate anymore. And then your body temperature will go up and you can become hyperthermic.

Your core body temperature is fighting to get lower and when you get out, your core body temperature continues to go. That's right. And the exact opposite happens when you get in the cold plunge. You feel cold on the surface. So your body goes, oh shit. hypothalamus, again, medial pre-optic area, gets a signal from, I mean, if you think about how beautiful this mechanism is, I still like goose bumps and no pun intended when I think about it, you have receptors on your skin surface that sense cold. Send that to your hypothalamus, which says, ah, it's cold out there. I'm going to generate heat. How do I generate heat? Well, there are two things you can do. I can make you shiver, which will generate heat, or I can make you move, another shiver, it's just another form of moving, or I can activate this very specialized fat tissue, which is not under the skin. It's not subcutaneous fat. But it's around your critical organs, which is the brown fat. Activate the mitochondria there. And basically, at that very core level, get electrons moving and the brown fat in term activates the thermogenic system and start heating you up. It's so crazy. And then what's beautiful is that the brown fat has a sort of memory of that experience. So even after you get out, you're walking around right now. I did cold plunges this morning. You did cold plunges this morning, right? Yeah. Okay. So your body temperature is about one to three degrees hotter. Probably about one or two degrees hotter than it normally would be. Dopamine's getting cranked out. And so all day long, you're warmer at, let's say, cool ambient temperature. In fact, in Scandinavia, I learned this in researching the soberg work. went deep into the this cold thermogenesis world over there that they've been researching this really carefully and they have a saying in Norway obviously don't know it in Norwegian but it translates to essentially in the spring as it's getting warmer in Texas what you want to do is to put they say put on more layers why so that you can prepare yourself for being able to cool yourself off easily in the summer when it's really hot you'll be more comfortable in the heat of summer in Texas, if you bundle up a bit more in the spring. Really? Yeah. Well, you're adapting. And then they say the opposite suits. But then they say in the fall what you're supposed to do is not walk around with a sweater, you wear a t-shirt and then guess what in the winter your thermogenicity.

Okay, let me be clear. It's the principle.

I'm not saying it's behind it. Yeah, I'm not saying where a sweatshirt in the spring is where what's comfortable Jesus Christ is. What I'm saying is that when we what's Jamie's laughing. He's from Ohio. They're just like, this is ridiculous. The, it's cold enough out there. You don't need to come from Boston. Well, I think the principle is what's interesting.

Is that if you teach your body to tolerate warm, then you will be more comfortable in very hot. It's sort of obvious. Yeah, and vice versa for cold.

Well, the contrast of heat and cold is we know very good for our cardiovascular system, because we think of the blood vessels and capillaries and arteries as just tubes, but they're really cells and the theolios cells, they're laid out like silly putty, linking them all in tubes, and they are very contractual. They need to do that because of the pulsing of blood through them. That's the whole basis of systolic and diastolic blood pressure. It's the top measurement. It's a pressure when it's not blood pumping through and it's pressure when it's relaxed, okay? Um, the system can become very dynamic. It doesn't be, you don't want it rigid, especially given, you know, what a T. It tells us, and I believe them is that the number one killer in the world is cardiovascular disease or cerebral vascular disease. You want the low microcap areas of your body be very flexible, not rigid. So when you go heat cold, you're basically going phase of constriction dilation, phase of constriction.

So that could be the drop, which is when your blood goes to the center of your body to preserve your core organs, and then the surface of your body is cold, and then as you start to heat up again, And there's phase of dilation. And it goes out to the surface. Your butt, your surface is cold. And it actually cools the blood at the surface. And that's what's called the drop. And that's when your body temperature goes down. Now, even when you put on clothes and head to your workout or head to work, what's going to happen is your body temperature is now going to increase more quickly. Normally, would do that anyway early in the day. As you wake up, your body temperature goes up, up, up, up, up, up. And then whenever you achieve a sort of a dip in energy in the afternoon. There's probably one time in the afternoon, whether or not you need a nap or not, that you feel a little bit lethargic and then you kind of come back. That represents the peak in your body temperature for 24 hours. In fact, most people, if they want to figure out their sort of optimal bedtime, I know this gets pretty down in the weeds. You just look at that number, so maybe it's three o'clock, and you say about seven hours after that, plus or minus an hour. That's probably when somebody should go to sleep. How do I know that? Because that's when body temperature starts dropping by one to three degrees. So doing cold early in the day makes total sense. Doing cold, deliberate cold exposure before it work out. Total sense. doing sauna before sleep, total sense.

First of all, I completely agree with you. Completely agree. And I'm not, you know, again, Craig Heller in our biology department at Stanford has been talking in this general theme for a long time on a Lemke who you had on here talked about. Patients of hers who got sober using cold plunges. You say, well, how do they get sober to use cold plunges? You know, taking one addiction and replacing it with another. No. What's very clear is that when you're, when you're suffering or you're lazy or you're procrastinating, doing something that's harder than the state that you're in, bounces you back much faster. This is all based in the dynamics of dopamine. It's sort of crazy if, you know how people are procrastinating to write something or just, and they start cleaning the house, something they normally don't want to do. Well, it's just something that's easier than the thing that you're supposed to do. It turns out, and I learned this from Anna, if you do something that's even harder than the thing that you're trying to avoid, all of a sudden you're able to do that. Oh, okay, what's just psychology, right? No, it's not psychology alone. It's psychology, but it's once dopamine is deployed at that level. You're a different person and I know this because if you take someone's dopamine and lower it That makes them depressed that gives them if you lower it even more and give a movement disorder Parkinson's if you give them their dopamine back Their focus increases. How do I know that? There's a reason there's an ADHD drug shortage right now. Ridlin Adderall they all tap into this system the dopamine ergic and adrenaline nor up in a friend system So one of the most prescribed and over prescribed classes of drugs is the drug designed to try and get exactly this effect of cold plunges. And so I completely agree. If people would just take a very cold shower or a very cold plunger's, a little bit longer at 50 degrees, although I agree with you that shorter, colder is better. What I didn't describe and I'm not trying to rescue myself here, but I do that daily, but then on Tuesdays is the typical day where I do very, very hot and very, very cold back and forth for well over an hour back and forth.

I'm trying to condition myself to really be able to tolerate heat and cold. The other thing I learned, again, from Suzanne, I take no credit for this is, and I'm not suggesting people replace the cold plunge with this or a cold shower with this. You're trying to see more of this on social media, and it's embarrassingly silly to think that that's a replacement. What I'm about to describe as a replacement for cold plunge is, but if you put, she taught me, she said, if you even just put a small portion of your skin in ice cold water, like your hand or your arm, you actually activate the brown fat system. That's how robust this system of surface temperature to body is. And so I don't think it's a good replacement, but now you're seeing people saying, oh, you just have to put your face in a bowl of ice water.

Yeah, so this was developed by Craig Heller's lab. It's called the cool mitt. It's a bit controversial and I'll tell you why. So you have on the surface of your hands on the bottoms of your feet and on your upper face, you have what's called GLABRIS skin. It's the only skin on your body that's incapable of growing hair because there are no hair stem cells there. It's also the place where, believe it or not, it goes normally in things go arteries, veins, capillaries. But in this case, you're missing one of those components. And what it is is that the top of your face, the palms of your hands and the bottom of your feet are like radiators. You can heat past as out of your body very readily. This is why animals like bears who are covered with hair will stand in cold water to cool off. It's very effective. It's also true that if you want to heat up, you do it through these portals. And so Craig's lab did two really important experiments. The first one was heating people up. It turns out when people come out of anesthesia, it's very slow. And this is a problem for all sorts of critical reasons related to keeping people alive. And if you measure people's body temperature when they're coming out of anesthesia, it's very low. And as it heats up, they wake up just like out of sleep. His laboratory developed these heating devices that would heat people's palms or the bombs of their feet. And they found that they could bring them out of anesthesia much faster and recovery rates were much better. super impressive result, not talked about often enough. And the reason it's not talked about often enough is all this stuff around thermogenic studies was really hot and like the 19th, no pun in the, sorry, in the 50s, 60s, 70s. And then it was sort of considered kind of like not lame, but it wasn't hot science. There we go again. I'm really not trying to pun here. Then what's happening in recent years is people who've gotten into these protocols and it's become more popular. His laboratory also showed that one of the reasons why we fail on a set of dips or chins, local muscular failure is due to heating of the muscle locally, due to work. And then there's an enzyme called pyruvate kinase, which is very heat dependent. When your muscle gets too hot, pyruvate kinase camp function and your muscle fails. It's one of the reasons you fail on a set. So what they figured out was if you cool people's core body temperature, they can do more work. Now, it got a little confused people say, oh, I didn't double my bench press after cooling my hands. Well, that's not really the point. The point is it, let's say you can do 10 sets of 10 in a given way with two minutes of rest of it in between. And that's all you can do. And you're hitting failure. Maybe you have to adjust the weight down on sets four, five, six, et cetera. Classic 10 sets of 10. that I want to have people to German volume training, or five sets of five. If you lower the core body temperature through the proper use of polymer cooling as it's called, or through some other device, what you find is people can continue to get the same number of repetitions provided they keep the rest the same, and they can double the amount or more of work that they're doing total, so they can increase their volume. The interesting thing is they preserve the training effect. So if you can go from doing, I don't know, how many dips, I saw you do a bunch of pushups right there on a podcast recently. It's like 75, right? Yeah. So in theory, if we'd been pooling your palms, you would have been able to keep going much longer, possibly 150. And you say, well, how could that be? Well, it's just, it's a local change in the enzymatic reaction at the level of muscle. Now, the problem with Palmer cooling is people will go out there and say, I'm going to hold ice packs. But if you do that, you'll constrict the portals. It has to be the right temperatures that you can continue to pass cool in. And that's why it requires a device to excuse me to cool your palms, but not so cold that you vase a constrict. And so there is the coolment device to be honest, is it a very effective device? They've never been very effective at marketing that device, but they use athletes at Stanford use it. But nowadays what athletes mainly are doing, and I talk to pro basketball players, football players, tier one military, they're doing cold before they're training, because it's just simpler, and you don't need a device. interwork out or interwork out, cooling is really an interesting topic, but it hasn't been perfected at the level of devices. They're still kind of clunky. You got to go put your hand in the thing. No knock on cool man. I mean, I think they're trying really hard. I actually got one for Cam that I still need to deliver to him.

