Andrew Huberman reveals how croissants trigger dopamine, then dissects COVID-19’s lab-leak plausibility—highlighting a 2018 Wuhan safety violation and CRISPR’s unethical human embryo experiments—while debunking pangolin-market claims. He links cold plunges (e.g., Stanford’s Cool Mitt) to ADHD-like focus via norepinephrine/dopamine spikes, contrasting with misguided Alzheimer’s research costing billions on falsified amyloid data. Fentanyl contamination in MDMA (60% of samples) and psilocybin’s blocked therapeutic potential—like Carhart-Harris’s suicidal-depression breakthroughs—expose systemic failures, while Huberman warns semaglutide risks muscle loss without resistance training. Their carnivore diet debate underscores NMN’s banned promise for longevity, urging FDA policy shifts through public advocacy. Science’s incentives, not just discoveries, shape health truths. [Automatically generated summary]
Yeah, Boyan Slott is a gentleman who's been on the podcast before, has developed this device for, it's like, it sifts the ocean, it floats over the top of the ocean, and it has this collector.
That sucks up plastic and then they take that plastic and use it and recycle it and make like eyeglasses out of it and all sorts of other different things.
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 love exotic animals, not to own them, right?
But I'm really interested in animal conservation.
And so the pangolin is an amazing animal.
They pinned it on the pangolin early on, right?
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, you know, the sequence of the virus in pangolins, which were being sold in the Wuhan market, etc., And I was pretty disturbed by this, mostly because of the pictures of the Wuhan market, the 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 pangolin meat is sold at, I forget what it is per pound, but it's a delicacy and it's considered very lucrative to get pangolin meat, of all things.
There's actually a female pangolin meat Influencer on YouTube and oh, yeah, no, it's like it's it starts to look like pangolin meat ASMR. It's crazy and disgusting.
So they're they're kind of mixing, you know, sexy women with exotic meats from these rare animals.
It's just awful.
So I was going deep down this rabbit hole of trying to understand this exotic animal trade and then 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 very high restriction viruses had done her training in the United States, which is true, has a master's degree, but was running a laboratory, which is unusual, right?
Typically the head of a laboratory is someone with a PhD, MD, or both.
Very rare for a so-called PI, a principal investigator.
Like me or, you know, another Matt Walker, for instance, principal investigator to have less than a PhD.
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, you know, that laboratory had deep ties to 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 who thought, yeah, you know, my laboratory works with rabies viruses, adenoviruses, synbis viruses.
None of these are as, It's biohazardous as something like the coronavirus, but you work with these viruses and you have to use, you know, lab coats, gloves, bleached sterilization, you're careful, you know, hoods of, 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 of 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 this is like it was an 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, it sucks up some fluid, you move things, you know, between little little tiny vials can be done by robots, too.
But typically it's done by humans and that's how they put in a center.
If you 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 it takes is that lab coat going on a rack.
All it takes is somebody leaving work, putting their lab coat on there and touching that lab coat and 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 pangolin sequence in the Wuhan market.
So I think 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.
I think to people who work in biomedical research, of course this sort of thing could happen.
Of course.
Because human error is the cause of most of these kinds of things.
Yeah, there too, you know, we hear about gain-of-function research, and now everyone associates gain-of-function of this particular virus.
Yeah.
Gain-of-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 function 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.
You know, the gain of function, actually there is that one CRISPR experiments beginning 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.
He mutated the HIV receptor, which everyone thinks, okay, that was designed to prevent these babies from getting HIV. It turns out that that mutation is thought to perhaps enhance memory by sort of 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 him in jail.
And so everyone is very tense and 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 was like, I had nothing to do with this guy.
Never had anything.
And you know, there was a deep excavation of emails and all sorts of everyone's like, I got nothing to do with this guy.
So it was pretty interesting.
Then China said, oh, we're going to, 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, you know, 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?
A Huntington's Korea mutation that has somebody at some point in their life, you know, unable to control their arms, hemibalism of the arms.
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 degenerates substantially.
Other things too.
And people with Huntington's chorea end up with these writhing ballistic movements.
And it's an inherited disease.
So you know what gene.
It's the Huntington's.
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 late onset.
So you can be normal a 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 Huntington's.
In which case with CRISPR, you could just put the gene back in and rescue function.
Yeah, so it's not just deterioration of those particular neurons.
It's deterioration of the neurons that control those neurons.
And everything's working in a kind of a top-down suppression all the time.
In fact, the head neurosurgeon at Neuralink, who's somebody I know quite well named Matthew McDougall, he came up through my laboratory and Elon made a great choice in hiring him.
told me recently the best way to think about the frontal cortex is that basically its 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 there's a 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.
come to some basic, you know, we call them housekeeping functions, you know, so they'll have to be on a respirator and they have to, you know, they have to use a catheter tube and, you know, they have to defecate 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 you knew was someday going to get Huntington's, you'd want to do a CRISPR mutation and put the healthy gene back.
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 eat salad dressing with mustard and have a huge inflammatory response and have a flare-up, blurry vision and get worse.
But I think one of the best ways to think about inflammation, and here I definitely hat tip to Lane Norton, who we both know, and Andy Alpin, who both really impressed upon me the fact that if we were to measure somebody's blood pressure, inflammatory markers, heart rate, and cortisol inflammatory markers, heart rate, and cortisol during a hard workout, and you didn't know they were doing a hard workout, I just handed you the data.
And you're a medical doctor.
