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

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

Nearly 1 in 7 Americans is taking a GLP-1 drug. 20% have tried them. What do you think the future looks like?

In theory, you could eradicate obesity. People can lose up to a third of their body weight. Melanotan, which makes people tan from the inside, raises energy and libido dramatically, with dramatic fat loss. BPC-157—body protection compound—is not legal, but it's not necessarily enforced. They list them as for research purposes only, not for human use. Who's doing research on these peptides at home? Anytime you're stimulating cell growth, it could start going awry, and then you might get a tumor or something like that. If that's within your margins of risk, then that's up to you.

I want to talk about what's happened over the last 5 years.

Slowly through the '80s, through the '90s, and then the early 2000s, everyone wanted to know what they could take to improve their immune system and their health.

Dr. Huberman, welcome to the a16z Show.

Thank you. Delighted to be here.

I want to talk about what's happened over the last 5 years. Since you launched your podcast, there's been an extreme increase in consumer interest in and focus on their own health. As an investor, we used to think people were only willing to spend on what we'd call sex or vanity drugs, like Propecia and Viagra, and that has totally changed in the last 5 years. 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.

I think the major driver was that there were a few breakthrough supplements that changed the way people think about health care and made them decide they needed to be more self-directed in their health care. I'll return to that in a second.

I think the other thing is that the health and fitness industry collided with mainstream medicine and self-care in the following way. When I was growing up, the only people who lifted weights were bodybuilders, football players, and people going off to the military. I was told that if you lift weights, the muscle will turn to fat if you stop, and that everyone in gyms is on steroids. I think what happened is that 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.” Yes, there are some extremes, but that was actually quite compatible with a normal, healthy life.

What happened during the pandemic was that everyone wanted to know—before and after the vaccines—what they could take to improve their immune system and their health. The first thing that broke through was vitamin D. Doctors weren't saying, “Don't take it.” The studies on it were mixed. They were like, “Okay, you know, take it.” Everyone started having some vitamin D around.

Mhm.

Maybe because it can be increased by sunlight, and everyone gets some exposure to sunlight. The melatonin craze had already come and gone. That's a hormone.

As time went on and people became more interested in physical fitness—not just jogging or doing cardio—but as resistance training came in—

Mhm.

—it inevitably brought with it an interest in protein needs. So, you're going to 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 g per pound of body weight. Some people feel poisoned or overwhelmed when they eat that much. I think you have to sense for yourself what you want and what you need.

In any event, people started realizing, “Oh, this is interesting. If I'm going to work out, caffeine beforehand seems to help.” Gradually, now, there's the creatine craze. It's funny—creatine was something that was popular in gyms when I was 16 or 17 years old. Then people realized there are all these cognitive benefits, et cetera. So, it came in with fitness. Vitamin D came in with COVID.

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. I think whether you were pro-vaccine, vaccine-skeptical, or anti-vax, what became very clear was that everyone realized—some bell went off: We are all responsible for our own health.

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

Mhm. A lot of the mental health issues that we saw during the lockdowns were disruptions in circadian biology. I know people were indoors more, there was more drinking, and there were a bunch of other issues, but I'll just say there's a really beautiful recent study with more than 80,000 subjects from the UK that shows that the brighter people's days are and the darker their nights, the healthier they are mentally. This is especially true for people with OCD, anxiety, mania, schizophrenia, and major depression. Basically, every psychiatric challenge is made worse by dimmed days and bright nights.

What we saw during COVID was that 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? 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 control their circadian biology and momentary anxiety, with things like long-exhale breathing, which simply reduces heart rate.

We know through something called respiratory sinus arrhythmia that it involves the vagus nerve. 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 heart rate. So, when you exhale deliberately, you slow your heart rate down.

You don't need to do breathwork. If you want to calm down, you do a long exhale. These are 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. I was literally in a closet with my bulldog, my producer, and a microphone, just talking out to the world. People became really strong advocates for themselves. They're like, “Oh, I need to go figure out how to take care of myself.”

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

I very deliberately did not join the MAHA panel to maintain the flexibility to say what I believe. A good example would be that I think some of the things they're doing are directionally right: trying to improve the food supply and get people embracing healthy behaviors.

These are very much like Huberman Lab things, right?

Mhm. At the same time, I, for instance, think that the mRNA vaccines for cancer are a transformative, incredible, life-saving technology.

And a lot of funding has been cut.