Yeah, you need to lower your core body temperature. So in 20 seconds, half hour. Yeah, probably here's what I think it could really help and you could try it. If you don't have access to a cool mitt and I can get you one for you to try, but if you hold on, you'd want to hold something cold between your hands for maybe 20, 30 seconds. I'll just dunk your hand into the cold plan. Could do that too.

Yeah, the relationship between temperature and sleep, temperature and the deployment of these neurochemicals, temperature and performance is one of these variables that right now professional sports teams and tier one military and scientists are really trying to understand like this is not a small variable. This is a super powerful variable. It's just not an easy one for the conventional gym to have. Maybe at some point in the future, every state they'll have stations in the gym where you kind of plug in. Yeah. And you can just do more work. It's all about the ability to do more work.

And recover. And recover. And it's clear that the cold after training is if your goal is to train again, well, then you want to inflammation down. But if your goal is to improve as a consequence of that training session, you have to be careful how much you're blocking the inflammation.

I mean, the ability to do more work is, I think, one of the not-so-secret secrets of performance enhancing drugs, too.

I mean, even at the level of being able to get a really good night sleep even when you're slightly over-trained. You know, people always say, well, what do these performance do steroids make you grow muscle? Well, they'll increase protein synthesis.

And I think, and I, I, for all, I know, I believe he's natural, but like you think about a guy like Floyd Mayweather, and I, I used to see him running in the middle of the night, and you know, it's Vegas. If his testosterone happens to be exceedingly high naturally, he can do more work and recover than the person who's testosterone is lower before they hit a wall. So I'm not saying he was using anything. What I'm saying is if somebody has higher levels of circulating testosterone, male or female, they can do more work and recover. That's just the way it is.

I mean, emphetamines cause a, it's gonna vary by dose, et cetera, but at least a thousand fold increase in basal catacolymine levels. That's what they do.

In the, I don't have a lot of friends in the finance world, but of the ones that are, you know, the friends I have who are in finance, 100%. The scientists I know, zero, but scientists generally aren't of the admiral type. Musicians, not so much. Those are kind of the categories and podcasters. I don't know. I don't know how many quite a few podcasters.

You know my feeling about writers and journalists. What's your feeling? Well, I don't know if we bring this up or not. But, you know, I think the tides have changed in recent years. And, you know, conventional media has used to kind of, they email you. They want a conversation, you know, I think sometimes they're surprised. You don't leap to have that conversation or, you know, I think one of the problems with the traditional press is that it's hard to know where their heart is. like where they are on a topic and so conversations with them have become a bit of a razor's edge frankly.

Yeah, well, the, the, you're right, they're incentivized by a whole set of things that are not obvious from the articles themselves. I'm a huge fan of what Saga and Crystal have done and are doing. Me too. Huge fan. It's incredible. It's incredible and it's important.

Yeah, I mean, my initial experience of them was long before I had a podcast, didn't interview with traditional media. And then it comes out. And I was They didn't say anything bad, but my quote was given to somebody else. Their quote was given to me. And then you say, and I wrote and said, hey, you know, this is factually incorrect. I didn't say this. First of all, I'm not a medical doctor. They swapped the names either, accidentally. And then I got this, oh, well, you know, kind of response, like two late, you know. But when it's your attraction. But what no, and when it's your neck on the line, you know, it's your name. I mean, the signs always have as our reputation. In science or anything, it's all we have as our reputation. So it's a scary thing to hand that over to somebody. So unless it's a particular few set of sources, I generally decline traditional media conversations. The other, and now that the fight isn't just for traditional, you know, over media, traditional or independent. You know, the universities too, right? We're asking, I have to say, and I'm not, this is not to be, you know, politically correct or incorrect. Stanford has been very good about letting different faculty at Stanford voice their differing opinions on everything from COVID to politics. You know, there's a free speech, a right to free speech, a petition that's been going around on the campus for a while, as you can find this online. Now, a lot of people also will hear things about, oh, I hear on college campuses like Stanford, you're getting a lot of pressure to do this or a lot of pressure to do that. Yeah, there are our pressures from students and top down, listen, students are under pressure, administrators are under pressure, faculty under pressure. But Stanford has been very good about allowing people to have their own independent social media channels and talk to the public the way they feel as best.

And I, and I have to say, it's one of the things that makes me really proud to be there. It's an amazing place too. If you, and I'm not going to throw out names here because it's not my place and they should probably just come on the podcast separately. But you've got people at every end of the major debates out there about public health and everything in between on Twitter, fewer on Instagram but on Twitter, voicing their opinion. And honestly, I think it's beautiful that they are allowed to do it.

What the value that he's given back to people in the last, what has been four or five months since he's been in there, is tremendous. I remember people picking on, oh, it's this feature of that feature. We're going to have to buy a verified check or whatever. These things that when you compare that to the ability for people that have honest, open discourse, honest for them because there's no regulator. Yeah. So that to me is incredible and fundamentally important. He's given people their voice back. Yeah. And that includes both sides. That's what's often not stated is that people on both sides are starting to get the axe, mostly on one side. But it's really incredible. And I think we're, I'm hopeful. I mean, I don't, I'm a live and let live type person. I really, as long as people aren't humming other people, I truly, just encourage people to do what feels right to them. It's kind of bananas where we went between, you know, in the last few years. But what's happened in health and public health, I think, is pretty remarkable and encouraging from my standpoint anyway, which is people now realize that medical doctors have a certain type of information that is extremely valuable, and they come in a range of flavors and qualities. same with psychologists, same with scientists, same with public health officials, same with everything from your your masseuse to your chiropractor like there is a range of quality and expertise and orientation and to silence any one of those at the exclusion of the others is not only foolish it's it's it's dangerous and so I think there's no going back there's no going back Now people seek advice on multiple dimensions. A few years ago, if you said supplements, people like, oh, that's expensive urine. Well, that's true if you're talking about vitamins and minerals. But how many people do I know who during the pandemic started taking vitamin D?

Well, I think when we hear the word supplements, it gets confusing for people. I actually am wishing for a better word because when people hear supplements, they think vitamin minerals isn't just expensive urine.

And if you over ingest fats, excuse me, water soluble vitamins, you will excrete some. But then there's a whole category of supplements like food supplements, protein, et cetera. And then there's an entire category of compounds that we call supplements that have nothing to do with proteins, fats, or carbohydrates, vitamins, or minerals. Things that are known to have very potent effects. There's a reason why the National Institutes of Health has a division now simply for these types of studies. Right. Things like Ashwaganda can totally reduce cortisol. Shouldn't be used long term but in the short term this can be very beneficial for people especially late day because late day peaks in cortisol. Not good for us. We know this correlate with depression, anxiety, insomnia. which then has a cascade of negative effects. Things like creatine. Not just for it, we think creatine muscles, and indeed it brings water into the muscles, and make you stronger. Most of the data, clinical data on creatine are to enhance for brain function. It's one, cause a new trope. It's a new tropic. It posts concussion, post surgery, postpartum depression, headache, I mean, fish oils. So there's this whole category of things that, in theory, you could get from food, but the volumes that you would have to eat and the sourcing is just impractical. And that's just the tip of the iceberg. I mean, there's rodeola roséa, which is, you know, reducing cortisol. There's interesting data on that. And then there's the stuff we've talked about before about hormone augmentation. But for the typical person out there nowadays, I think they're thinking about, well, what can I do? What can I eat? How can I take better care of myself? Am I magnesium deficient or not? Probably not, but we'll take some additional magnesium help me sleep. Yes, will it hurt me? No.

Oh, no, no, this is what other people say. Right, but they're wrong. No, this is what, you know, when I was young, I got into this training and supplementation early in people say, Oh, it's just expensive urine. You know, don't spend your money on that. There are certain things like within supplementation. Also, the foundational supplementation is, I call it, like things like athletic greens, right? They're, I guess, they call it AG1 now. Things that are in such combinations of herbs and plant-based compounds, like you can't take them one by one. And then other things like magnesiums for sleep or inocetal and the date on depression or inocetal and insulin sensitivity. You know, the number of people that are out there who are pre-diabetic or type 2 diabetes Of course, they need to exercise and eat right, but things like an acetal can improve insulin. What is an acetal? It's similar to a vitamin, but it works in a pathway that makes cells more insulin sensitive, which is good. So you can use the glucose in it and insulin that you make. So you're not overproducing insulin. Type 2 diabetes is essentially overproduction of insulin because your cells aren't able to use the insulin that surrounds you crank out more of it. Type 1 diabetes lack of insulin from the pancreas. That's why people in shaft inject it, who have type 1 diabetes. So things like an acetal. I mean, and the list just goes on and on. And so to me, I think the view is changing, I hope, that the idea previously was that before the pandemic, frankly, was that supplements are just kind of like, new tropic that or, you know, it's kind of, you don't need it. I'm not saying you need it, but they are a powerful argument. to good sleep, good nutrition, good training, good social connection.

Very beneficial, but I think for you and me, it's a, it's a duh, but I think for a lot of people out there, they seem to think that there's something unique about prescription drugs that makes them better than supplements.

I'm like, for a while? Yeah, D seems to have made it through the shoot. Like where anyone will take it because it doesn't seem scary to them.