You'd say, this person's dying.
So inflammation is robust 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.
And here I just, I always want to make sure I give proper attribution.
The Nobel Prize was given a couple 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 or 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 pain threshold.
And you and I have 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 if people have lower levels of testosterone, effort feels more...
How's that?
And the other thing is that ingestion of spicy peppers resets your calibration for what's spicy.
I think we know that too.
And in a way that also adjusts people's pain threshold.
So if people get better at eating hot peppers, they're better at 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 plunges.
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're 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 and disparage it.
They try and 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.
Susanna Soberg did her PhD in Denmark as, I think, one of the best scientists in terms of deliberate cold exposure and 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 sort of like the oil in the candle of your body increases mitochondrial function and thermogenesis heats you up.
Metabolism, subjective wellbeing, sleep, et cetera.
She did all of that and published this in Cell Reports Medicine.
And I realize it's just one study, but to do the 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 is 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 fat that they have, which means they fundamentally change the number of mitochondria in the brown fat, which means they fundamentally change their thermogenic properties of their body, increase their metabolism.
Now, the people who don't like cold say, well, the 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 this 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 Soberg Principle, which is when you end with cold, your body has to use its natural machinery to heat back up.
In talking to her 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, It increases the so-called parasympathetic activity of the autonomic nervous system, which is 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.
I really do because there's there's a moment when you get in the cold where There's a part of your brain that goes let's get out of here You can get out of this if you will just get out right now and you got to go shut the fuck up But if you don't say shut the fuck up then that thing runs rampant through your brain and that kicks your heart rate up and that kicks your anxiety up I really think it's psychological Well, it's psychological and it's physiological.
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, shh, 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 of, oh, this is actually good for me.
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 is a wall for me.
So I go, okay, I got over one wall just getting in the damn thing.
Then I'm like, oh God, here it comes.
Forebrain's shutting down.
I'm like panicking.
I'm going to get through this.
And then I'm watching for when I have the impulse to get out.
And what I start to notice is that the gaps between those walls start getting longer and longer.
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 a dopamine, epinephrine and norepinephrine release.
These three things together are called the catecholamines.
Those normally would increase from a cup of coffee and a hard sprint for 10 to 30 minutes, maybe an hour.
When you do the cold exposure, the way you're doing it, or longer exposures at about 50 degrees or so, You're seeing increases in dopamine, norepinephrine and epinephrine that are two to three X above baseline.
Whenever people criticize deliberate cold exposure, they go, it's not leading 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 catecholamines 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 at a place that actually has a plunge.
I don't know the temperature, but it felt cold to me.
So I did three minutes, three minutes, three minutes, and they had a hot tub, so I bounced back and forth for a minute in between.
And as you know, you feel better much of the day, if not the entire day.
That is not a coincidence.
Your system is circulating much higher levels of the catecholamines.
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 workouts.
Everyone now knows that it blocks hypertrophy if you do it after.
So sunlight during the day, morning and day, and trying to limit bright light exposure at night as much as normally possible.
Then I would say movement.
So you've got to move.
Cardiovascular 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 turning into a bodybuilder.
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 men and women.
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 then the other stuff.
And then I think in addition to that sleep, right?
I think Matt Walker, It deserves a tremendous debt of gratitude from everybody because 10 years ago, everyone was like, I'll sleep when I'm dead.
Now we know.
You're probably not gonna 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, right?
You can't stay isolated constantly or people lose their minds.
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, it rocks hypertrophy.
Okay, well, only if you do it in the four to six hours after a hypertrophy workout.
I mean, it lowers inflammation, which is what you want from the resistance training.
Again, it goes back to this, you know, it wasn't just these guys.
But again, I point to Lane and to Andy Galpin, who 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 know, you eat the hormetic effect.
You eat this, you become inflamed.
Well, how long and what's the hormetic effect?
And so in terms of You know, deliberate cold exposure, people like to say, oh, it doesn't burn much fat, it blocks hypertrophy.
But if you look at the mental benefits of having your catecholamines, dopamine or epinephrine and epinephrine systemically elevated to two to three X for four to six hours after a 30 second to three minute protocol, you're not going to show me a drug or a form of exercise that can do that.
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 medial preoptic 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 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 bodily temperature in the morning, that triggers a cortisol spike, that triggers norepinephrine, 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.
That your whole circadian 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 at 2 a.m.
when you went to bed 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 it.
Your peak time during the day.
If we looked 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.
Ah, but there's an easy experiment.
This has been done.
We just keep you awake 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.
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 get goosebumps, 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, ha, 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.
Shivering is just another form of moving.
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 turn activates the thermogenic system and starts 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.
Well, I certainly think that there's a great benefit to being able to tolerate temperatures, whether it's cold temperature or warm temperature, because I think there's a mental resiliency aspect to it.
What's interesting to me is when I get out of the cold, my entire body, my skin is bright red.
You know, where your body's trying to heat itself up, because you're in there for three minutes, or I'm in there for three minutes.
But when I get out of the sauna, generally I stretch, and my house is warm, right?
And at nighttime, I do the sauna in the house, and when I'm stretching, within a minute or two minutes after the sauna, I'm fucking freezing, because my body's trying to cool off so quickly.
You know, because it's gone through the whole 25-minute session.
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, endothelial cells.
They're laid out like silly putty, linking them all like tubes, and they are very contractile.
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?
The system can become very dynamic.