Yeah, I think it's interesting. 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 cancer was not cut. But there was some very tricky messaging around that at the time.

I'd gone on Bill Maher and said, “It's foolish to cut this funding for cancer research.” But I got a call from Washington, and they said, “We didn't cut the money for that. We cut the money for the other thing.” And I said, “Okay.” The messaging has been deliberately broad on both sides.

The challenge has been that because we now—let's just call a duck a duck—have right-wing media and left-wing media, and then we've got a few people in the middle like Bill Maher who are just calling shots, the way that clicks and ad revenue are working for these news outlets is: don't say anything positive about the other side, even if there's something they're doing that's favorable. Really paint with a broad brush. Both sides are really guilty of that.

The left has not been 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 that's rearranging deck chairs on the Titanic. That's their criticism.

My stance is that anything that gets people moving in the direction of their own health—doing things that are proactive for their own health, improving circadian health, reducing anxiety, improving sleep, eating cleaner food, and moving more—is fantastic. Is it the only thing I'd like to see done? No. But it certainly is important.

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. 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.

My personality 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. I understand why. Now, after 5 years, I really understand how media works.

In part because podcast channels have become bigger than a lot of the more traditional media houses, at least in the health domain. 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—

You also predate MAHA.

Yeah, yeah, they took it from me. No, I'm kidding. The—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 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 or $1,000—to make rent that they spend time on that.” I do think 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.

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. Are we really arguing about whether or not the food guidelines are perfect? They were cast as, “Oh, now they're promoting a lot of meat.” No, that's not what it was.

If you looked—if you actually read it—the servings of grains, fruits, and vegetables were at least as high as what they were recommending for meat. So, it's just silly. It's like red shirts, blue shirts, kind of like a playground.

Totally. Partisan shift plays, and I get it.

Yeah. So, 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, and I said, “I'd be happy to do it, except I was told that they didn't cut the funding for cancer.” 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 NIH basic research is not cut. It looks like—I'm not going to take credit for this at all—but it looks like there might be a 2% increase. There's bipartisan support to maintain funding for NIH research, basic research.

You can't put me in a camp, and I'm happy about that.

Let's talk about peptides. Nearly 1 in 7 Americans is taking a GLP-1 drug. 20% have tried them, and these numbers continue to rise. You've talked about retatrutide, a GLP-3 in Lilly's pipeline. What do you think the future looks like with regard to GLPs? Then let's talk about other peptides after that.

I'm hoping this analogy works. When I was growing up, if you could afford a nice car, you had a nice car. Otherwise, there were a lot of junky cars on the road. Then this thing called credit came along, where everyone could have a nice car. You don't really see run-down cars in a lot of places anymore. You do in 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. 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.

Retatrutide went through phase 3 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. This is also called GLP-3. 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 people have already 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 retatrutide. Compounding pharmacies and gray-market sources already sell retatrutide.

Many people are already taking it. It's not legal, but it's not necessarily enforced. I'm not necessarily suggesting people do it, but I think it's going to change society where, in theory, you could eradicate obesity.

In theory. 5 years from now, what percentage of Americans do you think are on GLPs?

I like to think that there are still some people who, because they've exercised good habits up until now, don't need them. I 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 going to be taking them. Probably taking them at lower dosages than are prescribed. I don't think that you can control the compounding pharmacies in the gray market, mostly because—I could be wrong here, so I want to be careful—but I'm not aware of a major adverse event.

It's a little bit the same way that steroids were discussed in the '80s and '90s, but people were dying, going into rages, and coming up with all sorts of problems. I'm not aware of anyone dying from taking BPC-157. 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.

Yeah. I mean, my understanding is that compounded drugs are probably generally safe, but the fear is contamination or a meningitis outbreak, or whatever has happened in the past with compounding pharmacies being just less regulated than traditional drug manufacturing.

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 BPC-157, 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 it healed so much more quickly.” But it goes systemically, so you can't compare the 2 shoulders. No one wants to be in the control group. People are just assuming it's the BPC they're taking.

I mean, we probably would have heard of an adverse event by now, but who knows? Maybe 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 and fitness community was saying, “Oh, you don't want to take a drug. You just need to eat right and exercise.”

I disagree. I think that some people have accumulated so much adipose tissue that it's modified their metabolism and perhaps even brain circuitry and appetite, and it really helps them. Obviously, behaviors and these drugs are going to 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 Pinealon as a sleep peptide. It gave me 3 hours a night of REM sleep, which was pretty awesome. There is very little human data. No, I just take AGZ, and that's the truth.