I mean, I know many physicians. Here it is.

You don't know what's real. I think that when I step back from what you were saying a few moments ago, you know, I think people need to remember that scientific journals of which I'm on the advisory board of several and have been for a long time and are well-meaning things. Let's keep in mind. They're run by people. And the goal of those journals, ultimately, is to publish papers that are true, but that get people to read them. The more subscriptions, the more they sell. So I have a good friend who is a senior editor at a journal. There's really only three top tier journals, nature cell and science. He said, and I asked him once, I said, what determines whether or not one paper is accepted or not? And he said, well, we get to determine, obviously, the reviewers have to give it thumbs up at some point. we get to determine the direction that the journal wants to go. So during the pandemic, there was enormous incentive for publishing papers in these journals that provided some, either hope or fear or whatever it was exciting at the time because people were buying up these journals like crazy. I mean, they have to pay their staff too. So it's a business like anything else. Unfortunately, there is aside from the federal research budget, which is frankly, over what you have a much greater budget than in other countries for research relative to the total amount available, but it's still very low compared to what we need. But money is what drives research. I mean, it's not going to have the more money you have, the more margin for error you can have in terms of the people in your lab. Like if you only have a million dollar a year operating budget, like it's a business, you can have two or three really good people and someone's not so good, that's bad. If you have a giant budget, You can have 20 people and 10 of them can suck. That's rare to see that. Usually it's a mixture of competent to talented. The occasional bad apple and those bad apples are very, very dangerous. And the bad apples I'm talking about are not the kind of people that necessarily go around creating data out nowhere. These are the people who slice off and make experiments that didn't work kind of disappear. Oh, there was something wrong with that now. That is a serious problem in science, far more than fabrication of data.

Oh, it's incalculable, but I would say that kind of, I've been in laboratories big and small across my career. I've been around them a lot. everyone in every field knows the papers that are like, yeah, nobody believes that.

Um, generally not directly. So the, the PIs, the lab, this is the way it works. The lab heads, genuine, to get to a position where you're running a laboratory at a major university. or any university, frankly, you have to love what you're doing. I mean, you don't make a lot of money as a university professor. There are incentives through things like companies and a lot of professors now of companies and we can talk about that and that's complicated sometimes and not complicated. But the point is that they want heads of labs want to make fundamental discoveries. They want to be true. The three biggest fears for a real scientist are to get something wrong and not, and to get it wrong for the wrong reasons. The wrong reasons would be someone comes to your laboratory and sees an opportunity to please the PI. This is, I think, one of the major sources of error in science. publishing papers as a postdoc is what gets you a job. So I've known over the years postdocs and there's a lot of discussion about this is inside ball science where someone gets there and realizes that the head of this lab has a pet hypothesis that's really exciting to them. Why is it exciting? Because it's exciting. They like the idea, but also it would allow them to renew their funding. Yes, definitely, money is involved. And then that person goes and does experiments and shows the PI, the experiments that work and doesn't show them the experiments that don't work. And then, tells themselves, those experiments didn't work because, you know, the centrifuge was off or the mouse was sick or, you know, gives themselves reasons why it was okay to remove data. That occurs, I think, I'm going to guess here. I don't know, but I'm based on my observation. That's probably about 10 to 15% of the top tier published papers. I think don't last, meaning in the years following, they don't replicate and they go nowhere. And I don't think it's because people made up data, quote unquote, I think it's because they threw out bad data or data that, excuse me, they threw out data that didn't fit their hypothesis and labeled it no good. That is very common. Now people who quote unquote, fudge data make up data. I would say that's two percent but that's the Alzheimer's study okay so the Alzheimer's stuff was legitimately a data fraud issue was really crazy which has really crazy it lasted for so long for people discovered so then you say why could that happen because you explained to people what happened yeah so um basically The theory of Alzheimer's that's still very prominent is that it's the accumulation of these things called plaques and tangles, which you can see under the microscope and they've always been considered a signature that you can see with your eyes, of neurodegeneration that's associated with Alzheimer's dementia. And it's been the way that people have measured whether or not a treatment has worked or not worked is whether or not it could decrease these plaques and tangles in mouse tissue and sometimes in human tissue. Now, we have to be clear that plaques and tangles do accumulate in the brains of people with Alzheimer's and mice that have mutations that make them kind of like good models for Alzheimer's. But early on in the research on Alzheimer's, so dating back well over a decade now, there was basically a data fraud, fudging of data we call it, where someone essentially said that there was a label for a particular plaque or tangle of protein that represented something that it didn't and then what this has cascaded into over many many years is an entire set of theories about which drugs ought to be beneficial for the treatment of Alzheimer's. And I would say now trillions of dollars put into research along those particular lines of inquiry. So what we're basically saying is one mistake can cascade into a series of thousands or tens of thousands of mistakes that can take a field really far a strike. And that's what's happened now. They realized that there was a problem with the early data. Now, the thing that's kind of baffling is how the field continue down this path for so long. without actually considering alternative hypotheses with any seriousness. Why somebody didn't say, hey, let's go back and test the initial premise of all of this. And part of that has to do with if biotech is neither good nor bad nor evil or anything, it's just, but it's a business. And there's a pretty quick runway from a big landmark discovery to a couple of verifications to people founding companies, to big dollars coming in through investments. And then how many times have we been told, blockbuster finding in mice and then when and then people with Alzheimer's say, well, when is there gonna be treatment? 10 years. How long? About 10 years. This 10 years thing has been kicked down the road for 50 years. I mean, I've been in the research game 30 years close to it, you know, and so many things have just been kicked down the road. Now there are kind of maverick folks within science who test very alternative hypotheses. And they are really the heroes of science, in my opinion, because they're saying, that's all finding good or maybe it's all false. I don't know, I'm going to go a different direction and explore. But in the sociology of science and science funding, it is very, very hard to impossible to get funding from the federal government to do truly high risk pioneering science. You might say, like, how could that be? In general, when you get funded by the government, my lab is in funded by the government for many years, you get funded for work that is already completed. You show it to them in a grant. You say, this is what I want to do. You get the money and wow, the paper comes out like the same year. How did that happen? And then you use the money to fund the next thing. Every card carrying laboratory head knows this. Why? Because when you put in a grant that says, this is a really exciting idea. They're not going to fund that. So this is why philanthropy and private money comes into science and is very exciting and enticing to scientists because they can start testing things that the federal government funding bodies are just too conservative to test.

The whole system is there's no way to pull it proof the system against bad actors, meaning people who fudge data or I think the more sinister aspect of my field. are these individuals who come to a laboratory and go, I want to job. Being a postdoc, you're not paid much. Oftentimes they have families, they're under stress. I'm not justifying their actions and people go, how do you get the job at the best places? We get it by publishing papers and really great journals and with your name first. So what does that lead to? It leads to really high ambition people working very, very hard and science is hard, a lot of experiments fail. And some people will just figure out that if they can just give the lab director the figure out their pet hypothesis, like figure out what mommy and daddy like what mommy or daddy like most and give them those results, those people get promoted very quickly. In the long run, they don't do well. Or what you'll find is they often just switch to an entire area of science when they start their lab. They kind of get there. And then years later, or even a year later, you go, whatever happened to that result. Well, if you ask people in the laboratory, postdocs and graduate students, it's sort of, I think probably like any career path. They know the truth. So if you ask them, what do you think of that paper? And they're like, yeah, I don't know. That means it's bullshit.

Well, the problem is they're all colleagues in this audience. Bulls June. It science is weird too because unlike in UFC or something like that, everyone's really nice to each other's faces. They're like, oh yeah, great to see you, great to see you. Then you get the paper, anonymous peer review, and then they're like, that's when people attack each other, kill people's grants, kill people's papers. Science is a, it's not a cut-throat game, but it's a very human game. And now, I also want to highlight because I feel like as an ambassador for my field, I do want to say that there are excellent scientists who care so very much about the truth and who go through every detail of every paper, their family's suffer. Everybody suffers as the consequence of their neurotic tendency, but those people are the heroes of science because they won't let something go to publication unless they know is absolutely water.

And a partner at home who's probably like, hey, when you're going to get out of graduate school and we're going to actually move out of this one bedroom apartment. I want kids or all our friends are like taking vacations into loom and we're like suffering here and or people who think, you know, oh, you get a PhD in that guarantees of win. I mean, all it does is give you the opportunity to keep competing. So when you see people at the high, the best institutions are even somebody at a not one of the top top institutions who's able to keep their lab funded over a long period of time. That says one of two things. It says they're either really good at picking questions and being very consistent or they are very good at hiring people that are extremely careful and hardworking or sometimes both. But listen, the bigger the labs, the higher the probability of a bad apple. And it happens all the time. All the time.