You don't want it rigid, especially given what Atiyah tells us, and I believe him, is that the number one killer in the world is cardiovascular disease or cerebrovascular disease.
You want the little microcapillaries of your body to be very flexible, not rigid.
So when you go heat-cold, you're basically going vasoconstriction, dilation, vasoconstriction, dilation.
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 vasodilation and it goes out to the surface, 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, once 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.
It 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 deliberate cold exposure before a workout, total sense.
The cold in the morning, the other thing that it does when I get out is it makes me like really fucking happy, which is what you were talking about with the dopamine race.
It's so significant.
I mean, it really, it is a joy of life feeling.
And then as I start my workout, I generally start really slow.
I just do like a lot of like shadow boxing and maybe I'll skip a little rope to try to get my blood up.
And then once I do that for a few minutes, then I have a series of 100 push-ups and 100 bodyweight squats that I do every day.
So I go through that and that's my warm-up for everything else because it's pretty low stress, low impact, very easy to do.
And then by the time the 100 is 100 squats and 100 push-ups are done, I'm warm.
And then I start whatever workout I'm gonna do.
But god damn, I feel happy.
The people that are trying to avoid it because, oh motherfucking, it doesn't do anything.
Shut up.
Just do it.
Stop your excuses and stop arguing about it.
You're only arguing about it because you don't want to experience discomfort.
I know what you're doing.
You know what you're doing.
We all know what you're doing.
Shut the fuck up.
Just get in there.
Just do it.
It's great for everybody.
And if you can't fucking handle it, don't talk about it.
But don't pretend that it's not good for you.
It's nonsense.
It's one of the most...
If you could sell that shit in a pill, it would be so valuable.
I mean, how many people are on SSRIs and they're like, I kind of feel better?
You know, again, Craig Heller in our biology department at Stanford has been talking in this general theme for a long time.
Anna 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 using cold plunges?
You just, you know, taking one addiction and replacing it with another?
No.
What's very clear is that 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.
You know how people are procrastinating to write something 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 Ana, 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.
And you're like, oh, okay.
Well, it's just psychology, right?
No, it's not psychology alone.
It's psychology, but 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 them 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.
Ritalin, Adderall, they all tap into this system, the dopaminergic and adrenaline norepinephrine system.
So one of the most prescribed and over-prescribed classes of drugs is a 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 plungers, 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, It's 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 Susanna, I take no credit for this, is I'm not suggesting people replace the cold plunge with this or a cold shower with this.
You're starting 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 plunges.
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.
There was a device that was going around a while back that people were using when they were lifting weights, where they were putting their hand into something that was freezing their hand, and it increased their ability to do work quite substantially.
Do you know what I'm 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 glabrous 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 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 passes 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 bottoms 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 in like the 19, no pun, sorry, in the 50s, 60s, 70s.
And then it was sort of considered kind of like, not lame, but it wasn't hot science.
Ah, there we go again.
I'm really not trying to pun here.
Then what's happened in recent years is people have gotten into these protocols and it's become more popular.
His laboratory also showed that one of the reasons why we fail on like 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 can't 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 that, let's say you can do 10 sets of 10 at a given weight with two minutes of rest 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. I don't know if people said, German volume training or five sets of five.
If you lower the core body temperature through the proper use of palmer 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.
So in theory, if we'd been cooling 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 a local change in the enzymatic reaction at the level of muscle.
Now, the problem with polymer 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 temperature so that you can continue to pass cool in.
And that's why it requires a device to heat, excuse me, to cool your palms, but not so cold that you vasoconstrict.
And so there is the Cool Mitt 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 their training because it's just simpler and you don't need a device.
Inter-workout or intra-workout cooling is really an interesting topic, but it hasn't been perfected at the level of devices.
They're still kind of clunky.
You gotta go put your hand in the thing.
No knock on CoolMed.
I mean, I think they're trying really hard.
I actually got one for Cam that I still need to deliver to him.
Here's what I think 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.
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 1 military and scientists are really starting 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, they'll have stations in the gym where you kind of plug in.
And I think, and I, for all I know, I believe he's natural, but like you think about a guy like Floyd Mayweather, and I used to see him running in the middle of the night, you know, in Vegas.
If his testosterone happens to be exceedingly high, naturally, he can do more work and recover than the person whose 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.
Well, they're also like deeply influenced by money.
Like that raccoon dog thing, I guarantee you there are some people behind the scenes that are trying to come up with some sort of a plausible scenario that's alternative to the lab leak theory.
And that's why they're coming up with this.
The people that I've talked to that understand this, I've had many conversations with virologists and evolutionary biologists who explain to me why this is most likely a lab.
They're not arguing with this.
So when someone comes along with this and they're saying, oh, we found it, like, no, you didn't.
No, you know you didn't.
You're writing this article because you're being influenced to do so.
Like someone is telling them That this is a good thing to put out.
Someone is giving them information and saying, we believe this and you should print this.
There's money behind that that doesn't reach independent journalism.
That's the difference.
Like the amount of money behind an advertisement that goes to CNN or an advertisement that goes to the New York Times.
It's a different thing than what goes to Breaking Points with Crystal and Sagar, than what goes to Matt Taibbi's Substack.
There's none there.
There's no influence there.
These people are influenced by gigantic corporations.
That's why they put out articles that are not plausible.
That's why people don't trust them anymore.
That's why, you know, people think they're fucking shady.
Like, they give you what is their actual take on whatever is going on in the news and it's well-researched.
