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

Welcome to the Huberman Lab podcast,

where we discuss science and

science-based tools for everyday life.

I'm Andrew Huberman and I'm a professor

of neurobiology and opthalmology at

Stamford 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 lifespan. 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. And while this

might seem kind of silly or trivial or

micro slicing, the identification of

these different subtypes 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 lifespan. 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 analyses 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 zerocost 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.

>> Great to be here. 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.

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 you go 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.

>> 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, grapes 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.

>> What's quickly?

>> Within uh 30 minutes maybe most 60

minutes. Um now I'm a special case. I'm

a type two 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, 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 want to 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. That

was already well known. diabetics will

spike their glucose through the roof too

high for too long. Uh and then that

people devis especially type ones

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 with named

glucotypes as it's a way of quantifying

this and uh and then some people are

spiking just as bad as diabetics and had

no idea uh and so it's a way of

revealing what was going on. So it's

recommended that you try to stay in this

7140 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 pretty strong papers out

there on that. So, 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 steadystate 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 65 or over, you're classified as

diabetic. If you're 57 to 64, 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 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 want to 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 the 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

spiked to bananas, some to potatoes,

some to pasta, some to white bread, some

to brown bread. And so uh this was shown

by Aaron Seagull's lab at the Weissman

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.

>> So different people 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 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 I don't know, sourdough bread or

something. By the way, I can eat

sourdough bread, but just by way of

example,

>> 100%. Yeah. And so, and so really the

only way to know, as you're pointing

out, is is to measure. I I want to talk

a lot about measurement today. For those

that are just listening, not watching,

uh Mike is wearing many sensors. How

many sensors? You have got four watches.

>> I have my four watches and my ring. And

even my hearing aids are sensors,

believe it or not. So,

>> we're for a hearing, but uh

>> we're going to get into all of that. Um

>> but maybe we could talk a little bit

about some of the subjective experience

of blood glucose excursions, both

healthy and unhealthy. Okay. 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, etc. Maybe

some alcohol too in some cases. But

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, right?

>> And I I don't think this is my

imagination. I mean, in one case, I want

to take a nap afterwards. In the other

case, I'm good to keep going, and I

generally have a lot of energy. So, is

what I just described atypical? What are

some subjective effects of high high

glucose spikes?

>> 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.

>> 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 and

I feel kind of like um yeah like I just

want to curl up and take a nap even if I

slept great the night before. Is that a

blood glucose response?

>> 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

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 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.

>> We've known for a long time that there

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Yeah, there was this idea that um if

something is rather high on the glycemic

index, meaning it spikes your blood

sugar robustly, that by combining that

food with another food or let's say some

fiber. Yeah.

>> Um you know, as opposed to fruit juice,

you know, eating the whole fruit, which

of course includes the fiber, um 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,

>> right?

>> And it's not the kind of crash where 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.

>> 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. Tell us about walks because

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, I think brisk walks seem to be

better. Uh there's d 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 um and yeah,

so there in fact some of these um

companies that have set up around

personalized management of glucose uh

I'm involved with one called January 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 can

they'll 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.

>> And is that simply due to the low-level

mus muscle contractions associated with

walking are just pulling they're just

acting as a glucose scavenger?

>> That's what I assumed. Yes. Uh that

you're burning it off. Did you see this

study out of um I forget the university

in Texas. I think it might have been

University of Houston where they looked

at um people doing what they called

soius push-ups. Did you see this study?

>> No, I haven't seen it.

>> This is wild. So they they basically had

someone uh subjects, it 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 a calf

push-up. But okay, that all that

nomenclature is kind of silly. What it

really is is keeping your toes on the

floor and lifting your heels. It's like

being like a knee bouncer in class what

we were all told we shouldn't do. It

turns out the soius 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 the the walking

>> okay

>> we've been talking about

>> and um now people had to continue doing

this but um it was pretty effective. I

know 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. If you're on a plane,

sure, you can, you know,

>> you don't want to fill the aisle because

people need to go to the bathroom. You

know, it gets it gets impractical. So,

it's kind of interesting to think about

just like what requirements are for

low-level muscular contraction. Okay?

>> And I and I would always want to 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 solius or

something like that. Just scaven or a

physical one maybe um you know I think

there's a lot of benefits as you know

from exercise per se. You make all of

these things called exind that have

>> a lot of benefits in general. So I I

think exercise probably broader than

simply injecting itself. 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

>> especially for people who sit all day.

the idea of getting up and used to be

well get up and walk uh you know some

brief walk but now there's 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

>> or air squats or something that

>> yeah exactly so we have people doing

some squats now running a study like

that and uh see what it does to their V2

max and overall you know health

measurement so so I'm a big believer

yeah yeah sitting for eight hours is

probably not good for you. In fact,

there are plenty of studies that show

that and these breaks are are good for

you. Even walking is better than

nothing.

>> Do you use a standing desk or a

treadmill under your desk?

>> 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

>> so I can be a little more engaged. Uh I

do have a lot of meetings, so for me

that seems to be more effective. But it

does mean I need to get up and take

these breaks

>> and uh so I I haven't but for other

people I know they like standing tests.

I've I've heard for some people though

or it may not be overall as effective.

So I don't know.

>> Interesting.

>> Yeah.

>> Yeah. I think the exercise snacks are a

terrific thing that you know air squats

even just pacing these kinds of things.

I think we underestimate the the extent

to which our um evolutionary history

drove a lot more movement every day than

we sat 8 hours a day uh in in ancient

times. Yes, I 100% agree. Yeah. Yeah.

>> People had to be active. They had to be

active to get gather their food and

>> deal with the elements. Yeah.

>> 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 and food

timing.

>> Sure.

>> 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.

>> Okay.

>> And I 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 a.m. or so, 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 p.m. I think it's pretty

typical, at least for Americans, is

better or worse for glucose um control

>> and general health. I know your lab's

been focused on um I guess it's called

intermittent fasting, but this

timerestricted feeding,

>> right?

>> We're not talking about weight loss now.

I'm just talking about glucose control.

>> There's a lot to unpack there. Um so we

have some studies where we put CGMs on

people, smartwatches, 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 resistance uh beta cell

defects things like that. So we were

trying to relate what was their what the

sto gl glucosis regulation sub phenotype

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. Some people had their

biggest meal or their biggest energy

consumption later in the day is dinner,

which is awkward socially because that's

what most of us have our big meal or

many of us do. Those folks will have

higher glucose and starchy vegetables is

well known. Those folks have higher

glucose but interesting fruits. People

ate a lot of fruits as their major

source of carbs had lower. That's

because of the fiber 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 disregulation you

have. If your muscle resistant, you

actually get better benefit by

exercising in the morning for glucose

the next day. if you're muscle insulin

resistant,

>> right?