Well, it was truly falsified data and there's a there's a whole other aspect of the sociology of science that I think is not often discussed, which is that there's a huge incentive to big to being promoted by your elders, by your graduate advisor and post-doc advisor, because they are the ones that write the letters that get you promotions, et cetera. And so what tends to happen is people tend to continue to do science that pleases their elders. Now, for myself, I had both the curse and the blessing of my undergraduate advisor, graduate advisor and post-doc, were all incredible people in scientists in different ways, as very, very blessed. But the first one killed himself, He had a bad depression killed himself. Second one, cancer at 50, third one, had a heart attack across the desk from me, first day of work at Stanford. He was my postdoc advisor, eventually died of pancreatic cancer. So the joke in my field is you don't want me to work for you, right? Like it's like a death sentence. Now they're all dead. But the good, you know, is a terrible thing to be orphaned in science, because promotions, things like that. Other people stepped in and helped me, and I'm very grateful to those people. But one of the blessings, the hidden blessings, the silver lining and all this is like, I didn't have to please anybody. And so when it came time to do a podcast or to look at data or review a paper, I was not worried about pleasing anyone. But prior to that, I'll tell you, I've been asked to write letters for people's tenure. You know, can this person have a job for life or not? You, they get 10 to 12 letters. And I've had people say, hey, listen, we're having a really hard time getting letters for this person. And this person really needs tenure and they've got a family and you look at the work and you know, and you want to say, no, and you can't because you don't want that person to review your paper and give an ax your next paper. Now, I've been very lucky because I don't, first of all, I think it's maybe just the way I'm wired. I just don't care about that aspect of human. You know, I'm one of these people, I'm sort of like my bulldog Costello. I was like, I'm going to go along with things until you try and push me. And then like, I just have kind of a resistance thing. It's down to some developmental error or something who knows. But probably healthy. I think it's helped me a lot because what I've told those people asking for letters is, listen, I think they're not getting strong letters because they're not good enough for tenure at this place. But that is unusual. Everyone plays this nice nice game because when you're nice to people, they think you get stuff. And it creates a rather dark underbelly of science that people don't talk about. So in this field of Alzheimer's, What ends up happening, what I think ended up happening was there was such incentive to go with the party line and publish things that were validating of previous papers because let's be honest. When you say nice things about other people in papers, it's easier to get your papers in. And you know, scientists on Twitter is changing things because now people will really pick apart a figure that will really go after them. I think it's great. It's great. And I learned from you early on and from Lex early on, If you're going to be out there as a scientist or on social media at all, you have to ignore a lot of stuff. But if there's something to pay attention to, like Lex and I talk about this, he and I all just reveal a writing an article for one of the nature journals about science and social media. The journals are now starting to pay attention to podcasts. conversation and being able to really rip something apart and having a pretty thick skin about it, that's the nature of good science. And I think that that field of Alzheimer's was all pre-social media and people knew there was bullshit in there and they just went along with it. Whole companies were founded, investor money, where are those companies? Where are those drugs?

Yeah, this is less in my wheelhouse, but you know, the whole it's also fraudulent work with a relationship between dietary cholesterol and serum cholesterol doesn't exist. The relationship between saturated fat and serum cholesterol, however, I think there is a link there. This is more atias territory than mine. But even the markers that he's really highlighted are so key things like APOB. He's a big on your APOB level. critical determinant of your longevity.

Oh, scientists, you know, I guess this is an opportunity to bring up Jeff Epstein. So, you know, people sometimes wonder, you know, like we're scientists, you know, hanging out with him to get, you know, to get with these young women or something. I know scientists. There are some scientists like that. They were spending time with him because he was giving their laboratories money that they didn't have to write grants for. Why was he doing that? Oh, there are very strong opinions. I never met him. I know people who knew him, but he clearly understood social engineering. He understood that rich people have, they can get anything they want. Anything they want. Except the one thing they can't easily control is their reputation. Because that requires other people's perceptions and just being rich doesn't make you necessarily respected. By certain people, yes, by certain people, no. So he understood that very wealthy people feel more important and can derive more sense of self-respect when they're surrounded by brilliant people. And he was very good at bringing truly brilliant people into that mix. People like Murray Gilman, who discovered the quark, right, is a particle physicist. I mean, head of the Santa Fe Institute, Nobel Prize. I mean, he's Gilman used to pick on Richard Feynman. He was one of the few people who could maybe not verbally jost with him, but at a scientific level could pin that guy. So, They were on more or less equal tier, but, you know, Gilman was right up there. So Epstein understood, like, bring around the Gilman. Bring around the top genetic researchers from Harvard. By doing that, he made these rich people feel like they were in the company of interesting, important people. And why would scientists spend time with rich people? I'll be really honest. I do a lot of work for these days. talking about science and trying to generate science philanthropy. That's a big part of my life now trying to generate money to give to studies that are really interesting and valid. We could talk about that if you like. Scientists will show up to dinners that normally they'd rather be in their labs or writing grants or with their families frankly. If there's the possibility of money being given to their laboratory, because then they can hire more people and do more science. Money alone doesn't drive good science, but the more money you have, the bigger margin of error you have. So if Epstein offers offered laboratories, you know, $1 million a year for four years. To a guy of that wealth as trivial to a laboratory, that is four national institutes of health grants per year. And the workload to maintain those four grants is immense. So they'd show up with the possibility of getting money. That's where they were hanging out with a dirt bag like him. And they had blinders on. Either they knew where they didn't know what he was up to. But they had blinders on because they weren't thinking about the implications.

Also, you know, sinister, diabolical, narcissistic and sociopathic, but brilliant social engineering on the part of it. That's the key understood that they felt comfortable in the room because of who else was there. Rich people will show up to a place for who's not there, as we know. They like to have space, right? And scientists generally don't like to hobnob. It's not really their thing. What they like to do is work on their projects. They're a little bit like comedians. They're in the sense that they have a craft they want to be working on. They're only going to do things like go out and get money if they have to get money and they do a lot to get money.

It's probably exciting, although I think that at some level scientists real scientists died in the world scientists would rather just be doing science in the short.

He had the whole thing. He had, I mean, he, he ingratiate himself in this community. He just understood. It was sort of like, I do some work with some professional sports teams, right? And the only people that they look up to are tier one special operators you tell a pro MBA player like oh in the NFL they do this to like whatever you tell them that you know this little increase your your output by 10% like whatever they don't care they want to play video games they do not care they want to handle their girlfriend or their four girlfriends whatever it is You tell them tier one operators who do high-risk high-consequence work and are on deployment schedules that would dissolve you into a puddle of your own tiers because it's a vampire schedule. You don't get to sleep when you want to and you get potentially die. You potentially all die and they're running times are faster. They're recovery times are faster. They're shooting accuracy is far better than you're shooting accuracy and that's where the gun and getting shot at and they go, okay, I'll listen. They look up to tier one operators. That's a fact. And so if you want them to listen, you understand that fact. You look at what tier one operators are doing. That's what professional sports teams are trying to glean that information. Billionaires, they have different interests, obviously. Some race yachts, some what, you know, want to start new projects. But they want to be around really innovative, interesting people. And in academia, there are very small subset of those running big laboratories. And Epstein just got that down to the detail. And then he understood, I think, with politicians. They can, their reputations are everything, and so he gave them a vaulted world where they could behave how they wanted. I mean, in some sense, I mean, his story is one of multiple psychology's not just his.

Oh, I'm sure that at some point he had information on other people and he just used it as, as a, and it doesn't have to be strong hand blackmail, right? He could just say, you know, we've got information and we'll hold it secure.

Well, I mean, in the unraveling of the, all the dark, sorted shit around Weinstein, it was discovered, I think, in New York, like in New York, near that down in alphabet city, police precinct, it turns out that there were, you know, a boatload of files that date back ages. And you know, there were, it's not that cops are corrupt, it's that they're incentivized by certain things too. And their bosses were telling them, you got to do certain things, you got to put away certain files. And, you know, people are trying to make careers. I think that's why that show, it's a little outdated now. from technology standpoint, but the wire was so brilliant is that every aspect of that was a human endeavor, and science is a human endeavor. And we're kind of paying attention to the darker, unfortunate side. They're also, again, I always feel like I got a shine light where it belongs to, which is that a lot of amazing science is happening because of excellent philanthropy of people that are not pedalling. Yes, of course. And those people, you know, but let's be honest, walk on to any university campus. Look at the names on the sides of the buildings. Do you think they're there to honor those people because those were great people? Sometimes they're great people. They're there because those people donated $50 to $100 million. Right. I mean, And this has been known in law schools and business schools for a long time because you'd see it on this, that was kind of more accepted there because it's business and law.

But if you walk on any campus, I don't care if it's UT Austin or Stanford or it's Harvard, the names on those, I'd say buildings. Sometimes it's the Kennedy building, sometimes it's the Rockefeller building. More often than not, these are names of people you don't recognize anymore. And names of people don't even live in the United States. They gave $100 million for a building that trains medical students. Universities are a business too. 100% and it doesn't mean that they're trying to corrupt anybody but they have to survive yet got to pay the janitor yeah pay the cops you get on the campus I mean so it is a business and I think you that's the human side actually to your credit I learned from you we I think you made your men out remember but a few years ago we were talking about everything was going on in the public health thing And you're like the reason I'm curious about this and I don't trust this. These are your words more or less was because I know about people and that's at the end of the day. It's all about people in their cycle.

Yeah, he's parked at home prison two blocks from Stanford campus.

You go visit him. Now, you need a haircut, that guy. Fuzzing? Well, have you seen? I don't know. I just can't remember how far it looks like it hasn't been really. I think what happened there is so... But no, there was a lot of celebrity endorsements as my partner.

and popular. How should I say this? If I had a super high powered psychiatric microscope, I'd go back and find out how everyone that you would ever work with or that you're getting information from, you would find out what their core developmental dissatisfaction is, right? Because I think they're in UC. It's like I'm sure everyone has this. I'm sure Bankman Fried felt like this big. is the consequence of something in his psychology or experience. And as a consequence, justified doing this horrible thing.