And the fact that that exists now is so important because if it was not for independent journalism, we would be in a pickle.
We would be in a really bad state because a lot of people got duped by the pharmacy, the pharmacological industry, the pharmaceutical industry, the medical industry, the military industrial complex.
They've been duped by so many different companies and corporations that have a vested interest in getting one narrative out.
And if you can get that narrative out through the traditional pipelines of mainstream media with no one fact checking, no one interfering, no independent journalist saying, actually, that's not true at all.
Here's why they did that.
This was the influence.
Here's where the money is.
We have emails.
We can show you they were influenced.
If it wasn't for them, we would be fucked.
And it's one of the beautiful things about the internet today.
The internet today allows people like that to thrive because these mainstream media corporations are so corrupt.
They're so obviously indebted to the companies that pay for their advertising.
Yeah, I mean my initial experience of them was long before I had a podcast, did an interview with traditional media and then it comes out and 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, this is factually incorrect.
I didn't say this.
First of all, I'm not a medical doctor.
They swapped the names accidentally.
And then I got this, oh, well, kind of response, like too late.
No retraction.
No.
And when it's your neck on the line, it's your name.
I mean, in science, all we have is our reputation.
In science or in anything, that's all we have is 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.
And now the fight isn't just for traditional, you know, over media, traditional or independent.
You know, the universities too, right?
We were asking, I have to say, and I'm not, this is not a, 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 petition that's been going around the campus for a while.
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 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 is best.
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.
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.
The value that he's given back to people in the last, what has it been, four or five months since he's been in there?
Yeah.
Tremendous.
I mean, I remember people picking on, oh, it's this feature, that feature, we're gonna have to buy a verified check or whatever, you know, these things that when you compare that to the ability for people to have honest, open discourse, honest for them, because, you know, there's no regulator.
So that to me is incredible and fundamentally important.
He's given people their voice back.
And that includes both sides.
That's what's often not stated, is that people on both sides are starting to get the ax, mostly on one side.
But it's really incredible.
I'm hopeful.
I'm a live and let live type person.
As long as people aren't harming other people, I truly just encourage people to do what feels right to them.
It's kind of bananas where we went 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 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 dangerous.
And so I think there's no going back.
There's no going back.
Now people seek advice on multiple dimensions.
You know, a few years ago, if you said supplements, people were 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, getting some sunshine?
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, etc.
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.
It's a nootropic, post 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 Rhodiola rosea, 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 will taking some additional magnesium help me sleep?
No, this is what, you know, my, you know, when I was young, I got into this, you know, training and supplementation early and people would 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, as I call it, like things like athletic greens, right?
I guess they call it AG1 now.
Things that are in such combinations of herbs and plant-based compounds, you can't take them one by one.
And then other things like magnesiums for sleep or inositol and the date on depression or inositol 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 inositol can improve insulin sensitivity.
Inositol, 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 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 have to inject it who have type 1 diabetes.
So things like inositol, I mean, and the list just goes on and on, you know?
And so to me, I think the view is changing.
I hope that, you know, the idea previously was that before the pandemic, frankly, was that supplements are just kind of like nootropic 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 augment To good sleep, good nutrition, good training, good social connection.
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.
That's the real problem is that the corporations who control these prescription drugs and sell these prescription drugs and sell advertising on television have got it into people's heads.
That's why it was maddening when I had Peter Hotez on the podcast.
And he was talking to me about the importance of vaccination.
I said, do you exercise?
How do you eat?
Do you take vitamins?
And there was zero going on with him.
He goes on walks occasionally.
I mean, there was heat, fucking junk food.
He wasn't taking vitamins.
You know, he told me that some internist told him to take vitamin D. So he took that for a while.
Well, there was a recent study that talked about people that died or were hospitalized from COVID and they could have prevented somewhere in the neighborhood.
See if we can find this.
It was a very high number, a very high percentage of hospitalizations and deaths could have theoretically been prevented with vitamin D supplementation.
This was based on the number of people that were in the ICU that were deficient from COVID, or excuse me, deficient from vitamin D that were in the hospital for COVID, and it was in the high 80s or in the low 80% rather.
And then they did this study showing what would have happened if they had just supplemented vitamin D. I mean, I know many physicians.
Here it is.
New study reveals vitamin D in the body can significantly reduce the risk of severe outcomes for COVID-19.
Does it have the numbers?
What year is this from?
Is this recent?
unidentified
Yeah, but this seems like a strange website, I'll be honest with you.
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, you know, 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, right?
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.
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, but We get to determine the direction that the journal wants to go.
So during the pandemic, there was an enormous incentive for publishing papers in these journals that provided some other 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, we're We 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 gonna, 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 if 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 of 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 mouse.
That is a serious problem in science, far more than fabrication of data.
The lab heads, 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 have companies, and we can talk about that, and that's complicated sometimes or not complicated.
But the point is that 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 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 of 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's 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 something, you know, gives themselves reasons why it was okay to remove data.
That occurs, I think, I'm gonna guess here.
I don't know, but 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...
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 astray.
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 continued 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, you know, biotech is neither good nor bad, nor evil, nor 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, I mean, how many times have we been told blockbuster finding in mice and then people with Alzheimer's say, well, when is there going to 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 fine and 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 has been 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 bulletproof 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 a 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?
Well, you get it by publishing papers in 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 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.
Now, in the long run, they don't do well, or what you'll find is they often just switch to an entire new area of science when they start their lab.
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 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 cutthroat 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 families suffer.