>> Okay.

>> So, to unpack that a little bit, um, so

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, stimulate your

cells to take that up. And if you're

insulin resistant, especially muscle,

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 one. Uh you can

still become uh insulin uh deficient in

making insulin later in life for type

two. 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 in type two diabetic

I have a beta cell defect. Took me a

while to figure that out. Meaning I make

insulin fine. My cells respond but I

don't release it from the pancreas. Uh

and then there's things called hpatic

insul in insulin resistance. So your

liver is insulin resistant in other

forms as well. Uh fat insulin resistance

as well. So we've now gotten into

dividing up diabetes. in you know

basically classically people will group

people in type one which is 10% of

people are 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 20 of them the last eight or nine

years. And I basically did gain 10

pounds of muscle mass. That had no

effect on my uh my glucose control. And

the reason for that was that I'm not

muscle resistant. I'm a beta cell

defect. So I can gain as much muscle as

I want. It's not going to help me

release uh insulin from my pancreas. So

knowing your sub phenotype is a big

deal. But then I respond to certain drug

repinolide that actually promotes that

release. So knowing your sub phenotype

determines your drugs. But it also turns

out this whole lifestyle thing I

mentioned earlier is a big deal. And

coming back to some of the food stuff.

So we found that if you're um uh

basically insul insulin resistant,

muscle resistant, you will spike to

potatoes and pasta, but not if you're

insulin sensitive. And if you have beta

cell defect, you also spike to potatoes.

So you actually you can sub phenotype

people according to what their glucosis

regulation 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 going to sub

phenotype? Well the way we do it now is

super expensive. It's, you know, we do

these gold standard tests, take 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 sub phenotype. So meaning if your

muscle resistant you have a certain

shape and if you're 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 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 resistant we can

quite accurately predict whether muscle

are resistant just from the shape of

that glucose curve which you can get now

from an over- the-counter purchase at at

a drugstore.

>> Super interesting. There's, as you

mentioned, a ton to unpack there. I just

want to make sure I understand a couple

of the points you made um before we go

forward.

>> Uh you said the vast number of of papers

that have explored ideal exercise timing

point to the afternoon as the best time.

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. 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 want to make sure that that that's

true before we conclude that. Well, we

haven't taken apart for that particular

study the difference between resistance

training and and okay, it's more a

general activity measurement.

>> So, people are more active in the

morning if their muscle resistant will

benefit have better glucose levels the

next day.

>> So, we haven't yet done resist but I'm

very interested in this. In fact, we

have a separate study around

highintensity training running versus

long distance running. uh and 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 any time is better

than not exercising at all. So I I think

we'd all agree with that. But we do

think you get better glucose benefits if

you are muscle resistant doing in the

morning. And I also do believe that

yeah, building your muscle mass will

help uh with actually reducing muscle

resistance.

>> Thank you for that clarification. Uh you

mentioned different types of diabetes.

So general categories are type 1

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. Type two diabetes I understand to

be insulin insensitivity

which um is bad. You want your cells to

be sensitive to insulin. So insulin can

bring the glucose into those cells so

they can use them. Right?

>> You're now subdividing this type 2

diabetes, the insulin insensitivity into

muscle insulin insensitive as well as

other tissues being insensitive. What

percentage?

>> But it's more than that. Meaning there's

a beta cell defect where you don't

release insulin from your pancreas.

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 kind of

interesting. Uh although we still don't

fully understand it. But um then there's

also incrretin defects. So incretin are

these GLPS that everybody's heard about.

Ompic is a mimic of those and Monero 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 incrretin defect. This one's

muscle resistant. This is 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.

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.

when you talk about type two diabetes

and these different um subphenotypes as

you're referring to them, um

>> what percentage of people in the United

States do you think are type 2 diabetic

that have some sort of either insulin um

insensitivity and that's the the reason

versus, you know, 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 type2 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,

>> uh well, if you include beta cell

defects as part of insulin management,

then the number is probably very high.

>> But I honestly don't know the answer. I

don't think we fully know the answer

because people haven't done the

subphenotyping like I've described. We

don't know how many people have

incrretin 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 then diabetics. Uh, and I'm a good

example. No one would call me overweight

by any definition, you know, 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. It's 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.

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. It 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

muscle as 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 incrretin

uh which are these GLP things that

promote insulin release, but they

probably have other effects as well. I

don't fully understand. I don't think

everyone does all the effects of

incrretins. They're these the receptors

are all over the place. And 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

>> as anti- longevity drugs or as longevity

drugs.

>> As longevity drugs. Sorry, thank you for

that correction. Yeah.

>> Yeah. Uh actually just for fun, let's

explore for a moment some of the things

that we've heard these GLP-1 drugs uh

are effective for.

>> Yeah.

>> Uh certainly for um diabetics to better

type two diabetics to better control

their uh blood glucose.

>> Yeah. If I can intersect there.

>> Yeah,

>> I am a type two diabetic and they work

great for me. I my hemoglobin A1C got to

84 which you know it's not the highest

but it's pretty high. And I went on the

JLPs and I went down to 5'7

>> just like that

>> pretty fast

>> independent of weight loss.

>> No, it c well initially yes it's a

little complicated. I went on a a lower

dose thing called um fa and that one

dropped me down to about the 64 65 level

and I didn't lose too much weight. I did

lose some. Uh and then I went on Monero

because I had some nausea effects that

is a common side effect. They were

modest, but they were there. And I went

and so I shift to Monero, which is a

more potent version. And that dropped me

down to 57. 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 as

over the last almost nine years. And I

could just see my fat evaporated once I

went on these. I I'm the coldest guy in

the room now. Uh,

>> but you maintain muscle mass because you

do resistance training

>> mostly. Yeah.

>> How many days per week are you doing it?

>> I do it every day. So, but I have light

days because you know you can't strain

yourself hard every day. 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. And so I do it every

day and the goal was to keep my muscle

mass up and I mostly did it because I do

get measured a lot although it plummeted

when I got in a bike accident and hurt

my shoulder. Uh and then certain

exercise 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 it's still there but yeah it

it's not 100%. And then there's a

question of 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 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 I actually am now

backing off on the monero. I don't do it

every week like you're supposed to. I'm

on the lowest though. So I'm a great

responder there. And by the way, when

you get in these drug response, it turns

out a metformin non-responder. I did try

that early on.