This overuse of emphetamines is, I mean, all we know is that we do know that they narrow your focus, they very outward and goal-directed. And that's what cocaine and emphetamines do. They make you very of what's in the future and what you can go get as opposed to being in bliss in yourself. Perhaps an interesting intersection of this idea of neurochemistry and psychology and universities and sciences recently I was asked to give a talk at Stanford to a bunch of potential donors and on the stage next to me was Michael Paulan. who I have tremendous respect for. Yeah, even though he's over at Berkeley like we tolerate him. Now I'm kidding, Michael, that's how Stanford Berkeley joke has. He is wonderful and amazing and such a pioneer of this whole psychedelic space. And you might say, well, there were others. There's Terrence McKenna and there's the classic people, but I started off that evening by saying, we need to take a step back. and just acknowledge what's happening here, which is, saying the word psychedelics on a podcast for me, five, six years ago, could have cost me my job. Easily, saying, yeah, taking MDMA as part of a clinical trial, three times it was tremendously beneficial. I think psilocybin can aid with depression. That would have cost me my job done, fired. I would have walked out of here, done. Now, just this last month, the cover of UCSF Magazine, end Stanford Magazine. Allison Wonderland, psychedelics. Deep feature about MDMA, ketamine, psilocybin, DMT. What's happened now is this is what used to cost university professors their jobs in the 60s and 70s and did cost them their jobs at places like Harvard in particular. Is now this objective research studies, clinical studies at Stanford and elsewhere, right UCSF Johns Hopkins. This is now really big science and pharma's moving in very quickly. What they're trying to do is create non-psychedelic psychedelics, figure out what sorts of chemistry changes that doesn't give you hallucinations and create new antidepressants. That's what they want to do with psilocybin. Because doing two journeys on a drug and then you're done, that's not good business. And what I love about what Michael Paul and his saying is that he's the one that's really, he's really hitting the drum on this one. He's saying, these things work, the clinical data are showing that 65% plus Success rate for what would otherwise be intractable, untreatable suicidal depression, incredible. And now the universities are behind it. But they're behind it because laboratories are getting funded to do it. Laboratories are getting funded to do it because there are grants. Why are there now grants from the federal government? Well, philanthropists came in early and provided money. And now, people are starting to see that there are big, big potential outcomes at the level of pharma. Now, the classic psychedelics community isn't going to like that. They're like, no, this is plant medicine. It's got 100,000 year history or more. Indigenous people, et cetera. I could aim in and farm. I don't care about that. I'm one of these people. I'm not saying they're bad and they're good. I'm saying that it's humans again. So why are university suddenly okay with the idea of discussions about psychedelics in front of their top tier donors? Would be able to literally supply the blood to the university? Well, because top tier donors are now really interested in psychedelics. So what drives every aspect of it from the student who's pipetting in the lab to the highest tier of administration and university all the way up to directors of NIH, it's all interconnected at the level of incentives.

and he went out and did them, or at least some of them, as a kind of late, the typical person, not, and then come out with wearing a robe, or sit in the lotus position.

Yeah, absolutely. And look, you deserve tremendous credit here. I know you're not one to, you know, take praise from your guests. But I'm going to just say that you've been talking about this for a long time about the tremendous value of these things, not just for gaining new perspective, because I think in the 60s and 70s, it was, remember it was tune in and drop out, right? Now we're talking about the use of psychedelic medicine to be able to lean into life in a healthy way. Yeah. That's the major difference. And you've really pioneered the discussion around that Michael Paul and, and there are others too, I realize, but it You know, at a time when it was considered really wacky and out there. Now it's becoming, it's headed towards mainstream medicine. And I think it's fundamentally important. I mean, I think Robin Cardard Harris's laboratory at UCSF has a paper out just today on the use of DMT for treatment of psychiatric illness. His laboratory has been looking at high dose psilocybin, two sessions, guided sessions. treatment of anorexia, ADHD, and depression with very high success. Nolan Williams lab at my university at Stanford. He's a triple board certified psychiatrist, neurologist, running the studies with veteran solutions. The group down in Mexico of tier one operators and other people who come back who are just messed up. They're light. They're either heading towards suicidal depression or they're just not feeling quite right. and using Abogaine DMT in tandem and getting tremendously positive results. So he's doing the neuroimaging on them. So times are really changing and you and Michael and I was really deserved our token of gratitude. I've completely revamped my stance on psychedelics. I'm still yet to do a high dose psilocybin journey. I haven't done that yet.

I don't want to lose my job and I'll be honest. So I was kind of a wild youth, barely finished high school and I did recreationally I took LSD and psilocybin in high school hung around the wild bunch and we were just parting with it. I didn't know what I was doing. So my view of it was it was associated with the time in my life where I was pretty wayward. Right. Then I never touched it. I drank a little bit, smoked a little bit. We had here and there, but never really liked weed very much. It just wasn't my thing. And then when I did this three sessions with MDMA, that completely transformed my understanding of how these drugs work. I also realized, and you might, you probably already know this, but I was very curious about MDMA and the reputation that puts holes in the brain, kill serotonin neurons. The study on MDMA that showed neurotoxicity is, was retracted from science. They actually inadvertently injected methamphetamine into those monkeys. But you never hear about that.

You don't hear about that retraction in here. So they now have data in humans asking, what are the safety profiles on MDMA for people that take it? Everyone's in a while to take hundreds of doses of MDMA. And there's one population of people that you can do this on that makes it a really good experiment. Those people can't do any other drugs because then it becomes confounded by, are they doing math, are they doing coke, or they're still alive and what else? It's not a good experiment. You want single variable manipulation. There's only one group that you can do that on, and that's who they did it on. And that's Mormons. So the church of Latter-day Saints has one drug that's not on the band substance list, and that's MDMA.

It was drink coffee. It makes it even better experiment. And so I'm not saying that Mormons are all taking M.D.M.A. But there is a substantial number of L.D.S., I think they call themselves no Mormons, as most people know them, who have taken tons of M.D.M.A. And they've done brain imaging and psychiatric profiles on them. Those data say that as long as it's not contaminated with something else, which is a serious issue, the neurootoxicity is niltonon. amazing, right? At the appropriate dosage is it, et cetera. That's amazing.

is super common. Well, the recent data I saw was that you go out and buy M.D.M.A. from a quote unquote trusted source and six out of ten are going to have potentially lethal levels of fentanyl in them.

And everyone nowadays knows to say, oh, this is from maps, you know, because it's like saying, right, you know, it's clean, right? Yeah. So in any way, I've completely changed my stance on psychedelics. I think they have tremendous power if done responsibly. I think that they hold the greatest promise for drug-based psychiatric treatments. And I think we're we're looking at a time in which it's it's absolutely clear that that these things should be available to people. Robin will tell you the worst part about running his laboratory is someone will come in with intractable suicidal depression. They'll do two psilocybin treatments and they're better and then two years later they'll come back and they'll say how can I do another one because it made me feel so much better and say sorry they're still illegal and he can't provide them. He'd lose his job. So right now the legalization effort is really important and I intend to get more vocal about this.

Amazing. Yeah. Yeah, this is really an opportunity to say that about that positive aspect of philanthropy. One thing that I know about very wealthy people is they almost always have at least one family member who's really screwed up, really screwed up, mentally, especially. I'm just wealthy people. More people too, but it's like, oh, yes, be it.

I have a family member that's fucked. Right. So what's happened is a lot of the money that's going into psychedelic research that's coming from philanthropy is coming from these very, they feel desperate. very wealthy people, and they're going to universities and saying, what can you do for my kid? And the university is saying, well, we've got trans-cranial magnetic stimulation in that works on some people but not others. And they're saying, great, what else do you have? And they're saying, well, we have talk therapy and they're saying, well, that's important too, but what else do you have? And they're saying, well, there's these interesting compounds that seem to relieve depression and they're like, well, why isn't that available? Well, it's still illegal, and we don't have money to fund it because the federal government's been very reluctant to get involved in it. I mean, it's an odd thing that we have, you know, we have bodies within the government that are designed to put people in prison for drugs. And then we also have bodies of the same government that funds from the top down that study drugs. But keep in mind that the NIH up until recently was only studying drugs of abuse. Remember it's NIDA, right? It's about drugs of abuse, addiction and abuse. So they're studying cocaine and vitamin for their addictive properties. studying psychedelics is becomes a little bit of a tricky thing. Where are you going to fund that? Is it because if anything, they're anti-addictive according to the data, right? And here I should be careful and say that like the I begin studies, you know, there is a heart risk. They do have cardity. They usually have someone measuring for I begin.

No, but I'd not that I know, but they're always monitoring. blood pressure and heart rates. For like veteran solutions, they have physicians there and they're very careful. Great organization.

I mean, how can you argue with the data? I mean, when you hear that, I mean, opioid addiction is one of the hardest things for people to kick. People die when they die trying to go cold turkey. I mean, it's unbelievable. Yeah, I think I began, was described to me by a friend who was a former seal team operator because he went down to veteran solutions and he said, it was eyes open, no hallucinations. Every time he would close his eyes, he would get a high definition, movie quality view of an experience from his life. and he had agency, he could move himself differently within that experience. And then it would move like a cube and he'd get another experience. And then he was in that experience, 22 hours. And then down there they follow that up with DMT, one or two. And he described DMT as being strapped to the shockwave of an atom bomb. This is somebody who's obviously been through some intense experiences anyway. And all of that might just sound really crazy and extreme, but keep in mind those same people are coming back to Stanford. and no one is scanning their brains before and after, and seeing incredible changes in the positive direction. I think most people, for most people, the psilocybin macrodos, two macrodos, this seems to be the depression treatment. So this is 25 milligrams of psilocybin. I think it translates to about 2.5 to 5 grams of mushrooms, is that about right? That's what Robin tells me.

The Herodos. And what's interesting is the microdosing, because now there's a comparison of daily 1 milligram, aka microdosing, versus the 2 Herodos. The microdosing has not shown impressive results for treating depression. And I think people should know that. I think they're, I'm not saying micro dosing is bad, but in terms of treatment and depression, it is not proved to in the clinical studies.

Can I ask you a question about that and sort of earlier in an earlier podcast, you brought up that when things got a little hectic in life that you were doing mushrooms. Yeah. Those were those mushroom doses higher dose mushrooms.

Yeah. Yeah. People in my field have been encouraging me to do the macredo-silocybin. It's in the, it's in the books. I really want to do it. Robin Carter Harris again describes it as one of the more quote unquote honest psychedelics like you can't really decide what's going to come up you know a key thing he mentioned is that people need this is you may find interesting I'd love to know if you believe this for your own experience as well He said there are a couple variables to the successful treatments of depression with high dose psilocybin. One of them is that people stay in the eye mask that if they spend too much time in the room with the eye mask off, they don't do enough of the introspective.