Everybody suffers as a consequence of their neurotic tendency, but those people Are they heroes of science?
Because they won't let something go to publication unless they know it's absolutely watertight.
You know, subject to human emotions and human instincts and ego and jealousy and and a partner at home who's probably like, hey, when are you going to get out of graduate school?
And we're going to actually move out of this one bedroom apartment where I want kids or all our friends are like taking vacations in Tulum and we're like suffering here.
And yeah, or people who think, you know, you get a Ph.D. and that guarantees a 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 or even somebody at a 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 there's a whole other aspect to the sociology of science that I think is not often discussed, which is that There's a huge incentive to being promoted by your elders, by your graduate advisor and postdoc advisor, because they are the ones that write the letters, they 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 postdoc.
We're all incredible people and scientists in different ways.
I was 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 in 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?
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, you know, this person really needs tenure and they've got a family and, you know, 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 ask 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, sort of like my bulldog Costello was.
Like, I'm going to go along with things until you try and push me, and then I just have kind of a resistance thing.
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 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.
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, I'll 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.
And so 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.
Oh, scientists, you know, I guess this is an opportunity to bring up Jeff Epstein.
So, you know, people sometimes wonder, you know, like, were 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.
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 Gell-Mann who discovered the quark, right?
He's a particle physicist.
I mean, head of the Santa Fe Institute, Nobel Prize.
I mean, Gell-Mann used to pick on Richard Feynman.
He was one of the few people who could maybe not verbally joust with him, but at a scientific level could pin that guy.
They were on more or less equal tier, but Gilman was right up there.
So Epstein understood, like, bring around the Gilmans.
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 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 offered laboratories, you know, a million dollars 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 dirtbag like him.
And they had blinders on.
Either they knew or they didn't know what he was up to, but they had blinders on because they weren't thinking about the implications.
Well, it's also one of the things about something like that must be that if you go there and you see Steven Pinker and you see Lawrence Krauss and you see Bill Gates, it seems like you should be there.
I mean, he kind of ingratiated 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 NBA player, like, oh, in the NFL they do this, they're like, whatever.
You tell them that, you know, this will increase your output by 10%.
They're like, whatever.
They don't care.
They want to play video games.
They do not care.
They want to hang out with 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 tears, because it's a vampire schedule, you don't get to sleep when you want to, and you get, you potentially die, you potentially all die, and their running times are faster, their recovery times are faster, their shooting accuracy is far better than your shooting accuracy, and that's with a 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 1 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 want to start new projects, but they want to be around really innovative, interesting people.
And in academia, there are a 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 psychologies, not just his.
Yeah, that's why people that have studied him and the whole case believe that—and from other evidence and information as well—that he was part of some sort of an intelligence operation, and there was compromising these people.
Well, I mean, in the unraveling of all the dark, sordid shit around Weinstein, it was discovered, I think, in New York, like near that avenue, 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, 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 to 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 pedophiles.
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 onto any campus, I don't care if it's UT Austin or Stanford or it's Harvard, the names on those sides of 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.
Yeah.
100%.
And it doesn't mean that they're trying to corrupt anybody, but they have to survive.
You've got to pay the janitor.
You've got to pay the cops.
You get on the campus.
I mean, so it is a business.
And I think the human side, actually, to your credit, I learned from you.
I think you may or may not remember, but a few years ago we were talking about everything that 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 were 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 and their psychology.
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 kind of core developmental dissatisfaction is, right?
Because I think therein you see.
It's like I'm sure everyone has this.
I'm sure Bankman-Fried felt like a...
Like this big as the consequence of something in his psychology or experience and as a consequence justified doing this horrible thing.
Yeah, even though he's over at Berkeley, like we tolerate him.
No, I'm kidding, Michael.
That's a Stanford Berkeley joke.
He is wonderful and amazing and such a pioneer of this whole psychedelic space.
And you might say, well, there were others.
There's Terence 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, I've taken 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 and Stanford Magazine, Alice in 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 the subject of 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 Pollan is 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?
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 gonna like that.
They're like, no, this is plant medicine, it's got 100,000 year history or more, indigenous people, et cetera.
Academia and pharma don't care about that.
And 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 universities suddenly okay with the idea of discussions about psychedelics in front of their top tier donors, the people that 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.
Right, but the top-tier donors are clearly influenced by the zeitgeist.
And the way people have approached and thought about psychedelics has radically changed over the last ten years.
And Michael Pollan is one of the reasons for that because of the omnivores dilemma.
He had established himself as a legitimate journalist who would comb through and parse through all the data to give you a comprehensive understanding of what exactly is going on.
Wanted to, you know, sit here and 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.
That's the major difference, and you've really pioneered the discussion around that, Michael Pollan, and there are others, too, I realize, but...
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 Cardhart 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 either heading towards suicidal depression or they're just not feeling quite right and using Ibogaine 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 others really deserve a token of gratitude.
I've completely revamped my stance on psychedelics.
I'm still yet to do a high dose psilocybin journey.
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 with a wild bunch, and we were just partying with it.
I didn't know what I was doing.
So my view of it was, it was associated with a time in my life where I was pretty wayward.
Then I never touched it.
I drank a little bit, smoked a little bit of weed here and there, but never really liked We'd 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 realize, and you might, you probably already know this, but I was very curious about MDMA and the reputation that puts holes in the brain, kills serotonin neurons.
You know, the study on MDMA that showed neurotoxicity was retracted from science.
