Andrew Huberman: Peptides, Sleep Tech, and the End of Obesity

You don't want to stimulate the sympathetic nervous system so much for so often. It can probably shorten your life. There's a whole category of what are called growth hormone secretagogues, which are very popular. People hear erection, fat loss, energy, tan, like, oh, great. This isn't the kind of thing you do to like go on vacation. You got to be real careful with these things.

0:00

Nearly one in seven Americans is taking a GLP1 drug. 20% have tried them. What do you think the future looks like?

0:17

In theory, you could eradicate obesity. People can lose up to a third of their body weight. Melanitan, which makes people tan from the inside, raises energy and libido dramatically. Fat loss dramatically. BPC157 body protection compound. It's not legal, but it's not necessarily enforced. They list them as for research purposes only, not for human use. I mean, who's doing research on these peptides at home? Anytime you're stimulating cell growth, it could start going awry and may then get a tumor or something like that. If that's within your margins of risk, that's up to you.

0:24

I wanna talk about what's happened over the last five years.

0:54

Slowly, through the 80s, through the 90s and then the early 2000s, everyone wanted to know could take to improve their immune system and their health. There's a very interesting drug that I think is going to become far more popular soon, which is

0:58

when the pandemic hit. People wanted to know what they could take to protect themselves. The first thing that broke out was vitamin D, innocuous enough that doctors didn't push back. That cracked the door open. Then resistance training went mainstream, bringing with it an interest in protein, creatine and caffeine. The vaccine debate got heated. The evening news health segment lost credibility and a realization set in. We are all responsible for our own health. Now. The conversation has moved well past supplements. Red X True Tide could reshape obesity. Peptides are circulating through compounding pharmacies and gray markets. And we may be approaching the point where we stop just reading our biology through wearables and start writing to it using neurotechnologies that control sleep, focus and cortisol directly. A16Z partner Daisy Wolf speaks with Dr. Andrew Huberman, professor of neurobiology and ophthalmology at Stanford University.

1:12

Dr. Huberman, welcome to the A16Z Show.

2:04

Thank you. Delighted to be here.

2:07

I want to talk about what's happened over the last five years. Like since you launched your podcast, there's been an extreme increase in consumer interest and focus on their own health. Like as an investor, we used to kind of think people were only willing to spend on what we'd like call sex or vanity drugs like Propecia Viagra. And that has totally changed in the last five years. And people are really interested in their health. I'm curious what you think the major drivers of that have been and what your role has been in it.

2:08

So I think the major driver was there were a few breakthrough supplements that changed the way that people think about healthcare and decided they needed to be more self directed in their healthcare. Return to that in a second. I think the other thing is that the health and fitness industry collided with mainstream medicine and just self care in the following way. When I was growing up, the only people that lifted weights were bodybuilders, football players, and people going off to the military. I was told if you lift weights, the muscle will turn to fat. If you stop that, everyone in gyms is on steroids. I think what happened is Slowly through the 80s, through the 90s and then the early 2000s, the world started accepting, oh, there are modes of fitness that allow me to eat healthily and take care of myself. And yes, there's some extremes there, but that it was actually quite compatible with a normal healthy life. So what happened during the pandemic was everyone wanted to know, this was before and after the vaccines, wanted to know what they could take to improve their immune system and their health. And the first thing that sort of broke through was vitamin D, maybe because it can be increased by sunlight and everyone gets some exposure to sunlight. It doctors weren't saying, don't take it. The studies on it were kind of mixed, but they were like, okay, you know, everyone starts having some vitamin D around then. The melatonin craze had already kind of come and gone, but that's a hormone. And then as time went on and people started getting more interested in physical fitness, not just jogging or doing cardio, but as resistance training came in, it inevitably brought with it an interest in protein needs. So are you gonna take supplements that increase your daily protein? We could argue about whether or not you need more or less protein. I don't necessarily think everyone needs 1 gram per pound of body weight. Some people feel kind of poisoned, like overwhelmed when they eat that much. I think you have to sense for yourself what you want and what you need. But in any event, people started realizing, oh, this is interesting, if I'm gonna work out, then caffeine before that seems to help. And then gradually now the creatine craze it's funny, creatine was something that was popular in gyms when I was like 16 years old, 17 years old, and then, oh, there are all these cognitive benefits, et cetera. So they came in with the fitness vitamin, came in with COVID and then with COVID people were very actively debating whether or not you could trust the government to give you what you needed to make you healthy. And I think whether you were pro vaccine, vaccine skeptical or anti vax, what became very clear is everyone realized some bell went off. We are all responsible for our own health.

2:42

Totally. I think Covid reminded people of their own mortality and they realized just because, like they go to a doctor for an annual physical does not mean they're healthy or protected or safe.