I did an episode on water. The water people are crazy. You think of all the topics that you could cover. You think, oh, you know, water is very benign, right? The prescriptive that comes out of the data, if you want to keep your cognitive and physical function best, it's an average, not every hour, an average of eight ounces for every hour. up to 10 hours after your wake. So that's 80 ounces during the daytime. And then yeah, it's probably good. And then less at night. But yeah, the water people because what happens is people go, oh, you know, pH water doesn't change your body's pH true, but there are some advantages to pH water like it has minerals. And then people go, no, it's all about deuterium depleted water near the ocean. There's more deuterium in water. It's not from ocean water and then people are like really into determy, dupli water for cancer. This is all these niche communities in water. Reverse osmosis water, which has no magnesium or calcium, then it's like people are really into that. People say that's terrible. And every free hydrogen water, structured water, and it's bananas. And so the key thing is there's the galpine equation, which is your body weight and pounds divided by 30 equals the number of ounces of water to drink for every 15 minutes you train. like Galpons figured out that can improve performance. Like there's all this like water gets super geeky and I love it. One thing before I forget the Robin Carter at Harris, he said, I'mask. And he said the power, I was so surprised. This is like a, like a hardcore researcher tells me the most important variables are the dose. So satin setting the, obviously, but the, the I mask and music. He's like, when people don't have music, somehow the music and that the music during a, a sell aside in journey. have a kind of a build, and then have a kind of more emotional soft tone in the kind of taper of the final hours or two. He said that he thinks that that's a very important component to guiding the introspection. And for me, as a biomedical researcher at a School of Medicine, and he's at the School of Medicine, to hear this conversation, like, I don't know whether that's a laugh or cry, because These are the kinds of conversations that A would cause you to lose your job for legal reasons in 10 years ago, or people would just say they've lost their minds. And this is the hottest topic. in biomedical research right now in terms of psychiatry. The hottest topic.

Just what's happening in a journey? How to do a journey properly? How much dosing? And so, you know, take your life five ten years ago or even before. Things that you've been talking about with people for a long time. And now it's being talked about by these live in the biomedical research community.

Well, this is my strongest stance in why I love your podcast, why I pay attention to podcast in addition to scientific journals is that If you look at, let's say, let's look at the like this really niche crazy field of body building. Like how many people want to look like Darine? Yeah, it's how many people want to look our own Schwarzenegger female body. Very few, very, very few. And yet, that niche community understood hormone augmentation at the extremes. And now we understand hormone augmentation at at a healthy dosages in men and women has tremendous longevity, health span, affects mental and physical in terms of. And so there's value in these early niche communities, you know, psychedelics or bodybuilding or martial arts or in yo get communities or in breath work. It's just that we see these extremes of like a whim-ha for a, you know, or somebody who's doing deliberate heat exposure and cold exposure and the question for a really good scientist should be, is there value there? What can we extract that the general population could benefit from at a more subtle level, like weight training? Everyone you say, you only have a lift weights if you're going to the military playing football, your bodybuilder. how about extending neural function in the brain by stimulating the neuromuscular system, right, in people in their 70s. I mean, that's being done now. So I think that an open-mindedness is really what's needed in biomedical research and public health. And I think, you know, I can't speak for you, obviously, but I get very frustrated, as I think you do and other people do, and people will immediately shut the door, like, oh, that's just like crazy, bro science, biohacking. Actually, there's a different name for it. It's called a head of its time. science. It's called paying attention to things that clearly have big effects and that at lower dosages or done in a particular way might actually have tremendously positive effects. And the best example I can point to would be physical training, resistance training, but also You know, if you jog in the 1950s, I'll never forget that scene in Mad Men where the woman's out for a jog and all the housewives are like, oh, what is she doing? No one ran outside of pee. Well, jogging craze. Now it's like accepted to be a runner. It's encouraged to be a runner. Yeah. Huge effects psychedelics. And so I think I'm old enough now in 47 to just see like, ah, the stuff that everyone thought was crazy supplements. You don't need that. This is the stuff that can make life better. And so I don't encourage people to die but I encourage many of them to retire. I'm like just a lot of voices just need to retire. Just go away and let the next generation come in and they'll eventually replace me too. I haven't placed us all, and they'll get replaced, but let these new ideas at least be considered and talked about. That to me is what's exciting about podcasting and social media.

bipolar stress is a frontier, very clearly. You ramp up the dopamine and or serotonin system, you amplify psychosis. In fact, I was studying cannabis for a while for an episode, clear health benefits of cannabis, and yet we also know that if young males, in particular, study out of Canada, who have a predisposition to psychosis. Do very high THC cannabis. They are at a much greater risk. The estimate is up to four times greater risk for a major and possibly permanent psychotic episode. Now, I am not saying that weed is bad. I'm saying that there are individuals for which it is not going to be a good idea. And there are other individuals for which it might be a very good idea.

Yeah, it's like a dentist with bad teeth.

It's just like, but you know, cosmetic surgeons and dentist with bad teeth. You don't see them. You don't see a wrinkle dock with like a prune face because it's right there. That's the product that people are paying for.

Well, and those their reputations, I'm, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've, I've It's interesting that, you know, you're talking about people won't do the thing. Right now, there's a lot of excitement about semi-glutide. Yeah. Okay, so this is a GLP-1, glucagon-like peptide. The story of that, since you like animals in the natural world, I guide down in South America. was looking at helomonsters, those really scary things. And he realized they don't have to eat very often. I wonder if they're hungry all the time or not. Turns out, takes their blood, isolates a peptide, which turns out to be GLP1. Put it into other animals and realize it suppresses appetite. Amazing, right? Like this is why I love about biology. Some dude who studies helomonsters, turns out humans make GLP1. GLP one is stimulated by things like yerbomata, T, certain other compounds plant compounds stimulated its release. But what does it do in the hypothalamus? It suppresses hunger, by way of there's a particular brain, an arquute pathway blah blah blah, but it also affects the mechanocensors of the gut, so that you feel like your gut's a full. It's almost like getting a pharmacologic stable stomach, right? So when people take a drug that mimics GLP one, Their brain is like, well, I'm not as hungry, and their stomach feels full, even though it's empty. And so people lose weight. It has other effects too, but it's working on body and brain. This becomes obviously the blockbuster drug of our times. This is reminiscent of the fenfen. Yeah, I remember. A couple of people died of fenfen, right? I do a gal who developed a heart problem. It's a valve thinning in some issues. They're gone. Done. It was an off-de-market. I remember those in Coach fenfen gone.

It was an infetamine. Yeah. And it probably felt pretty good to be on too, because things like Adderall, Riddling, all that, people like that, because it's him, it's him fed me. If I show you the structure of M fed me, I show you the structure of Adderall, Riddling, you don't have to be a chemist, you just go. Those look very similar. So JLP1 is changing everything. Type 2 diabetes, people are taking it, obesity, people are taking it. People crave food less. And somehow, and I don't know how to explain these data, a T.O. would know far more about this than I would, is somehow it's also allowing people to lose weight even though they're eating similar amounts. And so it's probably impacting metabolic pathways. It's not without its side effects, but getting, I think it's called a Zempic is the brand name. That's going to be like Adderall soon. It's going to be hard to find. Really? Soon it will be because it is so, I mean, everybody's trying to get this stuff. But one that's ramp up production of it? If they can, if they can keep up, but right now there's an overall shortage. There's an arrow. And there's a huge because of all the non-prescript people get the prescriptions and sell it. A big, big money on college campuses, big money in finance.

It's now being... It's being cut in reason. Yeah, so, but I think the semi-glutide thing, you know, I'm more of the, I always feel like behaviors first. nutrition supplementation and then prescription.

I have to imagine it would. I'm not aware of any trials. I mean, you know, doing human research is so tedious and expensive. You'd have to have people. You could do it. You could, you know, and, but you know, if you had 50 subjects in each group doing weight training and are they doing sets to near how hard it gets. It's hard.

It's an awesome study. You'd want to see that. You'd want to encourage people to weight train to offset the muscle loss and fat loss. One thing that's interesting is that when you trigger the hypothalamus with GLP1, The hypothalamus sends out signals to multiple tissues, if not all the tissues of the body. So it doesn't just send signals to the adipose tissue, saying, oh, you know, lose body fat. It's going to also signal to the musculature and laying an eye getting to some really deep dives on this kind of thing. You know, when years ago there's a study what's called need to non-exercise induced thermogenesis, if you look at people that move around a lot, bounce their knee, kind of moving around those people like very staccata with their movements, they can burn up to. up to 1,800 calories, more per day than a person that sits very still. Wow. This is beautiful work done by Rothwell and Stock if people want to look up those papers. Amazing. Papers.