You want more data.

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 the glial and other cells in the pineal.

Maybe you can just speak more broadly about the non-GLP peptide craze. There's been a lot of black-market activity around Chinese peptides. I love how that term has come about. There's looksmaxxing, like people are—what is a peptide? What do you recommend? What should people avoid?

A peptide is just a short chain of amino acids that makes up a protein. Insulin's a peptide. All the things we've been talking about up until now are peptides. So, the phrase “peptides” has been co-opted to mean a certain class of peptides.

Just like the word “steroids”: in people's minds, they think bodybuilders. But estrogen is a steroid hormone. People are always shocked to hear that. So, if you take estrogen, you're on steroids. But we know what people are saying when they say “on steroids.” There are androgenic steroids, estrogenic steroids, and corticosteroids.

In the same way, there are peptides that are designed to reduce hunger and appetite: the GLPs. Retatrutide is the newest-generation one, soon to be released through Lilly, but already out on the market from gray-market sources. These peptides are sold all over the internet by sources that are American or Canadian or whatever, and they're listed as “for research purposes only, not for human use.”

But they're selling them knowing that people are taking them. Who's doing research on these peptides at home, right? This is not you, unless you're my lab down the road or someone else's lab. Of course, people are taking these.

Gray-market sources for research purposes only, not for human use, tend to be 99% pure, which means they've been cleaned of most things. I would worry a bit about repeated injection of a substance that contains 1%, say, lipopolysaccharide, which can cause inflammation. So, maybe not in 1 injection, but perhaps repeatedly over time, as well as other contaminants.

Black-market sources—and when you hear “Chinese peptide companies” online, we don't know that it's all coming from China, by the way. They sort of get hit the hardest in this, but people refer to Chinese and black-market peptides as the ones people are going online to buy retatrutide from, and you have no idea if it's retatrutide.

In contrast, with gray-market sources, they might not be the cleanest, but they give you a data sheet that says this was tested. If it says retatrutide, or if it says BPC-157, that's what's actually in the vial, and only that. That's an important distinction.

Compounding pharmacies have been compounding all sorts of things, selling drugs more cheaply than drug companies. They're controversial for that reason. We could talk about that.

But other peptides that are interesting—excuse me. BPC-157, for tissue repair and reducing inflammation, seems to have a 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, 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 BPC-157 gets into your bodily tissues.

Pinealon, 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: tesamorelin, ipamorelin, sermorelin, and MK-677. 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 take these 30 minutes before sleep, ideally not having eaten anything in the previous few hours. They will increase growth hormone and IGF-1.

Some of those things I just mentioned are FDA-approved. Sermorelin, for instance—I forget the exact indication—but to increase height, for instance, or for tissue repair after surgery, increasing growth hormone can be beneficial.

Some people will just take growth hormone, but growth hormone is very expensive. Somatropin and Omnitrope—that's what these peptides are very commonly used instead of. Those have been researched.

Assuming the sourcing is clean, we have a lot of human data on the ones I just described, as opposed to Pinealon and BPC-157, where you have basically no human data. There is human data on things like melanotan, which makes people tan from the inside, raises energy and libido dramatically, and causes dramatic fat loss.

Do we put that in the looksmaxxing category, or energy-maxing or something?

I don't know. Or energy-maxing or something. Yeah, it's kind of interesting. I mean, there's a lot to like about melanotan, and some similar peptides have been FDA-approved for hyposexuality in women. I think Vyleesi is the drug for women. Men take it, too.

I have to say, those drugs—melanotan is very risky. Some of the skin-color changes, the kind of orangey-ness, can be permanent. So, you have to be careful. This isn't the kind of thing you do to go on vacation, right?

[laughter]

This might have more permanent effects.

Right. And there's a risk for men of priapism, which is—you know, the last erection you may ever have. It might last 8 hours, but that might be the last one you ever really have. It can cause damage to the nerves and penile tissue.

People hear, “Erection, fat loss, energy, tan,” and think, “Oh, great.” You have to be real careful with these things. They do get abused.

I just mentioned these things, and the melanotan 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. Then, in the summer, sunlight comes and hits this pathway, increases dopamine, pigments the fur, and they breed.

There's a relationship between sunlight, dopamine, fecundity, and these kinds of things. It's pretty interesting, right?