5:28

A lot of the mental health issues that we saw during the lockdowns were disruption in circadian biology. I know people were indoors more, there was more drinking, there was a bunch of other issues. But I'll just say there's a really beautiful study with more than 80,000 subjects out of the UK that shows, and this is a recent study that shows that the brighter people's days are and the darker their nights, the healthier they are mentally. And this is especially true for people with ocd, anxiety mania, schizophrenia, major depression. I mean, basically every psychiatric challenge is made worse by dim days and bright nights. And so what we saw during COVID was people were just drifting in a circadian sense. It was as if we had put people into a cave and done the cave experiment. And then there was Covid. Right. And then there's all the vaccine stuff, which frankly isn't my domain. But it was so important to me to give people tools to be able to control their circadian biology. Momentary anxiety with things like long exhale breathing, which just simply reduces heart rate, we know, through something called respiratory sinus arrhythmia involves the vagus nerve. You know, the vagus is sending a bunch of sensory information about the body to the brain, but then a percentage of the vagus is descending. It's motor, it controls the heart rate. So when you exhale, the deliberately you slow your heart rate down. You don't need to do breath work. You just, if you want to calm down, you do a long exhale. And so these little simple things for which there's mechanistic science to support them, that was really what we started putting out into the world. So I think that's what happened. And then there we were, you know, in my. I was literally in a closet with my bulldog and my Producer and a microphone and just like talking out to the world. And so people became really strong advocates for themselves and they're like, oh shit, I need to go figure out how to take care of myself.

5:38

What do you make of kind of Maha's role in this broader health awakening? What do you think the effects will be on our health?

7:29

Well, I very deliberately not joined a Maha panel to maintain the flexibility that I want to say what I believe a good example would be. I think that some of the things they're doing are directionally right. Trying to improve the food supply, get people embracing healthy behaviors. These are very much like Huberman Lab things. Right. At the same time, I, for instance, think that the MRNA vaccines for cancer are a transformative, incredible life saving technology.

7:37

And a lot of funding has been cut.

8:17

Yeah, I think that. Well, it's interesting. So the funding for MRNA vaccines for respiratory illnesses has been cut. I was told, and I don't know if this is true, that the funding for MRNA vaccines for cancers was not cut. But there was some very tricky messaging around that at that time. So much so that because I'd gone on Bill Maher and I said, it's foolish to cut this funding for the cancer research. But I got a call from Washington and said, we didn't cut the money for that, we cut the money for the other thing. And I said, okay. So it's like it's. But the messaging has been deliberately broad on both sides. So the challenge has been that because we now, let's just call it duck a duck, we've got right wing media and we've got left wing media, and then we've got a few people in the middle, like Bill Maher, who are kind of like just calling shots.

8:19

I said, you went on Bill Maher. It was a really good episode.

9:09

Yeah. So thank you. But for the most part, the way that clicks and ad revenue, et cetera, is working for these news outlets is don't say anything positive about the other side, even if there's something that they're doing that's favorable and really paint with a broad brush. And both sides are really guilty of that. The left has been not supportive of the moves that I think are directionally correct, which are improving the food supply, getting people more active, et cetera. Because their criticism is that's rearranging deck chairs on the Titanic. That's their criticism. My stance is anything that gets people moving in the direction of their own health, doing things that are proactive for their own health, circadian health, reducing anxiety, improving sleep, Eating cleaner food, more movement is fantastic. Is it the only thing I'd like to see done? No, but it certainly is important. And so I'll be supportive of the things I think are good. And I'm going to criticize the things that I think are not good, and I'm just going to continue to do that. It means I have fewer friends and more enemies. But I'm kind of used to that by now.

9:12

Your personality.

10:17

On the Internet, I often get referred to as an influencer or a health podcaster. They seem to have forgotten my science training, but I get it now. After five years, I really understand how media works, in part because podcast channels have become bigger than a lot of the. At least in the health domain, than the more traditional houses. So I think I've been called a Maha podcaster. I don't know how they got to that because I don't ever recall.

10:18

You also predate Maha.

10:45

Yeah, yeah, they took it from me. No, I'm kidding. The. Yeah. Thank you. I did make a comment about the food guidelines. I said that I thought it was directionally right, but that I would have liked to see more vegetables and fiber some, you know, low sugar fermented foods. And it's so interesting to see how that would get attacked. If I see something like that, that I said getting attacked, then I think, wow, they must be so poorly paid or just so desperate to write something for whatever, 500 bucks or a thousand bucks to make rent that like to spend time on that. I do think that there's been a real drop in standards of what we consider news. And that makes me sad. Frankly, it saddens me because it cheapens the entire health space. And so it's very easy to point at how health influencers and biohackers have contaminated the space. But I actually think that traditional media is more to blame because are we really arguing about whether or not the food guidelines are. Are perfect? They, they were cast as, oh, you know, now they're promoting a lot of meat. No, that's not what it was. If you looked, you act. If you actually read it, the servings of grains and fruits and vegetables were at least as high as what they were recommending for meat. So it's, it's just silly. It's just silly. It's. It's like red shirts. It's like red shirts, blue shirts. Kind of like playground.

10:47

Totally partisanship plays and it gets close.

12:07

Yeah. So I'm, I'm enjoying now I'm in this place where I love that I don't belong to any camp. I feel very free. I've been asked to write op EDS for the New York Times about the MRNA vaccine thing. And I said, listen, I'd be happy to do it. Except they didn't. I was told, I don't know if it's true, but I was told that they didn't cut the funding for cancer. So that makes it a tough op ed to write. At the same time, I've been asked to give my input to folks at MAHA and certainly nih. I've worked very hard behind the scenes to try and ensure that funding for for basic research is not cut. And it looks like I'm not gonna take credit for this at all, but looks like there might be a 2% increase. There's bipartisan support to maintain funding for NIH research. Basic research. So, you know, I. You can't put me in a camp.