>> Oh, this is interesting. So just to

remind people, metformin and then the

poor man's version of it is bourberine,

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

bourberine

that if you don't consume enough starchy

carbohydrates with it, it can give you a

brutal headache because you become

hypoglycemic. Oh,

>> I didn't know that.

>> Oh, it's it's really rough. Years ago, I

used to uh take a little bit of

bourberine. Um I used to do these uh

cheat days. It

>> 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

anything you wanted. Um, and

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 and you

go right back to it. But it wasn't

healthy. But taking bourberine, it was

remarkable because it would allow me and

other people 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 kind of you

become hypoglycemic and and you you get

you get these brutal headaches. Um, so

anyway, that's a little

>> 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.

>> Interesting. And this is because people

are taking Monaro and taking other

things that are dropping their blood

glucose.

>> Yeah. just it's probably been out there

more than people realize in the first

place that and now with the CGMs people

realize well if you we talked about

these glucose spikes well it's very

common if you get a really giant spike

you make a lot of insulin

>> so the consequences then you come down

on the other side and you actually get

too low glucose from those spikes so so

people are recognizing that and that can

people are now concerned about that

certainly leads to fatigue

>> yeah glucose troughs are definitely bad

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.

>> Yeah.

>> I don't eat non

or I aim for, you know, 90% of my food

intake to come from, you know, whole

unprocessed foods and 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 GLP1

agonists was basically what they are.

And we had a guest on here, Zachary

Knight, who was at UCSF, Howard Hughes

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 thousandfold.

>> 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 supra physiological increases in

GLP-1 that people are achieving with

these drugs. I know nowadays some people

are starting to get them from

compoundingarmacies and micro doing them

to great effect actually.

>> Okay.

>> 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

doses.

>> This is what I want to do by the way.

>> Yeah. no nausea and often times they're

combined with um

>> some other things that uh off the top of

my head I can't remember but oh right

some of these more um experimental

peptides like SS31 which are designed to

improve mitochondria and people are

getting really spectacular effects from

the micro doing of compounded um uh

compound pharmacy uh GLP-1 agonist but

even those are probably boosting GLP-1

several hundredfold so none of this is

like natural

>> uh for for the body And yet um there are

other positive effects like I've heard

of reduced craving of alcohol.

>> What are some others that you've heard

of?

>> 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

demention 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 you

may know that people used to talk about

metformin this diabetes drug as

potentially the longevity drug 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 JLPs

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 improve people. I I will

say as long as we're on this topic, um

you are a perfect example of a very

diligent patient, meaning you're taking

these GLP1 drugs. You're, as you

mentioned, aiming for taking lower

dosages, maybe even quote unquote micro

doing,

>> 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, etc. Uh while

taking these GLP1s, many people won't

>> or just unless they're highly motivated

to um they just they want a drug that's

going to melt the fat away and they are

unwilling or uninterested to do the the

exercise piece.

What if any data from your genomics uh

data and these large scale studies that

you're doing point to the fact that the

combination of augmenting GLP1 with

these drugs and exercise is is

beneficial? Is it all just about

maintaining muscle mass?

>> Uh good question. I don't know, but it's

pretty clear that people do do strength

training. Again, larger studies would be

nice, but it's pretty clear they can

reduce their muscle mass loss. That

that's clear. And it's definitely been

the case for me. I mentioned my bike

accident. I went from pretty good about

maintaining muscle mass and I did lose

some when I lost some of that. Um, so I

can tell you personally had an effect.

>> Don't cycle. I tell my friends we I know

so many people have been on a bicycle.

You're traveling next to these 3,000 lb

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 everyone I

know

>> who cycles regularly gets hit by a car

eventually. I know three Stanford

faculty that are dead.

>> Oh,

>> right. But then again, I lived in the

area for a long time

>> back on Woodside Road, you know, cars

just just taken out or or had to dodge a

car and and um ran to a tree. So dead,

brain damage, injured. What do I have to

do to convince you to run instead of

cycling?

>> Well, I do have a theory that you're,

you know, your cycling versus your

health. There's an inverse relationship

or it's a consonant, I should say.

Meaning, uh, I'll probably get killed by

a car possibly someday, but I'll say

healthy in the meantime because it is my

form of aerobic exercise.

>> We need you around, Snider. But I say

this, I don't know why anyone would

would do this instead. 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

>> cycling is the cars I work

>> yeah correct but there's no room in some

of those places 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.

>> Do you wear a helmet? Uh, of course.

Yeah. And that's turned out to be pretty

critical when I've had my 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 telling you Stamper

professors. This is the way Stamper

professors get taken out.

>> Yeah. Well, but I'll be I'll say healthy

in the meantime. And and I like to think

I'm pretty healthy now. Uh minus my

diabetes. And

>> you seem very robust. I mean I I hope

you don't mind uh me sharing that you

are uh about to hit 70 soon and you are

clearly cognitively uh whips smart and

um and fast and physically you seem very

robust. And um you mentioned getting

these M whole body MRIs and the fat just

kind of disappearing as you were doing

these GLP1 agonists and weight training.

I want to make sure I continue to, you

know, hammer on.

>> I'm big on the weight train. I'm glad

you're doing that because I think it's

huge.

>> Yeah, it's it's not just about taking a

drug. Um, and you can do a lot with just

lifestyle. And we'll talk more about

that. But I have a question about um

subcutaneous versus visceral fat.

>> 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, what do we know about the the

health risks of intraisceral fat versus

subcutaneous fat?

>> 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 lot of 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 cells 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. more obese

you are 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 of putting stress on

your organ systems uh yeah say versus

subcutaneous

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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? 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 poor 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 kind of high at night and

gradually goes down during the day and

spike in the morning. You get 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 sub

phenotype is is what we don't fully

understand. So we're trying to sort this

out and what you did the day and

especially the evening before eating

that big piece of pizza then go falling

right asleep probably is not a great

thing for you. You will go to bed with a

high glucose spike for many many people

again unless you have perfect glucose

control. So 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 kind of 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 then 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 like but I try when I'm not

traveling to keep constant hours. At

least that part I'm I'm okay at. But

yeah,

>> 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.

>> Okay.

>> 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?

