Transform Your Metabolic Health & Longevity by Knowing Your Unique Biology | Dr. Michael Snyder

[Andrew Huberman]
Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life.

[Andrew Huberman]
I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Michael Snyder. Dr. Michael Snyder is a professor of genetics at Stanford University School of Medicine. His laboratory focuses on how different people respond differently to different types of food and health interventions. And his overall goal is to figure out how different genes and proteins that different people express impact people's immune system function, reaction to different foods and diets, blood sugar regulation, immune system, and longevity. Today's episode could basically be summarized as, as you suspected, not everybody responds the same way to the same behavioral, drug, supplement, or other treatment designed to improve health span and life span. For instance, the Snyder Laboratory published a paper earlier this year showing that different people spike insulin in response to different types of carbohydrates. Things like the glycemic index, which we may be familiar with, because they are essentially a readout of how much a given food impacts blood sugar, depends on who you are. They identified so-called potato spikers, they literally refer to them as potato spikers in this paper, versus grape spikers, people whose insulin spikes in response to potatoes but not grapes and vice versa. While this might seem kinda silly or trivial or micro-slicing, the identification of these different sub-types of people in the general population who respond differently to different types of foods is extremely important. Because I think most all of us are getting a little bit tired of all these discussions about carbohydrates are good, carbohydrates are bad, these carbohydrates are good, these carbohydrates are bad, and on and on. Turns out, it depends on which genes and which proteins you make. In other words, individual variability matters. We talk about that individual variability in the context of nutrition, also in the context of fiber. It turns out that fiber is something that people generally believe is good for your health, I certainly believe that. Well, different types of fibers impact people differently. Some people experience systemic inflammation of their brain and body when they eat certain types of fibers. That's bad. Other people experience systematic decreases in inflammation when they eat certain types of fibers. The key is to identify which category you're in, and therefore, which fibers to eat. And as it turns out, different foods have different fiber types. So it's tractable. There are things you can do about it. We also talk about GLP-1 drugs and how those impact longevity. This is something that's very controversial and very timely right now. And we discuss how different psychological interventions, yep, the Snyder Lab has even looked at how different psychological interventions impact the genes you make and the proteins you make, and their effect on health span and life span. So today's discussion is sure to change your mind about a lot of things related to nutrition and fitness and medicine. However, I promise that thanks to Dr. Michael Snyder, it will not confuse you. In fact, it will clarify many things that perhaps before the episode were confusing to you and many other people. Dr. Snyder's laboratory is recognized for doing extremely rigorous analysis of the genes and proteins that can explain individual variability and what people should do or not do in order to maximize their health and longevity. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is however part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Michael Snyder. Dr. Michael Snyder, welcome.

[Michael Snyder]
Great to be here.

[Andrew Huberman]
I'd like to start by talking about glucose regulation and food and food choice, exercise, sleep, and how they all interact. But I want to make it very simple to start.

[Andrew Huberman]
How is it that what we eat impacts our glucose response? And maybe you could tell us a little bit about what a healthy glucose response looks like. Because by most people's view, any inflection in blood glucose is a quote unquote "spike". But what are the sorts of spikes that matter for health and what are the sorts of spikes in blood glucose, or what are called glucose excursions that, you know, okay, well, that's a normal response to eating some food and then it goes back down to baseline? I think this is especially important nowadays with all the interest in metabolic health, in how particular types of foods like processed foods are indeed far worse for us and on and on. So, um, if you could just give us your view and understanding of glucose excursions. What they mean, when they're good, when they're bad?

[Michael Snyder]
Well, I would say that, um, you know, high, long, prolonged spikes is obviously pretty bad. Um, but certain things, like if you eat a grape, grape's pretty loaded with sugar, but it's a pretty transient spike. It'll go up. Uh, and so that would be a transient one. Uh, actually, when you do strength training, for example, for exercise, you break down glucagon, which is a, you know, it's a polymer of sugar that you break down, gives you energy. That's important for when you're doing exercise and training. And that will give a glucose spike. I get a glucose spike every morning when I weight train. So that would be a normal, healthy one, but it's transient. It goes away pretty quickly.

[Andrew Huberman]
What's quickly?

[Michael Snyder]
Within, uh, 30 minutes, maybe most 60 minutes. Um, now, I'm a special case. I'm a type 2 diabetic so my spikes go higher and longer than most people. Um, so yeah, mine are not good spikes, but we can get into that. So what is a good spike? Well, I, the calibration people mostly uses time and range. It's a simple metric, meaning if you're a healthy person, your glucose is normally for most people around 90. Um, and if you're off-... you will go higher than that. For most people, you wanna keep your glucose between 70 and 140 if you're healthy. For diabetics, they say try and keep it between 70 and 180. And that is what people try to do. And, and most healthy people, it's pretty easy. And I think one of the things we've done, you've heard about continuous glucose monitors, these devices. And I'm wearing one and I, some of your staff, I know, are wearing them as well. And they're over the counter now. You put these on your arm and they measure your glucose every five minutes so you can see exactly what's going on. And so, uh, we put them on so-called normal people, pre-diabetics, and some diabetics. It was already well known diabetics will spike their glucose through the roof, too high for too long. Uh, and then the people devise, especially Type I's, control mechanisms for, for releasing insulin and controlling all of that. But for, um, the average person, that wasn't so well known at the time we were doing this, and it was a bit of a surprise to see that a lot of people... Some were, did have very good glucose control, but some pre-diabetics were what we call moderate spikers. We came up and named glucotypes as, it's a way of quantifying this in a, uh... And then some people were spiking just as bad as diabetics and had no idea. Uh, and so as a way of revealing what was going on. So, it's recommended that you try to stay in this 70, 140, but it is a bit arbitrary, but it's not a bad rule of thumb to, to work by for the average person. But again, some people have very, very good glucose control, some are moderate spikers, and some are severe. And it's pretty clear that excessive spiking, especially in diabetics, is associated with cardiovascular disease and other things. There's some, uh, pretty strong papers out there on that. So, uh, you do want to keep it under control. And there's a very strong correlation between this time and range measurement I mentioned, and something called hemoglobin A1c. That's a measure of your steady state glucose. And so if you have high hemoglobin A1c, that's typically how we classify people for diabetes and pre-diabetes. If you're over, uh, 6'5" or over, you're classified as diabetic. If you're 5'7" to 6'4", you're pre-diabetic. And if you're under that, you're, you're so-called normal. And this time and range will actually correlate very, very well with that. So it is an, it's a surrogate measure for that. But it's actually pretty cool because it's, you can precisely see what's going on in real time, unlike a hemoglobin A1c measurement, which you get periodically. So if you wanna dig into that further, I would say that , you know, what's cool about these CGMs is that you wear them, like I'm wearing one now. You can wear them, uh, for about 14 days, depends on the particular device, and you see exactly what foods do what to you. And we're all different. So some people spike to bananas, some to potatoes, some to pasta, some to white bread, some to brown bread. And so, uh, this is shown by Aaron Siegel's lab at the Waisman, and our lab had found something similar. Uh, and it's very personal. And so we've been spending a lot of time trying to dig into what's behind that.

[Andrew Huberman]
So different people's glucose spike to different foods. It's hard to predict on the basis of something like a chart of glycemic index, for instance. Um, so if I understand correctly, and I have glanced at those papers, um, you know, I might be able to eat mango with nothing else and my blood glucose doesn't go out of range, or at least not for very long. Whereas somebody else might have a s- a very big and prolonged spike in blood glucose to mango. But maybe there are things they can eat that I can't eat, like, uh, I don't know, sourdough bread or something. By the way, I can eat sourdough bread. But just by way of example.

[Michael Snyder]
100%. Yeah. Yeah.

[Andrew Huberman]
Mm-hmm. And so, and so really the only way to know, as you're pointing out, is, is to measure. I, I wanna talk a lot about measurement today.

[Michael Snyder]
All right.

[Andrew Huberman]
Um, for those that are just listening, not watching, uh, uh, Mike is wearing many sensors. How many sensors? You have got four watches on.

[Michael Snyder]
Uh, I have my four watches and my ring, and even my hearing aids are sensors, believe it or not, so...

[Andrew Huberman]
Okay, we're gonna get-

[Michael Snyder]
They aren't for hearing, but, uh...

[Andrew Huberman]
We're gonna get into all of that.

[Michael Snyder]
All right.

[Andrew Huberman]
Um, but maybe we could talk a little bit about some of the subjective experience of blood glucose excursions, both healthy and unhealthy.

[Michael Snyder]
Okay.

[Andrew Huberman]
Um, most people are familiar with eating a big meal like the, you know, the cliche is the, you know, the Thanksgiving meal after which you're, you're tired, where you stuffed yourself with protein and carbohydrates and dessert, et cetera. Maybe some alcohol too in some cases. But

[Andrew Huberman]
I think people are also familiar with, you know, eating a certain food. Um, like for me lately, I'll have my bowl of oatmeal with some berries and my protein drink after I train. And I'm noticing with each successive year, I'm getting really sleepy after I eat this. And I've swapped out the, the oatmeal for a different carbohydrate recently, just some white rice, and I feel fine.

[Michael Snyder]
Right.

[Andrew Huberman]
And I, I don't think this is my imagination. I mean, in one case I wanna take a nap afterwards. In the other case, I'm good to keep going and I generally have a lot of energy.

[Michael Snyder]
Right.

[Andrew Huberman]
So is what I just described atypical? What are some subjective-

[Michael Snyder]
Yeah, I think so

[Andrew Huberman]
... effects of high, high glucose spikes?

[Michael Snyder]
Yeah. Well, certainly, uh, sleepiness is one. I can put myself to sleep with a piece of pizza. Um, I'm diabetic. I'm a unusual diabetic. We can talk about that too. Uh, and yeah, if I eat pizza, my glucose goes through the roof and, um, I will get sleepy.

[Andrew Huberman]
So, uh, so does that mean that you eat and you feel sleepy, or there's a, uh, a period after you eat... Because this is what I experience, where I feel very energized for a short while, and then it's almost like my vision gets a little blurry.

[Michael Snyder]
Oh.

[Andrew Huberman]
And I feel kind of like, um, you know, like I just wanna curl up and take a nap, even if I slept great the night before. Is that a blood glucose response?

[Michael Snyder]
I believe so. I mean, there are multiple things that affect sleepiness. And you probably know this better than me since, uh, you've covered sleep more. But, um, yeah, that, like, tryptophan. Things like this can help induce sleep as well. But certainly glucose, these large glucose spikes, uh, I can say personally make me very, very sleepy.

[Andrew Huberman]
Hmm.

[Michael Snyder]
Uh, and alcohol can make a lot of people sleepy too. But you're right, there can be a lag because that first little shot of glucose can be a stimulant. Um, but, uh, very soon that...... shot can go very, very large, uh, of glucose. And at least for me, it makes me very, very sleepy. So I think it's very normal.

[Andrew Huberman]
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[Michael Snyder]
Yep

[Andrew Huberman]
... um, you know, as opposed to fruit juice, you know, eating the whole fruit, which of course includes the fiber, um-

[Michael Snyder]
Right

[Andrew Huberman]
... at least in a different form, um, or adding some fat. You know, so I've tried doing this, you know, adding a bit more fat to that meal, but, you know, in some cases, it still happens. It doesn't matter if you try and blunt the blood glucose response with, with fat or with fiber. You just find that you get that kind of like buzz and then crash.

[Michael Snyder]
Right.

[Andrew Huberman]
And it's not the kind of crash where y- you can't do anything. It's, it's actually more sinister than that. It's, um, it's more of a, like a brain fog that then transitions into the desire to take a late morning nap, which, if you slept well the night before, you really shouldn't be feeling.

[Michael Snyder]
Well, you can mitigate that, of course, by doing a walk and try and burn off a little bit of that glucose. We can get into that.

[Andrew Huberman]
Tell us about walks 'cause we, we've talked a little bit about those on this podcast before, but what is the effect of a short walk and does it need to be a brisk walk or can, yeah?

[Michael Snyder]
Yeah, I think brisk walks seem to be better. Uh, there's day, there's studies from, from other people on that, that a brisk walk for 15 minutes or 20 minutes after you eat will help suppress those glucose spikes. Uh, and so,

[Michael Snyder]
um, and, yeah, so there, in fact, some of these, um, companies that have set up around personalized management of glucose, uh, uh, I'm involved with one called January AI, and there's others out there too, they actually recommend that. If you eat something that spikes your glucose, you should take a, uh, a brisk walk, and that will suppress your spike, and they connect to actually teach you that. And you can see it personally. And so one thing, uh, we've done is, for example, most people spike to white rice, believe it or not. It's high glycemic index, but glycemic is more personal than people give credit for. Anyway, you will spike your glucose, but if you take a brisk 20-minute walk, you can just see that spike is much, much less.

[Andrew Huberman]
And is that simply due to the low-level mus- muscle contractions associated with walking are just pulling, th- they're just acting as a glucose scavenger?

[Michael Snyder]
That's what I assumed, yes, uh, that you're burning it off.

[Andrew Huberman]
Did you see the study out of, um, I forget the university in Texas? I think it might've been University of Houston, where they looked at, um, people doing what they called soleus pushups. Did you see this study?

[Michael Snyder]
No, I haven't seen it.

[Andrew Huberman]
This is wild.

[Michael Snyder]
Tell me about it.

[Andrew Huberman]
So they, they basically had someone, uh, subjects, there was more than one subject, of course, sit in a chair and, um, essentially do the equivalent of, of what gym-goers would call a seated calf raise. They called it a, uh, calf pushup, but-

[Michael Snyder]
Okay

[Andrew Huberman]
... uh, that, all that nomenclature is kinda silly. Uh, what, what it really is, is keeping your toes on the floor and lifting your heels. It's like being, like, a knee bouncer-

[Michael Snyder]
Oh, okay

[Andrew Huberman]
... in, in class, what we were all told-

[Michael Snyder]
Interesting

[Andrew Huberman]
... we shouldn't do it. It turns out the soleus, even though it's only 1% of the total body musculature, um, acts as more of a glucose sponge.... than, uh, other muscles in the body, which sort of makes sense given th- the walking thing we've been talking about.

[Michael Snyder]
Okay. Yeah, yeah.

[Andrew Huberman]
And, um, now people had to continue doing this, but, um, it was pretty effective. I, now I'm, I would prefer to see people go out and take a walk after they eat, but not all of us can get up and, and walk after a meal.

[Michael Snyder]
Yeah.

[Andrew Huberman]
If you're on a plane, sure you can, you know, y- you don't wanna fill the aisle 'cause people need to go to the bathroom. You know, it gets-

[Michael Snyder]
Right.

[Andrew Huberman]
It gets impractical. So it's kind of interesting to think about just, like what requirements are for low level muscular contraction.

[Michael Snyder]
Okay.

[Andrew Huberman]
And I, and I would always wanna see people exercising more as opposed to less. But you could imagine, given the number of devices that you're wearing, that after you eat a meal, that you would have just a low level muscle stimulator just stimulating your, your soleus or something like that.

[Michael Snyder]
Y- y- you mean electrical or a, uh, physical one?

[Andrew Huberman]
Just scavenging glucose. Yeah, electrical.

[Michael Snyder]
Yeah, maybe.

[Andrew Huberman]
Yeah.

[Michael Snyder]
Um, you know, I think there's a lot of benefits as you know, from exercise per se.

[Andrew Huberman]
Sure.

[Michael Snyder]
You make all these things called exercines that have a lot of benefits in general. So I, I think exercise is probably broader than simply injecting the juice yourself.

[Andrew Huberman]
Yeah, I, I do too. But, yeah.

[Michael Snyder]
So, but anyway, maybe what you say would be helpful for people. Uh, you know what I do, and I, and there are others who do this too, you've heard of this phrase exercise snacks.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
Uh, especially for people who sit all day. The idea of getting up. And used to be able to get up and walk, uh, you know, some brief walk. But now there are some ideas, well, maybe get up and do more than walk. Maybe do some of the things... I hadn't heard the one you said, but maybe that's a better thing to do.

[Andrew Huberman]
Or air squats or something of that sort.

[Michael Snyder]
Yeah, exactly. So we have people doing some squats .

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
Now, running a study like that and, uh, see what it does to their VO2 max and overall, you know, health measurements. So, so I'm a big believer, yeah, sitting f- for eight hours is probably not good for you.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
In fact, there are plenty of studies that show that and these breaks are, are good for you. Even walking's better than nothing.

[Andrew Huberman]
Do you use a standing desk or a treadmill under your desk?

[Michael Snyder]
I don't do the treadmill. I have tried the standing one. I find I don't concentrate as well when I'm talking with people. So, I have to confess, I do, I prefer to sit.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So I can be a little more engaged. Uh, I do have a lot of meetings.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So for me, that seems to be more effective. But it does mean I need to get up and take these breaks.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And, uh, so I ha- I haven't. But for other people, I know they like standing desks. I've, I've heard from some people though, or it may not be overall as effective. So I don't know.

[Andrew Huberman]
Interesting.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Yeah, I think the exercise snacks are a terrific thing. The, you know, air squats, um, or even just pacing, these kinds of things.

[Michael Snyder]
Yeah.

[Andrew Huberman]
I think we underestimate the, the extent to which our, um, evolutionary history drove a lot more movement every day than we currently envision.

[Michael Snyder]
There's no way we sat eight hours a day, uh, in-

[Andrew Huberman]
I know.

[Michael Snyder]
In ancient times. Yes.

[Andrew Huberman]
Right.

[Michael Snyder]
Uh, I 100% agree. Yeah.

[Andrew Huberman]
Yeah.

[Michael Snyder]
People had to be active. They had to be active to get, gather their food and-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... deal with the elements. Yeah.

[Andrew Huberman]
So these glucose excursions, if they're brief, not a problem. But if people are finding that certain foods or food combinations are making them feel sleepy afterwards, I do think that the glucose monitors are, are useful for parsing which foods are, are doing what. I- I'd like to talk a little bit about meal timing-

[Michael Snyder]
Okay.

[Andrew Huberman]
And food timing.

[Michael Snyder]
Sure.

[Andrew Huberman]
Um, for many years, just by virtue of preference, I will hydrate and I make sure to get electrolytes, water, and caffeine in the morning.

[Michael Snyder]
Okay.

[Andrew Huberman]
And I e- try to exercise in the morning. Um, if I don't, I'll do it in the afternoon. But generally in the morning, and my first meal always lands somewhere around 11:00 AM or so.

[Michael Snyder]
Okay. Yeah.

[Andrew Huberman]
Roughly. Plus or minus an hour. Is there any evidence that introducing a period of fasting at one point in the day versus, say, later in the day, like having breakfast, lunch, and an early dinner, versus lunch, an afternoon snack, and a typical dinner of, you know, between, you know, 6:30 and 8:30 PM, I think is pretty typical, at least for Americans, is better or worse for glucose, um, control?

[Michael Snyder]
Yeah.

[Andrew Huberman]
And general health? I know y- your lab's been focused on, um, I guess it's called intermittent fasting, but this time restricted feeding.

[Michael Snyder]
Right.

[Andrew Huberman]
We're not talking about weight loss now. I'm just talking about glucose control.

[Michael Snyder]
There's a lot to unpack there. Um, so we have some studies where we put CGMs on people, smartwatches so we could track their activity. Uh, they did food logging, uh, and exercise logging as well, tracked them in incredible detail. And they were also very well phenotyped for their glucose dysregulation. And we should probably talk about that a little bit about muscle insulin resistance, uh, beta cell defects, things like that. So we were trying to relate what was th- th- what this du- glucose dysregulation subphenotype with their lifestyle. And not just their lifestyle, what they did, but when they did it. And what we found is that, first of all, some simple things already known is that, uh, if you have your bigger meal first thing in the morning, you generally have lower glucose and, and don't, and not later at night. So people had their biggest meal, their biggest energy consumption later in the day is dinner, which is awkward socially 'cause that's when most of us have our big meal, or many of us do. Those folks w- will have higher glucose. And starchy vegetables is well known. Those folks have higher glucose. But interesting, fruits, people who ate a lot of fruits as their major source of carbs had lower. That's because of the fiber-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... that's in there that helps them. Turns out most people don't get enough sleep, and so those who slept longer actually had lower glucose. Uh, but some of the things we could tease out were when should you exercise? If you look at the party line out there from various studies, well, you should exercise in the afternoon to get your best benefit. But we found that that depends on the form of dysregulation you have. If your muscle insulin resistant, you actually get better benefit by exercising in the morning for glucose the next day.