12:10

Yep.

12:57

And I'm happy about that.

12:57

Let's talk about peptides.

12:58

Yeah.

12:59

Nearly one in seven Americans is taking a GLP1 drug. 20% have tried them. These numbers continue to rise. You've talked about retrotrutide, a GLP in Lilly's pipeline. What do you think the views looks like as it regards to kind of GLPs? And then let's talk about other peptides after that.

13:00

Yeah, I'm hoping this analogy works. You know, when I was growing up, if you could afford a nice car, you had a nice car. Otherwise there were a lot of kind of junky cars on the road. And then this thing called credit came along where everyone could have a nice car or at least a nice car. So you don't really see that like run down cars, you know, you do some places, but you really don't. I see the GLPs the same way. It used to be that being really fit at a certain age reflected the fact that you did a lot of exercise. And I think that the GLPs make it such that people can be a healthy weight without having to exercise. We know, however, that people should resistance train in particular to offset the muscle loss. But RET at Truetide went through phase three at Lilly. People can lose up to a third of their body weight in a pretty short amount of time with some degree of muscle sparing. So this is also called GLP3. It also seems to bypass some of the side effects that some of the previous GLPs created. Although no drug is perfect, of course. But the real reason retatrutide is interesting to me is that already people have realized that they can get Much lower cost and or take lower doses of GLP drugs by going through compounding pharmacies. Lilly is working very hard to make sure that compounding pharmacies do not sell retatrue Tide. Compounding pharmacies and gray market sources already sell RET at Trutide. Many people are already taking it. It's not legal, but it's not necessarily enforced, and I'm not necessarily suggesting people do, but I think it's going to change society. Where in theory, you could eradicate obesity. In theory, five years from now, what

13:19

percent of Americans do you think are on GLPs?

15:02

Well, I like to think that there's still some people who, because they've exercised good habits up until now, don't need them. I don't know why I like that, but I suppose if you can get away without having to take a drug and get the same result, that's better. I'm guessing that more than half, especially people who come from families or communities where there's a lot of obesity, are gonna be taking them, probably taking them at lower dosages than are prescrib. Um, and I, I don't think that you can control the compounding pharmacies in gray market, mostly because. And I could be wrong here, so I want to be careful, but I'm not aware of. Of a major adverse event. You know, it's a little bit the same way that steroids were discussed in the 80s and 90s, but people were dying, going into rages. They were coming up with als. You know, they're having a lot of problems. I'm not aware of anyone dying from taking BPC157. So there's a lot more room for experimentation. I'm not suggesting people do that, but the margins for error seem to be greater.

15:06

Yeah, I mean, my understanding is it's not the. Like, the compounded drugs are probably generally safe, but it's the fear of contamination or a meningitis outbreak or whatever. It's happened in the past. With compounding pharmacies being just less regulated.

16:09

Yeah.

16:24

Than traditional drug manufacturing.

16:25

Yeah. I think it's really interesting too, because as I watch this space, this peptide space emerge, which has mainly been around the GLPs. Right. And BPC157, body protection compound, which may or may not accelerate healing in animal models, it's very clear that it can improve cartilage growth, nerve regrowth, as well as vascular growth, which is a little bit worrisome. If you have a tumor, you don't want to vascularize the tumor. No one has the right control experiment in themselves because they'll say oh, I injected my shoulder and I healed so much more quickly. But it goes systemically so you can't like compare the two shoulders. And so but no one wants to be in the control group and the people are just assuming it's bpc they're taking it. I mean I think we probably would have heard of an adverse event by now, but who knows, maybe some something will pop up. I think that when it comes to the GLPs in particular, there was a lot of debate for a while the exercise fitness community were saying, oh, you know, you don't want to take a drug, you just need to eat right and exercise. I disagree. I think that some people, people have accumulated so much adipose tissue that it's modified their metabolism and even, perhaps even brain circuitry and appetite that it's really, really helps them. And obviously behaviors and these drugs are gonna be the best combination or just the behaviors if you can get away with them. I've never taken a glp, so I can't talk about the experience of it. I have tried various peptides. I've tried bpc. I don't know if it helped me or not. I didn't have an injury. I didn't notice that I recovered any more quickly from exercise. I've tried Pinealin as a sleep peptide. It gave me three hours a night of REM sleep which was pretty awesome. Very little human data. So now I just.

16:27

Are you continuing that?

18:04

No, I just take AGZ and that's the truth.

18:05

So you want more data.

18:07

I'm a little scared about taking something that in animal models has been shown to both improve the function of but maybe also the proliferation of pinealocytes which produce melatonin or that they and other cells in the pineal because anytime you're stimulating cell growth you could, it could start going awry and then get a tumor or something like that.

18:09

Maybe you can just kind of speak more broadly about the non GLP peptide craze. There's been a lot of kind of black market activity around Chinese peptides.

18:30

I love how that term has come about.

18:42

Don't. There's looks maxing like people. What is a peptide? What do you recommend? What should people avoid?