>> 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

exactly does that work on all your

different organs? Sleep, you know, I do

like the idea of sleep. You may know

your, you would know this better than

me, but your spinal fluid and such, you

know, expands and contracts. The idea of

emptying out the garbage, so to speak.

>> Yeah. Literally rinses out your system.

>> 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. 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 going

to 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 and 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 want to

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 micro sampling stuff but we

found that we had 32 people drink this

insure 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

pro-inflammatory for others

anti-inflammatory.

>> So interesting.

>> I assume a lot of this got set early in

life because your whole microbiome. So

backing up a little bit just so people

realize that you know you have a lot of

microbes you have in fact more microbes

in you than our human cells and they're

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 colon 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 posture.

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 like

fish heavy uh um veggie diets I think

are helpful for people. Um, but I do

think some of this gets set early 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 and it's estimated some work

from Justin Sonenberg that um uh you

know native populations these Aboriginal

they have three times the number of

microbes that say people in the US. 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

going to continue.

>> I totally agree. I think the gut

microbiome is 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,

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,

>> right? And um I I do want to um just say

one thing in fairness to uh 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

u more Mediterranean or plant-based. I

have seen that uh work for many people.

I will just also mention in fairness

there 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 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. your professor of

genetics. So hopefully that's not too uh

uh too heretical an idea.

>> By the way, some of this has been broken

down of of say how much is your

microbiome for general glucose levels

versus genetics. And I think for the

general uh um microbiome, it's about

20ome 20 to 30%, depends on the cohort

that was studied. This some work from

from the Weissman. Uh and then for

genetics, it may be about 20% as well.

So, so 20% of your microbiome is

determined by your genetics.

>> Uh, no, the other way around. Sorry. Of

your glucose levels,

>> 20% 20 to 30% is determined by your

microbiome and about 20% by your

genetics

>> and the rest by lifestyle.

>> Yeah.

>> Okay.

>> That's a useful set of metrics. 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.

>> And you you kind of have to acknowledge

that. I'm not saying you have to, but

I'm going to 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.

>> Yeah.

>> Um and 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.

>> Sure.

>> 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 Sonnenberg um and Christopher

Gardner,

>> yeah,

>> 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

inflammatome

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.

>> It is. Could you tell us about the two

major types of fiber? Which foods

tend to deliver one or the other type of

fiber? And if indeed there are

differences in which fiber are best for

different people,

>> 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. You can't lump that

broadly.

>> You can't. And their effects are very

very broad.

>> 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 arabinosylan and inulin which are

these two uh just commonly used razylans

and physium hus and it's associated with

mezamucil and inulins and these chory

pea fiber things.

>> Could you before we dive into this what

are some foods that one type of fibers

is more abundant in versus the other

type of fiber? Well, Metamucil is a good

example for the the um Arabland would be

in that and Rabyland's kind of

interesting as the name sounds to

chemist has arabinos and uh and it does

have some glucose but has polyphenols in

it too and I don't know if you probably

have covered this on your show.

>> No, not yet but they're super important.

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

anti-inflammatory.

>> So uh anyway they're part of a rabbis.

This inulin is a glucose polymer but

they're short chain and long chain that

has different properties as well too. Uh

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 say um well, inulin lowers your

glucose and others say no, has no

effect. And some saying it lowers your

cholesterol and others it doesn't. Same

with the rabbis island. It was all over

the map, although there might have been

more of a consensus about this rabbit

island lowering cholesterol. So, we just

did it. We took 18 people. Oh, 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 wash out and

then switch to the other one. So,

they're they're randomized. They might

do a radical island the first period and

then inulin the second, then a mix

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

omic measures many molecules of people's

blood and as well as clinical measures

and so what we discovered is that as a

general rule

did reduce cholesterol and actually

quite substantially it went down about

25%.

>> So this isn't metamucil but what other

um what sorts of foods contain high

amounts of of this compound?

>> Most do actually.

>> Okay. Broccoli.

>> Yeah, broccoli. Yeah.

>> Kale, lettuce, cabbage. Okay. Okay. So,

this is like the when we think of fiber,

we

>> But they have but they have other things

as well. 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 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

combination. So we're just finishing up

a study where same thing instead of two

fibers we added two more betaglucan 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 or both.

>> 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.

>> Wow.

>> 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 Rabos Island 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 rabidosine had zero effect,

meaning their cholesterol stayed flat

even when 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 maybe it's other parameters are

playing into this. So this is why

ultimately what I want to 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

>> which is remarkable I mean if we really

just take a step back it's like for ever

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

>> I agree

>> you know and as you said earlier I think

it's such a key uh thing for people to

keep in mind we understand the least

about the things we do the most 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.

>> Yeah,

>> it's just wild to think about. But then

when we 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 as 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 healthpromoting.

>> Yeah.

>> 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

versus what you burn. Yeah.

>> But you really view food as medicine.

>> Oh yeah. Because I think we are 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. That came up earlier

and I'm sure it will 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 that is the goal. It's to keep this,

you know, your car, right? You want, if

you want it to run forever, you want to

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 there's a problem with

medicine today. We wait till things are

broken and then try and fix it. And so

obviously what you want to 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 want to do,

keep people tuned. And so we probably

don't get off to a good start early in

life when we start people with all these

not so good diets like all the 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

because 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

>> seem to be doing a good job.

>> Yeah. Well, anyway, we'll do it the best

we can. So,

>> when I um travel, I will occasionally

take a probiotic 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, the different types of fiber

data.

>> I'm intrigued because I noticed 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, um, I'm

tempted to do the following experiment.

Tell me if this is a good experiment,

Snider. Uh, if I'd be, uh, get a shot at

a sbatical in your lab. Keep eating the

same thing I'm eating. exercise the

same, do do things that the way I'm I'm

doing them now, but

try a supplement like you said,

Metamucil, which is one particular type

of fiber, right?

>> And do the before and after um LDL

cholesterol, APOB, blood glucose

regulation with a continuous glucose

monitor, then stop, do a wash out, swap

that out for increasing like inulin

fiber through some other source. So, in

other words, add add in a a pure fiber

source,

>> right,

>> on top of an existing diet and see how

that impacts um bloodmetrics and

subjective well-being.

>> Yeah, I think that would be good. I'd

love to know your microbiome. 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 hydrolaces 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

enzymes hydrolaces that do break down

these fibers and my guess is that we

already know that yours is going to 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 well you need to add the right

probiotic the right microbe to go with

that fiber to better get the tuning

you're looking for.