Just burning calories. This is micro-movements, and so then, you know, for instance, in the treatment of anorexia, the most deadly, by the way, of the psychiatric illnesses. Most many anorexics die, and they have low muscle mass. This is where I'm going with this, because it relates to the semi-glutite thing. They are often in their treatment forbidden from doing these kinds of fidgeting things, because they're constantly trying to lose weight all the time. Anorexics are very aware of the caloric content of food. It's almost, they have a near precision calculator in their head of the caloric content in foods. They can look at a hamburger and they can tell you how many fats, carbohydrates, and proteins are in there. They're a computer, and it's to horrible, and they're also always trying to lose weight, always trying to burn calories. And so this meat, non-exercise, induced thermogenesis, thermogenesis, excuse me, is very robust. In people that move around even, there's a study out of you, see a Texas Houston, this is wild. The solely asmuscle, the wider muscle of the calf for those that, you know, don't know that. There's a guy down there who's running a human physiology laboratory and he's like, you know, insulin and insensitivity is a real problem, type two diabetes. The solely asmuscle's 1% of our total musculature. And he asks a really great question. He's like, what if when people are sitting during the day, because everyone's sitting, they just bounced one, you know, what he called a solius push-up, which is kind of, it's a one-legged seated calf raise, right? With no way. And they're just bouncing their heel like this, like I used to do in class. What turns out the solius is an unusual muscle, because it's very small percentage of our total musculature, but its energy utilization is enormously high. What does he see? Well, when people just bounce their heel, their insulin sensitivity improves, their resting glucose improves, and all they're doing is moving a bit more, but they are moving their solace. What's happening? It's likely that they're mimicking walking enough during the day that they're getting these positive effects. Now, I'm not encouraging people to just do this. And when I put some of this out on social media, you know, that the The Jim Jockeys, you know, who I'm friends with, right? They sort of, they were like, do, come on, don't get people thinking this is exercise. I'm not saying that people should just do this. But these micro movements that we do add up a lot during the day. So there's nothing wrong with facts. No, there's nothing wrong with that.

I'm never a, I try and avoid the words only, you know, as much as I can in life, unless it's appropriate. So you asked about loss of musculature. When we are losing weight, or when we have high levels of GLP1, signals are actually sent to the musculature to become catabolic. Like the body wants to conserve its most precious resource, which is muscle and fat. And so GLP1, very likely, based on the output of the hypothalamus, the animal studies tells that it's signaling to the most metabolically expensive tissue of the body, to conserve itself, or to catabolize itself. So, you know, fat is one of the harder reserves to lose for that reason, but losing muscles bad, and I guess the short and sweet of this is anyone trying to lose weight should be doing resistance exercise, especially if they're in a caloric deficit.

And your body temperature, core body temperature goes down because you're less thermogenically active. Jamie, I don't think I've ever asked you.

You know, there's so many confusions in exercise science and weight loss that I've learned about recently from Lane that just make me like, I'm baffled. So for instance, you hear that if you eat fewer carbohydrates, you burn more fat, right? Okay. So it seems like a simple statement. So people go, yeah, I'm going to have a low carb diet. I'll burn more fat. But when you say fat, what they're talking about is not necessarily body fat. Like when people mistake body fat from dietary fat, this is how, this is how like kindergarten or nursery school or illiterate we are about our own health because people, so it is true that if you lame this benedicame on this, if you reduce your carbohydrate intake, yes, you burn a greater percentage of your calories from fat. But if you're eating a lot of fat, you're going to burn a greater percentage of it from those fat calories that you're eating. It doesn't necessarily mean you're losing fat stores. All that matters in the end is that calories in calories out balance.

Well, part of that is the blood sugar response. Some people will say, why do I crave a big dessert or dessert? Something sweet after a big meal. I should make no sense, right? Well, that's a blood sugar increase. But the other reason is, your gut has neurons in it. Those neurons signal to the dopamine centers in your brain. And those neurons are looking for basically three things. They want amino acids. We are basically amino acid foraging machines. Fatty acids, because fats are good for us too. That's my opinion, not in excess, but they're good for us, and sugar. And when you get enough steak, you're getting enough amino acids and fatty acids. And that signal is sent to your brain and a pathway shuts down that says, I need more. The moment you throw in a cookie after that steak, all of a sudden your appetite goes, and it's not blood sugar. or at least not blood sugar alone. It's those neurons in your gut going, oh, they're sugar coming into my system. Get more of that because it's a evolutionary, conserve system designed to get you more resources. So this is why if you look at your gut brain access, yes, there's a microbiome and that's important too. But if you think about it as it's sensing things independent of taste, it's actually looking for specific nutrients. Then I think if people forage most for high quality protein, and high quality fats, it's kind of obvious that that's the best way to build the basis of your diet. And then carbohydrates on a kind of as needed basis, right? If you're doing a lot of weight training, depleting glycogen, et cetera. So that's why I think there's a place for low or zero carbohydrate diets. I tried carnivore with the fruit and honey and all that, and I just could gorge myself and gorge myself. I didn't do well on that. If I've ever just done meat, I actually feel pretty good. I confess. But I am an animal.

So I've done just me and I felt pretty good. It's a great. I mean, you feel lighter. You definitely lose weight. You're holding less water. I found it hard to train really hard with the weights.

Yeah. And so I asked Paul Saladino. I said, I want to bring in some of my rice and oatmeal here because I'm suffering in the gym and that's my I love working out. And he said, well, do fruit and honey in addition to that. So I added in fruit, non-pasturized cheese and honey of the way they do that. And sorry Paul, for me, all it did was just send my appetite through the roof. I was just like gorging myself with cheese and fruit and meat. All it didn't feel well. And I still couldn't train well. So for me, what works best is mostly quality proteins and quality fats. And I get some I eat a bit of butter and saturated fat, but also carbohydrates.

Yeah, you and I eat pretty similar. I do eat rice oatmeal typically after I train and in the evening I like some carbohydrates for my meal because it helps me sleep.

Oh, Shayna's one when they're foul eights.

Yeah, I think the nutrition, you know, it's clear. Again, I'm citing him a lot because frankly he's like an encyclopedia for this stuff and he can call up meta and I'll see like nobody's business. You know, lanes made it very clear by pointing out the data that carbohydrates aren't going to disrupt your ability of burn fat, right? It's about keeping calories in your calories.

Well, I have one idea that I'm hoping someone will test, which is when you're on a low carbohydrate diet, or you're doing intermittent fasting. One thing that's very clear is that you're adrenaline and nor adrenaline. App and effort levels are higher. And one of the things that you see is that people are more alert, and when they're more alert, they move more. And that brings us back to meat. This non-exercising due summer chances. As you said, you eat a big bowl of pasta and it tends to make you feel kind of sedentary. Whereas when you just eat meat, you can go go go. I ran into Jordan Peterson, not that long ago. And he's really big. He does three stakes a day. And not just for his age, he looks very fit. And he feels strong. I don't know what he's doing in the realm of training.

So I don't think he has to replenish glycogen the same way many people do. But I think for people who are doing mostly cardiovascular exercise, some resistance training, I think he does some. the carnivore thing may work very well. But I think that also just being a mobile moving person. And you know, this thing about meat was discovered because they noted that people that were very thin tend to move a lot. It was a reverse core, it was kind of correlation in both directions. Whereas people who are larger tend to be pretty sedentary and they move slower.

He looks, he looks super fair. Great. I know a number of police officers and firefighters are doing that now because a lot of their job especially police officers is sedentary and then it's go-go-go. They seem to like that. There's a study on intermittent fasting that was done by Sachin Pandas lab out of the salt on firefighters because their schedules are crazy. And being a night owl and then swing shifts is just terrible wreaks havoc on your metabolic system. I mean, it's just one of the quickest ways to make yourself ill, but we need shift workers, right? Thank you shift workers. So the intermittent fasting and these more, let's call them elimination diets, where it's mainly carnivore, really help them, those communities stay fitter and more active. There's a guy on Instagram, I don't know his name, but I love his police posts, he shows us amazing. And he sometimes puts up this post, I love these ones, I do see how intense that job is, and like, wow. And then, but he'll post, like, supplements, and it's a stake. You know, he's just all about protein, training, and the job, you know, in other aspects of life, he keeps quiet. for good reason, of course. But it's clear that for people that need to be active or just or who are sitting at ton, that the carnivore diet might be a great thing. And now I'm not talking about the carnivore fruit meat, honey thing, genealogy's Paul, I'm not saying that's bad. But these are people who mainly just doing meat. And they just feel like their appetite is more regular. And cops use kind of see it's a binary distribution. They're either really fit or they're really unfit. And listen, it's got to be an incredibly hard job. Firefighters. the fitness part, it seems a little bit more aligned to like working out at the station and things like that. In any case, they have a lot more downtime.

Yeah. Yeah, I think that we were talking a thing last time we spoke about supplementation as it relates to metabolic pathways. And one thing I've been tracking pretty closely is this whole, you know, the end of end thing has not taken a touch.

So, NAD is critical to energy production in all cells, vital, levels of NAD tend to go down as we age. It's an absolute requirement for cell or health in life. You need it. Some years ago, as Davidson Clare came on this podcast and discussed that his laboratories, tenure professor, genetics, Harvard Medical School, and other laboratories that are starting to explore, stimulate the NAD pathway as a tool for extending life span in mice and that there are already some data from yeast. There are now some clinical trials in humans. You can't just take an AD. or you can, but it doesn't get into cells for easily, here I'm painting with a prod brush. But there are basically two ways that you can tickle this pathway, increase an AD. One is to take NMN, right? Some people will try different B vitamins, but NMN, which the idea is that it gets into cells and is converted into an AD. Some people are more proponents of taking NR. Okay, so which, and the end product is thought to be the same. However, there's a lot of controversy about whether an AD or an R are better. NR is that what was initially sold under the brand name, Alicia, with an unbelievable cast of scientific advisors, Nobel Prize winners is a very East Coast oriented thing, but a colleague of mine right downstairs from the Stanford School of Medicine was a Nobel Prize for studying this for discovering the structure of RNA, Roger Cornberg, his daddy discovered RNA, Arthur Cornberg, there was literally an ad of him holding a true nitrogen bottle like this, you know, and it's like, okay, I'll start paying attention to this. NR and NMN are taken in oral form in capsules. Some people are giving NAD infusions out there. This is a more expensive boutique thing. But after David started talking about NMN, a lot of people, including myself started experimenting with it. Now, just to take a step back, I note a lot of people out there Like, if there isn't a double blind placebo-controlled trial, you know, random trial, then why would you ever take something? And then there are a lot of people, like David or me or a lot of people out there who think, well, if there are some malsteader or something safe, why wouldn't I try? Right? Because when it comes to longevity, nobody wants to be in the control group. Right? Right? Right? You know, so this is a highly contentious field. But then what's happened is,

Okay, that's, there are people who will argue NR.