[Andrew Huberman]
If you're muscle insulin resistant?

[Michael Snyder]
Right.

[Andrew Huberman]
Okay.

[Michael Snyder]
So to unpack that a little bit, um, so y- you probably know that, you know, we, you eat something, you get glucose if it's sugary. And your insulin obviously, you know, helps control that, stimulates your cells to take that up.... and if you're insulin resistant, especially muscle insulin, 'cause muscle is a major consumer of glucose, means you're not taking up your glucose right. So you're insulin resistant and you're, don't take up glucose and you wind up with high glucose spikes. But there are other forms of diabetes, so to break this down, or glucose dysregulation, there are people who don't make insulin early in life. That would be called type 1. Uh, you can still become, uh, insulin, uh, deficient and making insulin later in life for type 2. But, um, you can also have what are called beta cell defects. So insulin's produced by your pancreas, your beta cells, and I myself am type II di- diabetic. I have a beta cell defect, took me a while to figure that out. Meaning I make insulin, my cells respond, but I don't release it from the pancreas. Uh, and then there's things called hepatic insu- insulin resistance. So your liver is insulin resistant and other forms as well. Uh, fat insulin resistance as well. So we've now gotten into

[Michael Snyder]
dividing up diabetes. So in, you know, basically classically people will, uh, group people into type one, which is 10% of people, or type two, which is the other 90% of diabetics. Well, it turns out that's a really broad category. That can easily be subdivided into what we call subphenotypes, these different forms of glucose dysregulation, and we think that's a big deal because it affects the drugs you take. So for example, I am a beta cell defect and I didn't respond. I, I, um, went through exercise, used to be a runner, and I shifted to weight training about, uh, it'll almost be nine years soon, uh, with the idea of building muscle mass, which failed miserably. My glucose was gradually going up, so I shifted to weight training. I gained 10 pounds of muscle mass. I do whole body MRI, uh, 20 of them the last eight or nine years, and I basically did gain 10 pounds of muscle mass, had- had no effect on my, uh, uh, my glucose control. And the reason for that was that I'm not muscle insulin resistant, I'm a beta cell defect. So I can gain as much muscle as I want, it's not gonna help me release, uh, insulin from my pancreas. So knowing your subphenotype is a big deal. But then I respond to certain drug repenilide that actually promotes that release. So knowing your subphenotype determines your drugs. But it also turns out this whole lifestyle thing I mentioned earlier is a big deal in coming back to some of the food stuff. So we found that if you're, um, uh, basically insu- insulin resistant, muscle insulin resistant, you will spike to potatoes and pasta, but not if you're insulin sensitive. And if you have beta cell defect, you'll also spike to potatoes. So you actually, you can subphenotype people according to what their glucose dysregulation is and that affects how you react to foods. And so then the obvious thing to do is modify your eating behavior on those foods so that you can basically live a healthier life, is the idea. Um, and so how are you gonna subphenotype? Well, the way we do it now is super expensive. It's, you know, we do these gold standard tests, takes several hours, hundreds if not thousands of dollars, depends how you do it. Uh, we, believe it or not, can do it just from a simple glucose curve. So you may or not realize that when you put one of these glucose monitors on you, you, and you drink a shot of glucose, you'll have a curve. And that shape is different for different people, and that depends on their subphenotype.

[Andrew Huberman]
Hmm.

[Michael Snyder]
So meaning if your muscle insulin resistant, you'll have a certain shape, and if your beta cell, it's a different shape, and if you're a combination of things, and there are other factors by the way that play in here, like your microbiome. So the guts in your, uh, the microbes in your gut all play in this. And so they basically affect the shape of your curve. And now we're not there yet, but we're good for some of these, like for muscle insulin resistance, we can quite accurately predict whether you're muscle insulin resistant just from the shape of that glucose curve, which you can get now from an over-the-counter purchase at, at a drug store.

[Andrew Huberman]
Super interesting. There's a, a, as you mentioned, a ton to unpack there. I just wanna make sure I understand-

[Michael Snyder]
Sure

[Andrew Huberman]
... a couple of the points you made, um, before we go forward. Uh, you said the vast number of, of, uh, papers that have explored ideal exercise timing-

[Michael Snyder]
Right

[Andrew Huberman]
... point to the afternoon as the best time.

[Michael Snyder]
Right.

[Andrew Huberman]
I've seen those papers also, and my takeaway from those, the kind of gestalt of, of, of those papers in my view, is that if you're interested in performance, that the afternoon is better because your body's warm, body temperature tends to be appropriate for performance. Whereas although some people wake up ready to go first thing in the morning, most people don't feel as energized first thing in the morning. Some do, but most don't. Um, but if I understand correctly, for many people, in particular people with muscle insulin resistance, doing resistance training would be preferable to doing cardiovascular training for blood glucose regulation. And doing that resistance training early in the day, uh, it sounded like you were going to tell us that it sets a, a kind of a, a trend toward better glucose regulation throughout the day. But I don't want to, uh, lead the witness here. I wanna make sure that, that that's true before we conclude that.

[Michael Snyder]
Well, we haven't taken apart for that particular study the difference between resistance training and, and-

[Andrew Huberman]
Okay

[Michael Snyder]
... is more a general activity measurement.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So people are more active in the morning if their muscle insulin resistance will benefit, have better glucose levels the next day.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So we haven't yet done resistance, but I'm very interested in this. In fact, we have a separate study around high intensity training running versus long distance running. Uh, and-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... can happy to talk about that, that, but that's still in progress. So I, I wouldn't say we've totally done what you've gotten at, but we would like to dissect the resistance training versus a aerobic or endurance type of training. Uh, I mean the bottom line is of course exercising anytime is better than not exercising at all.

[Andrew Huberman]
Sure.

[Michael Snyder]
So I, I think we'd all agree with that. But we do think you get better glucose benefits if you are muscle insulin resistant doing the morning. And I also do believe that yeah, building your muscle mass will help...... uh, with actually reducing muscle and through resistance.

[Andrew Huberman]
Thank you for that clarification. Uh, you mentioned different types of diabetes. So general categories are type one diabetes. Uh, these people don't make insulin. They need to inject insulin or- or- or deliver insulin through a time release mechanism or something of that sort.

[Michael Snyder]
Right.

[Andrew Huberman]
Type two diabetes I understand to be insulin insensitivity, which, um, is bad. You want your cells to be sensitive to insulin so that insulin can bring the glucose into those cells, so they can use them.

[Michael Snyder]
Right.

[Andrew Huberman]
You're now subdividing this type two diabetes, the insulin insensitivity into muscle insulin insensitive as well as other tissues being insensitive. What percentage-

[Michael Snyder]
But it's more than that, meaning there's a beta cell defect where you don't release insulin from your pancreas.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
That's, has nothing to do with insulin resistance. That's more a mechanistic thing. Now why that, that defect exists isn't so clear. Uh, Mike is kinda interesting, uh, although we still don't fully understand it. But um, then there's also incretin defects. So incretin are these GLPs that everybody's heard about. Ozempic is a mimic of those and Mounjaro and things like that. Uh, and so there are people with defects that way. So we're all different and we can now subtype that. We can say this person's got mostly an incretin defect, this one's muscle and through resistance. There's a beta cell defect. Uh, and so... And some people are combinations of those. It's not pure one or the other. So we think actually the subtyping is a big deal because again, it determines your lifestyle choices you might make to better control your glucose. And of course drug responses as well. So we think that's important.

[Andrew Huberman]
Mm-hmm. We know that many, many people in the United States and elsewhere sadly are overweight or just clinically overweight, and I think it's about 30% of people in the United States are clinically obese.

[Andrew Huberman]
When you talk about type two diabetes and these different, um, sub-phenotypes as you're referring to-

[Michael Snyder]
Right

[Andrew Huberman]
... um, what percentage of people in the United States do you think are type two diabetic that have some sort of either insulin, um, insensitivity and that's t- t- the reason versus they're making plenty of insulin but they can't release it? I mean, what, what sorts of numbers are we talking about here? Because I think for listeners, they're probably thinking like, "Okay, like I, as long as I don't eat too much sugar I feel fine." Does that mean that they don't have type two diabetes? People who, um, perhaps are of a healthy weight does that mean they don't have type two diabetes or any of these insulin management problems? It sounds like we don't know the real numbers, but if you were to guesstimate what the percentages are of people out there who have some issue with insulin management at a physiological level.

[Michael Snyder]
Uh, well, if you include beta cell defects as part of insulin management then the number is probably very high.

[Andrew Huberman]
Mm-hmm, yep. Like-

[Michael Snyder]
But I honestly don't know the answer. I don't think we fully know the answer 'cause people haven't done this sub-phenotyping like I've described.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
We don't know how many people have incretin defects. We are getting there with insulin resistance and such, but I don't think we're fully there. But I want to correct something that you said. I mean, it's very much the case when you see someone who's thin you can't assume they're not diabetic. This is very common, especially in South Asians to see than diabetics. Uh, and I'm a good example. No one would call me overweight, uh, by any definition, yet I'm a diabetic and I have a beta cell defect. Uh, and I used to think a lot of people who are thin diabetics probably have beta cell defects, but it's not that simple. Some do and some don't. Some are, some are insulin resistant. And so, um, and then there are other people, believe it or not, who are very obese by any clinical measure what have you, and they have very good glucose control. So there are a lot of things we don't fully understand and a lot of it probably does, uh, fits in this idea that this is not a simple process. Uh, we have many organ systems involved in glucose control, your liver, your pancreas, your muscles we mentioned, but even your brain is a major glucose consumer. Uh, and so we have all these different organ systems. Then on top of that we have all these different biochemical pathways that are engaged as well. We mentioned the insulin one, but there's incretin, uh, which are these GLP things that promote insulin re- release, but they probably have other effects as well. I don't fully understand. I don't think everyone does all the effects of incretins. They're, these, their receptors are all over the place. In fact, some of these drugs you may have heard are actually now being touted as maybe anti-longevity drugs because they seem to improve cognition and stuff. Now whether that's tied to weight and things like that is less clear, but-

[Andrew Huberman]
As anti-longevity drugs or as longevity drugs?

[Michael Snyder]
As longevity drugs.

[Andrew Huberman]
Got it.

[Michael Snyder]
Oh, thank you for that correction, yeah.

[Andrew Huberman]
Uh, actually, just for fun-

[Michael Snyder]
Yeah

[Andrew Huberman]
... let's explore for a moment some of the things that we've heard these GLP-1 drugs, uh, are effective for.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Uh, certainly for, um, diabetics to better, type two diabetics to better control their, uh, blood glucose.

[Michael Snyder]
Yeah. If I can intersect there?

[Andrew Huberman]
Yeah.

[Michael Snyder]
I am a type two diabetic and they work great for me. I, my hemoglobin A1C got to 8.4 which, you know, it's not the highest but it's pretty high. And I went on the GLPs and it went down to 5.7.

[Andrew Huberman]
Just like that?

[Michael Snyder]
Pretty fast, yeah.

[Andrew Huberman]
Independent of weight loss?

[Michael Snyder]
No, it c- well, initially yes. It's a little complicated. I went on a, a lower dose thing called, um, Farxiga, and that one dropped me down to about the 6.4, 6.5 level. And I didn't lose too much weight. I did lose some. Uh, and then I went on Mounjaro because I had some nausea effects. That is a common side effect. They were modest but they were there. And I went, so I shifted to Mounjaro which is a more potent version. And that dropped me down to 5.7, and I did lose weight. I went from 144 to what I am now, 128, which I didn't like to be honest. And it- it... But I can tell you my, I mentioned I do whole body MRIs, I've done 20.... uh, a sale, uh, over the last almost nine years. And I could just see my fat evaporate once I went on these. I g- I'm the coldest guy in the room now. Uh-

[Andrew Huberman]
But you maintain muscle mass because you do resistance training?

[Michael Snyder]
S- mostly, yeah.

[Andrew Huberman]
How many days per week are you doing it?

[Michael Snyder]
I do it every day. So, but I have light days 'cause, you know, you can't strain yourself hard every day or that's a problem. So I have light days with more reps and then heavier days for more of the strength stuff. And then I have a specialty day where I do like snatches and things to build my core, this sort of thing. Uh, and so, uh, combination of, of those things. So I do it every day, and the goal is to keep my muscle mass up. And I mostly did it 'cause I do get measured a lot, although it plummeted when I got in a bike accident and hurt my shoulder. Uh, and then certain exercises I couldn't do, and so those things, as you might imagine, diminished. So I did lose some muscle as a consequence of that. I have mostly built my strength back up, not entirely back to where it was. So, uh, it's still there, but yeah, it, it's not 100%. And then there's a question on how much strength versus muscle mass is important. I don't have... Maybe you know the answer to that. I don't know. Uh, but anyway, I, I do try to keep it up. It's down a bit, uh, in terms of muscle mass and, and a touch in strength as well. I do... My... Uh, again, my hemoglobin A1c isn't too bad, but I don't like losing that much, I'll be honest with you. I, I thought I looked a little gaunt. So actually am now backing off on the Mounjaro. I don't do it every week like you're supposed to. I'm on the lowest dose, so I'm a great responder there. And by the way, e- at... when you're getting these drug response, it turns out I'm metformin non-responder. I did try that early on.

[Andrew Huberman]
Oh, this is interesting. So just to remind people, metformin and then the poor man's version of it is berberine which is sold as a supplement. They basically do the same thing. They lower blood glucose. In fact, I will tell, uh, anyone that decides to take metformin or berberine

[Andrew Huberman]
that if you don't consume enough starchy carbohydrates with it, y- it can give you a brutal headache because you become hypoglycemic.

[Michael Snyder]
Oh, I didn't know that.

[Andrew Huberman]
Oh, it's-

[Michael Snyder]
Yeah

[Andrew Huberman]
... it's really rough. Years ago, I used to, uh, take a little bit of berberine. Um, I used to do these, uh, cheat days.

[Michael Snyder]
Okay.

[Andrew Huberman]
This was many years ago. I would eat really clean all week and then I would, like a Saturday, I would just go for it, like, a- anything you wanted. Um, and

[Andrew Huberman]
I felt lousy. You'd have these energy, you know, peaks and valleys, and then you just felt like by the end of the day, you're just like, "I'm done with food for the next 10 years." And of course, you fast the next day, you feel fine, you go right back to it. But, it wasn't healthy. But taking berberine, it was remarkable because it would allow me and other people, uh, that recommended it to me, that you could just eat like an entire box of donuts and feel fine because it would blunt your blood glucose response. However, if you don't have enough glucose in your system, you gonna... You become hypoglycemic and, and you, you get c- y- you get these brutal headaches. Um, so anyway that's a little-

[Michael Snyder]
And this is becoming a big deal now, right? Hypoglycemia is now being recognized as a big concern actually. So, and people are picking up a lot of this with the CGMs.

[Andrew Huberman]
Interesting.

[Michael Snyder]
So-

[Andrew Huberman]
And this is because people are taking Mounjaro and taking other things that are dropping their blood glucose?

[Michael Snyder]
Yeah. And just, it's probably been out there more than people realized in the first place-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... that... And now with the CGMs, people realize, well, if you... Uh, uh, we talked about these glucose spikes. Well, it's very common if you get a really giant spike, you make a lot of insulin.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So the consequence is then you come down on the other side and you actually get too low glucose from those spikes.

[Andrew Huberman]
Yeah.

[Michael Snyder]
So, so people are recognizing that and that can... People are now concerned about that. Certainly leads to fatigue.

[Andrew Huberman]
Mm-hmm. Yeah. Uh, glucose troughs are definitely bad.

[Michael Snyder]
Right.

[Andrew Huberman]
I, I don't do any sort of cheat day anymore. I, I actually just a few years ago, I just quit eating bad food.

[Michael Snyder]
Yeah.

[Andrew Huberman]
I don't eat non, uh, I don't eat-

[Michael Snyder]
Well, that, that's gotta be best, right?

[Andrew Huberman]
You know, or, or I aim for, you know, 90% of my food intake to come from, you know, whole unprocessed foods.

[Michael Snyder]
Yeah, great.

[Andrew Huberman]
And-

[Michael Snyder]
Ult- ultra-processed is the way. Yeah

[Andrew Huberman]
... then occasionally a slice of pizza or a bowl of ice cream or something. No big deal, right? Um, especially if you're exercising regularly. But so to go back to, um, these, uh, these drugs, these, these GLP-1 agonists, which is basically what they are.

[Michael Snyder]
Right.

[Andrew Huberman]
And I... We had a guest on here, uh, Zachary Knight who's at UCSF.

[Michael Snyder]
Yeah.

[Andrew Huberman]
How he was an investigator who, um, kind of shocked me by telling me that these drugs all increase levels of GLP-1 in the blood and brain by about a thousand-fold.

[Michael Snyder]
Yeah.

[Andrew Huberman]
That any less doesn't really have an effect on appetite, doesn't have an effect on the various things they're designed to, uh, to do. Um, so these are massive supraphysiological increases in GLP-1 that people are achieving with these drugs. I know nowadays some people are starting to get them from compounding pharmacies and microdosing them-

[Michael Snyder]
Right

[Andrew Huberman]
... to great effect actually.

[Michael Snyder]
Okay.

[Andrew Huberman]
The big pharma companies don't like this because it's sold at a fraction of the price and you can get away with very low dosages.

[Michael Snyder]
This is what I wanna do, by the way.

[Andrew Huberman]
Yeah.

[Michael Snyder]
I wanna, I wanna-

[Andrew Huberman]
And no nausea.

[Michael Snyder]
Right.

[Andrew Huberman]
And oftentimes they're combined with, um, some other things that, uh, off the top of my head I can't remember. But I... Oh, right, some of these more, um, experimental peptides like SS-31, which are designed to improve mitochondria. And people are getting really spectacular effects from the microdosing of compounded, um, uh, compound pharmacy, uh, GLP-1 agonists. But even those are probably boosting GLP-1 several hundred-fold. So none of this is like natural-

[Michael Snyder]
Right

[Andrew Huberman]
... uh, for, for the body. And yet, um, there are other positive effects. Like I've heard of, uh, reduced craving of alcohol.

[Michael Snyder]
Mm-hmm.

[Andrew Huberman]
Um, what are some others that you've heard of?

[Michael Snyder]
Cognition is a big one. And it's certainly something people worry about a lot as they get older. It's almost becoming the number one thing people worry about as they get older, getting dementia and, uh, related conditions. So, and there's... You know, we'd like to see more studies out there, but there's some evidence that it may improve cognition. Now, how much of that is intertwined with weight loss and things like that, I don't think has been totally deconvoluted. So I think we need to sort all that out. But, um, yeah. But people are now... You know, y- you may know that people used to talk about metformin, this diabetes drug as potentially the longevity drug-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... that this may be the way to live a lot longer, healthier. Um, and the side effects are not high as far as we know, if, if at all for most people. Uh, and now a lot of people are very interested in these GLPs as possible longevity drugs. And there are trials underway to look at this sort of stuff. So we'll, we'll see, you know, what ways they apr- improve people.

[Andrew Huberman]
I, I will say as long as we're on this topic, um, t-... you are a perfect example of a very diligent patient. Meaning, you're taking these GLP-1 drugs. You're, as you mentioned, aiming for taking lower dosages, maybe even, quote, unquote, "microdosing."

[Michael Snyder]
Yeah, I'd like to. Yeah.

[Andrew Huberman]
Um, but you're also resistance training daily, alternating heavy and light days. You do your exercise snacks. Uh, you, you, you know, you're getting brisk walks after you eat. I mean, I think it's important to point out that, um, you're doing all the things that help maintain muscle mass, cognition, et cetera, uh, while taking these GLP-1s. Many people won't-

[Michael Snyder]
Yeah

[Andrew Huberman]
... or just, uh, unless they're highly motivated to. Um, they just, they want a drug that's gonna melt the fat away, and they are unwilling or uninterested to do the, the exercise piece. Wh- what, if any, data from your genomics, uh, data and, and these large-scale studies that you're doing point to the fact that the combination of augmenting GLP-1 with these drugs and exercise is, is beneficial? Is it all just about maintaining muscle mass?