They actually inadvertently injected methamphetamine into those monkeys, but you never hear about that.
So they now have data in humans asking what are the safety profiles on MDMA for people that take it every once in a while to people who have taken 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 meth?
Are they doing coke?
Are they getting psilocybin?
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 banned substance list, and that's MDMA. Wow.
And I'm not saying all Mormons— They can't even drink coffee.
It makes an even better experiment.
And so I'm not saying that Mormons are all taking MDMA, but there is a substantial number of LDS, Latter-day Saints, I think they call themselves now Mormons, as most people know them, who have taken tons of MDMA. 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 neurotoxicity is nil to none.
The recent data I saw was that you go out and buy MDMA from a quote-unquote trusted source, and 6 out of 10 are going to have potentially lethal levels of fentanyl in them.
Which is kind of crazy because that's one of the more interesting aspects of the way podcasts have infected the popular opinion on things because it's sort of changed people's understanding through data and through talking to people like Michael Pollan or Rick Doblin or, you know, any of these experts that really could tell you What's actually going on and how this helps.
And then there's many people that have these stances on these drugs that hear these things now and go, you know what?
God damn it, maybe I'm ruining my life by not being open.
Like maybe this could actually help me.
Maybe this could help my mom.
Maybe this could help my father.
Maybe this could help my brother.
You know, there's so many people out there that really could use some help.
And human beings have been using these compounds, these substances and these mushrooms and these psychedelics for thousands of years.
There's a reason why they put them in rituals.
They may be the source of most religious experiences.
They may be the source Of many religious texts.
In fact, John Marco Allegro, one of the head, the guys who was hired to decipher the Dead Sea Scrolls, he wrote a book called The Sacred Mushroom and the Cross after translating the Dead Sea Scrolls for 14 years.
His belief was that the entire Christian religion was initially based on psychedelic mushrooms and fertility rituals.
And so he wrote this book that was bought out by the Catholic Church.
It's reprinted now, but you had to buy used copies of it online to get it.
And so then he made another book called The Dead Sea Scrolls and the Christian Myth that was based on the same material.
Yeah, 22 hours and horrific experiences were just...
Intensely introspective breaking down of all the pathways in your mind that have been carved throughout all of your traumatic experiences your whole life that led you to be the person you are today I know multiple people that have done it because of an addiction to opiates and it's helped them it's helped them tremendously kicked them 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.
I mean, people die trying to go cold turkey.
I mean, it's unbelievable.
Yeah, I think Ibogaine 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 Nolan is scanning their brains before and after and seeing incredible changes in the positive direction.
I think for most people, the psilocybin macrodose, two macrodoses 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?
Yeah, I would imagine that's the case because you're just distracted by visuals and you could concentrate on that instead of just – Terence McKenna used to always say silent darkness is the most important aspect to a real trip where you're learning and you're going in with the intention to interface with this divine consciousness and learn something.
Of all the topics that you could cover, you'd 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 you're awake.
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 in it.
Then people go, no, it's all about deuterium depleted water.
Near the ocean, there's more deuterium in water.
Not from ocean water.
And then people are like really into deuterium deplete water for cancer.
This is all these niche communities in water.
Reverse osmosis water, which has no magnesium or calcium.
And 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 Galpin equation, which is your body weight in pounds divided by 30 equals the number of ounces of water to drink for every 15 minutes you train.
Like Galpin's 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 Harris, he said, eye mask, And he said the power, I was so surprised.
This is like a hardcore researcher tells me the most important variables are the dose.
So set and setting, obviously, but the eye mask and music.
He's like, when people don't have music, somehow the music and that the music during a psilocybin 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 a school of medicine dude, to hear this conversation, like, I don't know whether or not to laugh or cry because These are the kinds of conversations that A, would cause you to lose your job for legal reasons 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.
Stance in why I love your podcast, why I pay attention to podcasts in addition to scientific journals is that if you look at, let's say, let's look at like this really niche, crazy field of bodybuilding.
Like how many people wanna look like Doreen Yates?
How many people wanna look Arnold 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 a healthy dosages.
In men and women has tremendous longevity health span effects, mental and physical.
And so there's value in these early niche communities, you know, psychedelics or in bodybuilding or martial arts or in yoga communities or in breath work.
It's just that we see these extremes of like a Wim Hof or 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 used to say, oh, you only lift weights if you're going to the military, playing football, you're a 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, I can't speak for you obviously, but I get very frustrated as I think you do and other people do when people immediately just shut the door like, oh, that's just like crazy bro science biohacking.
Actually, there's a different name for it.
It's called ahead of its time.
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 If you jogged 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 PE class.
Well, jogging craze.
Now it's like accepted to be a runner.
It's encouraged to be a runner.
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, you know, 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.
And they'll replace 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.
And also, if you're getting advice, particularly advice about physical health, about metabolic health or about mental health or about the possible – the actual benefits, whatever they may be.
And it's very – It's not just dose-dependent when we're talking about psychedelics.
It's dependent upon the psychology of the individual.
It's dependent upon your life experiences, whether or not you have a tendency to schizophrenia.
Like if you're talking to someone who's fat and they're talking to you about health, maybe that person is not really qualified to have this discussion.
Maybe they haven't taken care of their own physical health.
So they really shouldn't be distributing information.
If you knew something that could radically change the way your body responded to diseases, the kind of energy levels that you would have, your mental health, but yet you were ignoring it for some strange reason, well that person has a giant hole in their life game, right?