>> And in the long run if you probably want

permanent you know uh um

incubation of this this probiotic into

your gut you may actually have that 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 what a

prolonged use can can help colonize some

of that may be possible.

>> And they're cumbersome. They're

expensive. They require refrigeration

most of them. Um

>> yeah, that's right.

>> I personally feel fortunate that I don't

have what I would consider chronic gut

issues. I just avoid certain foods.

>> 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

>> Yeah.

>> inflammation? It's more of an

inflammatory response.

>> Yeah.

>> Like it just kind of feel like you don't

feel well and you feel kind of like

overtaken by some process, which that's

what I'm like, you know, this is a poor

man's uh I extract to uh you know, um

>> but if you can figure out which fibers

might be inducing that specifically,

maybe you can avoid those foods with

those fibers. 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 because ultimately I want to

understand the effect of every fiber and

make combinations that would be

personalized for people.

>> But uh you know, if you were to get

apple fiber, oatmeal is yes, it's got a

lot of metamucil and the raisin, but it

has other things in there too.

>> And it's probably true that the

combinotaurics are important. Uh, and

we'll get there at some point with the

cominatorics. I mean, I I guess I'm a,

you know, I am a big data guy. I like

the idea with 8 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

the combinatorics all figured out.

>> Well, you've got a hundred 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.

>> Yeah, we have studies running all the

time.

>> Yeah, I because I know a number of

people will be interested to do that and

we're going to talk more about sensors

and uh air quality. We've got a 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

>> uh is really important. And a family

member of mine was told that they needed

to take Metamucil to get more fiber. Had

zero impact on their LDL, zero impact on

um other important markers. I might

suggest to them that they consider

taking a different uh fiber supplement

in an effort to control.

>> Maybe for them inulin will be the trick.

>> 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

100 person lab is um exceedingly rare

and um

>> well, we're a little smaller now, but

yeah, we're still very impressive. Your

your vigor is undeniable and um and

>> I'm I'm just lucky to have amazing

people in my lab. I consider myself very

fortunate.

>> Well, I will say not just because you're

sitting here. I'm not just saying it to

be kind. Uh many people in your lab have

reached out uh for reasons related to

collaborations, etc. and everyone in

your lab speaks extremely highly of you

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

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to get early access to function. I'd

like to talk about organ aging and organ

health.

>> Okay.

>> As a separable set of features from

general aging and general health. I

think um you were 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 and then

it cascades into other things. Uh we

need to start thinking about organ

health in the same way we think about

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 about at at kind of

particular phases of life. Can you talk

about these things?

>> 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 health care. So we

started when I moved to Stanford now 16

years ago this idea maybe we should

first of all you don't measure people

very much when they're healthy. You

don't measure them very often. So just

you know it started with me but the goal

was to do a bigger group which we did uh

profiling people collecting as much data

as possible while they're healthy. So

we, you know, people would get blood,

their microbiome, uh, all urine, uh, and

we would take these and do what's called

OMIX 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. Well,

some have dropped off by now because 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 OMIX technologies like um uh

something called RNA seek 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 them omix

technologies. So it's ways of collecting

big data from your again your blood your

urine uh and even your microbiome. So we

basically sequenced people's genome,

made all these measurements and and

followed them over time. Oh, I was going

to 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 seeking 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 maybe

they're a little more interesting than

just fitness trackers. So we put them on

for health monitoring and and I can tell

when we started it was a bit

controversial at the time. A lot of the

physicians are not like a 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're worried we're going to

turn everybody into hyperchondria. It's

going to 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. Sure. We'll talk about that.

But um anyway, we did show that a lot of

people learn 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 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 a major

health discovery just in the first three

and a half years of running the study

and some were

>> with the wearables

>> with all kinds of things. It was the

thing it was no one technology. What

we're doing is we're getting a much more

complete picture of people's health and

we discovered these things then before

they have symptoms. So we're profiling

people while they're healthy and we're

we're looking for things that might be

off. 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 piece they

just don't get a very good picture.

We're trying to measure five or six

hundred pieces, get a much clearer

picture. And so 49 people, we uncovered

something pre-ymptomatically. Caught

someone with early lymphoma, two people

with precancer, several two people with

serious heart issues, one from the

genome sequencing, one from the

wearable. So

>> this is part of a study. Is this been um

commercialized? like like if I want to

if I want to uh RNA seek or or uh

deepseek or this is by the way just uh

norm if I want to um look at mutations I

might have or um how healthy or how sick

different uh organs or cells of mine are

what's available to me nowadays.

>> Yeah. So we spun off a medical version

of this Q bio that does whole body MRI

which most people will tell you that

most physicians will tell you you should

not do that. Oh, let's pause there for a

second because I will say I've done a

Proo scan.

>> Yeah.

>> Um they're not a sponsor of the podcast.

Um but I did POV scan. Yeah.

>> Um and

>> what' you think?

>> 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

>> high impact sports early in my life 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. Okay.

>> Um

>> I learned

>> that my intracaler fat is very low. So I

was uh relieved to to see that.

>> Um and you know for the most part it

provided 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

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 kayazm

or I've got a small gloma 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 he's a surgeon. Surgeons

like to cut. He's a he's he's perhaps

one of the finest neurosurgeons in the

world. I I think all the neurosurgeons

I've spoken to 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 quote unquote

hypochondrics. 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 100% agree.

>> I mean I mean I mean it's kind of if you

step back from it's kind of crazy,

right? Like you doctors

>> it's just I mean from a purely just like

if we just made it completely a

emotional 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. And it

doesn't make any sense to me. Like like

wouldn't you want your patients to be

healthminded?

>> I think it's part of the broken health

care system, right? They have 15 minutes

to spend with you. Yeah.

>> 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. Men have

them in their prostate, women, their

ovaries. If you go high enough

resolution 100% of the time,

>> then people show up and say, "Well, I

got these nodules." And you know,

>> nodules are cell growths and they can be

benign cell growth.

>> Yeah. Or they're just not even growing.

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 the point is, it's not

whether you have nodules or not. Do you

have any growing nodules? Right.

>> 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. And I know that.

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 MRI f later and

they found three more nodules. So the

question is were they there to begin

with

or had his tumor metastasized? No way to

know. They had no baseline.

>> So I think having these baselines is

super important for everyone.

>> I think people bulk 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

whole genome sequencing is is going to

come down. Maybe even insurance would

cover it at some point. I mean, it's so

trivially easy to do.

>> Uh once you have, you know, uh a place

that will do it 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.