[Michael Snyder]
Uh, good question. I don't know. But it's pretty clear that people who do do strength training, again, w- larger studies would be nice, but it's pretty clear they can reduce their muscle mass loss. That, that's clear. And, and it's definitely been the case for me. I mentioned my bike accident. I went from pretty m- good about maintaining muscle mass to then I did lose some when I lost some of that. Um, so I can tell you personally, had an effect.

[Andrew Huberman]
Don't cycle. I tell my friends, we... I know so many people who've been on a bicycle. You're traveling next to these three- ... thousand-pound, uh, vehicles moving much faster than you. People are texting. I, I say this out of love, uh, for the audience and for, and for you, even though we, we just met. Uh, we're colleagues at Stanford, um, all these years. And, and I have to say, uh, everyone I know who cycles regularly gets hit by a car eventually.

[Michael Snyder]
I-

[Andrew Huberman]
I know three-

[Michael Snyder]
Yeah, I've been hit by a-

[Andrew Huberman]
... Stanford faculty that are dead.

[Michael Snyder]
Ooh.

[Andrew Huberman]
Right? But then again, I lived in the area for a long time.

[Michael Snyder]
Yeah, right.

[Andrew Huberman]
Back on Woodside Road, you know, cars just, just taken out or, or had to dodge a car and, and, um, ran into a tree. So, dead, brain damage, injured.

[Michael Snyder]
Well-

[Andrew Huberman]
What do I have to do to convince you to run instead of cycle?

[Michael Snyder]
W- well, I do have a theory-

[Andrew Huberman]
You know

[Michael Snyder]
... that your, you know, your cycling versus your health, there's an inverse relationship, or it's a constant, I should say, meaning, uh, I'll probably get killed by a car possibly someday but I'll stay healthy in the meantime because it is my form of aerobic exercise.

[Andrew Huberman]
But we need you around, Snyder. But I say this.

[Michael Snyder]
So-

[Andrew Huberman]
I don't know why anyone would, would do this instead of swimming or-

[Michael Snyder]
But I don't go up those... but I don't go up those mountain things where there's no even bike paths that they have in Palo Alto.

[Andrew Huberman]
It's not the cyclists. It's the cars I worry about.

[Michael Snyder]
Yeah, correct.

[Andrew Huberman]
Yeah.

[Michael Snyder]
But there's no room f- in some-

[Andrew Huberman]
Right, right

[Michael Snyder]
... of those places-

[Andrew Huberman]
All right

[Michael Snyder]
... to go. So I mostly... I mean, I, I do it to go to lab and back, and I do it... it's also a form of mental release for me at the end of... I do, I love what I do, but I do work long hours. And I, it's just a great release to get that bike ride home at the end of the day.

[Andrew Huberman]
Do you wear a helmet?

[Michael Snyder]
Uh, of course, yeah. And that's turned out to be pretty critical when I've had my a... I've had more than one accident, I hate to say. Uh, but, um, but never... no car has run into me, I'm thankful for. But I, I hit a rock and got knocked out once. So I, or something like that, I, I don't know, I woke up briefly in a, in a ambulance and then more in-

[Andrew Huberman]
Telling you-

[Michael Snyder]
... emergency rooms .

[Andrew Huberman]
... Stanford professors, this is the way Stanford professors get taken out.

[Michael Snyder]
Yeah. Well-

[Andrew Huberman]
Yeah.

[Michael Snyder]
Uh, but I've been, I'll say, healthy in the meantime. And, and I like to think I'm pretty healthy now, uh, minus my diabetes and that sort of thing.

[Andrew Huberman]
You seem very robust. I mean-

[Michael Snyder]
Yeah

[Andrew Huberman]
... I, I hope you don't mind, uh, me sharing that you are, uh, about to hit 70 soon.

[Michael Snyder]
Yeah.

[Andrew Huberman]
And you are clearly cognitively, uh, whip-smart- ... and, um, and fast, and physically, you seem very robust. And, um, you mentioned getting these MR, whole-body MRIs-

[Michael Snyder]
Yeah

[Andrew Huberman]
... and the fat just kind of disappearing as you were doing these GLP-1 agonists-

[Michael Snyder]
Right

[Andrew Huberman]
... and weight training. I, I wanna make sure I continue to, you know, hammer home the fact that you're-

[Michael Snyder]
I'm big on the weight training.

[Andrew Huberman]
Yeah, y-

[Michael Snyder]
I'm glad you're doing that-

[Andrew Huberman]
Yeah

[Michael Snyder]
... 'cause I think it's huge.

[Andrew Huberman]
Yeah, it's, it's not just about taking a drug. Um, and you can do a lot with just lifestyle. And, uh, we'll talk more about that. But I have a question about, um, subcutaneous versus visceral fat.

[Michael Snyder]
Yeah.

[Andrew Huberman]
You know, we hear that fat around the viscera, around our organs, is the one to really worry about. Um, and anytime I hear something like that, I think, "Okay, that sounds like a reason to not lose fat elsewhere." But, you know, wh- what do we know about the, the health risks of intraviseral fat versus subcutaneous fat?

[Michael Snyder]
Yeah, I'm not an expert here, but it does seem pretty clear that obviously fat around your organs isn't good, fatty liver being a good example. And by the way, when I went on GLPs, my, I had a little bit of fatty liver, just disappeared. So, I think a lotta people are thinking this way, that your pancreas is, and beta cells in particular, are very subject to stress. And fat does put stress on your organs. No question. And so, it may be one of the reasons, you know, your pancreas, your beta cell in particular, is very sensitive to fat, is because it does cause stress. We know fat's very associated with inflammation. So obesity a good example. Uh, the more obese you are, the higher BMI. Again, not perfect correlation, but higher inflammation. And so, all that does tie together. And, and your immune system is tied in this in ways I would say we don't fully understand. But, uh, in general, the party line is that visceral fat is worse, and I think it's because it's putting stress on your organ systems, uh, yeah, say, versus subcutaneous.

[Andrew Huberman]
I'd like to take a quick break and acknowledge one of our sponsors, David. David makes a protein bar unlike any other. It has 28 grams of protein, only 150 calories, and zero grams of sugar. That's right, 28 grams of protein and 75% of its calories come from protein. This is 50% higher than the next closest protein bar. David protein bars also taste amazing. Even the texture is amazing. My favorite bar is the chocolate chip cookie dough, but then, again, I also like the new chocolate peanut butter flavor and the chocolate brownie flavor. Basically, I like all the flavors a lot. They're all incredibly delicious. In fact, the toughest challenge is knowing which ones to eat on which days and how many times per day. I limit myself to two per day, but I absolutely love them. With David, I'm able to get 28 grams of protein in the calories of a snack, which makes it easy to hit my protein goals of one gram of protein per pound of body weight per day, and it allows me to do so without ingesting too many calories. I'll eat a David protein bar most afternoons as a snack, and I always keep one with me when I'm out of the house or traveling. They're incredibly delicious, and given that they have 28 grams of protein, they're really satisfying for having just 150 calories. If you'd like to try David, you can go to davidprotein.com/huberman. Again, that's davidprotein.com/huberman. Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. One of the best ways to ensure a great night's sleep is to make sure that the temperature of your sleeping environment is correct. And that's because in order to fall and stay deeply asleep, your body temperature actually has to drop by about one to three degrees. And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees. Eight Sleep automatically regulates the temperature of your bed throughout the night according to your unique needs. Eight Sleep has just launched their latest model, the Pod 5, and the Pod 5 has several new important features. One of these new features is called Auto Pilot. Auto Pilot is an AI engine that learns your sleep patterns to adjust the temperature of your sleeping environment across different sleep stages. It also elevates your head if you're snoring, and it makes other shifts to optimize your sleep. The base on the Pod 5 also has an integrated speaker that syncs to the Eight Sleep app and can play audio to support relaxation and recovery. The audio catalog includes several NSDR, non-sleep deep rest, scripts that I worked on with Eight Sleep to record. If you're not familiar, NSDR involves listening to an audio script that walks you through a deep body relaxation combined with some very simple breathing exercises. It's an extremely powerful tool that anyone can benefit from the first time and every time. If you'd like to try Eight Sleep, go to eightsleep.com/huberman to get up to $350 off the new Pod 5. Eight Sleep ships to many countries worldwide, including Mexico and the UAE. Again, that's eightsleep.com/huberman to save up to $350. I'd like to talk a little bit about meal timing and sleep. I do my best to eat my last bite of food at least a couple of hours before I go to sleep. Doesn't always happen. What do we know about how evening and nighttime meals impact sleep and next-day glucose levels and regulation?

[Michael Snyder]
Well, the party line is that you should not eat three hours before sleeping, uh, and I believe that. And that's true from the studies we've run, that people who do have a gap, and actually people who walk after dinner, have lower glucose the next day. And if you go into the evening with a high glucose spike, in general, that correlates with poorer sleep. So, um, I, I think it's more complicated than that. I think the... Again, the party line will be, well, your glucose is kinda high at night and gradually goes down during the day and spike in the morning. You got a cortisol spike, as you probably know, when you wake up, and that's normal and that's healthy. Helps energize you for the day. And, and cortisol and glucose are related. Uh, but when you actually look at people's glucose patterns, it's much more complicated than that. And I think a lot of that has to do with what their subphenotype is, is what, uh, we don't fully understand as we're trying to sort this out. And what you did the day and especially the evening before, eating that big piece of pizza and then go- falling right asleep probably is not a great thing for you. You will go to bed with a high glucose spike for man- many people. Again, unless you have perfect glucose control. So, uh, you know, I, I think getting your glucose under control, it is a bit of a problem for me. We tend to eat late in my household just because both my wife and I work kinda late. Uh, and so we tend to eat a little bit later, but I definitely do better if I can try and eat earlier, and, and I definitely don't snack before bedtime, that sort of thing. And these days, I try not to make my biggest meal my dinner, uh, which again, can lead you into sleep with that. And we always take a walk. We have dogs, and walk our dog after dinner. It's become a routine. You mentioned earlier about behavior, and I think the key for good behavior is to get into these routines, uh, where you can just get into that. And I think it really makes a difference. So, um, yeah, always, and as I'm sure you know, going to bed, people... We had found that in some of our studies as well, going to bed the exact same time, those folks have lower glucose than those who have highly variable sleep timing. Now, that's not so great for me because I travel a fair amount.

[Andrew Huberman]
Yeah, likewise.

[Michael Snyder]
But, but I try when I'm not traveling to keep constant hours. At least that part I'm, I'm okay at. But, you know...

[Andrew Huberman]
I think we forget sometimes the number of interesting things that happen in sleep. And one of the most interesting papers, to me anyway, in the last few years was a paper that I saw where they essentially had people breathe into a tube while they were sleeping.

[Michael Snyder]
Okay.

[Andrew Huberman]
And evaluated the different types of metabolism that were occurring during sleep. And it turns out that as we go from light sleep to deep sleep and then more rapid eye movement sleep as the night progresses, the brain and body transition through essentially every form of metabolism, glucose metabolism, ketogenic metabolism, a mixture of the two. And it seems like sleep is this, um...We don't know if it's a, like a test run or if it's a reboot or we don't know what to call it, right? But it's just very clear that during sleep there's a lot of metabolism happening. So when you tell me that getting to bed at roughly the same time or the same time every night improves blood glucose regulation, my first thought is, oh, well, that makes sense because if you go to bed at the same time, then you're eating at roughly the same time, you're exercising at roughly the same time. But it could also be the case that in sleep we're getting a- a- a tuning up of the, of the metabolic processes for the brain and- and body. Is there any evidence that, that supports that?

[Michael Snyder]
Yeah. Again, I don't know from the metabolism standpoint. I- I like to say the things we do the most, we understand the least. Nutrition, right? How does it exactly does that work on all your different organs? Sleep. You know, u- uh, I do like the idea of the sleep. You may know your ,

[Michael Snyder]
y- you would know this better than me, but your spinal fluid and such, it, you know, expands and contracts, the idea of emptying out the garbage, so to speak, while you sleep.

[Andrew Huberman]
Mm-hmm. Yeah, it literally rinses out your- your system.

[Michael Snyder]
Yeah, and I- I like that concept. I think, uh... And, and, you know, to what extent that is beneficial, I'm sure it is, I don't know. And all the other facts, but even people argue what's better for you, REM versus deep sleep. E- even some of that is debated by experts in the field. Again, I'm not a sleep expert. Um, I have a tendency to move into fields I know nothing about, so because I'm so naive, I hope to learn something, uh, especially these areas that aren't so well understood. So it's an area we're gonna be studying a lot more around the glucose control. But there's no question, if you look at some people, they're spiking really bizarrely. A- and I have mixed days myself. I'm trying to sort that out. Some where I do hit the party line, higher glucose gradually go down by the morning, but then I have nights where I'm quite irregular and I wanna correlate that with what's going on. And it's not just me, it's true of a lot of people. And I don't think that's sorted out in my mind. And I think metabolism in general, uh, at some point we can talk about the microsampling stuff, but we found that ha- we had 32 people drink this Ensure shake while they were fasted. And they all reacted very differently to it. This is during the day now, not- not sleep. And, um, for some people it was proinflammatory, for others antiinflammatory.

[Andrew Huberman]
So interesting.

[Michael Snyder]
I assume a lot of this got set early in life because your whole microbiome... So backing up a little bit, uh, just so people realize that, you know, you have a lot of microbes, you have in fact more microbes in you than are human cells. And they are critical for digesting your food and all this. And, and they're, they heavily interact with your immune system. 70% of your immune cells are in your gut. So you have this whole interplay between your immune system and your gut. And obviously then the food you eat, which, uh, it goes through your small intestine first and the small molecules like glucose get absorbed, but then all the fibers, the big molecules go into your- your- your culinary, your large intestine, where they basically, you know, are interacting with these immune cells. So I think a lot... And a lot of that gets probably set early in life. In fact, people have shown your microbiome gets set in your first three years of life. So I think that interplay all gets established and- and then you are reacting to some of that, your food later in life. That's at least the postulate. Not that you can't modify it. In fact, you know, switching from carnivore to veggie diets and/or Mediterranean-type diets, which are sort of healthier, f- like fish-heavy, uh, um, veggie diets, I think are helpful for people. Um, but I do think some of this gets set early.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And I think getting that set right, I- I think we probably need to, as a society, get that all set a lot earlier probably now too. And, uh, and it's estimated, some work from Justin Sonnenburg, that, um, uh, you know, native populations, these aboriginal, they have three times the number of microbes that, say, people in the US. Uh, so we just don't have the same community that is probably handling diverse foods and- and probably making essential ingredients for our health that we're now missing. So we probably need to restore that in some fashion. Otherwise, this obesity and diabetes trend is just gonna continue.

[Andrew Huberman]
Mm-hmm. I totally agree. I think the gut microbiome is

[Andrew Huberman]
without question one of the more fascinating aspects of our biology. And, um, in no small part because of the way that it interacts with the brain by the vagus nerve. You know, e- everyone's obsessed these days with the vagus nerve as a calming pathway. But it's a- got a bunch of different avenues within it and, um, and it is the major route by which your gut communicates with your brain.

[Michael Snyder]
Right.

[Andrew Huberman]
And, um, I- I do wanna, um, just say one thing in fairness to, uh, m- an observation. Um, I completely agree with you that many people who've been eating certainly standard American diet, sad to think that anyone still does that anymore because it's such a terrible diet. I think everyone agrees on that, a lot of processed foods. But, um, you mentioned, uh, switching, uh, carnivore for, uh, more Mediterranean or plant-based. I have seen that, uh, work for many people. I will just also mention i- in fairness that there, and this relates to the gut microbiome, there do seem to be some people who, despite their best effort to eat fiber, fruits, vegetables, fish, so-called Mediterranean diet, that for whatever reason, um, they have persistent autoimmune issues. And I have observed over and over again that if they switch to an elimination diet that's largely just meat...... believe it or not, and nothing else, they seem to resolve those autoimmune issues. Now, I personally don't follow that diet. I don't think it's the mo- the healthiest diet out there. It's very hard to f- uh, to stick to. But in my mind, it seems like the data are pointing to the idea that there are diverse microbiomes out there set up early in life, and probably genetics play a role also. You're a professor of genetics- ... so hopefully that's not too, uh, uh, too heretical an idea.

[Michael Snyder]
By the way, some of this has been broken down of, of say, your, how much is your microbiome for general glucose levels-

[Andrew Huberman]
Yeah

[Michael Snyder]
... versus genetics. And I think for the general, uh, um, microbiome, it's about 20 some, 20 to 30%. Depends on the cohort that was studied. There's some work from, from the Weissman. Uh, and then for genetics, it may be about 20% as well. So-

[Andrew Huberman]
So 20%-

[Michael Snyder]
... it may be even a little less

[Andrew Huberman]
... of your microbiome is determined by your genetics?

[Michael Snyder]
Uh, no, the other way around. Sorry. Of your glucose levels-

[Andrew Huberman]
Hmm

[Michael Snyder]
... 20%, 20 to 30% is determined by your microbiome-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... and about 20% by your genetics for glucose.

[Andrew Huberman]
And the rest by lifestyle?

[Michael Snyder]
Yeah.

[Andrew Huberman]
Okay.

[Michael Snyder]
And by the way-

[Andrew Huberman]
That's a very u-

[Michael Snyder]
Yeah

[Andrew Huberman]
... that's a useful set of metrics.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Yeah. I mean, I, I just have to believe, based on the observation of people who are really careful, really care about their health, they're not doing standard American diet, and they've tried vegan, they've tried vegetarian, they've tried omnivore without many processed foods. And then they try ketogenic diet and they feel better, and then they go full just meat, and their issues disappear.

[Michael Snyder]
Yeah.

[Andrew Huberman]
And you g- you kinda have to acknowledge that.

[Michael Snyder]
Right?

[Andrew Huberman]
I'm not saying you have to, but I'm gonna acknowledge it. I will also say that most people seem to do well on an omnivorous diet. I think 90% of people in the world are probably omnivores.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Um-

[Michael Snyder]
Yeah

[Andrew Huberman]
... and I, I find it so interesting that as we support the gut microbiome, our health generally improves. That just seems to be the case. I'd like to talk for a moment about fiber.

[Michael Snyder]
Sure.

[Andrew Huberman]
Because I think there's general agreement in the medical community that fiber is important. Um, reduces risk of cancer, improves digestion, adds bulk to food, reduces inflammation, just on and on and on. But then again, our colleague, Justin Sonnenburg, um, and Christopher Gardner-

[Michael Snyder]
Yeah

[Andrew Huberman]
... both of whom have been on this podcast before, did this really nice study of comparing increasing fiber in the diet versus increasing intake of low-sugar fermented foods. And it's very clear that the increase in low-sugar fermented foods supported proliferation of the healthy gut microbiota, reduced the inflammatone. Whereas increasing fiber allowed some people to reduce inflammation, other people's levels of inflammation went up. And so this brings us to this question of when we talk about fiber as a general category, maybe that's too broad.

[Michael Snyder]
It is.

[Andrew Huberman]
Could you tell us about the two major types of fiber, which foods

[Andrew Huberman]
tend to deliver one or the other type of fiber, and if indeed there are differences, and which fiber are best for different people?

[Michael Snyder]
Right. So, uh, as you're alluding to, fiber is very heterogeneous, very different. And we even break it down further than that. You're probably thinking of, you know, soluble versus insoluble, uh, or resistant starch versus starch, but I look at fiber as like just a giant community of different substrates, if you will. So we have long chain, short chains, hydrophobic, hydrophilic, positive, negative. It's like saying all animals are the same. Humans are the same as cockroaches, the same as cats and dogs.

[Andrew Huberman]
You just can't lo- You just can't lump that broadly.

[Michael Snyder]
You can't.

[Andrew Huberman]
Yeah.

[Michael Snyder]
And their effects are very, very broad.

[Andrew Huberman]
Yeah.

[Michael Snyder]
And so we've started tearing this apart. I was a chemistry undergrad by training, so I guess that's where I'm coming at this. So we just started... And being somewhat practical too, we started putting people on... We took two common fibers, arabinoxylan and inulin, which are these two, uh, just commonly used, uh, arabinoxylans and psyllium husks and it's associated with Metamucil, and inulins and those chicory pea fiber things. And-

[Andrew Huberman]
Well, could you, before we dive into this-

[Michael Snyder]
Oh

[Andrew Huberman]
... what are some foods that one type of fibers is more abundant in versus the other type of fiber?