18:44

Sure. Short course. A peptide is just a short chain of amino acids make up a protein. Insulin's a peptide. All the things we're talking about up until now are peptides. So the phrase peptides has been kind of co opted to mean a certain sort of clique of peptides. Just like the word steroids in people's minds. They think bodybuilders. But you know, estrogen is a steroid hormone. People are always shocked to hear that, you know, so if you take estrogen, you're on steroids. Okay? But we know what people are saying when they say on steroids. So there are androgenic steroids, they're estrogenic steroids. There's corticosterone, okay? Just in the same way there are peptides that are to reduce hunger and appetite. The glps retatrutide being the newest generation one soon to be released through Lilly, but already out on the market from gray market sources are these sources that are sold all over the Internet that are American or Canadian or whatever, and they list them as for research purposes only, not for human use. But they're selling them knowing that people are taking them. I mean, who's doing research on these peptides at home, right? This is not your. Unless you're my lab down the road or someone else's lab, like, of course people are taking these. They tend to be the gray market sources for research purposes only, not for human use, tend to be 99% purity, which means they've been cleaned of most things. Except I do worry a bit about repeated injection of substance that contains 1%, say LIPI polysaccharide, which can cause inflammation. So maybe not in one injection, but maybe repeatedly over time, as well as other contaminants. Black market sources. And when you hear Chinese peptides are companies online, we don't know that it's all coming from China, by the way. They sort of get. Get hit the hardest in this. But people refer to Chinese and black market peptides as people are going online buying red at truetide and you have no idea if it's red at truetide. In contrast to the gray market sources where they might not be the cleanest. But you know, we. They give you a data sheet that says this was tested. And if it says red or true tide, if it says BPC157, that's what's actually in the vial and only that. Okay, so that's an important distinction. Compounding. Pharmacies have been compounding all sorts of things, selling drugs more cheaply than drug companies. They are controversial for that reason. We could talk about that. But other peptides that are interesting, excuse me, BPC157 for tissue repair, reducing inflammation, seems to have very, very high LD50. No one's really discovered it. And people have been injecting enormously high amounts of this. I've not heard of an adverse event. I don't recommend doing that, however, because you don't want to vascularize a little tumor you might have on your liver or in your brain. But maybe for short term use to treat an injury, if that's within your margins of risk, you know, I mean, that's up to you. Ideally you'd get it from a compounding pharmacy, if you can, or from one of these gray market sources before you would go to a black market source. Injectable. Injecting locally seems to be better than taking it systemically. Taking the oral forms. It's unclear how much of that BPC157 gets into your bodily tissues. Pinealin, as I mentioned for sleep, has become very popular. There's a whole category of what are called growth hormone secretagogues which are very popular. Tessamorelin, Ipamorelin, Sermorelin, MK677, these all stimulate the pituitary to release growth hormone, but they themselves are not growth hormone. They will increase the amount of deep sleep that you get at night. Typically you'll take these 30 minutes before sleep, ideally not having eaten anything in the previous few hours. Increased growth hormone and IGF1. Some of those things I just mentioned are FDA approved. So sermorelin for instance, I forget the exact indication, but to increase height, for instance, or tissue repair after surgery, increasing growth hormone can be beneficial. Some people will just take growth hormone, but growth hormone is very expensive. Somatotrope omnitrope. So that's what these peptides are very commonly used. Those have been researched. So assuming the sourcing is clean, we have a lot of human data on the ones I just described as opposed to Pinealin and BPC157 where you have basically no human data. So there are human data on things like melanitan, which makes people tan from the inside, raises energy and libido dramatically, fat loss dramatically.

18:50

Do we put that in the looks maxing category?

23:38

I don't know. I. Or energy maxing or something? Yeah, it's kind of interesting. I mean, I mean there's a lot about. So melanitan and some similar peptides have been, have been FDA approved for hyposexuality in women. I think that Vi Lisi is the drug for women. Men take it too. I have to say those drugs, Melanitan is very risky. Some of the skin color changes, the kind of oranging of the skin can be permanent. So you have to. This isn't the kind of thing you do to like go on vacation, right. This is, they might have more permanent,

23:40

not the pre wedding.

24:14

Right. And there's the risk for men of priapism, which, you know, the, the last erection you may ever have, it might last eight hours, but that might be the last one. It can cause damage to the nerves and penile tissue. So people, you know, people here like erection, fat loss, energy tan, like oh great. You know, and you think you gotta be real careful with these things with they do get abused, but I just mentioned these things and the melanotin whole pathway is super interesting because it raises dopamine. Dopamine and pigmentation are linked through an enzyme called tyrosinase. Not to get technical here, but some animals look like they're albino in the winter, except they have dark eyes like an arctic fox. And then the summer sunlight comes, hits this pathway increases dopamine, pigments the fur and they breed. So there's a relationship between sunlight, dopamine, fecundity and these kinds of things. It's pretty interesting, right? So people are taking these things and they're getting them either through black market, which I don't recommend gray market, which is risky, or compounding pharmacies. So now we're sort of ascending levels of stringency and then you get to pharma, sells it, you can buy sermorelin from one of the drug companies, you can buy retatrutide soon from Lilly. The cost tends to be, you know, three to 10 times higher, the dosage recommendations tend to be higher. People have figured out doing their own kind of rogue experiments that you can get by taking much lower doses of things. So I think one of the more interesting uses of GLPs that I'm hearing about mainly from people getting it from compounding pharmacy and gray market sources, is that you can get by with taking much lower doses. Some people are using it for reducing alcohol craving, for reducing just cognitive noise more generally, which I think is pretty interesting. And this is probably a good opportunity to just mention things for focus, since we were going to talk about that. You know, if, if you ever have in your copious amounts of spare time, which I'm sure you never have because no one seems to have it anymore. There's some pretty interesting conversations that have taken place on X about drugs for focus because all the other hackers like to focus and program and work. And so we all have heard of Modafinil, used to treat excessive daytime sleepiness. It may have a slight cognitive enhancing effect, but it's mostly a focusing thing. It increases energy when you have poor sleep. It was designed to treat narcolepsy and other things.