>> Um not just for making money, but for

improving people's health. I mean, as

you said, when you go to the doctor,

they measure like they give you 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 calling

them up on the phone. At this point, you

can do all of that stuff at home.

>> You can, and in fact, we should be doing

that stuff at home anyway. We can talk

about that later. But yeah, what QIO

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. 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 transcript on

the RNA seek 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.

>> Great. And so um and yeah it turns out

just like you're saying just from the

first 100 plus people they discovered

early ovarian cancer all

presymptomatically just like in our

study the 49 people um who found their

things pre they found you know

cardiovascular conditions are 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

we might see one thing off 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 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 have been a clue for

something big. And we've seen that in

our study. We'll see somebody who

shifted off their liver enzymes and and

they'll come to me and say, "Mike, I'm

still in the normal range." Even um you

know, there there and this is why we're

big on baselines. That's a big theme in

our work. no way 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 said I don't know

why don't you go get another measurement

sure enough then they shift it 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 think just like

your car if you see something going off.

You want to 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.

>> Amen to that. Um, a thousand times over.

Uh, let's talk about some of the sensors

you're wearing and what people can

monitor now.

>> Yeah.

>> Uh, you talked about continuous glucose

monitors and that's non-invasive. I

mean, you don't even feel it going in.

That's just basically a

>> right

>> sticker size thing. But what are some of

the other things? Um

>> most people are familiar now with sleep

tracking,

>> right?

>> 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 with non-invasive uh trackers and

maybe um

>> just yeah, let us know which particular

ones you're wearing. This isn't a you

know, like a promotion of of particular

products. I'm just very curious. You're

you're uh armed to the teeth with

sensors here. So yeah, what do you got?

>> I'm a big measurement guy.

>> Well, your st your Stanford faculty

after all.

>> So I have my um this is my Fitbit. This

is my Apple Watch. And then I happen to

have a company that called Sensomics

that has two different this is a new one

they have out um 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 aura ring. Uh and

>> it's not an aura ring. What is that?

>> It's called circle. Um they have they're

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 5 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 it's not

accurate. Depends on the device. Uh,

some measure skin temperature. Again,

some of that's accurate, some it's not.

Depends on the device. They also measure

something called galvonic 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 has value for hydration

because when you have drier, like when

you're diabetic, you'll have drier skin.

And I should have figured this out

earlier when I first became diabetic. I

got itchy because my skin got dry. Uh

anyway, you can measure that with your

smartwatch. um and get that in real

time.

>> The galvanic skin response.

>> 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 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, super important. Their

accuracy for the stages is still

questionable. It depends on the device.

They're getting better though.

>> 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.

>> Okay?

>> Because I'm doing an experiment on

myself where I measure my subjective

feelings of rest and and alertness and

energy

>> 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.

Okay?

>> Right? Because it just biases how you

feel. Our colleague Ally Chrome at

Stanford has done some nice experiments

where they tell people after a 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, etc. 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 Alli's

done cuz she finds stuff like this all

the time 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,

>> right?

>> 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.

>> I'll have to give it a try. Yeah, Matt

taught me that trick and I'm getting

close to two and a half hours of REM

sleep now.

>> Wow.

>> And I only sleep about six and a half,

seven hours to feel rested. So, it's

pretty spectacular. And I thank I got to

try it.

>> I thank Matt for that tip.

>> It's one of my biggest weaknesses. I

don't sleep that well.

>> Yeah. So, cool bed in the beginning of

the night and then the opposite toward

morning. And so, Matt taught me that

trick and it's like, whoa, it's so cool.

I I now emerge from sleep feeling so

much better. Unless I was having a

disturbing dream, in which case you got

to like go think about something else.

But in any case, 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. I don't

know. I haven't measured it and I

haven't looked at the data on that.

Yeah.

>> So, what about HRV? Uh, we're hearing

more and more that HRV is um perhaps

even more interesting than resting heart

rate.

>> I think it probably is.

>> 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 kind of thing.

>> Well, exercise is supposed to be one of

the best ways to do this. Again, I'm not

a cardiologist. I'm not an expert there.

I don't know for sure, but I know

personally um keeping my stress down and

sleeping better seems to help. I I've

noticed that makes sense.

>> Recently, yeah. Um you know, one of

these AI programs, this again happens to

come from January. 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

it. And I think I'm sleeping better

actually. Are you a meditator?

>> No, I used to and I need I know I need

to make more time in some sense. Maybe

my bike ride is the equivalent of that

at the end of the day and on the

weekends I try and do a little bit of

gardening at that's my form fun.

>> I am 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.

>> There's 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

which which activates the veagal pathway

to the cyanoatrial node slows your heart

rate down there's evidence that will

improve your HRV both in waking and

sleep states yeah just try it out see

what you think

>> one minute every day or

>> 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

>> really the long exhale which I try the

breathing that'll slow your heart rate

interperse it so there's no breath work.

You don't have to set aside time. I'll

ask you something different related to

stress.

>> Um it goes back to some sleep data. Um

you seem to love your work like you're h

before we we came in here. You're like I

love my job, 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. Oh,

>> I didn't know that. Yeah. 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 of

quality sleep you get is higher.

>> So maybe you don't need to meditate, you

just need to continue to do what you

love.

>> Maybe. Yeah. 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 it

also is a way of showing the stuff

really works and that it's not all BS

that you're doing in the lab. So I I do

love what I do. Um and um I don't know

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 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 realized we got away

from the a organ aging part. If you want

to go back to that,

>> let's go back to that. And then I I

would like to also get back to

psychological factors and mental health.

>> 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

this 109. Some have dropped off as 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 path dilated

cardio myopathy pathway changing and or

sorry that was dilated uh sorry that was

hypertrophic cardia myopathy uh

signaling pathway shifted other people

it's metabolic some are immune we call

these age types aging pathways and I

kind of 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 you know inflammatory

inflammation that's kind of crossorgan

as well. So we call these agot types

aging patterns that we see and it turns

out everybody's different. So some

people will be the cardio, some people

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 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

gagger when you you actually see that

they'll see how they're shifting. And

again, have another company involved in

this. They do this micro sampling. I'm

sure we'll get into where they're

measure your metabolic patterns. And by

the way, we think your metabolism is the

best way to see these shifts of all the

different proteom is good too. And my my

colleague Tony Vores, he basically has

looked at this organ aging stuff as well

from the proteomic st from uh proteomics

meaning group of proteins. He's he's

followed this and and same thing you can

follow this these agot types if you will

these aging patterns and the information

is totally actionable. You can see as I

say for metabolic age or some of the

folks seeing this they lost weight or

they exercised and they improved their

patterns. Now I'm not saying they got

younger but they did improve their agot

types. And so I think the information is

very actionable and so again uh and this

is one where we commercialize because I

want 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.