And there's a lot of people out there distributing health advice that have a giant fucking hole in their health game.
He's got this big fat belly and he's telling people they have to get vaccinated.
Like this kind of binary thinking, this kind of ridiculous way of looking at the world through only pharmacological interventions, through only medicine, through only this, through only that.
There's so many different things that you have to do to be healthy and it's too much work.
For most people.
So they're not going to weight train enough.
They're not going to eat the proper foods.
They're not going to supplement their hormones.
They're not going to do blood work on a regular basis and have someone who is a qualified physician who goes over that blood work with them and gives them a comprehensive understanding of what they need to do or not need to do.
Hey, your blood pressure's too high.
Hey, your body fat's too high.
Hey, you're this.
You're dehydrated.
You're this.
You're that.
You have low vitamin D. You have low magnesium.
All that shit is massively important.
So when you see someone who's distributing advice and they clearly aren't paying attention to everything that we know today, well, they're not on the cusp.
They're not ahead of the game.
They shouldn't be the type of person that's telling the rest of the world what to do.
Yeah, I mean, it's, you know, I did an episode on hair recently, and it was like the guy who did a hair transplant for the first time, his name escapes me for the moment.
You know, he figured out how to make his practice popular.
He worked on politicians and celebrities, and word spread quickly.
And, you know, he was the one who was the mind behind that brand Clinique.
He said, we should call it something clinical, so it sounds like medicine.
Oh, that's hilarious.
Yeah.
Oh, and he died at 96, with a full head of hair, by the way.
It's interesting that, you know, you were talking about people won't do the thing.
Right now there's a lot of excitement about semaglutide.
The story of that, since you like animals and the natural world, a guy down in South America, It was looking at Gila monsters, 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 it takes their blood, isolates a peptide, which turns out to be GLP-1, puts it into other animals and realizes it suppresses appetite.
Amazing, right?
Like this is what I love about biology.
Some dude who studies Gila monsters, turns out humans make GLP-1.
GLP-1 is stimulated by things like yerba mate tea, certain other compounds, plant compounds stimulate its release.
But what does it do in the hypothalamus?
It suppresses hunger by way of, there's a particular brain arcuate pathway, blah, blah, blah.
But it also affects the mechanosensors of the gut so that you feel like your gut's full.
Like you got, it's almost like you're getting like a pharmacologic tummy, stapled stomach, right?
So when people take a drug that mimics GLP-1, 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.
Because things like Adderall, Ritalin, all that, people like that because it's amphetamine.
If I show you the structure of amphetamine, I show you the structure of Adderall, Ritalin, you don't have to be a chemist to just go.
Those look very similar.
So GLP-1 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, Atiyah 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 Zempick is the brand name.
I have a question for you about the semaglutide stuff because one of the things that we've discovered when we started going into it and talking about it on the podcast was that 34% of the weight loss was muscle mass, bone mass, and connective tissue.
My thought was, was that because they were losing weight?
Because if you just get someone to lose weight, if someone just stops eating food and just starts like really kind of starving themselves, they are 100% going to lose bone mass, they're going to lose muscle mass, and they'll probably lose some connective tissue mass too.
Is there anything that's been done where they've examined people who have done weight training and done resistance training while they're taking semaglutide and does that mitigate the effect of that stuff?
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, how hard are they, it's hard.
So I'm not dismissing it.
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 GLP-1, 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 Lane and I get into some really deep dives on this kind of thing.
Years ago, there's a study of what's called NEAT, 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 staccato with their movements, they can burn up to 1,800 calories more per day than a person that sits very still.
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 semaglutide 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.
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 horrible.
And they're also always trying to lose weight, always trying to burn calories, always.
And so this neat non-exercise induced thermogenesis Thermogenesis, excuse me, is very robust.
In people that move around, even there's a study out of University of Texas, Houston.
This is wild.
The soleus muscle, the wider muscle of the calf, for those that don't know that, there's a guy down there who's running a human physiology laboratory.
And he's like, you know, insulin insensitivity is a real problem, type two diabetes.
The soleus muscle is 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, did what he called a soleus pushup, which is kind of, it's a one-legged seated calf raise, right?
With no weight.
And they're just bouncing their heel like this, like I used to do in class.
What turns out the soleus 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 soleus.
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, The gym jockeys, who I'm friends with, they were like, dude, 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.
I try and avoid the words only 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 GLP-1, 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 GLP-1 very likely, based on my knowledge of the output of the hypothalamus, the animal studies tell us 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 muscle is 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.
There have been a few studies of muscle loss of semaglutide so far, but Japanese researchers reported that people lost half a kilo of muscle after three months on the drug.
That's not that much.
Half a kilo of muscle is a pound.
Why are they saying it that way?
unidentified
Like they're making it look like it's one pound of muscle.
It's a common problem with interventions to lose fat, but yes, that is a common problem with interventions to lose fat.
It makes it imperative to also prescribe resistance training to prevent muscle loss, but my concern is that semaglutide is seen as a magic bullet by some people and isn't always combined with exercise.
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 like kindergarten or nursery school or illiterate we are about our own health because people, so it is true that if you, Lane has been educating me on this, if you reduce your carbohydrate intake, yes, you'll 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 and calories out balance.
Some people will say, why do I crave a big dessert or dessert something sweet after a big meal?
That 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, there's sugar coming into my system.
Get more of that because it's an evolutionary conserved system designed to get you more resources.