[Michael Snyder]
Well, Metamucil is a good example for the, the, um, uh, arabinoxylan would be in that. Arabinoxylan's kind of interesting. It's name sounds to chemists, it has arabinose and, uh, and it does have some glucose, but it has polyphenols in it too. And I don't know if... You probably have covered this on your sh- show.

[Andrew Huberman]
No, not yet, but they're super important.

[Michael Snyder]
They are. They're, they're, and they're being, especially in the last, I'd say, you know, six, 10 years, being more and more appreciated for all their positive effects as antioxidants-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... anti-inflammatory.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So, uh, anyway, they're part of arabinoxylan. This inulin is a glucose polymer, but there's short chain and long chain that has similar properties as well too. That's in various, uh, um, certain fruits and certain, uh, other things. And when we went into this, if you read the literature, you would say, "Well..." There'd be some says said, um, "Well, inulin lowers your glucose," and others say, "No, it has no effect." And some saying it lowers your cholesterol, and others it doesn't. Same with arabinoxylan. It was all over the map, although there might have been more of a consensus about this arabinoxylan lowering cholesterol. So we just did it. We took 18 people. I know it doesn't sound like very many, but they did a, what's called a crossover study, where they went on increasing doses, where they took either 10 for the first 10 grams a day for the first week as a supplement, 20 the next week, 30 the next week, and then did a washout, and then switched to the other one. So they're, uh, they're randomized. They might do arabinoxylan the first period, and then inulin the second, then a mixed fiber, which the party line would say is, is supposed to be the best for you. So we put... And then we do what we're known for, these deep measurements, these deep omi- We measures many molecules of people's blood, and as well as clinical measures. And so what we discovered is that as a general rule, uh-... arabinoxylan did reduce cholesterol, and actually quite substantially. It went down about 25%.

[Andrew Huberman]
So this is in Metamucil, but what other, um, what sorts of foods contain high amounts of th- of this compound?

[Michael Snyder]
Most do, actually.

[Andrew Huberman]
Oh, okay.

[Michael Snyder]
It's very-

[Andrew Huberman]
So broccoli.

[Michael Snyder]
Yeah. Broccoli, yeah.

[Andrew Huberman]
Kale, lettuce, cabbage.

[Michael Snyder]
Yep.

[Andrew Huberman]
Okay.

[Michael Snyder]
They'll all ha-

[Andrew Huberman]
Okay. So this is like the, when we think of fiber, we think of bo-

[Michael Snyder]
But, but they have, but they have other things as well.

[Andrew Huberman]
Okay.

[Michael Snyder]
So these are generally mixtures. Like apple fiber will have three major types of fiber. It's back to this heterogeneity of fibers. So we're now getting into others like beta glucans, another fiber. Resistant starch is yet another one. So there's a whole series of these fibers out there, yet they're not studied for their individual effects. And that, and it may be the case, of course, the complex mixture is a big deal, uh, as well, meaning getting the right combination. But we're starting with individual fibers, trying to see what their effects are, and then we will do combinations. So we're just finishing up a study where, same thing, w- instead of two fibers, we added two more, beta glucan and resistant starch, and we're trying to see their effects as supplements. Uh, and the idea ultimately is, is I think people do supplements. That's why we're doing supplements. Not that I'm a big fan. I'd rather they eat, you know, healthier, unprocessed food.

[Andrew Huberman]
Or both.

[Michael Snyder]
Or both. But yeah, most people don't get enough. You probably know that, um, it's recommended women have at least 25 grams of fiber a day, men, 35. And the number that people get is something like 12 to 15.

[Andrew Huberman]
Wow.

[Michael Snyder]
They're off by a factor of two in their amount of fiber they consume. So, you know, minimally, supplements could help bring that up. Anyway, uh, I mentioned that arabinoxylan as a general rule lowered most people's cholesterol. And by the way, neither affected glucose. So we think other things are important for that. And, um, but if you look at individuals, we did see some people where arabinoxylan had zero effect, meaning their cholesterol stayed flat, even when m- they went to the higher dose of 30 grams per day. Yet their inulin promoted their decrease, uh, in, in cholesterol. So what's going on? Well, we don't know. But to me, it's logical that your microbiome, maybe it's your mu- maybe it's other parameters are playing into this. So this is why ultimately what I wanna do is just get your microbiome, do a blood draw and say, "Aha, here's the foods that will be healthy for you, and here's the ones that won't." I think this is very personalized and complex. It comes back to what you were saying before about meats and things having different effects on people. And you probably know a lot of people with bipolar, now the, the solution for a lot of people is a ketogenic diet, right? Which, and it seems to really work. There's studies out there where it's been very transformative.

[Andrew Huberman]
Which is remarkable. Uh, I mean, if we really just take a step back, it's like forever, you know, bipolar, depression was one of the most difficult things to treat. And it turns out the ketogenic diet can be very effective in some people. In some cases, curing people. Not every person, but that's a remarkable breakthrough.

[Michael Snyder]
I agree.

[Andrew Huberman]
You know? And, and as you said earlier, I think it's, uh, such a key, uh, thing for people to keep in mind, we understand the least about the things we do the most.

[Michael Snyder]
Yeah.

[Andrew Huberman]
So you can imagine for many years, people are eating like every- everyone eats sooner or later. And, um, some of these people are dealing with serious mental health issues, and the foods they were eating very well were exacerbating their symptoms.

[Michael Snyder]
Yeah.

[Andrew Huberman]
It's just wild to think about. But then when we, y- we talk about, and I've heard you say, you know, food is medicine. I think most people don't think of food as medicine. I think most people think as food is something, uh, they need, that they crave, that they enjoy, uh, and that eventually becomes problematic for them. You know, I don't think people really understand the extent to which what they put in their mouth can support them, that it really can be health promoting.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Right? I think it's because we are so calorie oriented. Like, oh, you know, it's all a battle between what you take in-

[Michael Snyder]
Yeah

[Andrew Huberman]
... versus what you burn.

[Michael Snyder]
Yeah.

[Andrew Huberman]
But you really view food as medicine.

[Michael Snyder]
Oh yeah, because I think we are, uh, I mean, the way I look at it, we're homeostatic systems. We're very, and complex ones at that, right? We have all these organs, all these biochemical pathways. And, you know, the one we also understand least is people's behavior.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
That came up earlier, and I'm sure it'll come up again. Uh, and you have to tune all this stuff to keep it right. And in general, most people do pretty well, but I think we could, uh, all improve that, I'm sure. And, and that is the goal, to keep this... You know, your car, right? You want, if you want it to run forever, you wanna keep all the systems working right and in balance. You don't let things get off too far. And I think there's a tendency, and I think this is the problem with medicine today, we wait 'til things are broken and then try and fix it. And so obviously what you wanna do is have people as well-tuned cars for their entire life, and then, you know, pass away then. That's how it should work. Uh, and so I think that's what we wanna do, keep people tuned. And so we probably don't get off to a good start early in life, uh, when we start people with all these not so good diets, like all this excessive processed food and sugar and losing our microbiome diversity. I think we really want to keep our car off and running right from the get-go. It's, you know, it's a little bit late for some of us 'cause we're probably a little bit hardwired, although I think we can tune that. I try to do that as best I can, I guess.

[Andrew Huberman]
Seem to be doing a good job.

[Michael Snyder]
Yeah. Well, anyway, we'll do it the best we can so...

[Andrew Huberman]
When I t- um, travel, I will occasionally take a probiotic-

[Michael Snyder]
Okay

[Andrew Huberman]
... in addition to all the other things I'm doing to support my gut microbiome. I do take a supplement to support gut microbiome. I also try and eat lots of fruits and vegetables. I will say I'm very intrigued by the- these fiber data-

[Michael Snyder]
Okay.

[Andrew Huberman]
... the different types of fiber data.

[Michael Snyder]
Yeah.

[Andrew Huberman]
... I'm intrigued because I notice that some vegetable foods just don't agree with me, even if I'm careful to chew them properly and do all that. Um, and I find that over time, I've just oriented towards eating the same, you know, six to eight vegetables. But, uh, I'm tempted to do the following experiment. Tell me if this is a good experiment, Snyder, uh, if I'd b- uh, get a shot at a sabbatical in your lab. Keep eating the same thing I'm eating, exercise the same, do, do things the, the way I'm, I'm doing them now. But try a supplement, like you said, Metamucil, which is one particular type of fiber.

[Michael Snyder]
Right.

[Andrew Huberman]
And do the before and after, um, LDL cholesterol, apoB, blood glucose regulation with a continuous glucose monitor. Then stop, do a washout, swap that out for increasing like inulin fiber through some other source. So, so in other words, add, add in a, a pure fiber source-

[Michael Snyder]
Right

[Andrew Huberman]
... uh, on top of an existing diet and see how that impacts, um, blood metrics and subjective well-being.

[Michael Snyder]
Yeah, I think that would be good. I'd love to know your microbiome. And, and these are the sorts of things we're trying to sort out now. I don't have an answer, but I imagine the microbes you have in you, they have certain hydrolases that break down these fibers. And everybody's microbiome is very, very different. Uh, so we, we have communities of microbes and, and every person's community is different. And so, they, we have these enzyme hydrolases that do break down these fibers. And my guess is that we already know that yours is gonna be different from mine. And so, it may be if you eat a certain fiber, you're not as prepared to handle it as the next person. So, this is why we need to collect the right data. And it may be at the end where you need to add the right probiotic, the right microbe to go with that fiber to better get the tuning you're looking for.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And in the long run, if you probably want permanent es- you know, uh, um, incubation of this, this probiotic into your gut, you may have to add a community because they're all interdependent. They get personalized, again, early. And so, you basically formed your own personal guild. And so, one problem with probiotics is that they, you know, they don't stick that well. Uh, a lot of them wash out. Although when a prolonged use can, can help colonize, some of that may be possible. Anyway.

[Andrew Huberman]
And then probably something, they're expensive. They require refrigeration-

[Michael Snyder]
Yeah

[Andrew Huberman]
... most of them. Um-

[Michael Snyder]
Yeah, that's right

[Andrew Huberman]
... I personally, uh, feel fortunate that I don't have what I would consider chronic gut eith- issues. I just avoid certain foods. Um-

[Michael Snyder]
Yeah, but are you avoiding it because you're getting inflammation? You said some don't agree with you. Is that because of gas or is that because of-

[Andrew Huberman]
Yeah

[Michael Snyder]
... inflammation?

[Andrew Huberman]
It's more of an inflammatory response.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Like you just kind of feel... Like you don't feel well-

[Michael Snyder]
Right

[Andrew Huberman]
... and you feel kinda like overtaken by some-

[Michael Snyder]
Right

[Andrew Huberman]
... process, which that's what I'm, like, you know-

[Michael Snyder]
Yeah, same here

[Andrew Huberman]
... this is a poor man's, uh, way of... Like extract to, uh, you know, um, inflammation.

[Michael Snyder]
But if you could figure out which fibers might be inducing that specifically, maybe you can avoid those foods with those fibers.

[Andrew Huberman]
Yeah.

[Michael Snyder]
I don't know. And again, fiber seems to be very personalized. So, I think it is something you can try. It's a pretty easy experiment to do. I think most people like the idea of, um, fibers... Again, we like to do individual fibers 'cause ultimately, I wanna understand the effect of every fiber and make combinations that would be personalized for people.

[Andrew Huberman]
Mm-hmm, mm-hmm.

[Michael Snyder]
But, uh, you know, if you were to get apple fiber oatmeal, it's, yes, it's got a lot of, uh, Metamucil and, and, uh, arabinoxylan, but it has other things in there too.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And it's probably true that the combinatorics are important. Uh, and we'll get there at some point with the combinatorics. I mean, I, I guess I'm a, you know, I am a big data guy. I like the idea with eight billion people on the planet, if we even got 1% of those, uh, doing food logging with sugar monitors and things like that, we'd have a lot of combinatorics all figured out.

[Andrew Huberman]
Well, you've got 100 people in your lab. You're running clinical trials all the time, right? Uh, your human subject, uh, requirements are, are big. Uh, I, maybe we'll provide a link to, uh, where people can participate in some of these studies. Um-

[Michael Snyder]
Yeah, we have studies running all the time.

[Andrew Huberman]
Yeah. Yeah, I... 'Cause I know a number of people will be interested to do that.

[Michael Snyder]
Great.

[Andrew Huberman]
And, uh, we're gonna talk more about sensors and-

[Michael Snyder]
All right

[Andrew Huberman]
... uh, air quality. We've got, uh, uh, a bit more to cover in each domain. But I think it's really important, uh, and thank you for breaking up this broad category that we've all heard about, fiber, into meaningful categories. And just even people's understanding that different people react differently to different fibers-

[Michael Snyder]
Yeah

[Andrew Huberman]
... uh, is really important. A family member of mine was told that they need to take Metamucil to get more fiber. Had zero impact on their LDL.

[Michael Snyder]
Uh-huh.

[Andrew Huberman]
Zero impact on, um, other important markers. I might suggest to them that they consider taking a different, uh, fiber-

[Michael Snyder]
Yeah

[Andrew Huberman]
... supplement in an effort to control their-

[Michael Snyder]
Maybe for them, inulin will be the trick.

[Andrew Huberman]
Mm-hmm. Great. I, I... This is the first I'd heard of it, well, when I was listening to one of your talks. Um, it's a good thing you have 100 people in your lab. By the way, folks, having a hundred-person lab is, um,

[Andrew Huberman]
exceedingly rare. And, um, and-

[Michael Snyder]
But we're a little smaller now. But yeah, we're still, uh-

[Andrew Huberman]
Yeah. Well, it's very impressive.

[Michael Snyder]
... a good, a good bunch, yeah.

[Andrew Huberman]
Uh, your, your vigor is undeniable. And, um, and I'll-

[Michael Snyder]
I'm, I'm just lucky to have amazing people in my lab. I consider myself very fortunate.

[Andrew Huberman]
Well, I will say, not just because you're sitting here, I'm not just saying it to, to be kind. Uh, many people in your lab have reached out, uh, for reasons related to collaborations, et cetera. And everyone in your lab speaks extremely highly of you-

[Michael Snyder]
Oh

[Andrew Huberman]
... and working with you. Um, which is not always the case in large laboratories or small ones. But they, they adore you. I'd like to take a quick break and acknowledge one of our sponsors, Function. Last year, I became a Function member after searching for the most comprehensive approach to lab testing. Function provides over 100 advanced lab tests...... that give you a key snapshot of your entire bodily health. This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more. They've also recently added tests for toxins such as BPA exposure from harmful plastics and tests for PFASs or forever chemicals. Function not only provides testing of over 100 biomarkers key to your physical and mental health, but it also analyzes these results and provides insights from top doctors who are expert in the relevant areas. For example, in one of my first tests with Function, I learned that I had elevated levels of mercury in my blood. Function not only helped me detect that, but offered insights into how best to reduce my mercury levels, which included limiting my tuna consumption, I'd been eating a lot of tuna, while also making an effort to eat more leafy greens and supplementing with NAC and acetylcysteine, both of which can support glutathione production and detoxification. And I should say by taking a second Function test, that approach worked. Comprehensive blood testing is vitally important. There's so many things related to your mental and physical health that can only be detected in a blood test. The problem is blood testing has always been very expensive and complicated. In contrast, I've been super impressed by Function's simplicity and at the level of cost. It is very affordable. As a consequence, I decided to join their scientific advisory board and I'm thrilled that they're sponsoring the podcast. If you'd like to try Function, you can go to functionhealth.com/huberman. Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman Podcast listeners. Again, that's functionhealth.com/huberman to get early access to Function. I'd like to talk about organ aging and organ health-

[Michael Snyder]
Okay

[Andrew Huberman]
... as a separable set of features from general aging and general health. I think, um, you are one of the first people that I ever heard say, "Listen, our organs don't all age at the same rate." Just like most people eventually die because some organ goes first

[Andrew Huberman]
and then it cascades into other things, uh, we need to start thinking about organ health in the same way we think about w- organ disease. We need to start thinking about organ age, um, as an independent things. Like, maybe my liver is much older than my heart at a genetic level, at a functional level. Uh, what are your thoughts on this? And how can we start to parse organ age? Um, so I'd like you to comment on that. And also, um, perhaps this idea that we just age, uh, linearly is not correct, that maybe that there are some cliffs, uh, that come at, come about at, at, uh, particular phases of life.

[Michael Snyder]
Right.

[Andrew Huberman]
Can you talk about these things?

[Michael Snyder]
Yeah. Let me tell you a little how we got into this. So, um, we set up... It comes from my philosophy that I think, you know, medicine is broken. We tend to do sick care rather than healthcare. So we started when I moved to Stanford now 16 years ago this idea maybe we should... First of all, you don't m- measure people very much when they're healthy. You don't measure them very often. So just, you know, started with me, but the goal was to do a bigger group, which we did, uh, uh, profiling people, collecting as much data as possible while they're healthy. So we, you know, people would give blood, their microbiome, uh, all urine, uh, and we would take these and do what's called omics measurement. We'd make as many measurements from their blood as possible on top of deep clinical measurements using all these new tools. Uh, and we would do it every three months and, and we do it while they're healthy. If they got ill like from a, a viral infection, things like that, we would take more samples to be able to, to collect more carefully to see what was going on when they first got ill. And so we've been running this study on me now for about 15 and a half years, uh, and for this group of people about almost 12 and a half years. So we've been profiling this group of people. Some have dropped off by now 'cause it takes a lot of energy to be part of one of these, that particular study. But anyway, others have come in. And so, uh, yeah, we've been running this for some time. And the idea is to see what a healthy profile looks like. How does it change over time, which we interpret as aging? You know, what happens when people first get ill? And we are very enamored by these technologies. In fact, we invented some of them, our lab did, for these omics technologies like, um, uh, something called RNA-Seq where we can measure all your, your transcripts. And we have ways of following all your proteins with protein chips and things like that. So, so our lab, uh, did invent a lot of these, so they're called omics technologies. So it's ways of collecting big data from your, again, your blood, your urine, uh, and even your microbiome. And so we basically sequenced people's genome, made all these measurements, and, and followed them over time. Oh, and I was gonna say, we, we're also curious whether we could use some of these technologies like genome sequencing and, uh, you know, this, this method for measuring transcripts, RNA-Seq, and things for better, uh, you know, maybe managing people's health. And then we brought in the wearables when they were first fitness trackers. We thought, "Well, maybe they're a little more interesting than just fitness trackers." So we put 'em on for health monitoring. And, and I can tell when we started, there was a big controversy at the time. A lot of the physicians are not like sequencing the genomes of healthy people. This shows when we... It was right after genome sequencing was first coming out. And, uh, you know, they were worried we were gonna turn everybody into hypochondriacs, it's gonna cost millions of dollars. And most people have warmed up to it now, not 100%. A lot of people still don't like that. They still don't like the wearables. I'm sure we'll talk about that. But, um, anyway, we did show that a lot of people learned some pretty important things from their genome. One young guy turned out he had a mutational heart gene and his father died right, right around time we sequenced his genome. His father died of a heart...... problem. And sure enough, he has a heart defect that was uncovered by his genome sequence. So we had examples like that. Uh, and then same with the wearables, uncovered things. All kinds of things popped up. Actually, 49 people had what we would call major health discovery just in the first three and a half years of running this study. And similar-

[Andrew Huberman]
With the wearables?

[Michael Snyder]
With all kinds of things. It w- that was the thing. There was no one technology. What we're doing is we're getting a much more complete picture of people's health. We, and we discover these things and before they have symptoms. So we're profiling people while they're healthy, and we're l- we're looking for things that might be off.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And, um, so the way I like... The analogy I like to use is that if your health is a thousand-piece jigsaw puzzle, the way when we... You go to a physician's office today, we would say they measure five or six of those thousand pieces. They just don't get a very good picture. We're trying to measure five or 600 pieces, get a much clearer picture.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And so 49 people, we uncovered something pre-symptomatically, caught some with early lymphoma. Two people with pre-cancer, several, two people with serious heart issues, one from the genome sequencing, one from the wearables. So-

[Andrew Huberman]
This is part of a study. Has this been, uh, commercialized? Like-

[Michael Snyder]
Well-

[Andrew Huberman]
Like if I wanna r- if I want to, uh, RNA-Seq or, or, uh, DeepSeq, or... This is by the way just a nomenclature. If I wanna, um, look at mutations I might have, or, um, how healthy or how, uh, sick different, uh, organs or cells of mine are, what's available to me nowadays?