People are taking these things and getting them either through the black market, which I don't recommend; the gray market, which is risky; or compounding pharmacies. Now we're sort of ascending levels of stringency.

Then you get to pharma sources, where you can buy sermorelin from one of the drug companies. You can buy retatrutide soon from Lilly. The cost tends to be 3 to 10 times higher, and the dosage recommendations tend to be higher.

People have figured out, through their own rogue experiments, that you can get by taking much lower doses of things. I think one of the more interesting uses of GLP-1s that I'm hearing about, mainly from people getting them from compounding pharmacies and gray-market sources, is that you can get by with taking much lower doses.

Some people are using them to reduce alcohol craving and to reduce cognitive noise more generally, which I think is pretty interesting. This is probably a good opportunity to mention things for focus, since we were going to talk about that.

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 have been some pretty interesting conversations on X about drugs for focus. All the other hackers like to focus, program, and work.

We've all 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.

Mhm.

It was designed to treat narcolepsy and other things.

Is it better than Adderall?

It's different from Adderall because Adderall is more of an amphetamine-type stimulant. A very interesting paper came out recently from WashU showing that—and it wasn't really Adderall specifically, but Ritalin and other stimulants seem to improve focus about as well as a good night's sleep.

Mhm.

But a lot of people aren't getting the good night's sleep they need because of it, too.

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, why there are no drugs to increase focus per se.

The 2 things are tethered enough: you need alertness to allocate focus, and sleep gates alertness, unless you take a drug like Adderall or modafinil.

There's a very interesting drug I think is going to 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. It did very well in a trial for ADHD.

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 hits serotonin a little bit. It seems to have a much gentler arc of alertness and focus.

I confess I've tried it. It was a bit too much, and I thought, “I don't think I'm going to stick with that. I'm going to stick with caffeine for now.”

People will take Wellbutrin, the atypical antidepressant—

Mhm.

—at low dosages to increase norepinephrine and dopamine a little bit for focus. People are doing this all the time. Nicotine. There's a lot of stimulant use right now for focus.

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.

You don't want to stimulate the sympathetic nervous system so much, so often. It can probably shorten your life.

What does a proactive approach to health look like, maybe 5 years from now, and what technology do you think needs to be built to enable that? Maybe put another way: it feels like you've covered every single health topic on your podcast. You're still going.

What do you think you're going to be covering in '26, '27, and '28?

Yeah, we need to do autoimmune disease and cancer. We've got a bunch of things to go, but, yeah, maybe this is a good opportunity to weave in reading and writing to biology.

Reading, I mean, people are wearing sleep sensors. This is commonly done now, right? But you can't write to the sleep system yet. I think in 5 years we're going to look back and say, “Can you believe it? We were cooling the room to try and fall asleep.”

I think we'll still have cooling mattresses, but it's going to be so crazy, because there should be a way that you could cool the core of the body more efficiently through the palms and the soles of the feet.

There are reasons for this. The vasculature there actually lacks capillaries. You’re not really cooling the blood directly, but you’re essentially dumping more heat. It’s cool technology from Stanford. 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.

Yeah. You’re wearing an eye mask that’s moving your eyes back and forth, and within 6 minutes or less, you’ll be asleep. When you wake up in the morning, you’ll flip that thing on and 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 I’ll look at a 10,000-lux thing over there.”

It’s just so easy to move these things to the body. So, writing to our biology around sleep is going to be a big one. 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. I’d love to see real-time cortisol sensing.

The morning cortisol peak—getting that—I can’t overstate the importance of it for everyone: women, men, premenopausal, 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.

Who is working on these things? Like, right now, for our listeners, there are continuous glucose monitors, and they put kind of a little piece of dental floss under your skin that monitors glucose in real time, normally for diabetics. But people are working on multibiomarker sensors that could tell cortisol or a variety of things.

Yeah, I think 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 afterward? These blips in cortisol aren’t a problem if they come back down. Sometimes, if that whole curve gets shifted to the right a bit, it’s actually associated with worse cancer outcomes and reduced longevity.

There are a lot of reasons to want that cortisol spike to be really big and then have it trough into the afternoon. That’s one that I’d love to see. Once you see that, if at 5 or 6 p.m. your cortisol is riding high, you’d love to have a way that you could dial it down. You could do that through conventional methods like long-exhale breathing or a short meditation, maybe eating some starchy carbohydrates.