I was taking both for a while. I felt like I had more energy. Now, it's subjective, it's an NN1 thing, but I still take NMN sublinguoli. I take a pretty high dose. So the recommendation was anywhere from 500 milligrams to about a gram of the house.

So, should I say how it was banned and how I'm still getting it? I was buying it. You could buy it from Renew by Science? And now it's banned? Yeah, I have no relationship to Renew by Science.

Yeah. So what happened was this last year, something was sent to the FDA. There's a company called Metro International Biotech, sometimes just referred to as Metro Biotech. This is a company that has a trial. They're studying something similar to NMN, it's a slight variation on NMN. It's an experimental drug, and the way the FDA works is if something has been, is being explored as an experimental potential prescription drug or pharmaceutical compound, it cannot be sold as a supplement. So it's a question of what went in first. Now this was, this happened a few years ago for something called NAC, and they see the system. And NAC is still available despite it initially getting banned. I'll tell you how it was rescued from that. So what it turns out that Metro International Biotech is a company that has a pretty impressive advisory board leeway sigh from MIT, who I know, Alzheimer's research or some other folks. Davidson Clare is part of the company. It's either his company or he's certainly on the head of the advisory board or on the advisory board. That's what the website says. So there are a lot of people that are a bit inflamed, if you will, because this thing was popularized through the discussion of MNM, and it's potential virtues. And then now the FDA sent out a ruling early this year that supplement companies cannot sell it. Many supplement companies responded to that and said, OK, we won't sell it. Other companies, such as Renew by Science, we'll see what happens after this podcast, have continued to sell it. If you go on there this morning, you could buy an amendment.

Yeah, I have a boat load. I'll give you some too. And it's clean. Yeah, so the bags of it are the best way to go because you can buy it in pre-high volume in the bags or canisters. And I personally take because I'll tell you the results that I experienced which I really liked. I take about two grams per morning under my tongue. um, definite increase in subjective feeling of increase in energy.

Yeah, and that's because a Tia who again Peter forgive me if I'm speaking here, but a Tia does was like, there's no way that's going to get into your cells, taking it, taking his capsules. And I said, what about sublingualies? Like, I just don't see how it could happen. And um, but it's get, it's been proven that it gets in through IV. Right, it gets in through IV and they're also electraphritic patches. Some NAD patches. I managed to stock up on those. I can send you some of those. I have a huge patch of those. So this is a patch you put on at slow release of NAD. Yeah, it's got two electrodes and you just put it. Yeah, it's pretty. It's good stuff. That's robot shit. So Alex Friedman, you know, who takes no supplements. He lives on me athletic greens element and mint tea, you know.

Yeah, so people are upset because they feel like they were turned on to this stuff and then it's now. So this could soon be a prescription drug. Now, just keep in mind that the risk of error trowel thing was similar in the sense that There was a variation on risk veritrol that was patented and sold to a company. And that sort of didn't pan out or is still a work in progress. And you can still buy risk veritrol. That's not a problem because it was different enough. So the FDA decided to let and knack stay on the market because many many people wrote letters to the FDA saying this is ridiculous this is a value and it was out as a supplement you can't do this a benefits of knack knack has again in these metabolic pathways for metabolic health this isn't my area of expertise so I don't want to talk out of turn here and I don't know the specific details of why people are taking I don't take that So part of the reason I think it's healthy to have this conversation is to understand how this stuff happens. And a man could soon be a prescription drug that you can only get with a prescription. And then I think Metro International Biotech will likely hold the patent. If people are interested in certain compounds remaining on market, they should definitely write to the FDA. The FDA, as much as that's a mysterious big stone block kind of company, very opaque to us, I think they listen when things happen in large volume. And so I'm certainly going to write letters. And I think that keeping an amendment on the market as a supplement would be wonderful for many people that want to take it. Now, the folks who are involved with NR companies are delighted because for them, this is, again, I'm not going to get into the debate of what's better NR and MN because I just don't have the expertise to parse that. There are other people that are better suited to do that. But the people that work on NR are thinking like, this is great. Like, let this all end up in thing pan out because it's a market competition.

I have to imagine it is. I didn't refrigerate my true nitrogen. And I liked true nitrogen. I experienced the same effects. Again, I have no relationship to that company that I'm a podcast sponsor. They don't pay me a dime. The problem is it's very expensive to take the kind of dosages that I'm taking.

I did that. I just didn't experience much of a subjective effect at low.

I was getting up to a gram and a half.

I was up to like seven or eight pills. I think we don't quite recall, but I will say with NMN a couple of things happen. First of all, energy, my recovery from workouts much better. I had to take it early day because it was giving me a lot of energy. And then I'm not into my nails and hair frankly. I don't know one of those when my hair start, which is starting to go, I'm just gonna let go. But I did notice like my hair and nails are growing at a ridiculous rate. And then I came off it just as a control experiment slowed down again. So it was really interesting. I think there's something there in seller growth path was interesting. And I didn't change anything else. I was doing blood work. I still didn't blood work regularly. So, you know, is it going to make me live longer? I don't know. But I don't know how the day I die, I won't know whether or not I would have lived shorter or longer.

Yeah. So I really like the sublingual element.

Yeah, they don't want it by telehealth. Yeah. So I think I saw one of, um, because of Chris Bell that put. Yeah, something about this. Um, there are a lot of, click, click clinics as I call them online clinics who are prescribing testosterone. whatever dosages that they've deemed appropriate for someone. Um, based on blood work. I mean, if you go to the doctor, you're basically going to get the same blood work.

Well, originally what they wanted to do with TRT. Remember, people are going in and getting their full 200 milligrams because it's typically testosterone sippinate in this country. 200 milligrams per mill, which is, you know, one, you know, one syringe full if it's a one ML syringe. Obviously people are getting that once every two weeks. And that's a crazy dosage scheme. You're supposed to the best way we know is to divide it up.

Well, there are, I mean, things like oxandrolone and, and of our, we're always taking his pills, but there was a liver.

There's the dermal scrodo patches that gets weird.

Yeah. Every other day, every three days at a lower dose, so spread it out because the testies normally kick out somewhere between seven and 15 milligrams of testosterone per day. So, and you got two testies, most people anyway. So, most men have two testies, obviously. What you're talking about is 200 migs on one day and then coming back two weeks later is crazy, but that was really serving the physicians well because you had to go in for a clinic this time, et cetera.

And the conversion to estrogen from a massive dose all at once is ridiculous dose that you should never take. And sometimes, and too big, a dose can crush libido, it's a mess. So I think if people are, people need to be able to self-administer. And all this ruling would do, frankly, is send people into gray market route. That's all it would do. There's a, there's a, like, zero message going to happen. I sure hope not. I sure hope not, because I think the number of people that can afford to go to a physician who's really good, who's going to dose it correctly. is so infinitesimally small. And, you know, I'm, I'm, testosterone is not particularly expensive, but I'm very sensitive to the idea that, you know, a lot of the things that hold great health benefits are just outside the financial reach of a lot of people.

Now, I think it's going to kick up the black market. Yeah. So right now, I'm sure there are people who are trying to stock up sipping it, so they can sell it. It's sending us back into the dark ages, frankly, of that stuff. So hopefully not, if someone tells me who to talk to or petition, you know, as you can tell I'm getting more vocal about stuff, I also feel safer nowadays to talk about things than I did a few years ago, because things are becoming more commonplace, mostly because I have colleagues who contact me and say, like, hey, how do I, how do I get on testosterone? Do I need testosterone?

Yeah, absolutely. And I, to say, because we were trying my NMN in David, you think, Larry, I mean, he's going to know the nuance there. I mean, I don't know all the nuance. I haven't talked to him in a while. But, you know, I think he's definitely in the camp of people in science who are thinking, you know, what's possible, taking some significant steps based on mouse work. And I do want to be fair to people that do that, right? I do that, too. I mostly focus on human studies and human stuff. There are many people out in the world that are interested in things they can do for their health and they know that if they're waiting for the random controlled trial and huge numbers of subjects and especially for people with diseases and their family or have diseases, they're not interested in waiting. They don't want to do anything sketchy or dangerous, but they're not interested in waiting. So I think David's, you know, he's really driving certain things hard and some people agree with him, some people don't, but he's got a vision. The one thing I can say for sure about David is he's got a vision and he's going for it. And there are, you know, this thing about FDA controlling or not FDA controlling, I think it's vexing some people. And it'll be interesting to see how it goes, but if you're interested in keeping NMN or anything on the market, right letters, I know it sounds like a high school thing, right letters to you. But in the absence of those letters, there's no chance of things going the way you want. In the presence of those letters, it's like one letter, you can type it and just email it, or email it five times, you know, and see what happens.

Well, thank you for having me on. I always enjoy these conversations. I always learn from you and I really appreciate you and your team. I really do. The podcast is human and lab. That's how we so human and lab.com you can find all our episodes and their linked out and all the formats from there and then wealth of information. Yeah, you just scroll it sort of infinite scroll one thing that we have that I'll maybe I'll just mention is if you go to the menu and you go to newsletter We have a lot of people don't have time to listen to the whole podcast. You can subscribe for free. But if you scroll down, I've got PDFs of like deliberate heat exposure protocols, deliberate cold exposure. You don't have to sign up. You can literally just get the PDF. And so there's no ask here. You can just get toolkit for sleep and all that stuff with link out.

You know, because I do realize that, you know, not everybody has four and a half hours or two hours to listen to all the details with a notebook. I would hope people would listen, but anyway, that's all there for people and so they can grab that content if they want.