24:16

Better than Adderall.

26:52

Different than Adderall because Adderall is more of an amphetamine type stimulant. Very interesting paper came out recently from Washu showing that Adderall. It wasn't really Adderall specifically, but Ritalin and other stimulants seem to improve focus about as well as a good night's sleep. But a lot of people aren't getting the good night's sleep they need because of it also. Right? Exactly. And it's not increasing focus per se. It's increasing alertness, which allows you to allocate your focus. This is as far as I know. There are no drugs to increase focus per se now. But the two things are tethered enough. You know, you need alertness to alertness. Gates focus, sleep. Gates alertness. Unless you take a drug like Adderall or Modafinil. There's a very interesting drug that I think is gonna become far more popular soon, which is already FDA approved, called Sunosi S U N O S I which is approved for excessive daytime sleepiness very well in a trial for adhd. And it's a little bit of a dirtier drug in the sense that it doesn't just hit the dopamine and norepinephrine pathways that some of the other drugs I mentioned do. It also hit serotonin a little bit. Seems to have a much gentler arc of alertness and focus. I confess, I've tried. Was a bit too much. And I was like, I don't. I think I'm gonna stick with caffeine for now. People will take Wellbutrin, the atypical antidepressant at low dosages to increase epinephrine. Dopamine a little bit for focus. I mean, people are doing this all the time. Nicotine. So there's a lot of stimulant use right now for focus. So I do think that if there is a peptide that can be taken safely, that can reduce the amount of noise in the system and allow people to be more focused and allocate their attention in a more deliberate way without having to take stimulants, I think that would be fantastic. I think there's an excessive amount of stimulant use. And this is coming from somebody who drinks a lot of caffeine and frankly, would love to have a drug that could increase focus. But you always pay the piper somehow, either in sleep or in cardiac challenges. I mean, you don't want to stimulate the sympathetic nervous system so much for so often, it can probably shorten your life.

26:53

What does a proactive approach to health look like maybe five years from now? And what technology do you think needs to be built to enable that? Maybe put another way, like you. It feels like you've covered every single health topic on your podcast.

29:08

Still going.

29:22

What do you think you're gonna be covering in kind of 26, 27, 28?

29:23

Yeah, we need to do autoimmune cancer. We've got a bunch of things to go. But, yeah, I mean, maybe this is a good opportunity to kind of weave in reading and writing to biology. So reading. I mean, people are wearing sleep sensors. This is, like, commonly done now, right? But you can't write to the sleep system yet. I think in five years, we're gonna look back and we'll be like, can you believe it? We were, like, cooling the room to try and fall asleep. I think we'll still have cooling mattresses, but, like, it's gonna be so crazy because there should be a way that you could just put, like, a small. Like, you can cool the core of the body more efficiently through the palms and the soles of the feet. There's reasons for this. The vasculature there actually lacks capillaries, so you can pass. You're not really cooling the blood directly, but you're essentially dumping more heat. This is cool technology from Stanford. I mean, I think someday, not long from now, you'll go to sleep with a little thing in your palm or on your feet, and your core body temperature will just drop. You wear an eye mask that's moving your eyes back and forth, and within six minutes or less, you'll be asleep. When you wake up in the morning, you'll flip that thing on. It'll give you a burst of 10,000 lux light, and then you'll go outside. These are trivially straightforward technologies to build, but no one's really building them right now because we're like, oh, we'll just cool the whole room and we'll, you know, and I'll, you know, look at a 10,000 lux, you know, thing over there while I. It's. It's just. It's so easy to move these things to the body. So writing to our biology around sleep is going to be a big one. The re. The other forms of reading that I think are happening now that are soon going to be writing as well. Well, I'd love to see. Not just real time Glucose sensing. Love to see real time cortisol sensing, morning cortisol peak. Getting that. I mean, I can't overstate the importance of for everyone, women, men, pre menopausal, postmenopausal, pregnant, not pregnant, kids, you want a big morning cortisol pulse and then you want that to trough in the late afternoon and stay low. You get that and you win 90% of the game. But we don't have real time cortisol measures.

29:27

People are working on these things. Like right now for our listeners, there are continuous glucose monitors and they put kind of a little piece of like dental floss under your skin that monitors glucose in real time. Normally for diabetics, but people are working on kind of multi biomarker sensors that could tell cortisol or a variety of things.