People forget that cortisol’s main job is to deploy energy in the body. This is why it gives you a glucose bump. There’s a reason why starchy foods are called comfort foods: They provide the 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. 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 it’s 11 p.m., you’re fried, 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. Sure, you’ll have more energy, but you can really mess up your sleep. You heard it here: You can have carbs at dinner.

Do it. Please do it. Please.

In fact, if you’re going to have carbohydrates at any time, it should be within a couple of hours after resistance training or maybe 3 or 4 hours before sleep, maybe even a couple of hours before sleep. People who reduce their carbohydrate intake too much aren’t going to sleep well. They’re just not—not nearly as well as they could if they had some moderate carbohydrate intake. Obviously, you want to try not to eat too close to bedtime.

Yeah.

And so forth. I think the whole peptide thing—the horse is out of the stable. In 5 years, you and I are going to have a little cocktail. It’s going to be 1 injection or 1 pill, and it’s going to have a little bit of Pinealon in it at night combined with something else. In the morning, it’ll have something—whatever it is that you need to, not you specifically, of course, but whatever I need to ramp up my dopaminergic system a little bit to make sure that I’m getting enough micronutrients.

Maybe I’m going to put a little Klotho in there to protect me against Alzheimer’s. I think all of that stuff is going to be commonplace, the same way that people aren’t afraid of vitamin D, or they’re taking some creatine or magnesium. People are taking magnesium; it’s kind of the next wave of accepted supplements, I think, that feel safe enough for most—not all—people. I think most everyone is going to be doing that, and I think the cost is going to be low enough that “most everyone” is a real statement.

I love the read-versus-write breakdown. I think on the read side, it feels very clear where the world is going. ChatGPT is already an incredible doctor, probably better than an average doctor an American can get access to. It knows nothing about you today, but we have these health information exchanges coming online—functions we’re building, something that pulls in all of your health records from EHRs, all of your wearable data, all of your functional 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.

We saw the 1.0 version of that in COVID, when people’s wearables realized they had COVID before they even felt sick. When we have these continuous glucose monitors that can monitor a whole lot more, the diagnostics and read side feel like a very clear picture of where the world is moving. The write side is super interesting, and that’s where I think there are a million more ways this world could go.

Yeah, I mean, I borrow this read-write thing from my life as a neuroscientist. 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 neurons, 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 in mice. I mean, everything—rat, cat, monkey, bat. But it was mice, and it was nonhuman primates, and now humans.

When I think about reading and writing to our physiology, it’s like, let’s figure out what the 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, well, ashwagandha reduces this. This herb reduces cortisol.”

People will take it 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 Eight Sleep. It’s a phenomenal technology, so much so that I miss it when I travel. But ultimately, we’re going to be cooling the body to just cool your core, right?

I should travel with a little thing I can put on my feet, in the socks, that’ll cool my core so I sleep. One way to really improve the amount of REM sleep you get, without taking anything, is to warm your sleeping environment in the last hour before you wake. REM levels go up. So, you want to cool, then get really cold, then warm.

We shouldn’t be relying on external hardware so much. So, that’s why I think the sleep-mask thing, et cetera, is interesting. 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 and who is now at Neuralink. He’s phenomenal. Dan Adams—I think that group is terrific. Our friend Eddie Chang, chair of neurosurgery at UCSF, is 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—that your hippocampus is going to be pulling in twice as much memory at twice the rate or something like that.

It’s not going to 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 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 the conditions right. You’ll work for that 40 minutes, and then you’ll click that you’re done. You’ll take those things off, and you’ll go do something else.

I try to create that for myself.

That’s coming. That’s coming. I keep pointing to the eyes, like the sleep mask that moves the eyes to make you fall asleep, but the main 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 noninvasive technology will get good enough. Right now, I’m not really seeing it, but it’s coming.

The amount of things that you can do to modify brain state through this region—the eyes, ears, and the superficial nerves that run around there—is 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.

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

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 podcasts, which would allow me to do other things. I’m sort of half-kidding there.

Here’s what I know for sure: There are many easy ways to generate a list of the 10 most important things to do to get great sleep, or 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?

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.

Mm-hm.

When you understand mechanism, I think it gives a higher probability that somebody is going to implement the advice. 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 a window where, if you miss too many days, it becomes problematic. Once you understand how it’s summing photons, et cetera, you understand how to be flexible.