>> What what is the name of this company?

>> It's called Iolo. I O L O. And

>> and this is now commercially available.

So if I want So if I want to figure out

my age type, did I get that right? My

agot type. Um I can do that by sending

in a few drops of blood and it will tell

me

>> they'll send you a kit. It's a very

special kit because 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. And

they'll with something called

metabolomics and mass spectrometry you

can profile. It's a targeted assay 650

metabolites. And they cover all these

areas and many there 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 or 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. maybe eat more of certain things

and avoid other things.

>> Cool. I'm I'm going to 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 Brian 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 Aia who will be very direct in

telling you that he doesn't think much

of biological age when 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.

>> I think the hor 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

that's a modification of DNA has shifted

and it gives you an overall value. Well,

what do you do with that? You don't

know. You wouldn't. Yeah. and they can

predict something called grim age these

days your time to death your mortality.

Oh nice.

>> Same thing. I mean, what are you going

to do with that? What's special about

the age ofotypes 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

oxidative stress is off, you do Y." So

it's basically actionable information.

So, I think it makes all the difference

and it conceptually it makes a lot of

sense, too. It's like your car. I know I

keep coming back to that analogy, but

your car gets older, but certain parts

wear out first. You don't Well, maybe

some people do. They replace their whole

car, but generally you would fix the

parts that are wearing and ideally you'd

catch it before they break. And I think

that's how we think of a types. you can

go in and so I mentioned this company

earlier I what they do is they're

tracking your agot types because they're

doing these deep metabolic a 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

going to 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.

>> 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,

>> and some people she may have cheated,

but it's not clear.

>> Oh, really? That was a French woman. Um,

>> yeah, that's right.

>> 120 plus or minus five years seems to be

kind of what people consider a, you

know, a spectacularly long life.

>> Yeah, that's right.

>> Yeah.

>> And that does seem to be the cap. And

so, you know, most of our research is

built around extending health span. It

is the case that for

lifespan in general it's estimated to be

about 16% of your lifespan's due to

genetics.

>> That's it.

>> Yeah. 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 live to be a

hundred or older then it might be

higher. Some people have said 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 suit lifestyle. Uh but for the

average person, it's only one six. 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 live to

be 100 or more. They have several things

in common. One is they tend to eat a

diet with not much ultrarocessed foods

or processed foods in general. And

generally they tend to be towards the

Mediterranean vegan kind of diet.

>> They eat animal proteins as I

understand, but it's more fish and

chicken.

>> Yeah, that's correct.

>> And less less red meat. And they're

eating a lot of vegetables.

>> Yes, for sure. Uh and getting fiber

through that as well. And then uh they

tend to have um uh they're fairly active

meaning but their form of activity can

vary and they have really good social

networks.

>> 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 it 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 kind of thing we want

to look at. Again, I view people as a

combination of things or genetics or

epigenetics. You know, I I don't know if

I told you all the details when I became

diabetic. It was predicted from my

genome. Matul but actually predicted

this from something called apologenic

risk score these ways of analyzing

genomes and I'm at the extreme end that

doesn't work for most people by the way

but I'm at the extreme end that work for

me so you predict I was high risk for

diabetes but I didn't become diabetic

until after a viral infection it's very

strong correlation and because I measure

myself a lot I figured this out as

respiratory sensitial virus which uh

actually you know it's not that common

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

it's it's the thought is that I was

genetically at risk. And then in

combination with this viral infection,

it's environmental. That's what

triggered my diabetes. Now I don't think

that's true of most people. We're

tracking people. I may have mentioned in

the first part of study we saw nine

people become diabetic as we've been

tracking them and seven gradually became

diabetic as though it was you know

accumulation of something. But two

people, one of which was me, something

triggered it, meaning it kind of got

there and stayed. It wasn't just a

transient spike.

>> Uh, and so how often this you get these

gen 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. It 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 pathogen.

It's not always clear what's causing it.

Seems to be different for different

people. But the idea of these intense

stresses maybe 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. 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, etc. 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, kind of like

flicking the domino that was already

kind of, uh, uh, tilted. Um and

>> once again that homeostatic system

concept that you're yeah maybe if your

genetics is a little bit weaker

>> uh we've noticed um yeah that you know

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 and other things could trigger

that sort of thing. So I like that

general concept that we're and in some

cases maybe that's beneficial. 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

cickle cell, right? That folks with

cickle 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 more

makes you more susceptible. Let's put it

that way.

Yeah, I've heard um 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 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 HSV1 um which is very common

right I think um and most people just

combat it and they don't get cold sores

um

>> but that something about that the

inflammation of that trigeminal nerve

pathway maybe it breaches the blood

brain barrier in certain people and then

it sets off a cascade that we eventually

call Alzheimer's so these these uh these

correlations because that's really all

that they are correct and the these

multiffactorial um

>> uh 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 want to 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

presumably are different combinations of

puzzle pieces missing.

>> I think so. And I think until now

medicine and the general public 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.

>> Yeah. I mean there are

>> it can't be that. It can't be that

simple.

>> That's correct. A a good example would

be Huntington's, right? Where you have

an expansion of a specific genetic

locus. Uh there elements that shift

there. Uh and that's highly associated

with Huntington. Those would be single

condition things that trigger it. And

that does happen, but that's not most

disease. That's more of the exception

than the rule. And by the way, even in

those cases, there are people that

escape it.

>> Oh, you have escapers.

>> Yeah. Who have somehow escaped that. not

always understood, although they may

hold clues to perhaps how others could

be helped.

>> 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 and super oxide duty

um being involved in the degeneration of

motor neurons, which is why ALS used to

be called L Garri's disease, but ALS

people uh Stephen Hawin had ALS, right?

Absolutely.

>> Um what is the role of of superoxid

mutation and it is there anything

protective in terms of behavior

supplementation drugs that people can

take to protect themselves against neuro

degeneration 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, right, by doing or

taking X,

>> right? Well, first of all, I'm not an

ALS expert. This is where my genetics

came in. 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

you know an amazing posttock uh Saison

and and a great collaborator Jonathan

Cooper Knock 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 that 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 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

sbatical at UC Irvine right now. And

there's, you know, people who are trying

to take this sort of thing on. We we'll

see how well it works. It is clear there

is a study that if you overex exercise

that's worse for you for ALS. Uh, but

whether that helps you predict, I don't

know. 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.