[Michael Snyder]
Yeah. So we spun off a medical version of this. This is qBio that does whole body MRI, which most people will tell you they... Most physicians will tell you you should not do that.

[Andrew Huberman]
Oh, well, let's pause there for a second, 'cause I, I will say I've done a Prenuvo scan.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Um, they're not a sponsor of the podcast.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Um, but I did Prenuvo scan.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Um, and-

[Michael Snyder]
What'd you think?

[Andrew Huberman]
I thought it was great. I watched the first segment of a documentary on Netflix while my body got scanned. Um, I'm not claustrophobic, so going into the tube was no big deal. Um, I got to see... Thankfully, I... You know, I think you're allowed one white spot on the brain per decade of life. I'm approaching 50 in a few months. I've got... So up to five would be okay. I've got one little one, which is good because I did some, uh, i- m- high impact sports early in my life.

[Michael Snyder]
Uh-huh.

[Andrew Huberman]
And some martial arts where I got hit in the head. And I don't recommend doing that, folks. Um, so I was a little worried about that.

[Michael Snyder]
Okay.

[Andrew Huberman]
Um, I learned that my intraviseral fat is very low, so I, I was, uh-

[Michael Snyder]
Great

[Andrew Huberman]
... relieved to, to see that.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Um, and, you know, for the most part, it, it provided a, a useful baseline. A good friend of mine since childhood, who's a chair of neurosurgery, um, not at Stanford, but at a nearby university, uh, told me that it is not uncommon for him, like on a monthly basis,

[Andrew Huberman]
someone will reach out saying, "Hey, I went in for a whole body MRI and discovered that I've got a tumor on my optic chiasm," or, "I've got a small glioma." And you said physicians don't like that people are getting these whole body MRIs. I'll set him out as an example of a physician who, uh, appreciates that people are doing this. Now then again-

[Michael Snyder]
I love it

[Andrew Huberman]
... he's a surgeon. Surgeons like to cut. Uh, he's a, he's a, he's perhaps one of the finest neurosurgeons in the world. I, I think, uh, all the neurosurgeons I've spoken to, uh, admire him tremendously. So, um, but I agree that many physicians don't like the idea of people getting scanned because that means they get calls of concerned, "hypochondriacs." But in my mind, that speaks to the deficits of the medical community, not to the deficits of, of, of these scanning technologies. Right? I mean-

[Michael Snyder]
100% agree.

[Andrew Huberman]
I mean, I mean, I mean, it's kind of... If you step back from it, it's kinda crazy, right? Like, it... Doctors... It's just mo- I mean, from a purely just, like, if we just made it completely aemotional, it's more business for them if somebody has problems. So that doesn't square with their response. There's something about people advocating for their own, um, health exploration, controlling their own health exploration, that really seems to vex a lot of doctors. They don't like it.

[Michael Snyder]
Yeah.

[Andrew Huberman]
And it doesn't make any sense to me. Like, like, wouldn't you want your patients to be health-minded?

[Michael Snyder]
I think it's part of the broken healthcare system, right? They have 15 minutes to spend with you.

[Andrew Huberman]
Yeah.

[Michael Snyder]
So when people show up with their... I mean, the number one concern about whole body MRIs is they'll find nodules, right? If you go high enough resolution, you're guaranteed to find nodules.

[Andrew Huberman]
Yeah.

[Michael Snyder]
Men Adam and the prosser, women are ovaries, if you go high enough resolution.

[Andrew Huberman]
Yeah.

[Michael Snyder]
100% of the time. Then people show up and say, "Well, I got these nodules." And, you know, if you-

[Andrew Huberman]
Nodules are cell growths, and they can be benign cell growths.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Yeah.

[Michael Snyder]
Or they're just not even growing.

[Andrew Huberman]
Yeah.

[Michael Snyder]
They're just there. They may have showed up early in life. And I, I mentioned I've had 20 of these things, and I have nine nodules. And, and, and the point is it's not whether you have nodules or not. Do you have any growing nodules?

[Andrew Huberman]
Right. Right.

[Michael Snyder]
And that's the key. And if you've never done a baseline, you'll never know if they're growing. So I'm happy to say none of my nine nodules that have been spotted are growing.

[Andrew Huberman]
Relieved to hear that.

[Michael Snyder]
And I know that.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So, uh, and you probably have seen a similar situation, but a friend of mine, uh, you know, woke up one day and couldn't move his arm. And so they rushed him to the emergency room. They did... They scanned the relevant area. They saw he had a tumor on his spine, so they took it out and, uh, things seemed fine. Then they did a whole body, uh, MRI follow-up later and they found three more nodules. So the question is, were they there to begin with

[Michael Snyder]
or had his tumor metastasized? No way to know. They had no baseline.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So I think having these baselines is super important for everyone.

[Andrew Huberman]
I think people balk at the cost. So it's about... As I recall, it's about $2,000 to get one of these whole body scans. I think we can assume that the cost is going to come down, just as everything-

[Michael Snyder]
Correct

[Andrew Huberman]
... whole genome sequencing is, is gonna come down. Maybe even insurance will cover it at some point. I mean, it's so...... trivially easy to do, uh, o- once you have, you know, uh, a place that will do it.

[Michael Snyder]
Right.

[Andrew Huberman]
That if the cost were to come down, I think you'd save tons and tons of lives. I, I see it as a boon to the medical industry-

[Michael Snyder]
Right

[Andrew Huberman]
... um, not just for making money, but for improving people's health.

[Michael Snyder]
Right.

[Andrew Huberman]
I mean, as you said, when you go to the doctor, they measure, like, like, give you a th- They put a thermometer in your mouth. They take your blood pressure, take your height, take your weight, ask you a few questions, ask you if anything's changed. And then you're, like, it's almost, like, better off just, like, c- calling 'em up on the phone at this point. You can do all of that stuff at home.

[Michael Snyder]
You can. And in fact, we should be doing that stuff at home anyway. We can talk about that later. But yeah, what qBIO does is they do whole body MRI and they've designed ways that, uh, they can do it in about 40 minutes, 35 to 40 minutes.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So it saves a lot of time. And then they also do some, a medical version of what I was telling you before. They don't do, for example, the transcriptome, the RNA-seq stuff, some of that, uh, because they have set it up in a way that it's actionable information. Because they... You can then take the data to your physician who will know what to do with it.

[Andrew Huberman]
Great.

[Michael Snyder]
And so, um, and yeah, it turns out, just like you're saying, just from the first a hundred plus people, they discovered early ovarian cancer, all presymptomatically, just like in our study of the 49 people, um, w- who found their things presym- They found, you know, cardiovascular conditions that were pretty serious. They found even early pancreatic cancer, which is almost never found early. Uh, and so they discovered these things, and sometimes it was by the longitudinal measurements, they saw things shift. Sometimes what we call multivariate, they'd see several things shifting. We discovered that in as well. But we might see one thing off

[Michael Snyder]
and you'd say, "Well, I don't know." But when you see three things all going in the same direction, you, you worry about that. And a good example is if you go to a physician today and your glucose is high, and it's normally been low and it might spike up, they'll say, "Well, you know, have you... Were you ill yesterday or something like that? Oh, that explains it. Let's ignore it. Come back in two years." Right? And that's just not enough. Uh, and yeah, and that might've been a clue for something big, and we've seen that in our study. We'll see somebody who shifted off in their liver enzymes, and, and they'll come to me and say, "Mike, I'm still in the normal range even." Um, you know, they're, they're... And this is why we're big on baselines. That's a big theme in our work. Know what your healthy baseline is, like the MRIs. And they'll be running in the low end of a normal range for their liver enzyme, and suddenly it'll double but still be in a normal range. And they'll call me up and say, "Hey, what's going on here?" I'll say, "I don't know. Why don't you go get another measurement?" Sure enough, then they've shifted out of normal. So I think the trajectories of these measurements is key. I think knowing how you're progressing is a big deal, and that's how we need to think. Just like your car, if you see something going off, you wanna see it when you catch the first symptoms, not once your car is broken down on the side of the road, the engine's blown up or something. So, I think that's how we have to shift medicine.

[Andrew Huberman]
Amen to that, um,

[Andrew Huberman]
a thousand times over. Uh, let's talk about some of the sensors you're wearing.

[Michael Snyder]
Sure.

[Andrew Huberman]
And, and what people can monitor now.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Uh, we talked about continuous glucose monitors. And that's non-invasive. I mean, you, you don't even feel it going in. It's just basically a-

[Michael Snyder]
Right

[Andrew Huberman]
... sticker-sized thing. But what are some of the other things? Um, most people are familiar now with sleep tracking.

[Michael Snyder]
Right.

[Andrew Huberman]
Um, and of course, that's pulling heart rate data and a few other things. But yeah, walk us through, uh, what's possible now-

[Michael Snyder]
Sure

[Andrew Huberman]
... with non-invasive, uh, trackers. And maybe, um, just, yeah, let us know which particular ones you're wearing.

[Michael Snyder]
Sure.

[Andrew Huberman]
Uh, th- this isn't a, a, you know, like a promotion of particular products.

[Michael Snyder]
No, there's-

[Andrew Huberman]
I'm just very curious.

[Michael Snyder]
Right.

[Andrew Huberman]
You're, uh, armed to the teeth with sensors here.

[Michael Snyder]
Yeah, I'm, I'm-

[Andrew Huberman]
So what do you got?

[Michael Snyder]
I'm a big measurement guy, obviously.

[Andrew Huberman]
Yeah, well-

[Michael Snyder]
Yeah.

[Andrew Huberman]
... you're a Stan- a Stanford- ... faculty after all.

[Michael Snyder]
All right. So I have my, um... This is my Fitbit. This is my Apple Watch. And then I happen to have a company that's called Sensomyx that has two different... This is a new one they have out, um, that, um, and then the older one. And so they all measure heart rate, heart rate variability, and reasonably accurate, meaning, you know, not that far off. And so, uh, again, for the listeners, resting heart rate, everybody knows. And, but heart rate variability is an important measurement more and more appreciated these days. When you're ill, your variability drops. And both those are fairly accurate these days for most devices. Oh, and I have a ring, um, this one happens to be a Circle. I used to wear an Oura Ring. Uh, and-

[Andrew Huberman]
It's not an Oura Ring? W- which, which one is that?

[Michael Snyder]
No, my... It's called Circle. Um, they have their different parameters, so there's no right or wrong to this. You have to... Same thing, you have to match it to your, uh, lifestyle. Some, you know, you charge them while you're in the shower, they're charged for five days. And others, you have to charge for an hour, hour and a half to keep it going. So you have to find the one that works best for you. I do think wearing them overnight, it's a great time for health monitoring. So I'm a big fan of that. Anyway, they measure that. Some measure blood oxygen. Some of that's accurate, some of it's not accurate. Depends on the device. Uh, some measure skin temperature. Again, some of that's accurate, some of it's not. Depends on the device. They also measure something called galvanic stress response, some do. That's conductance on your skin. And that is not something we normally measure in a doctor's office, but it turns out it has value for our hydration. Because when you have drier s- Like when you're diabetic, you'll have drier skin. And I should've figured this out earlier when I first became diabetic. I got itchy 'cause my skin got dry. Uh, anyway, you can measure that with your smartwatch, um, and get that in real time.

[Andrew Huberman]
The galvanic skin response.

[Michael Snyder]
Yeah. And also it's a measure of stress. When you're stressed, you sweat more. And so you can pick that up as well with this-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... with these devices. So there's a fair number of things. And then some of them you can measure, you know, an EKG. And sleep, of course.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
Super important. Their accuracy for the stages is still questionable. It depends on the device. They're getting better though.

[Andrew Huberman]
I use an Eight Sleep, um, and I-... will look. I- I'm now in the habit of only looking at the data every few days.

[Michael Snyder]
Okay.

[Andrew Huberman]
Because I'm doing a, an experiment on myself where I measure my subjective feelings of rest and, and alertness and energy.

[Michael Snyder]
Oh.

[Andrew Huberman]
And compare it to the data. And the only way to do that properly is to not glance at the data first thing in the morning.

[Michael Snyder]
Okay.

[Andrew Huberman]
Right? Because it-

[Michael Snyder]
Yeah

[Andrew Huberman]
... just biases how you feel.

[Michael Snyder]
Right.

[Andrew Huberman]
A- our colleague, Alia Crum at Stanford-

[Michael Snyder]
Yeah

[Andrew Huberman]
... has done some nice experiments where they tell people after a p- a genuinely poor night's sleep, they got a great sleep. Or they tell people after a great night's sleep, they got poor sleep. And they, they show them a sleep score, and they give them some data. And it's false data, basically. And people's levels of alertness, well-being, et cetera, are strongly biased by what they are told their sleep was like, as opposed to what it was actually like. This is a big deal, right? And I think, um, speaks to all the beautiful studies that, uh, Alia's done 'cause she finds stuff like this all the time.

[Michael Snyder]
Right, right.

[Andrew Huberman]
In, in nutrition and well-being, and these mindset effects are really powerful. So I look at my sleep data maybe once every two or three days.

[Michael Snyder]
Right.

[Andrew Huberman]
Um, and I'm constantly striving to get more REM sleep. By the way, warming your sleeping environment in the last two hours of sleep will dramatically increase the amount of REM sleep you get. I learned that trick from Matt Walker, and it works spectacularly well.

[Michael Snyder]
Oh, I'll have to give it a try.

[Andrew Huberman]
Yeah, Matt taught me that trick. And I'm getting close to two and a half hours of REM sleep now.

[Michael Snyder]
Wow.

[Andrew Huberman]
For ab- and I only sleep about six and a half, seven hours to feel rested.

[Michael Snyder]
Nice.

[Andrew Huberman]
So it's pretty spectacular. And I thank Matt-

[Michael Snyder]
I gotta, I gotta try it. It's-

[Andrew Huberman]
I thank Matt for that tip.

[Michael Snyder]
It's one of my biggest weaknesses.

[Andrew Huberman]
Yeah, yeah.

[Michael Snyder]
I don't sleep that well. Yeah.

[Andrew Huberman]
Yeah, so cool bed in the beginning-

[Michael Snyder]
Right, I do do that

[Andrew Huberman]
... uh, uh, of the night, and then the opposite toward morning.

[Michael Snyder]
Interesting.

[Andrew Huberman]
And, and so Matt taught me that trick. And it's like, whoa, it's completely-

[Michael Snyder]
That is so cool.

[Andrew Huberman]
I, I now emerge from sleep feeling so much better.

[Michael Snyder]
Right.

[Andrew Huberman]
Unless I was having a disturbing dream, in which case you gotta, like, go think about something else. But in any case, uh, the, um, sleep trackers, right? Um, on the Eight Sleep, because the tracker is, is stationary, it's the, it's fixed to the mattress, my understanding is that it's more accurate than if the tracker is on a limb where you could be moving, because that will disrupt sleep stage measurement. Um, but I don't know if that's actually true or not.

[Michael Snyder]
I don't know. I haven't measured it.

[Andrew Huberman]
Okay.

[Michael Snyder]
And I, I haven't looked at the data on that.

[Andrew Huberman]
Okay.

[Michael Snyder]
Yeah.

[Andrew Huberman]
So what about HRV? Uh, we're hearing more and more that HRV is, um, perhaps even more interesting than resting heart rate.

[Michael Snyder]
I think it probably is.

[Andrew Huberman]
Um, what are some things that we can do to improve our HRV? What should our HRV be? How much control do we have over HRV range, this kinda thing?

[Michael Snyder]
Well, exercise is supposed to be one of the best-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... ways to do this. Again, I'm not a cardiologist. I'm not an expert there.

[Michael Snyder]
I don't know for sure, but I know personally, um, keeping my stress down and sleeping better seems to help. Uh, I've noticed that-

[Andrew Huberman]
That makes sense

[Michael Snyder]
... recently, yeah, um, you know, on one of these AI programs, this is again, happens to come from January. Uh, they take all your data, bring it in, and they were, like, looking at this. And my HRV, believe it or not, went up, like, 28% or some incredible number. Yeah, and I was trying to figure out what it was due to. And I, I think I'm sleeping better actually. I, I've been-

[Andrew Huberman]
Are you a meditator?

[Michael Snyder]
No. I, I used to, and I need, I know I need to make more time. In some sense, maybe my bike ride's the equivalent of that at the end of the day. And, and on the weekends, I try and do a little bit of gardening. That, that's my form.

[Andrew Huberman]
Oh, fun.

[Michael Snyder]
I'm a big believer you need some form of calmness. And I used to meditate for, like, five minutes after exercise. I need to get back to that, for sure.

[Andrew Huberman]
Some interesting data on just maybe give this a try as an experiment. Uh, periodically throughout the day, just do a deliberate, to lungs empty, exhale.

[Michael Snyder]
Uh-huh.

[Andrew Huberman]
Which, which activates the vagal pathway-

[Michael Snyder]
Right

[Andrew Huberman]
... to the sinoatrial node, slows your heart rate down. There's evidence that will improve your HRV, both in waking and sleep states.

[Michael Snyder]
Is that right?

[Andrew Huberman]
Yeah, just try it out. See where you think.

[Michael Snyder]
So one minute every day, or-

[Andrew Huberman]
No, no, no. Just periodically throughout the day, just remember to, to, uh, dump all your air, as the, uh, free divers would say. Just .

[Michael Snyder]
Yeah.

[Andrew Huberman]
Really long exhale between-

[Michael Snyder]
I haven't tried the breathing stuff.

[Andrew Huberman]
Which means that, which will slow, that'll slow your heart rate.

[Michael Snyder]
Yeah, a lot of people are saying that's really good.

[Andrew Huberman]
You just, you just intersperse it so there's no breath work.

[Michael Snyder]
Right, right.

[Andrew Huberman]
You don't have to set aside time.

[Michael Snyder]
Yeah.

[Andrew Huberman]
I'll ask you something different related to stress. Um, it goes back to, uh, some sleep data. Um, you seem to love your work. Like, you're ha-

[Michael Snyder]
Oh, I love it.

[Andrew Huberman]
Before we, we came in here, you're like, "I love my job." You know, you know? Um, there are really interesting data out of the sleep lab at Stanford that show that positive next-day anticipation is one of the strongest determinants of sleep quality.

[Michael Snyder]
I didn't know that, yeah.

[Andrew Huberman]
And that it really does seem to be that if you are excited about your life, you can get by with less sleep because the amount-

[Michael Snyder]
Oh

[Andrew Huberman]
... of quality sleep you get is higher.

[Michael Snyder]
'Kay.

[Andrew Huberman]
So y- maybe you don't need to meditate. You just need to continue to do what you love.

[Michael Snyder]
Maybe, yeah.

[Andrew Huberman]
Yeah.

[Michael Snyder]
No, I do love what I do. And, um, for me, there's no better rush than a great result. Uh, I'm an academic at heart. We spin off the companies to try to get, I think, the things we're doing, you know, I hope out to a broader group of people. Uh, which, you know, I, and also as a way of showing the stuff really works and that it's not all BS that you're doing in a lab. So I, I do love what I do. Um, and, um, I don't know, I'm, I'm very fortunate. I have amazing people in my lab, as I mentioned before, who they come up with a lot of the ideas. I, I view us as a team -

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... that try to push forward on these various things. I try to create an open environment, uh, where people aren't afraid to share ideas and, and, and push things forward. Yeah. Anyway, I realize we got away from the a- organ aging part.

[Andrew Huberman]
Yeah, let's, let's-

[Michael Snyder]
If you wanna go back to that.

[Andrew Huberman]
Let's go back to that, and then I, I would like to also get back to psychological factors in mental health.