31:34

Yeah, I think that, you know, real time cortisol would be very interesting. Of course you'll get little blips of cortisol as you stress throughout the day. And the real question is, can you bring your cortisol back down afterwards? These blips and cortisol aren't a problem. If they come back down sometimes if that whole curve gets shifted to the right a bit, there's actually worse cancer outcomes, reduced longevity. There are a lot of reasons to want that cortisol spike really big and then have it trough into the afternoon. So that's one that I'd love to see. And then once you see that, you know, if at 5 or 6pm Your cortisol's riding high, you know you'd love to be have a way that you could dial it down and you could do that through conventional methods like long exhale breathing or short meditation, maybe eating some starchy carbohydrates. People forget that cortisol's main job is to deploy energy in the body. Is why it gives you a glucose bump. And there's a reason why starchy foods we call comfort foods is that it provides this sort of energy that allows cortisol to come down. This is why a lot of people who follow very low starch diets oftentimes feel really stressed or at the edge of stress. I can't sleep well unless I've had enough starches during the day.

31:54

Interesting.

33:00

Now if I haven't done any exercise or anything, I don't really need many starches. But if you're weight training, you're busy, you're using your mind, you're moving about, then you know it's 11 o' clock at night and you're fried and you Fall asleep and then you're up at 3 in the morning. I'm willing to bet that had you had maybe a bowl of rice with dinner, you might actually sleep a lot better. People don't talk about this, especially in the context of ketogenic diets, which, sure, you'll have more energy, but it can really mess up your sleep.

33:00

You heard it here. You can have carbs at dinner. I love that.

33:25

Please do it. Please. In fact, if you're gonna have carbohydrates at any time, should be within a couple hours after resistance training or maybe three, four hours before sleep, maybe even a couple hours before sleep. People who reduce their carbohydrate intake too much are. You're not going to sleep well. You're just not. Not nearly as well as you could if you had some moderate carb intake. Obviously, you want to try not to eat too close to bedtime and so forth. So I think that the, the. I do think that the whole peptide thing is, you know, the. The horse is out of the stable. I think in five years, you and I are going to have a little cocktail. It's gonna be one injection or one pill, and it's gonna be a little bit of pinealin at night combined with something else. It's gonna be in the morning. Something. Whatever it is that you need to. Not you specifically, of course, but whatever. I need to, you know, ramp up my dopaminergic system a little bit to make sure that I'm getting enough micronutrients that maybe I'm gonna put a little Clotho in there to protect me against Alzheimer's. I mean, I think all of that stuff is gonna be commonplace. The same way that people are not afraid of vitamin D or they're. Or magnesium, people are taking. Magnesium's kind of the next wave of accepted supplements. I think that feel safe enough for most. Not all people, but safe enough. I think most everyone is going to be doing that, and I think the cost is going to be low enough that that statement, most everyone is a real statement.

33:28

I love the Reid vs. Wright breakdown. I think on the Reid side, it feels very clear where the world is going. Like, ChatGPT is already an incredible doctor, probably better than an average doctor in americ and can get access to it. Knows nothing about you today, but we have these health information exchanges coming online. You know, function. We're building something that pulls in, you know, all of your health records from EHRs, all of your wearable data, all of your function blood test results, your imaging and Feeds it into this model in real time where it's going to diagnose issues with you before you even feel symptoms. And we saw like the 1.0 version of that in Covid when people's wearables kind of realized they had Covid before they even felt sick. And then when we have these continuous glucose monitors that can monitor a whole lot more like the diagnostics and read side feels like very kind of clear where the world is moving. The right is super interesting, the right side. And that's where I think there are a million more ways this world could go.

34:56

Yeah, I mean I borrow this read write thing from my life as a neuroscientist. I mean for many years we wanted to chart the cell types of the nervous system. What are the connections? So you're looking at the hardware. Then it was, let's record neurons, individual neurons, groups of neur, extracellular intracellular calcium imaging, voltage dyes. Okay. Now let's do causal experiments. Let's quiet those cells, increase the activity of those cells in the context of a perceptual experiment or a behavioral experiment in humans, ideally. Right. But it was done first, you know, mice, I mean everything, rat, cat, monkey, bat. But it was, you know, it's got, you know, mice and it was non human primates and now, and now humans. And so I think, when I think about reading and writing to our physiology, it's like, let's figure out what the normal, normal patterns of activity are and let's have simple ways to implement what's needed. Push that cortisol bump a little bit right now. It's so crude, it's almost funny. It's like, oh, will ashwagandha reduce this herb? Reduce cortisol?

36:00

Yeah.

36:55

People take you in the morning, that makes no sense. You want your cortisol elevated in the morning. People will take a little bit in the evening and yeah, it'll calm them down a bit, but if they take it for too long, it can start to have some off target effects. So I always say you don't want to take high doses for too long. We're cooling the room. Great. Everyone should cool the room. I cooled the room in my hotel yesterday. I love, love, love the eight sleep. Yes, they're a sponsor, but I think it's of my podcast. But I think it's a phenomenal technology. So much that I miss it when I travel. But ultimately we're going to be cooling the body through. Just cool your core. Right. I should travel with a little thing I can put on my feet. And socks. That'll cool my core. So I sleep and wake me up by one way to really improve the amount of REM sleep you get not taking anything. Warm your body in the last. Warm your sleeping environment in the last hour before you wake. Remember, levels go up. So you want it cool, then really cold, then warm. We shouldn't be relying on external hardware so much. And so that's why I think the sleep mask thing, et cetera. I also think the real holy grail in all this is the ability to dial in cognitive states. I don't think I know I'm going to. Matt McDougall, who I knew when he was at Stanford, now is at neuralink. He's phenomenal. Dan Adams, I think that group is terrific. I think our friend Eddie Chang, chair of neurosurgery at ucsf. Phenomenal. They're reading and writing to the nervous system. But I do not think in the next 10 years I'd love for them to prove me wrong, but I do not think that your hippocampus is gonna be pulling in twice as much memory at twice the rate or something like that. It's just not gonna happen. We don't even understand how the hippocampus does that under normal conditions well enough yet. But I can imagine putting on a pair of glasses to sit down and do some work and your visual field goes and there's some sort of level of stimulation, external stimulation, that ramps up your level of focus. You set a timer and for the next 40 minutes you'll experience the kind of focus that you've only had a few times when you had all conditions right. And you'll work for that 40 minutes and then you'll click that you're done. And then you'll take those things off and you'll go do something else.