So this is why if you look at your gut brain access as 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 where I think there's a place for lower 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.
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-analysis like nobody's business.
You know, Lane's Made it very clear by pointing out the data that carbohydrates aren't going to disrupt your ability to burn fat, right?
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 your adrenaline and noradrenaline, epinephrine 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 NEAT, this non-exercise-induced thermogenesis.
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 you know, he's really big.
He does three stakes a day.
And not just for his age, he looks very fit and he feels strong.
Now, 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.
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.
Mm-hmm.
They seem to like that.
There's a study on intermittent fasting that was done by Sachin Panda's lab out of the Salk on firefighters that, because their schedules are crazy and that 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 Let's just call them elimination diets, where it's mainly carnivore, really help 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.
I'm like, wow.
But he'll post supplements and it's a steak.
He's just all about protein training and the job.
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 who are sitting a ton, that the carnivore diet might be a great thing.
And now I'm not talking about the carnivore fruit, meat, honey thing.
Again, apologies, Paul.
I'm not saying that's bad.
But these are people who are mainly just doing meat.
And they just feel like their appetite is more regular.
And cops, you kind of see it's a binary distribution.
They're either really fit or they're really unfit.
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 cellular health and life.
You need it.
Some years ago, as David Sinclair came on this podcast and...
And discussed that his laboratories, a tenured professor of genetics, Harvard Medical School, and other laboratories are starting to explore, stimulating the NAD pathway as a tool for extending lifespan in mice.
And that there were already some data from yeast.
There are now some clinical trials in humans.
You can't just take NAD, or you can, but it doesn't get into cells very easily.
Here I'm painting with a broad brush, but there are basically two ways that you can tickle this pathway, increase NAD. 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 NAD. Some people are more proponents of taking NR. And the end product is thought to be the same.
However, there's a lot of controversy about whether or not NAD or NR are better.
NR is what was initially sold under the brand name Elysium with a unbelievable cast of scientific advisors, Nobel Prize winners.
There's a very East Coast oriented thing, but a colleague of mine right downstairs from me at Stanford School of Medicine who has a Nobel Prize for discovering the structure of RNA, Roger Kornberg.
His daddy discovered RNA, Arthur Kornberg.
There was literally an ad of him holding a true Niagen bottle like this, and it's like, okay, I started paying attention to this.
NR and NMN are taking an 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 know 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 mouse data or something safe, why wouldn't I try, right?
Because when it comes to longevity, nobody wants to be in the control group, right?
So this is a highly contentious field.
But then what's happened is, So you can take NMN as a sublignal powder.
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. And it's an experimental drug.
And the way the FDA works is if something 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 happened a few years ago for something called NAC, N-acetylcysteine.
And NAC is still available despite it initially getting banned.
And I'll tell you how it was rescued from that.
So it turns out that Metro International Biotech is a company that It has a pretty impressive advisory board, Li Wei Sai from MIT, who I know, Alzheimer's researcher, some other folks.
David Sinclair 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 NMN and its 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, okay, 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 NMN. So the FDA... I want to buy some before this podcast gets to air.
Yeah, I have a boatload.
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 pretty high volume and the bags are 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.
Definite increase in subjective feeling of increase in energy.
And that's because Atiyah, who, again, Peter, forgive me if I'm misspeaking here, but Atiyah was like, there's no way that's going to get into your cells, taking his capsules.
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, keep in mind that the resveratrol thing was similar in the sense that There was a variation on resveratrol 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 resveratrol.
It's not a problem because it was different enough.
So the FDA, We decided to let NAC stay on the market because many, many people wrote letters to the FDA saying, this is ridiculous, this is of value, and it was out as a supplement.
You can't do that.
What's the benefits of NAC? NAC is 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.
I don't know the specific details of why people are taking it.
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.
NMN 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 NMN 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, NMN, 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 whole NMN thing pan out because it's a market competition.
So I really like the sublingual NMN. There's some other talk about the FDA making testosterone something where you're going to have to go to your doctor once a month.
Well, originally what they wanted to do with TRT, remember people were going in and getting their full 200 milligrams, because it's typically testosterone cipionate in this country, 200 milligrams per mil, which is one syringe full if it's a one ml syringe, obviously.
Every other day or every three days at a lower dose to spread it out because the testes normally kick out somewhere between 7 and 15 milligrams of testosterone per day.
And you got two testes, most people anyway.
So most men have two testes, obviously.
So...
What you're talking about is 200 mg 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 visit, etc.
Because I think the number of people that can afford to go to a physician who's really good, who's gonna dose it correctly, Is so infinitesimally small.
And, you know, 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.
Once they start getting older and they see you still look healthy.
Psilocybin.
Psilocybin, testosterone, so many different things that are, like, very beneficial.
Just look at people that are healthy and happy.
Like, what are they doing?
And are they honest?
Talk to them.
You know, and beautiful thing about a podcast is people who are healthy and happy will tell you this is what I do and this is what you can do and this is the pros.
This is the cons.
Go to a doctor.
Get yourself checked out.
Don't do it if you're this.
Don't do it if you're that.
But there's probably a great number of people that could benefit from these things.
And to say, because we were talking about NMN and David Sinclair, 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.
But...
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 in their family or that 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 non-FDA controlling, I think is 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, write letters.
I know it sounds like a, It's like the high school thing, like write letters to your...
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.
You know, because I do realize that, you know, not everybody has, you know, 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 so they can grab that content if they want.