[Michael Snyder]
On the aging, I mentioned how we're doing all these measurements and tracking people over time. We've now been doing this for over 12 years on those 109. Some have dropped off, as I say. New ones have popped on. And, uh, what we discovered by just looking at the healthy time points is that people...... you know, they do change over time, uh, even in the healthy times, but they're all changing differently, meaning we look at the biochemical pathways. Some will have their top biochemical pathway, dilated cardiomyopathy pathway changing and... Or sorry that was d- dilated, uh, sorry, that was hypertrophic cardiomyopathy. Uh, signaling pathway shifted. Other people, it's metabolic. Some are immune. We call these ageotypes, aging pathways. And I kinda like that a little bit better than organ aging because some of the things you pick up are like oxidative stress, which go across lots of organs. Or, you know, the i- uh, you know, inflammatory, inflammation, that's kinda cross-organ as well. So we call these ageotypes, aging patterns that we see. And it turns out everybody's different. So some people will be the cardio, some people will be the metabolic, some are liver, some are kidney, based on the markers we see in the blood. And some are immune and some are all, all of the above or parts thereof. So we're all different. And what's cool about it is it's actionable information, meaning we... A metabolic ager, when you, you actually see their, they'll see how they're shifting. And again, I have another company involved in this. They do this micro-sampling, I'm sure we'll get into, where they measure your metabolic patterns. And by the way, we think your metabolome is the best way to see these shifts of all the different... Proteomics is good too, and my colleague, Tony Viscoras, he basically has looked at this organ aging stuff as well from the proteomic stand- from, uh, proteomics being the group of proteins. He's, he's followed this. And, and same thing, you can follow this, uh, uh, these ageotypes, if you will, these aging patterns. And the information's totally actionable. You can see, as I say, for the metabolic ager, some of the folks seeing this, they lost weight or they exercised and they improved their patterns.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
Now, I'm not saying they got younger , but they did improve their ageotypes.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And so I think the information is very actionable. And so a- again, uh, and this is one where we commercialize because I wanna... It's a very simple test. You can get these little drops of blood, mail it in, and they'll profile 650 metabolites. And, and the information is actionable. They make recommendations. And it's not just exercise more, eat better, but very, very specific.

[Andrew Huberman]
What, what is the name of this company?

[Michael Snyder]
It's called Iolo, I-O-L-L-O. And-

[Andrew Huberman]
And this is now commercially available?

[Michael Snyder]
It is.

[Andrew Huberman]
So if I wanna, so if I wanna figure out my ageotype-

[Michael Snyder]
Right

[Andrew Huberman]
... did I get that right? My ageotype, um, I can do that by sending in a few drops of blood?

[Michael Snyder]
Correct.

[Andrew Huberman]
And it will tell me-

[Michael Snyder]
They'll send you a kit. It's a very special kit, 'cause not any... Like, putting things on cellulose is not the best way to save your blood. Uh, anyway, it's a special kit. You mail it in. Yeah, no, with s- something called metabolomics-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... and mass spectrometry-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... you can profile. It's a targeted assay, 650 metabolites. And they cover all these areas of many... They're, most of it's in the scientific literature. It's just not in the clinical labs, uh, like things around your kidney function, your heart, things like this. And they give you these profiles and they say, "These are normal. These are going off." And then they can even predict your, again, biological age. So you may know your biological age is not necessarily as your chronological age, your age in years. And if that goes, if things are off and maybe a not so good direction, you can actually take action. You can say, "Well, all right, my, my inflammation's fine. My, but my heart age is off." And they can give you very specific recommendations to do around that. Or if it's kidney, again, same thing. "Well, maybe eat more of certain things and avoid other things."

[Andrew Huberman]
Cool. I'm gonna, I'm gonna try it. So let's talk about biological age. Because I think the first time I heard about the concept of measuring one's biological age versus chronological age was from David Sinclair when he was referencing Horvath clocks. That was some years ago. Um, and then of course, Bryan Johnson, um, likes to boast his biological age. He has a biological age competition, I think, online, uh, with some folks. And then there are also folks like my friend Peter Attia, who will be very direct in telling you that he doesn't think much of biological age when

[Andrew Huberman]
it's a number to assess whole body age. He's like... I won't use the words that he uses, but he doesn't think it's worth anything at all, frankly, um, as a measure. But here, you're talking about something distinctly different. You're talking about the progression of aging of different organs or different organ systems.

[Michael Snyder]
I think the Horvath clocks are correct. Um, meaning they do measure biological age. But the problem is it's not actionable. What do you do? Your methylation pattern, uh, that's a modification of DNA, has shifted and it gives you an overall value, but what do you do with that? You, you don't know, you wouldn't... Yeah. And they can predict something called GrimAge these days, your time to death, your mortality.

[Andrew Huberman]
Oh, nice.

[Michael Snyder]
Same thing. I mean, wh- what are you gonna do with that? What's special about the ageotypes is that they're breaking it down. And so they say, "All right, your immune age is off. You can do X." Uh, "Your other, you know, your, your oxidative stress is off. You do Y." So y- it's basically actionable information, so I think it makes all the difference. And it conceptually makes a lot of sense too. It's like your car.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
I know I keep coming back to that analogy. But your car gets older, but certain parts wear out first. You don't rep- well, maybe some people do, they replace their whole car.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
But generally, you would fix the parts that are wearing, and ideally you'd catch it before they-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... break. And I think that's how we think of ageotypes. You can go in. And so I mentioned this company earlier, Iolo. What they do is they're tracking your ageotypes 'cause they're doing these deep metabolic a- uh, profiles. And they actually make... They use AI. They pull in things and make very specific recommendations. And then, um, you can... Some, you know, they'll tell you exact foods to eat and things like that. Uh, and 95% of people improve their markers. Again, I'm not gonna say they're getting younger, but at least they're improving their metabolic markers in the right direction. And so it, it's actionable information and it makes a lot of sense.

[Andrew Huberman]
How powerful a role do genetics play in determining potential lifespan? Uh, shortly before starting this discussion, I looked at the chart of longest living humans. Um, they're all deceased now, but I think the record is 122 years and some change. Um, I think that was a Fr-

[Michael Snyder]
And some people think she may have cheated, but it's not clear.

[Andrew Huberman]
Oh, really? That was a, a Frenchwoman?

[Michael Snyder]
Yeah. Yeah, that's right.

[Andrew Huberman]
120 plus or minus five years seems to be kind of-

[Michael Snyder]
Yeah, that's right

[Andrew Huberman]
... what, what people consider a, you know, a spectacularly long life.

[Michael Snyder]
Yeah, that's right.

[Andrew Huberman]
Yeah.

[Michael Snyder]
And that does seem to be the cap. And so, you know, most of our research is built around extending healthspan. It is the case that for

[Michael Snyder]
lifespan in general, it's estimated to be about 16% of your lifespan's due to genetics, one-six.

[Andrew Huberman]
One-six? That's it?

[Michael Snyder]
Yeah. And now, there's a big error bar on that. That comes from twin studies and family studies. Uh, so although it's thought that for people who live to be 100 or older, then it might be higher. Some people have said-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... 60%. So to live to be really long, you may need good genes in general. But there's still a lot there, right? There's another 40% that's due to lifestyle. Uh, but for the average person, it's only one-sixth, so your lifestyle is by far your biggest factor. And you look at people in these Blue Zones, these areas where people... There's an enrichment for people who live to be 100 or more. They have several things in common. One is they tend to eat a, a diet with not much ultra-processed foods or processed foods in general. And generally, they tend to be towards the Mediterranean vegan kinda diet.

[Andrew Huberman]
They eat a- animal proteins, as I understand, but it's more fish and chicken-

[Michael Snyder]
Yeah, that's correct

[Andrew Huberman]
... and, and less, less red meat.

[Michael Snyder]
Less, yeah, yeah.

[Andrew Huberman]
And they're eating a lot of vegetables.

[Michael Snyder]
Yes, for sure-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... uh, and getting fiber through that as well. And then, uh, they tend to have, um, uh... They're fairly active, meaning, uh... But their form of activity can vary. And they have really good social networks.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So either through family or through community networks. And so that's pretty clear. My prediction is they probably sleep pretty well too. I, I don't know if that's been as well measured as the, as the other parameters. So, so I think you do need all of those things if you want to live a long, healthy life. And, and, uh, and that, you know, that weight may vary from one person to the next. And I, I, I think that's the kinda thing we want to look at. Again, I view people as a combination of things, their genetics, their epigenetics. You know, I do- I don't know if I told you all the details of when I became diabetic. It was predicted from my genome. Atul Bute actually predicted this from something called a polygenic risk score. These ways of analyzing genomes, and I'm at the extreme end. It doesn't work for most people, by the way. But I'm at the extreme end. It worked for me. So he predicted I was high-risk for diabetes, but I didn't become diabetic until after a viral infection. It's very strong correlation. Uh, because I measure myself a lot, I figured this out. It's respiratory syncytial virus, which, uh, actually, you know,

[Michael Snyder]
it's not that common in adults. It's more common now. But, um, anyway, I was literally in bed, which is a little unusual for me. I, uh, and I got a very high temperature, uh, and I wound up several weeks later becoming diabetic. It's very fascinating because we actually looked at the modification of my DNA. It's called DNA methylation. It actually shifted in something like 100 metabolic genes in the, in their control regions called the promoters. And so

[Michael Snyder]
it's, it's, the thought is that I was genetically at risk, and then in combination with this viral infection, it's environmental. It's what triggered my diabetes.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
Now, I don't think that's true of most people. We're tracking people, I may have mentioned. In the first part of the study, we saw nine people become diabetic as we've been tracking them, and seven gradually became diabetic. So it was, you know, accumulation of something. But two people, one of which was me, something triggered it, meaning it kinda got there and stayed. It wasn't just a transient spike.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
Uh, and so how often this, you get these genet- ep- they're called epigenetic modifications happening is not so clear. But it's now the case, you may know, with COVID, 2 to 4% of people are becoming diabetic after a COVID infection. So it's not unreasonable to think that they're having epigenetic changes like me that hasn't been measured. That's something we'd like to pursue. But the effects of these viral infections and stuff, you may know, a lot of people get something called chronic fatigue syndrome after some adverse, say, pathogen. It's not always clear what's causing it. It seems to be different for different people. But the idea these intense stresses may be from a viral infection or other pathogen triggering some long-term chronic effects is maybe more common than people realize. For autoimmune disease, for, uh, chronic fatigue syndrome, in my case, for diabetes, maybe, as I say, more prevalent than people realize.

[Andrew Huberman]
It's so interesting to think about viral infections setting off a bunch of things that are acute, like rise in temperature, GI tract disruption, et cetera. But then, uh, as you said, longer term changes in, uh, genes related to metabolism, inflammation, and other pathways setting a predisposition, uh, a genetic predisposition in motion, kinda like f- flicking the domino that was already kind of, uh, uh, tilted.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Um, and-

[Michael Snyder]
Once again, that homeostatic system concept that you're... Yeah, y- maybe if your genetics is a little bit weaker...

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... uh, we've noticed, um, yeah, that...Uh, yeah, we found a new, if you will, set of genes involved in ALS and that those genes tend to be underexpressed in, in, you know, called IPS-derived motor neurons, the relevant cell types for ALS patients. So it may be that, you know, if your genetics is a little weaker in some areas than others, then other things could trigger that sorta thing. So I like that general concept that we're... And, and in some cases, maybe that's beneficial. Uh, I'm not saying getting ALS is beneficial, but maybe we're attuned certain ways because, in ancient times, we had to deal with things like TB and stuff, and the idea that you would be... Well, the classic is sickle cell, right? Uh, folks with sickle cell mutations might be more resistance to malaria. So, so maybe some of this tuning helps you in some ways, but is adverse in other ways, or mo- makes you more susceptible. Let's put it that way.

[Andrew Huberman]
Yeah, I've heard, um,

[Andrew Huberman]
you know, here and there, uh, about data linking, um , herpes virus to Alzheimer's, for instance. Um, and you could imagine how, uh, it might not be directly related to the, the symptoms or the, uh, pathology of, of herpes virus. But that something about the neural inflammation caused on the trigeminal nerve, which is where the herpes virus lives, that's why people get cold sores. This is, or HSV-1-

[Michael Snyder]
Right

[Andrew Huberman]
... um, which is very common.

[Michael Snyder]
Right.

[Andrew Huberman]
I- I think, um, and most people just combat it and they don't get cold sores.

[Michael Snyder]
Sure.

[Andrew Huberman]
Um, but that something about the, uh, the inflammation of that trigeminal nerve pathways, m- maybe it breaches the blood-brain barrier in certain people, and then it sets off a cascade that we eventually call Alzheimer's.

[Michael Snyder]
Right.

[Andrew Huberman]
I mean, so t- these, these, uh, these correlations, uh, 'cause that's really all that they are-

[Michael Snyder]
Correct

[Andrew Huberman]
... and th- these multifactorial... Um, uh, I j- I think that the way you described it earlier is, is the best way. You know, if you have a, a thousand-piece jigsaw puzzle, you wanna know which pieces are, you know, slightly out of alignment or missing entirely. Um, but what we call diseases, like Alzheimer's or autism or diabetes, it, presumably, are different combinations of puzzle pieces missing.

[Michael Snyder]
I think so.

[Andrew Huberman]
And, and I think, until now, medicine and the general public, uh, uh, has been trained to think of disease as like those puzzle pieces are missing. And that's what we call Alzheimer's. That's what we call autism. That's what we call diabetes. And what I'm realizing in talking to you today is that that's far too simplistic.

[Michael Snyder]
Yeah. I mean, there are cases-

[Andrew Huberman]
Like, okay, it can't be that, it can't be that simple.

[Michael Snyder]
Yeah. I, uh, that's correct.

[Andrew Huberman]
Yeah.

[Michael Snyder]
Uh, a good example would be Huntington's, right? Where you have an expansion of a specific genetic locus, uh, other elements that shift there. Uh, and that's highly associated with Huntington's. Those would be single condition things that trigger it. And that does happen, but that's not most disease. That's more the exception than the rule. And by the way, even in those cases, there are people that escape it.

[Andrew Huberman]
Oh, you have escapers?

[Michael Snyder]
Yeah.

[Andrew Huberman]
Hmm.

[Michael Snyder]
Who have somehow escaped that. Not always understood, although they may hold clues to perhaps how others could be helped.

[Andrew Huberman]
You mentioned ALS. We've not covered ALS on this podcast, uh, before, but just very briefly. Um, my understanding is a few years ago, there was a lot of interest in SOD, in superoxide dismutase, w- an enzyme-

[Michael Snyder]
Right

[Andrew Huberman]
... um, being involved in the degeneration of motor neurons-

[Michael Snyder]
Right

[Andrew Huberman]
... which is what ALS, uh, used to be called Lou Gehrig's disease.

[Michael Snyder]
Right.

[Andrew Huberman]
But ALS, people... Uh, Stephen Hawking had ALS, right?

[Michael Snyder]
Absolutely.

[Andrew Huberman]
Um, what is the role of, of superoxide dismutase? And, and i- is there anything protective in terms of behavior or supplementation, drugs that people can take to protect themselves against neurodegeneration of motor neurons or central neurons? You know, we talk a lot about what to do once it's started, but there's not a lot of discussion about how to protect your neurons, um, just as a general theme. Like, protect the health of your neurons-

[Michael Snyder]
Right

[Andrew Huberman]
... by doing or taking X.

[Michael Snyder]
Right. Well, first of all, I'm not an ALS expert. Those where my genetics came in.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
We came up with new ways of analyzing genomes, and we applied it to ALS for reasons we thought might work. Um, here I just had, uh, an amazing post-doc, uh, Sai Song, and, and a great collaborator, Jonathan Cooper-Nock-

[Andrew Huberman]
Mm-hmm

[Michael Snyder]
... who, uh, basically sort of said, "Mike, this is a great problem to apply these new methods we had for analyzing." So there were seven genes known, and we wound up finding 690 genes just... And tha- that's true with these new AI methods we have for analyzing genomes. And it explains a lot more what's called the heritability of the disease. And, and then, yeah, and tha- that's how I got into it. But, I mean, there still is no cure for ALS. Uh, and how to modify lifestyle, I don't know. But I do know, uh, I'm on sabbatical at UC Irvine right now, and there's, you know, people who are trying to take this sorta thing on. We'll, we'll see how well it works. It is clear there is a study that if you overexercise, that's worse for you for ALS. Uh, but whether that helps you predict, I don't know.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So I, I think it's still, yeah, not very much known there, at least not to me. You may know more than I do.

[Andrew Huberman]
No, I, I... You know, I'm very interested in what one can do to protect against neurodegeneration.

[Michael Snyder]
Yeah.

[Andrew Huberman]
The one that I'm very intrigued by, and here I am not promoting

[Andrew Huberman]
this specifically for everybody. But, um, years ago, and this is purely anecdotal, uh, but years ago, I was in the office of Richard Axel at Columbia.

[Michael Snyder]
Mm-hmm.

[Andrew Huberman]
He's a Nobel Prize winner for discovering the molecular basis of olfaction, et cetera. And I observed what many people had told me I would observe, which is that he chewed no fewer than, like, six pieces of Nicorette in a 90-minute meeting. And I asked him, I said, "What's the deal?" And he said, "Well, I used to smoke, but I don't smoke because it causes cancer. But I like the nicotine for the cognitive stimulation." And he looked at me and he said, "And it's protective against Parkinson's and Alzheimer's." I said, "Really?" And he goes, "Yeah, read up about it." So, and indeed, I went and looked, and, and it does seem to be, um, neuroprotective.... now, it also raises blood pressure. It's highly habit-forming/addictive. Most people I know that take two milligrams of a, of a nico- nicotine gum or a pouch suddenly are taking four, six, eight, then they're taking a canister every two days.

[Michael Snyder]
Wow.

[Andrew Huberman]
Like, it's very habit-forming-

[Michael Snyder]
Wow

[Andrew Huberman]
... very fast. So it's not something I recommend. Um, but I'm very intrigued by the idea of this substance, nicotine, when it's not smoked, vaped, you know, dipped, or snuffed, that it might actually be neuroprotective. Richard's a molecular biologist by training. He's not somebody, um, who just says stuff when it comes to science. Sometimes he just says stuff. He's kind of an out- known to be kind of an outrageous guy. But, um, the data are kind of interesting, like in rodent studies, that nicotine can be protective in the face of a, of a, a bunch of different insults to, um, dopamine neurons, like, uh, a com- a combined low-grade, uh, head, uh, injury with something else, like hypoglycemia.

[Michael Snyder]
Ah.

[Andrew Huberman]
Right, the, the two-hit model.

[Michael Snyder]
Right.

[Andrew Huberman]
That it's not a head injury that would kill neurons, it's not hypoglycemia that would kill neurons, but when they, they, when they coincide, the so-called two-hit model-

[Michael Snyder]
Right

[Andrew Huberman]
... then you start losing neurons.

[Michael Snyder]
Right.

[Andrew Huberman]
And in some cases, like, nicotine can be prot- this kind of thing.

[Michael Snyder]
Okay.

[Andrew Huberman]
So I'm intrigued by things that one could potentially do to protect neurons-

[Michael Snyder]
Yeah

[Andrew Huberman]
... um, aside from wearing a bike helmet-

[Michael Snyder]
Yeah

[Andrew Huberman]
... which I'm relieved to hear that you do.

[Michael Snyder]
Okay.

[Andrew Huberman]
In any case, uh, room for further exploration.

[Michael Snyder]
Yeah, of course, there's the motor neurons for ALS versus others.

[Andrew Huberman]
Yeah. Right, motor neurons for ALS. Yeah.

[Michael Snyder]
So I, I don't know how similar or different, yeah, that, that those things are.

[Andrew Huberman]
Yeah. Yeah, it's super interesting.

[Michael Snyder]
It is.

[Andrew Huberman]
I don't think anyone wants to lose their motor dopamine or any other neurons.

[Michael Snyder]
Yeah, for sure.

[Andrew Huberman]
So it's, it's, uh, you know, with rare exception, we don't replace them. So, um, I think that's gonna be a really important area going forward.

[Michael Snyder]
Yeah, agree.

[Andrew Huberman]
Right now, it's mostly the don'ts. Don't get a head injury. If you do, don't get a second one. Quit the sport. People always say, "I," you know, "I, I play rugby and I got a really bad concussion. What should I do?" And I go, "Find a new sport." And they never like that answer.

[Michael Snyder]
Yeah.

[Andrew Huberman]
But, you know.

[Michael Snyder]
Wow. Back to behavioral modification, yeah, yeah.

[Andrew Huberman]
Yeah, exactly. It's mostly don'ts. Um, I'd like to talk about some things that might seem a little bit more in the esoteric realm.