36:55

I love that. I try to figure out myself, that's

39:01

coming, coming, that's coming. And I keep pointing to the eyes. Like the sleep mask that moves the eyes to make you fall asleep, et cetera. Most of the access to the brain and nervous system is going to be maybe through the vagus, through some superficial stimulation for calming effects or other things. Actually, vagal stimulation mainly causes alertness. But maybe some non invasive technology will get good enough. Right now I'm not really seeing it, but it's coming. But the amount of things that you can do to modify brain state through this region, just the eyes, ears and the superficial nerves that run around there, is just phenomenal. So if I were going to personally invest in any companies that were doing that sort of thing, that's the body area and the sorts of things that I'd be really focused on.

39:04

Question on AI, you've rose to prominence distilling kind of complex health information and studies into something that people can understand easily. This is now something like AI can do quite well. How do you think about that? How do you use AI in your day to day life?

39:49

Well, I use Claude to quiz myself. Claude is really good at generating tests for me on knowledge, so that's where I've been using it the most. I love the idea that an AI version of me could potentially deliver a podcast. It would allow me to do other things. Sort of half kidding that there, here's what I know for sure is that there are many easy ways to generate a list of the 10 most important things to do to get great sleep. The 10 most important things to do to ensure brain health. Given what we know, it's very easy to generate a list. But given that, why don't people just do those things? And I think it's because there's something about the human brain where the probability that we take on a protocol or change our behavior is highly dependent on a, of course, the effectiveness of that behavior as we experience it, but also how we learn the information. When you understand mechanism, I think it gives a higher probability that somebody is going to implement the advice and it may even change the way the protocol works. Now you could say that's all placebo or belief effect, but maybe not right. Some of it is also the flexibility that's provided when you understand mechanism. You understand that if you can't get sunlight in the morning today, you just double up tomorrow. Because it's a summation system. It's not, it's a window that yes, if you miss for too many days it becomes problematic, but once you understand how it's summing photons, et cetera. And AI could probably deliver that information, but I don't know that it can build the, build it well enough. But maybe I'm just telling myself that because I don't like the idea of being replaced by AI, but I don't know. I mean, I'd probably build the platform where the AI version of me was doing it. So I don't, I don't have a problem poaching myself.

40:05

Longevity, escape velocity. Do you think that's real or fantasy?

41:59

I mean, I think the way that people are defining longevity now, it's, it's got a lot of pretzel twists in it to try and say, well, I Didn't say we were gonna live forever. I might, you know, I'm gonna, might upload my content. Like if we're talking about of this physical body that we currently inhabit, minus any robotic architecture inserted, I think it's pretty clear that the genetic upper limit is about 120. And for most of us it's probably closer to about 105. So taking great care of ourselves, aiming for 100. I think aim for 100 is my motto. Just aim for 100 healthy. I think that's doable. I'm very excited. I guess it's a little bit of a edgy topic, but I'm very excited by Tony Weiss, Corey's work from Stanford. And he had a company that's now sold Alkist, which talked about factors in young blood and in exercised blood that can rejuvenate the brain and body. So some of these factors that circulate after exercise are really beneficial. And yes, there are factors in younger blood that seem to be beneficial. This gets people worried about vampires and stuff. But we're talking about ethical things here. Provided, ethically gathered and provided ethically, of course. What I think is really interesting is that there are some proteins that really appear to be rejuvenating. I also think if someone came along tomorrow and said, andrew, why don't we collect your blood after exercising for the next six months and let's just bank your blood so that if you ever have an injury, you can get some really healthy, healthy of your own blood. I would do that. It's kind of primitive from the standpoint of, you know, AI and all these things being available. But we know that infusion, blood infusions are beneficial. There's been a clinical trial for this. We know that blood infusions of exercise blood are even more beneficial. We also know that after a brain injury or a bodily injury that things that are not just pro inflammatory circulate in the blood that are bad for all organs. So. So I think a very low bar but useful technology would be to bank a bunch of my own blood after exercise. And look, I'm healthier now at 50 than I'm likely to be at 70. I would love my own blood at 70. Just get an infusion once a week. Totally. I do that before I get some glutathione nad infusion, which is probably fine, but I don't know that it provides that much.

42:04

Last question. You have a pet octopus?

44:33

I do.

44:36

That is unusual. Tell us about him or her.

44:36

Van Gogh.

44:39

Van Gogh.