AI could probably deliver that information, but I don’t know that it can build it well enough. 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’d probably build the platform where the AI version of me was doing it, so I don’t have a problem poaching myself.

Longevity escape velocity: Do you think that’s real or fantasy? I mean—

[sighs and gasps]

I think the way that people are defining longevity now, it’s got a lot of pretzel twists in it to try and say, “Well, I didn’t say we were going to live forever. I’m going to upload my content.”

If we’re talking about 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. For most of us, it’s probably closer to about 105.

Taking great care of ourselves and 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 an edgy topic—by Tony Wyss-Coray’s work from Stanford. He had a company that’s now sold, Alkahest, which talked about factors in young blood and in exercised blood that can rejuvenate the brain and body. 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 it’s ethically gathered and provided, 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 6 months? Let’s just bank your blood so that if you ever have an injury, you can get some really healthy blood of your own,” I would do that.

It’s kind of primitive from the standpoint of AI and all these things being available, but we know that blood infusions are beneficial. There’s been a clinical trial for this. We know that infusions of exercised blood are even more beneficial.

We also know that after a brain injury or a bodily injury, things that are not just pro-inflammatory circulate in the blood and are bad for all organs. I think a very low-bar but useful technology would be to bank a bunch of my own blood after exercise. 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 and NAD infusion, which is probably fine, but I don’t know that it provides that much.

Last question: You have a pet octopus. That is unusual. Tell us about him or her.

Van Go. Van Go. Yeah, it’s a starry night octopus, hence Van Go. Then it got even eerier because Van Go lost one tentacle in the fan, so it was like—

When my lab was in San Diego, before I moved to Stanford, I worked on a different cephalopod called cuttlefish. They’re like little underwater monkeys. They’re incredibly intelligent and 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. I was studying their vision. They’re very interesting because they can see panoramically and they’re very placid. But when they want to hunt, their eyes translocate to the front and they generate depth perception—stereopsis—to hunt.

I was very interested in whether or not they had 2 visual systems. 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, energy, and attention go up. When your gaze is dilated, like you’re viewing the corners of the room, the ceiling, and the floor, that tends to put us into a calmer state. Some animals only exist in one state or the other. We’re unique in that we can switch back and forth. Some other animals can, but I was studying that in cuttlefish.

When I moved to my current home, I converted an art gallery into a living space. I put in a gym and a place to work downstairs where there’s no Wi-Fi. I don’t bring my phone down there. That’s where I prepare for podcasts, do some drawing, and work on illustrations for my book and a few other things.

I’ve always loved aquaria, so I decided to put in a freshwater discus tank. I put in a huge freshwater discus tank, and I thought, “I think I need cephalopods again.” So I got an octopus. I got a starry night octopus.

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.

We say, “Oh, they’re like aliens. They’re so intelligent.” We get the camouflage, and they’re very interactive. But an underwater iPad and the appropriate use of a touchscreen and AI, I’m hoping, will allow this or another octopus to communicate something about what it’s thinking.

So, how would you do this? You can’t apply a typical large language model. You have to do it based on the coloration patterns, the camouflage patterns.

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 is swimming around and hunting and doing various things.

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 am to come up with something. It’s not an LLM. I don’t know, something related to camouflage patterns—could start revealing that certain camouflage patterns relate to certain behaviors, which relate to certain nuances in the behaviors. Then it could start teaching itself.

The idea would be that the AI would present something to Van Go or another octopus—I’ve got more on the way—that would start to influence behavior. There could be not just conversations between octopuses, but maybe I could speak, and it would translate that into octopus.

What do you call it?

And then we could communicate.

Here’s the reason for doing this. There’s this idea that other animals have all this intelligence. Normally, we measure that through behavior or through some highly specialized aspect of their nervous system or body, like barn owls. They all do these fantastic feats.

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. All that tells you is more about how hard humans are willing to work to train a different organism to do something pretty rudimentary compared to what humans can do.

It 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 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?

I think you need a whole podcast outlining your experience.

Yeah, well, maybe this is what happens when we run out of topics to put on the HLP. I'm probably not thinking about this as cleanly as I could or should, but, just wrapping up this monologue, you get to the point, doing public-facing health information, where you can kind of feel the saturation point.

We need more technologies and tools, and I think that's great. I really am excited for what's coming. But at some point, the conversations become clear: We need more, right?

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 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.

Amazing. Peter Godfrey-Smith, thank you for coming on the a16z Show.

Thanks for having me here.