[Michael Snyder]
Okay.

[Andrew Huberman]
Let's start with low esoteric, but still in the kind of area that now people are talking about, um, which used to be considered kinda woo, which is air quality.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Everyone agrees pollution is bad. What people don't agree upon so much is how much otherwise, like, permissible air. Like, not during a fire, or, um, living in a city versus a suburb versus, uh, in a rural area, uh, pesticides, et cetera. You know, how air quality impacts our health. You've got a device on the table that literally is measuring... How's our air quality in here, by the way?

[Michael Snyder]
Uh, you're good. You're at PM2.5 of three, PM10 of four.

[Andrew Huberman]
Okay.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Yeah, so what's-

[Michael Snyder]
Which is very low, by the way. Yeah.

[Andrew Huberman]
Yeah. We've turned off the AC for, for recording purposes.

[Michael Snyder]
I see.

[Andrew Huberman]
Afterwards, we tend to ventilate the room a little bit.

[Michael Snyder]
Yeah, it was one earlier. So, uh-

[Andrew Huberman]
Yeah.

[Michael Snyder]
So it's let in-

[Andrew Huberman]
But we had fires here in LA not long ago.

[Michael Snyder]
Right.

[Andrew Huberman]
How-

[Michael Snyder]
Probably woulda gotten to 200, maybe more.

[Andrew Huberman]
I mean, th- it was dreadful.

[Michael Snyder]
Yeah.

[Andrew Huberman]
It was really bad.

[Michael Snyder]
Probably, yeah.

[Andrew Huberman]
And a lot of people and animals are still suffering, um-

[Michael Snyder]
Yeah

[Andrew Huberman]
... symptoms, you know. So, um, so what's the logic behind this device and, and what's the... Or w- I mean, I imagine you brought it here for a reason.

[Michael Snyder]
Well, no, I bring it all the time. It's, it's always next to me.

[Andrew Huberman]
Oh, you carry this everywhere you go?

[Michael Snyder]
Oh, yeah. I've been doing this for eight or 10 years now.

[Andrew Huberman]
And if a restaurant or another space doesn't have, uh, good air quality, you, you just leave? Is that...

[Michael Snyder]
No, uh, probably-

[Andrew Huberman]
You, you inform them and then leave?

[Michael Snyder]
Uh, people ask, and I, I'm always honest. I tell them what it is. I- it hasn't been so bad. Where it'll get bad is during the fires. But there are a few times. Um, so I'm doing it, backing up a little bit, it's a very underexplored area. And that's kinda, again, the academic side of me. I want to understand how does your environment impact your health? And it's not just air, but I, that's the area we decided to start in. And, you know, what are you breathing right now? You have no idea, right?

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And so that's the principle. I'm a sorta big data guy, as you can tell. I do all these measurements on the inside. What about the outside? And we know from plenty of work from others, you mentioned, you know, particulates in the air. This is where the PM2.5, that's thought to be the stuff that penetrates your lungs and causes all kinds of problems.

[Andrew Huberman]
Goes from the lungs into the bloodstream and can cross the blood-brain barrier.

[Michael Snyder]
Yeah, and it's-

[Andrew Huberman]
Yeah.

[Michael Snyder]
Yeah, not good.

[Andrew Huberman]
Yeah.

[Michael Snyder]
So anyway, the, um, and these days, as you know, plastics and microplastics have, have erupted as a, as a pretty big health concern. But e- nobody's 100% sure what it means, but they do know now that when you dissect people's brains of folks who have died, then you'll see microplastics. They're everywhere.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
Um, and so what is it doing to your health? I don't think we fully know, but we're starting by just trying to measure the stuff. So we've decided to start with airborne, but you could argue, you know, what are you drinking, what's in your food? That's all very relevant, by the way. Um, but we'll start with the air. Uh, and, and so what we're doing here, it's not just measuring PM2.5 and PM10. It's basically, um, it, there's, it's a, it's sucking up air. There's a pump in here. And underneath the intake valve, there's a filter that captures all the particulates like pollen, bacteria, fungi, and under that, there's a chemical absorbent. It's called zeolite, captures both hydrophobic, hydrophilic, positive, negative. Uh, and then not in real time, but offline, we'll measure all the biologicals like the fungi, the pollen, the whatever that's captured on the filter, and we'll measure the chemicals using something called mass spectrometry, the things they have in airport that measures, you know, bombs and things like that. So we're trying to measure that in real time to see what's going on. And then we try and correlate what's outside with what's inside, 'cause we'll measure your blood as well with these deep profiles. And so what we've discovered is first of all, they're, you know, you'll be getting exposed to... We, we, for me, I'll do one of these during the week, one on the weekend. So it's not, we don't do it every five minutes kinda thing, 'cause you have to collect enough sample. But we will basically determine, you know, what kind of exposure you're getting.And if you're at high risk for certain things, you may wanna know this. Like asthma or allergies, wha-... Are you exposed? And I... There I can give you an example. I used to have moderate allergies. Now they're pretty mild, but... 'Cause allergies can fluctuate a bit. And they would come every spring. And I just assumed it was pollen, but, uh, uh... Well, it is pollen, uh, in the end. Uh, but I assumed it was pine. But, uh, when we did the correlation, well, turns out it correlates better with eucalyptus. And then it's like, "Duh, I should've realized this." But, um, I don't get them on the Northeast, where there's no eucalyptus.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And so in the end, it makes a lotta sense. So, um, a-... That one hasn't affected my lifestyle, meaning I still have a big eucalyptus tree out back that I have not chopped down. Mind you, it's on Stanford land, so I can't do that anyway. But, um, it... Yeah, a- at least I know what's going on.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
Um, but then, uh, like on the chemical side, which is very interesting, we discovered there's DEET everywhere, even in my office -

[Andrew Huberman]
DEET?

[Michael Snyder]
... at Stanford. DEET, yeah.

[Andrew Huberman]
The insect repellent?

[Michael Snyder]
That's the thing you're using. Yup, yup.

[Andrew Huberman]
The carcinogenic insect repellent?

[Michael Snyder]
Yes, uh-

[Andrew Huberman]
I used it years ago when I was a camp counselor. And then one day, someone said... Someone on the maintenance staff said, "Take some DEET, put it into a Ziploc bag-"

[Michael Snyder]
Uh-huh

[Andrew Huberman]
... "and put that Ziploc bag into a glass jar."

[Michael Snyder]
'Kay.

[Andrew Huberman]
And I was like, "W- okay," and I did that. And within a few hours, the plastic bag was completely disintegrated.

[Michael Snyder]
Ouch.

[Andrew Huberman]
And I was slathering that stuff on my skin way back when.

[Michael Snyder]
Yeah.

[Andrew Huberman]
And I lived with mosquito bites for the rest of the summer. I'm like, "I'm not putting that stuff on my skin."

[Michael Snyder]
Yeah, of course, now you have to worry about getting West Nile or h- h- something else.

[Andrew Huberman]
Not in Yosemite.

[Michael Snyder]
Yeah.

[Andrew Huberman]
You had to worry-

[Michael Snyder]
Oh, okay. That's why-

[Andrew Huberman]
... about getting Giardia.

[Michael Snyder]
Yeah. Okay.

[Andrew Huberman]
But that's a different issue-

[Michael Snyder]
Yeah.

[Andrew Huberman]
... yeah-

[Michael Snyder]
Yeah, yeah

[Andrew Huberman]
... from the water. Yeah.

[Michael Snyder]
Interesting. Anyway, we did... But... And, and same with pesticides. They're m- most places. Uh, and carcinogens, of course, are everywhere, uh, but their types vary and the amounts vary a lot. So, like, when I was... When I'm in UC Davis giving talks or something, I get a pesticide exposure-

[Andrew Huberman]
Yeah, that's why we're all here

[Michael Snyder]
... 'cause of all the fields are out there. Yeah. And same with when I was in Fresno. So, you can see these correlations. And, and so that's what we're doing. We'll measure what's where, and then we'll measure, "How does that relate to what's going on inside?" So, we can see what microbes are outside relating to inflammation markers, like cytokines, things like that, on the inside, and same with, uh, some of the chemical markers like your glucose levels. And right now, that's mostly been built, those models, around me, but we're trying to run this study with a lotta people, uh, so we can, first of all, e- even break it down further. What's the difference between your kitchen and your living room and outside your house? And then same thing, how does that relate to some of the levels of key markers, your metabolites, your, your, um, inflammatory markers?

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
So, so we wanna correlate that. We know f- studies from others, uh, have shown, right, pesticides correlate with Parkinson's and things like this. So, we want to, um, see what's going on there. I can tell you some fun stuff that we just may... Again, these are all correlations. Now we do something called mediation analysis. It can let you get a little better about causality. Not p- proof in many cases, but a better idea. Anyway, here's a fun thing we discovered. We found a correlation between something called pyridine, which is... used to be common in paints and it's in other places too. They've... Recently they don't put it in paints. But pyridine exposures are associated with lack of fungi, meaning I'll have more bacterial, plant, or other exposure. So, my house was painted by a green guy. No pyridine in the paints there, so I get a fungal exposure when I'm at home.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And so is that good or bad? I don't know. But imagine I was al- very allergic to black mold. So, maybe I do want pyridine in my plate, paint, to-

[Andrew Huberman]
I know a lot of people who struggle with mold

[Michael Snyder]
We can make that association with the allergies, of course. Anyway, you get the idea. We're trying to correlate what's going on in the outside with the inside. Well, in that case, with, with other outside things, but later with the inside. So, um, yeah, where measurements will make these things, that'll lead to hypotheses that we could then probably test by either mouse models or in humans who live in certain places who wind up sort of testing whether they're trying to or not. Imagine you live near... You know, obviously you live near a certain area. As you will see, uh, if you live near, you know, mines, you will see autoimmune disease, things like that. So, we can, uh, try and make these associations. And then you correlate with similar people who aren't living near mines to s- you know, try to test that.

[Andrew Huberman]
I love that you're linking outside environment with internal, uh, you know, internal, and-

[Michael Snyder]
Yeah, I feel like it's a totally unexplored area, and a pretty important one.

[Andrew Huberman]
Yeah. Yeah, and I think the fires in LA-

[Michael Snyder]
Yeah

[Andrew Huberman]
... among other things, have sensitized people to this notion of air quality-

[Michael Snyder]
Right

[Andrew Huberman]
... um, in a real way. Um, it's a shame it took that. Um, but it does seem to be a theme that's persisting. People are starting to think about like, "Yeah, how, how clean or dirty is my air?"

[Michael Snyder]
Right.

[Andrew Huberman]
And I think the, the interest and emphasis on microplastics recently-

[Michael Snyder]
Right

[Andrew Huberman]
... um, is interesting. I did an episode about microplastics. We had Shawna Swan on the podcast. I mean, I think it's been known for a long time that these microplastics, BPAs, and phthalates, so-called forever chemicals, have been an issue. I think that, um, people are now sh- just shocked to learn how many of these things we've accumulated and maintained in our body.

[Michael Snyder]
And they're all over our body, too. It's like, uh, yeah.

[Andrew Huberman]
Yeah, and the health effects are still unclear.

[Michael Snyder]
Right.

[Andrew Huberman]
Like, it's... I mean, it's really unclear. I-

[Michael Snyder]
They've been talked about, endocrine disruptors and things-

[Andrew Huberman]
Yeah

[Michael Snyder]
... like this, yeah.

[Andrew Huberman]
Yeah. I mean, I filter my water and, um, uh, I try not to drink out of plastic disposable bottles.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Um, that seems to be an important one. And, but, you know, there was a recent study-

[Michael Snyder]
I've only recently switched. I should've done it eons ago. Yeah, yeah.

[Andrew Huberman]
Yeah. We, we should've done it years ago, right?

[Michael Snyder]
Yeah.

[Andrew Huberman]
But, but there's a recent study showing that actually the glass bottles contain more pl- microplastics than plastic bottles because of the... what's on the lines of the underside of the caps.

[Michael Snyder]
I see.

[Andrew Huberman]
But what's less discussed around that study is that t-... that was focused on the glass and plastic cap configuration in Europe. It's different here. So it's, it's, like, it really needs to be explored. I think simple ways to measure one's own environment using sensors like the one that you have here for the air, uh, as well as for, for water, um, is gonna be really, really important.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Um, so I'm, I'm grateful that you're commercializing so many of these things. I, I can tell you are a, a data guy. But the fact that you translate things into real world tools is so valuable. Speaking of which, um, I'm gonna be very direct about this. Uh, two Stanford faculty talking about measuring lots of biomarkers from a single drop of blood, screams of Theranos. Let's just call it what it is and-

[Michael Snyder]
Sure

[Andrew Huberman]
... not dance around it. Uh, which was a, um, spectacular failure, uh, that involved, apparently, at least the courts decided, um, seems there was a lot of corruption and lying and stuff there. However, that was some years ago, and you were not involved with that. And so the, the technology has now evolved to the point where my understanding is that you are able to measure lots of biomarkers from a single drop of blood.

[Michael Snyder]
Right.

[Andrew Huberman]
Um-

[Michael Snyder]
Thousands.

[Andrew Huberman]
Thousands. So that's exciting, um, i- because no one likes to get their blood drawn. I guess if, there might be a subset of people. But, uh, so tell us about that. Uh, like what w- what is that, um, pursuit called? Uh, what, what are you measuring? Why are you measuring it? And, and maybe underscore the, the real value of, like, single drop of blood analysis.

[Michael Snyder]
First of all, we don't get measured very often when we're healthy. Uh, this idea that we mostly practice sick care not healthcare. And why do you go to a physician all the time when you're healthy to get measured? I think that's a barrier to getting measured. So can we come up with more, you know, facile ways of measuring people? The wearables are obviously one. And they're perfect because they're, you know, passive monitoring and continuous so you're really collecting a lot of data just in the background all, uh, I mean, i- the inconvenience is wearing them, charging these things. But, um, we don't measure what's on the inside. And I think that still has value. And the idea about trying to set up home tests for this sort of thing, I think is powerful. So that was the motivation. That was the motivation for our Theranos, I think, too. Uh, and our, you know, shtick, if you will, was to try and do this but, um, we're not trying to measure the exact clinical values because some of that is hard. How do you measure LDL droplets, uh, in micro samples? It's probably doable but it's a lot trickier. We were just trying to... it fits with our idea of doing deep data profiles on little drops of blood. And the key is to find a format that would keep the, the analytes as we call them, the molecules stable. And so we tested, we spent seven years actually trying different things, finding formats that... the old format was to do, use paper actually, cellulose, to collect the stuff and that doesn't work very well. The, the analytes oxidize. It's a mess. And so ultimately, we test a lot of things out there, we were trying to invent a few of our own, and the net result was we, we did settle on some that were out there, tested them. They're being used in a more limited fashion. And then we showed you could actually do the kinds of things we do, the metabolomics it's called, lipidomics, uh, and proteomics. And, and again, with certain configurations, the proteins turn, most of them are quite stable, not 100% but most are. We can measure all those. Um, metabolites, same thing, most are lipids, some are, some aren't. So we figured out which ones are, which ones aren't, and then we basically did just that. We, we showed you could do this, did fun experiments. Like, uh, my case we, we took a sample every hour for seven straight days to try and correlate -

[Andrew Huberman]
Around the clock?

[Michael Snyder]
Y- well, at night when I was sleeping, no. But although when I did wake up I would take a sample-

[Andrew Huberman]
Wow

[Michael Snyder]
... sometimes. Yeah. Um-

[Andrew Huberman]
Well, it's just a drop.

[Michael Snyder]
Yeah, uh, not so great for sleep disruption, I suppose. But anyway, the, um, and the idea there was to correlate, you know, what's going on with... and, and I was wearing a CGM and a smartwatch so I could follow activity, doing food logging, all that sort of stuff. And in the end, we're trying to correlate basically people's activities and physio- people's biochemistry and physiology with their activities and, and heart rate and things like that. And, and so we found out literally thousands of correlations, so it's pretty cool, a lot of which is known, right? After your, your, your insulin goes up, after your glucose. But we can precisely measure. For me it's 10 minutes. We know exactly the magnitude with certain kinds of food and that sort of thing. Uh, we also discovered, I don't know if this will go anywhere but we're, we're pursuing it, alpha-synuclein which is involved in Parkinson's and dementia. It actually showed an interesting pattern. It seemed to fluctuate with stress, actually. S-

[Andrew Huberman]
Goes up with stress?

[Michael Snyder]
Y- yeah. Well, that's what we're trying to figure out, what kinds of stress. So I don't think we have that sorted out yet. Um, y- yeah. So anyway, I'll leave it at that 'cause we don't have it all sorted but... so that's the thing. We're trying to measure that, see exactly what it correlates with. And then maybe that's a useful assay for trying to manage that, and therefore push off dementia. That's the hypothesis. No guarantee that's right. But these are the kinds of observations we make that I'd like to see if they, they turn into real world value that we could then help, you know, maybe, uh, get out there to help people in some fashion or other.

[Andrew Huberman]
Very cool.

[Michael Snyder]
So this is the kind of stuff we do at... these are what you're calling observational trials. They... deep data measurements on people to better see what's going on, make hypotheses, and then, yeah, ideally roll it out into the real world.

[Andrew Huberman]
I love it.Well, let's go further into what most people consider kind of esoteric, at least in this, uh, half of the world, but it's not really, um, esoteric at all. It has tremendous precedent, which is acupuncture.

[Michael Snyder]
Okay.

[Andrew Huberman]
Um, I think for people who know, uh, acupuncture makes perfect sense as something that would be a valuable tool, right? Thousands of years of data, uh, and, and practice, um, less known about mechanism. But Qiufu Ma's lab at Harvard in recent years has been studying how different needle configurations, um, impact different organs. That's in mouse models, but you know, different inflammatory molecules or anti-inflammatory molecules. So there's some mechanistic data starting to come out. You have an interesting story about acupuncture, and, um, and perhaps what it can, uh, offer or, or not offer in terms of, of health support.

[Michael Snyder]
I'm down on sabbatical at UC Irvine with Shaista Malik, who, uh, runs an integrative health institute where they bring in nutrition, exercise, and things like acupuncture to try to better manage people's health and lives. And it's been very fascinating for me because they're doing it on the clinical side. I'm kind of a big data measurement guy, and, uh, and so I wanna see what's going on, if there's ways that make sense to collaborate. And as you point out, acupuncture's been around for 3,000 years or some incredible number. There must be something to it, right? People use it a lot for pain and apparently for fertility and other things as well.

[Andrew Huberman]
Yeah, it's shown to be effective in a number of domains. And I've had, quote unquote, "standard MDs," including our director of pain medicine, Sean Mackey, on this podcast.

[Michael Snyder]
Yeah.

[Andrew Huberman]
He's like, "Yep, a- there is evidence acupuncture can work."

[Michael Snyder]
And there are plenty of people swear by it. And, and she uses it for blood pressure, okay? For blood pressure management. So I run a little high on the blood pressure, not... Nobody's overly panicked. Um, but you know, I tend to be in the high 130s, but I guess 'cause I was getting a very large grain out , I was in the low 140s. And so I, I measured myself right before acupuncture, you know, um, very specific time of day with my monitor at home. And, uh, yeah, I was running 140 over the low 80s, something like 82, 83. Did, you know, five measurements. So did the acupuncture, which is designed for blood pressure and diabetes, and maybe I can go off the GLPs if all those works. But anyway, the next day I measured it the exact same time, and son of a gun, it was 25 points lower. It was the high teens, like 118 kind of.

[Andrew Huberman]
Wow.

[Michael Snyder]
It was unbelievable. I can show you the data. Uh, and, and the other one went to, like, 72, right? Some, uh, the diastolic. So I just with one treatment... That was electroacupuncture, I should say, so they zap you.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
Um, and they, yeah, had 30-some points, and, and they've added a few more since. You do it every week for eight weeks. So I've now done four of these things, and I can tell you that my blood pressure stayed low. It's running in this one, high one teens, maybe 120, uh, which is pretty good.

[Andrew Huberman]
Yeah.

[Michael Snyder]
Roughly where you wanna be, and the other is always around maybe 74. So it's like... It was never running like that before. I can show you my data.

[Andrew Huberman]
That's great.