44:41

Van Gogh, yeah. It's a Starry Night Octopus, hence Van Gogh. And then it got even more eerie because Van Gogh lost one tentacle in the fan. So it was like a. So when my lab was in San Diego, before I moved to Stanford, I worked on a different cephalopod called cuttlefish, which are like little underwater monkeys. They're incredibly intelligent. They're known for being great camouflagers. There's also this twist in their sociobiology where the males will camouflage as females, infiltrate and then mate with the females. So I was studying their vision. They're very interesting because they can see in panorama and they're very placid. But then when they want to hunt, their eyes translocate to the front and they generate depth perception, stereopsis to hunt. And I was very interested in whether or not they had two visual systems. And I'm very interested in depth perception and prey capture and how that relates to bodily states. Just to weave this into what we were talking about earlier, when your eyes are focused on a single point, your levels of arousal and energy, attention go up. When your eyes are sort of. When your gaze is dilated, like you're viewing the corners of the room and the ceiling and the floor, that tends to make. Put us into a calmer state. Some animals only exist in one or the other. We are unique, that we can switch back and forth. Some other animals can. But I was studying that in cuttlefish. When I. I moved to my current home, I converted an art gallery into a living space. I put a gym, I put a place to work downstairs where there's no wifi. I don't bring my phone down there. That's where I prepare for podcasts. I do drawing. I'm doing some illustrations these days for my book and a few other things. And then it's like, oh, I've always loved Aquaria. I'm going to put a freshwater discus tank. And I put a huge freshwater discus tank. I was like, you know, I think I need cephalopods again. So I got an octopus, I got a Starry Night octopus. And here's what I'm trying to do with the octopus. This has everything to do with AI. I'm trying to get the octopus to report to me what it's thinking, because I do think they're very intelligent. And we say, oh, they're like aliens. They're so intelligent. But we get the camouflage. They're very interactive. But an underwater iPad and the appropriate use of touchscreen and AI, I'm hoping, will allow this or another octopus to communicate something about what it's thinking, okay, so how would you do this? Right. So you can't apply a typical large language model, so you have to do it based on the coloration patterns on the camouflage patterns. So it turns out AI can actually learn a lot by correlating the behaviors of an octopus with its camouflage patterns. The problem has always been that you have to do that in real time as the animal. Animals swimming around and hunting and doing various things. So the challenge now is to get it to interact with stimuli that will give enough information so that this model, I don't know what we call it. We don't have someone more clever than I can come up with something. It's not LLM, I don't know. It's something else. Something related to camouflage patterns could start revealing that certain camouflage patterns relate to certain behaviors, which relate to certain nuance in the behaviors. And then it could start teaching itself. And then the idea would be that the AI would present something to Van Gogh or another octopus. I've got more on the way that would start to influence behavior. There could be not just conversations between octopi, but where maybe I could speak. It would translate that into octopus, we call it. And then we could communicate. And here's the reason for doing this. Okay, so there's this idea that other. Other animals have all this intelligence. Normally we measure that through behavior or through some, you know, highly specialized aspect of their nervous system or body, like barn owls or, you know, they all do these fantastic feats or what you find. And I don't like it, for instance, when I see, oh, this guy taught an octopus how to use a piano. I saw that. That's not interesting. Actually, all that tells you. That tells you more about how hard humans are willing to work to train a different organism to do something pretty rudimentary century compared to what humans can do. Tells you everything about humans obsession with teaching other animals to be more human. I'm interested in what the octopus understands about the world and can communicate that to me, because I don't know that stuff. I can learn to play a piano. Why would I want to teach an octopus to play a piano? That's still.

44:41

That's fascinating. I think you need a whole podcast outlining your experience.

49:15

Yeah, well, maybe this is what happens when we run out of topics to put on the hlp. And I'm probably not thinking about this as cleanly as I could or should, but it was, I have to say, just in kind of, you know, wrapping this, you know, monologue, it you get to the point doing public facing health information where you can kind of feel the saturation point. And we need more technologies and tools, and I think that's great, and I really am excited for what's coming. But the at some point the conversations become clear that we need more. And then you think about this whole vast landscape of animal intelligence, and people have placed this thing on the cephalopods. Like they're really smart. They know. I mean, they might be idiots for all we know, just dazzling us with colors. I don't think they're idiots. I think that they are accessing a certain perceptual landscape and they're thinking hard about what's there based on things I've observed and others have observed. But we really need to figure out a way to let them tell us what they're thinking.

49:20

Amazing. Bandre Huberman thank you for coming on the A16Z Show.

50:24

Thanks for having me here.

50:28

Thanks for listening to this episode of the A16Z podcast. If you like this episode, be sure to like, comment, subscribe, leave us a rating, or review, and share it with your friends and family. For more episodes, go to YouTube, Apple Podcasts, and Spotify. Follow us on X8A16Z and subscribe to our substack@A16Z substack.com thanks again for listening and I'll see you in the next episode. As a reminder, the content here is for informational purposes only, should not be taken as legal, business, tax, or investment advice, or be used to evaluate any investment or security, and is not directed at any investors or potential investors in any A16Z fund. Please note that A16Z and its affiliates may also maintain investments in the companies discussed in this podcast. For more details, including a link to our investments, please see a16z.com disclosures.

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