[Michael Snyder]
It's pretty incredible. So it does seem to be working. Now, how long does it last? I'm only halfway through my treatments. I don't know, but I will track all this stuff, right? So

[Michael Snyder]
I'm a responder, no question, to this treatment.

[Andrew Huberman]
I love hearing it. I haven't done acupuncture in years, so it's... And I've no sk-

[Michael Snyder]
So you have done it?

[Andrew Huberman]
Yeah, years ago when I was a postdoc, a stressful time in my life, and then a junior professor, also stressful time in my life. You know, g- a lot of uncertainty, writing grants and things of that sort. Um,

[Andrew Huberman]
my sister suggested I go see a acupuncturist, and I got a lot out of it in terms of stress reduction. We'll put it... a link to it in the show note captions, but I'll also send you these papers from Qiufu Ma's lab that I mentioned a few moments ago.

[Michael Snyder]
Yeah.

[Andrew Huberman]
Uh, first of all, not that this means everything, but published as articles and letters in Nature, which has a very high bar for, you know, for-

[Michael Snyder]
Sure.

[Andrew Huberman]
Uh, not... Most papers get rejected, obviously, as you know. Um, and what they found is interesting, that the, the, the combination of needle placements turns out to be vitally important. So in this one paper that Qiufu has, he shows that, for instance, if the, if the needles are inserted into, like, the, the equivalent of, like, the palm area and the foot area and some flank area, you get an increase in inflammatory cytokines. Whereas if you change that combination, you get a decrease in inflammatory cytokines. But what's really beautiful about these papers is he maps it to, um, specific output from the spleen-

[Michael Snyder]
Ah.

[Andrew Huberman]
... regulated by the vagus nerve, regulated by the, um, these receptors at the level of the skin. So mechanistically, it all makes sense. It's just that these thousands of years of, of, of charts and data that have been collected in humans, you know, clinical practice has never been parsed mechanistically.

[Michael Snyder]
Right.

[Andrew Huberman]
So I'm 100% a believer that there's a mechanistic basis, that it's not just all placebo.

[Michael Snyder]
Right.

[Andrew Huberman]
Some of it might be placebo-

[Michael Snyder]
Right

[Andrew Huberman]
... much like some of the GLP appetite suppression might be, be placebo, b- but a lot of it probably isn't. So, um, in any case, I, I'm a, I'm a fan of the

[Andrew Huberman]
rigorous exploration of things that have been thought to work for many, many years. And it's always gratifying when you see, oh, like here's a mechanism that makes sense.

[Michael Snyder]
Yeah, it really does work.

[Andrew Huberman]
So-

[Michael Snyder]
I mean, I go into the stuff completely open. It may not work.

[Andrew Huberman]
Mm-hmm.

[Michael Snyder]
And I don't know, I didn't even... She said, "Oh..." 'Cause first of all, she said, "Well, just try acupuncture." I wasn't even sure what kind she was gonna try. So in the end she said, "Oh yeah, we'll do blood pressure and diabetes." Now they've added on some stress points as well. And I don't consider myself, uh... I'm probably in a high-stress job, but I don't consider myself a very stressful person.

[Andrew Huberman]
You don't seem stressed.

[Michael Snyder]
Yeah, I, I think I generally handle all right. But anyway, they're putting all these things on me, and I didn't know I was ca- you know, 24 hours later, is it gonna work? I don't know. But it... the data, I mean, that was a pretty big jump, right?

[Andrew Huberman]
Speaking of fun and, uh, things that are...... at least on the face of them, kinda out there. Uh, I have one final question. Um, which is,

[Andrew Huberman]
my understanding is a few years ago, your laboratory was involved in looking at big data sets, genomics, proteomics, et cetera, from people who had attended a Tony Robbins event . I don't know what the control condition was. And I only know this because, uh, I believe it was a post-doc or a student in your lab had reached out about some protocols, uh, that we had going in my lab i- in collaboration with, uh, the psychiatry department. Um, could you describe the contour of this study and ...

[Michael Snyder]
Yeah.

[Andrew Huberman]
And I realize it's not published yet, but if there were any preliminary findings that you could share with us, I think that would be interesting. I, um, I'm interested generally in immersive events and psychological health. And, um, there are interesting data comparing attendance of these events, but ... Which by the way, I have no financial relationship to. Never met Tony in person or, or anything like that, with prescription antidepressant treatments. And they actually measure up pretty well in terms of ... Uh, I forget how long term the study was. So I'm generally an open person when it comes to ideas. What was the study and what did you find?

[Michael Snyder]
Maybe to put it in context. So this all started when a post-doc joined my lab, who was very interested in mental health and knowing that we're good at measurements and the idea ... And, and I thought about it a lot and I realized that we don't measure mental health very well, right? Surveys are still the gold standards for most things. And so how do you know if you're getting better? You do more surveys. That whole concept is very, uh, unsatisfying to me. So we thought with the wearables, right, there's gotta be a lot of physiology around this thing, this, this biochemistry. We do a lot of microsampling, I mentioned earlier, where you can now profile deeply. So we thought we could bring this kinda stuff maybe, and we're still ... It's an a- it's a growing area in the lab. I'm very interested in this because I've, I feel like there's a lot going on in the mental health space. It's just unexplored. A- and the biggest problem is we just don't have good biomarkers. For the meetings I've been at, for the stuff, that keeps popping up, number one. We don't have good biomarkers. So we think the digital, meaning from the wearables, the, um, uh, um, the microsampling could ultimately prove to give us good biomarkers. We're already seeing some evidence of that now. So we ran several studies. We did one with Byron Katie, who runs one of these immersive programs.

[Andrew Huberman]
Oh, yeah.

[Michael Snyder]
And I don't know anything about this stuff. And so I bas- sorry, if we're gonna do this, let's bring in for as we ... Brought in a colleague, George Slavich, who you may or may not know. He's, he's, uh, basically an average childhood ex- but knows a lot more than I do about the childhood. And I've met, met him and he's a very, very bright guy. So he ... You know, we came up with some surveys 'cause we have to compare up against something. We put smartwatches. The one on Byron Katie didn't quite work out, but we did do blood sampling and stuff for her and, and even microbiome for people before and after. And that case, it went out for a way. And then we ... So we ran that study. And then shortly thereafter, we ran a, a pilot one with Tony Robbins where we had a smallish number of people who did the Tony Robbins . Uh, and we profiled them, you know, uh, before, right before, uh, i- immediately after and then at, at that point. I think that study was done out for several months. Um, and then I'll tell you about the large one in a minute. And so we had them do these surveys and things. And, and I went in. I have no idea if this stuff works or not. And son of a gun, these people really did improve by these questionnaires, by the standards in the field. Uh, basically, they improved their markers.

[Andrew Huberman]
Their mental health improved.

[Michael Snyder]
Their mental health, yeah, by the surveys. So that first ... And, and that was true for the Byron Katie one. It was true for the Tony Robbins one. And the Byron Katie one, we now have some of the omics data back, and they're im- they do seem to improve in their inflammatory markers as well.

[Andrew Huberman]
Wow.

[Michael Snyder]
So we have some data there. That's not yet published.

[Andrew Huberman]
Her stuff, for people that aren't familiar, and I'm, I'm ... This is a very top contour thing, is, uh, a lot of reframing, um, as I understand-

[Michael Snyder]
Yeah

[Andrew Huberman]
... through language, testing assumptions, counter ... Y- you know, uh, challenging internal beliefs, external beliefs.

[Michael Snyder]
Right.

[Andrew Huberman]
Uh, I, I'm, I'm ... Again, I'm just scratching the surface and I'm probably getting some of it wrong. But just so ... For those that don't know who Byron Katie is. Whereas Tony Robbins, I think m- more people are familiar with. Those are very immersive events. There's a lot of high energy activity. Also, b- some breath work stuff done. Um, some, uh, almost hip-

[Michael Snyder]
It sounds to me very intense.

[Andrew Huberman]
Yeah.

[Michael Snyder]
I've never done it myself.

[Andrew Huberman]
Almost like, um, hip- self-hypnosis type stuff where people direct themselves down a, a memory that's very painful, a memory that's very positive. A lot of somatic, um, stuff. I mean, you know, the- there's a wide palette there.

[Michael Snyder]
Right.

[Andrew Huberman]
But anyway, that ... Hopefully, that gives a little more context for people.

[Michael Snyder]
Right. So anyway, we did see a positive result, uh, on the pilot study. And that was 20 ... I don't know, 27 people. I may have the number wrong, but it's a small number. Uh, and then we now have done a, um, a f- a follow-up. And, um, well, I should tell you, actually, for, uh, the first one, they actually went out even further now. They have some additional data points. But in the follow-up, there we did a much bigger one at 600, almost 700 people who went through Tony Robbins. And then we had another set of people who didn't do Tony Robbins , who we also profiled. And same thing. Basically, they wore smartwatches. We had to scramble to get the IRB approval. It's always a rate-limiting step. Uh, so we didn't get as many wearables on folks ahead of time, but we do do the microsampling. We did do all the surveys, and we have a, a battery of wellness surveys. It wouldn't be official depression scores and things, but they're things about, you know, are, are you depressed and anxiety and burnt out and all kinds of stuff. So we, we ... It's a series of questionnaires. They, they did it before, they did it immediately after, one month, three months, six months, one year. And it's a pretty sizable study now. Like I say, it's almost 700 people who did it. 700 people who were controls. But I will say, the cavities are not randomly assigned because the people who did it, did it, uh, signed up for it. And the people who didn't do it, well, they did it separate. So, um, that's the only caveat that I see. But the bottom line is the ones who did do it, once again, they improved in a l- like virtually all these...... things, anxiety, depression.

[Andrew Huberman]
Significantly.

[Michael Snyder]
Significantly, yeah. Uh, and we have just put together paper on the psychological part now. Uh, and then on the... We're still doing the omic stuff, so we actually did the microsampling I mentioned earlier where they gave samples before for not everybody, not everybody signed up for that, but it's like 130, 140 people who did the microsampling before the... You know, immediately after each of those same time points. And so, we will see. That data is still coming in. Uh, and hopefully we'll know in a few months. But, uh, at least on the survey stuff, these people did all improve, and that control group which was separate did not. And it is significant, so I'm sure we'll put the paper up on either bioRxiv, which is this pre-print thing, uh, or can even send you a copy. I'll, uh, see if my, uh, person who's been running that's up for that. So anyway, um, yeah, it does work. It's pretty amazing actually. So again, people, a lot... Not everybody's into so-called depressed state or whatever. It's, it kinda worked out half and half. Uh, and their values all improved. Not... Again, not 100%, but

[Michael Snyder]
pretty darn most of them. It sorta surprised me. And we didn't... Obviously, in the control group we didn't see anything, so it looks pretty good.

[Andrew Huberman]
Wow. Well, I love how you are willing to explore these sorts of things. Um, yeah.

[Michael Snyder]
Yeah. People are... have asked me, "Mike, what the hell are you doing here?" And I said, "I don't know. I'll just let..." But let's take a... Like, thousands of people-

[Andrew Huberman]
Yeah

[Michael Snyder]
... do this stuff.

[Andrew Huberman]
Yeah, yeah.

[Michael Snyder]
Shouldn't somebody look at this?

[Andrew Huberman]
I know-

[Michael Snyder]
I think the answer is yes.

[Andrew Huberman]
I know people, um, who I would characterize as highly motivated generally toward their health and, um, careers, et cetera, uh, relationships, um, who had, uh, pain points of struggle in one or several domains of life or just were in a kind of a, like, you know, aimless part of life or struggling with something, uh, uh, who went and did these, uh, one of these immersive seminars and, and

[Andrew Huberman]
r- reported, and it does seem from the outside as well to be positively transformed.

[Michael Snyder]
Right.

[Andrew Huberman]
Uh, they continued to do the work on their own. Um, y-

[Michael Snyder]
That's correct, yeah. They're, they're-

[Andrew Huberman]
You know, they continue to do practices that, that they learned there on their own.

[Michael Snyder]
Right.

[Andrew Huberman]
Seems to be an important component. But, you know, I think, um, what's exciting about these, these kinds of experiments and conversations to me is that whereas five years ago, certainly 10 years ago, any discussion about... Let's just think about some of the themes that we've touched on, right? Um, breathwork. Long exhales slow your heart rate. We know that. It's the respiratory sinus arrhythmia. Increases HRV. We know that, right? Um, I asked you about meditation. You don't meditate. But, uh, but exercise, r-

[Michael Snyder]
Well, I used to-

[Andrew Huberman]
Yeah

[Michael Snyder]
... but... And I'd like to get back to it. It's-

[Andrew Huberman]
And certainly there are data to support it. Yeah.

[Michael Snyder]
Absolutely.

[Andrew Huberman]
Yeah. Resistance training. You know, when I was... I'm about to turn 50, as I mentioned. When I was in high school, the only people who did weightlifting were bodybuilders, people going off to the military, or preseason football players. They told us it would turn to fat if we stopped and we shouldn't weight train, right? We know that's completely false.

[Michael Snyder]
Right.

[Andrew Huberman]
Everyone should weight train.

[Michael Snyder]
Right.

[Andrew Huberman]
Women should weight train. Men should weight train. We're... E- especially as you get old, right?

[Michael Snyder]
Yeah.

[Andrew Huberman]
Um, Byron Katie, Tony Robbins have entered the conversation. Um, uh, their work, that is. Acupuncture. You're parsing diabetes into these subcategories or phenotypes. We're now, we're no longer talking about, talking about fiber as a single thing. You've now divided that into separable, actionable, uh, paths for, you know, addressing one's health, improving one's health. And so, you know, this really just brings me to what I, you know, been thinking more and more as I've read your work and, and certainly after today's conversation, which is that

[Andrew Huberman]
I'm so grateful that somebody like you who is into big data. You like numbers. You like statistics. You like, um, proteomics, genomics, RNA seq. You know, I mean, this is serious science. That you're willing to look at what's out there, what people are doing, what they're willing to do and ask, "What are the things to avoid? What are the things to do more of?" And really customizing it for peoples' needs. Um, I think it's truly important/heroin work because it really would take somebody in your position, uh, you know, at... At least until very recently you were Chair of the Department of Genetics, but you're a professor of genetics, trained at Caltech and all these places, to really embrace, you know, the... these different, uh, directions in health with serious mechanistic reductionist approaches. But then be able to step back and say, "Here's what I do. Here's what people are doing. Here's what seems to help. Here's what we don't know." And, uh, uh, there seems to be basically no limit to what, um, you're willing to explore using these highly rigorous tools. So I just wanna really extend my gratitude. And I know the gratitude that people who listen to this and watch this are, are surely feeling because things have been very siloed up until recently. And n- you're one of the people I really see as, as putting, um, sand and hopefully concrete between those silos, because this notion of health and health practice is really just one thing. And, and we g- we need to be less siloed. So thank you for doing that.

[Michael Snyder]
Oh, sure. I think...So you bring up a good point. I think we're trained to be siloed, that's part of the problem, is you go through graduate school and things like that. Even medicine, right? You have people trained in very specific areas so they never look at the whole. Yet we know, again, that we are homeostatic systems that involves all these different things. And you'll never solve it. Like, I, I like to say when I got, um... 'Cause pe- everybody on my father's side has died of heart problems and I used to have high cholesterol until I went on statins. I'm on PCSK9 inhibitors and they're amazing. Uh, and you know, um, my heart guy would tell me, "Well, you need to raise your statins." He didn't think it was low enough. I said, "Well, when I do that, my glucose goes up." And that's very textbook by the way. Uh, and I, and I finally called him. I said, "Look, your job is to stop me from getting a heart attack. But you don't care if I have all these other complications, right?" And I would say the same to the diabetes people. I'd say, "Well, you know, you're trying to control my glucose but you did so many other things." And I just don't think that's the right way you wanna look at people. We need to bring in all the data. All these things we've touched on these points about genetics and epigenetics and lifestyle, and I think the whole, you know, communication side, the whole socialization, very understudied. I also like it from the academic side, 'cause when you go into these areas where you don't know anything, you're... Even when you stumble around, you're gonna learn something. So that's kinda how I view our work in mental health and now socialization, I hope. Uh, so I just hope that we can learn some kinda cool stuff that will be useful. And then I think now we're in a, an amazing position, right, where we have the tools with AI, 'cause no one person can do this, right? You don't want a doctor who doesn't use AI now. You want someone who can pull in all that information, and this is what the companies are really good at. Again, it's one of the reasons we spin these things off. Like, January AI has this thing called Mirror that builds kind of... Like, it'll take all your data, your genomics data, all your reports, all these various things, and runs an AI engine, obviously trained in a certain fashion, and gives you back a incredibly long report. But though you do get a summary so you can decipher it. And then it pulls all the stuff together to make insights. And so for example, I didn't realize I knew my CD8 T cells. Again, this gets a little specialized, but they were low, uh, which I did see on the report, but it has this whole zinc recommendation thing. And I don't know if that's right, but I'm gonna look into it more. It can make suggestions that no doctor's gonna figure out with all the stuff. So you do need these new systems, and that is the future. We're all gonna have our own personalized systems pulling data. I mentioned earlier about iolo. Same thing about your metabolic profile, pulling other information to give you recommendations. That's gonna be true. Again, those are specific examples for me, but I think that's... Your d- every one of your doctors of the future is gonna have to do this stuff. Otherwise, you're not gonna get full value o- out of all these measurements, which we should be doing, that will better improve our health.

[Andrew Huberman]
I love it. It's a, it's a beautiful vision and I can see a day not too far from now where if somebody has a whole body skin data set, uh, some blood tests, maybe they have some tracking data, they just upload it to a website and their physician runs it through AI and makes of it what they can. Um, it certainly won't be everything that's possible, but that's certainly better than not taking those data into account.

[Michael Snyder]
Correct.

[Andrew Huberman]
And of course physicians can also still choose to ignore it all, most of them do now, by being totally unaware that it exists or saying, "Oh yeah, you said your heart rate variability was reduced for a week, but what does that mean to me?" It could be any number of things, right? But now that they can start to make sense of it if they choose to-

[Michael Snyder]
Right

[Andrew Huberman]
... I think, um, it's important, uh, important. 'Cause after all, people, we can't forget, the physicians work for you, not the other way around.

[Michael Snyder]
.

[Andrew Huberman]
So...

[Michael Snyder]
100% agree, yeah.

[Andrew Huberman]
Well, thanks so much for the work that you're doing. Uh, I've been told and I strongly believe that in the world of science, there are map makers and there are explorers. And the explorers are the ones that really, uh, make the discoveries that matter, and you're clearly an explorer. And I'm grateful for the work you're doing. I'm also grateful that you took the time to come talk to us today. So I'd love to get updates in the, in the not too distant future. Meanwhile, I'll see you back at the farm.

[Michael Snyder]
Thanks so much for having me here. It's been a blast.

[Andrew Huberman]
Thank you for joining me for today's discussion with Dr. Michael Snyder. To learn more about his research and to find links to the various things discussed during today's episode, please see the show note captions. If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us. Another terrific zero cost way to support us is to click the follow button on Apple or Spotify Podcasts, or both. And on YouTube, Apple and Spotify, you can leave us comments. So if you have comments for me about today's episode or you have guests or topics you'd like me to consider for the Huberman Lab episode, please put those in the comment section on YouTube, Apple or Spotify. I do read all the comments. Please also check out the sponsors mentioned at the beginning and throughout today's episode. That's the best way to support this podcast. And I should mention that I only work with sponsors whose products I absolutely love and personally use. And if you're not already following me on social media, I am hubermanlab on all social media platforms. So that's Instagram, X, formerly known as Twitter, LinkedIn, Facebook and Threads. And on all those platforms, I discuss science and science related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the content covered on the Huberman Lab podcast. Again, that's hubermanlab on all social media platforms. And if you haven't already subscribed to our Neural Network Newsletter, the Neural Network Newsletter is a zero cost monthly newsletter that includes protocols, brief one to three page PDFs, that explain the critical to-dos to, for instance, improve your resistance training, your strength, that is, your cardiovascular fitness, nutrition, dopamine regulation, how to optimize your sleep, learning plasticity, and on and on. Again, all available completely zero cost, all in the form of brief one to three page PDFs. To sign up, you simply go to hubermanlab.com, go to the top right corner menu, scroll down to newsletter and enter your email. And I should mention that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Michael Snyder. And last but certainly not least, thank you for your interest in science.

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