>> No I I you know I'm very interested in

what one can do to protect against ner

degeneration. the one that I'm very

intrigued by and here I am not promoting

this specifically for everybody but um

years ago this is purely anecdotal uh

but years ago I was in the office of

Richard Axel at Colombia Nobel Prize

winner for discovering the molecular

basis of whole faction etc. And I

observed what many people had told me I

would observe, which is that he chewed

no fewer than like six pieces of

nicarette 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." 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 slashaddictive. Most people I

know that take two milligrams of a of a

nicot nicotine gum or a pouch suddenly

are taking four, six, eight, then

they're taking a canister every two

days. Like, it's very habit forming 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 lowgrade uh

head uh injury with something else like

hypoglycemia, right? The the two hit

model. 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, then you start losing

neurons. And in some cases, like

nicotine can be protect. This kind of

thing.

>> Okay.

>> So, I'm intrigued by things that one

could potentially do to protect neurons.

>> Um, aside from wearing a bike helmet,

>> which I'm relieved to hear that you do.

>> In any case, uh, room for

>> motor neurons for ALS. Motor. So, I I

don't know how similar different. Yeah.

>> Yeah. Yeah. Super interesting. I don't

think anyone wants to lose their motor

dopamine or any other neurons. So, it's

it's uh you know, with rare exception,

we don't replace them. So, um I think

that's going to be a really important

area going forward. 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.

But, you know, um,

>> back to behavioral modification.

>> 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.

>> Okay.

>> Let's start with, uh, low esoteric, but

still in the kind of area that now

people are talking about, um, which used

to be considered kind of woo, which is

air quality.

>> Yeah.

>> 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 etc. 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.

>> Uh you're good. You're at PM 2.5 of

three PM 10 of four.

>> Okay.

>> Yeah. which is very low by the way.

>> We've turned off the AC for for

recording purposes. Afterwards, we tend

to ventilate the

>> Yeah, it was one earlier. So, uh it's

in,

>> but we had fires here in LA not long

ago. How

>> probably would have gotten to 200, maybe

more.

>> I mean that it was dreadful.

>> Yeah,

>> it was really bad.

>> Yeah.

>> And a lot of people and animals are

still suffering um symptoms, you know.

So, um so what's the logic behind this

device and and what's I mean, I imagine

you brought it here for a reason. Well,

no. I bring it all the time. It's It's

always next to me.

>> Oh, you carry this everywhere?

>> Oh, yeah. I've been doing this for eight

or 10 years now.

>> And if a restaurant or another space

doesn't have uh good air quality, you

you just leave. Is that

>> No. Uh probably

>> you inform them and then leave.

>> Uh people ask and I I'm always honest. I

tell them what it is. I It hasn't been

so bad. Where it will 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 kind of 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 decide to start in

and you know what are you breathing

right now? You have no idea,

>> right? And so that's the principle. I'm

a sort of 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.

>> Goes from the lungs into the bloodstream

and can cross the bloodb brain barrier.

>> Yeah. And it's Yeah. Not good. 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 nobody's 100% sure what it

means. But they do know now that when

you dissect people's brains of folks who

have died, and you'll see microplastics,

they're everywhere.

>> 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

this 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 PM 2.5 and

PM10.

It's basically um 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

particullet like pollen, bacteria, fungi

and under that there's a chemical

absorbent. It's called zeelite. Capture

is both hydrophobic, hydrophilic,

positive and 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 that have an

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

because 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 kind of thing because

you have to collect enough sample but we

will basically determine you know what

kind of exposure you're getting and and

if you're at high risk for certain

things you may want to know this like

asthma or allergies what are you exposed

and there I can give you an example I

used to have moderate allergies now

they're pretty mild but because

allergies can fluctuate a bit and they

would come every spring and I just

assumed it was pollen

But what is pollen in the end? 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 have

realized this, but um I don't get them

on the northeast where there's no

eucalyptus. And so in the end, it makes

a lot of sense. So, um, that one hasn't

affect 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, yeah, at least I know

what's going on. Um, but then like on

the chemical side, which is very

interesting, we discover there's DE

everywhere, even in my office,

Stanford. DE insect repellent. The

carcinogenic insect repellent. Yes. Uh

>> 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 DE put it into a Ziploc bag

>> and put that Ziploc bag into a glass

jar.

>> Okay.

>> I was like okay. And I did that and

within a few hours the plastic bag was

completely disintegrated.

>> Ouch.

>> And I was slathering that stuff on my

skin way back when

>> and I lived with mosquito bites for the

rest of the summer. I'm like, I'm not

putting this stuff on my skin.

>> Yeah, of course. Now I had to worry

about getting West Nile or something

else.

>> Not in Yusede. Yeah. You had to worry

about getting jardia. Yeah,

>> that's a different issue.

>> Yeah. From the water.

>> Interesting. Anyway, we But and same

with pesticides are most places.

>> Uh and carcinogens of course are

everywhere, 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.

Yeah. Because 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

cytoines, 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 the study with a lot of

people. Uh so we can first of all even

break it down further. What's the

difference between your kitchen and your

living room and outside your house? And

the same thing, how does that relate to

some of the levels of key markers, your

metabolites, your your um inflammatory

markers. So So we want to correlate

that. We know 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 made. Again, these are all

correlations. Now we do something called

mediation analysis. I can let you get a

little better about causality, not proof

in many cases, but it's better idea.

Anyway, here's a fun thing we

discovered. We found a correlation

between something called pyodine which

is used to be common in paints and it's

in other places too. They've recently

don't put it in paints but purodine

exposures are associated with lack of

fungi meaning I have more bacterial

plant or other exposure. So my house was

painted by a green guy. No purodine in

the paints there. So I get a fungal

exposure when I'm at home. And so is

that good or bad? I don't know. But

imagine I was very allergic to black

mold. So maybe I do want purity in my

plate.

>> I know a lot of people who struggle with

mold.

>> We can make that association with the

allergies, of course. Anyway, you get

the idea. We're trying to correlate

what's going on 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 certain

areas you will see uh if you live near

you know mines you will see autoimmune

disease things like that. So we can try

and make these associations and then you

correlate with similar people who aren't

living their minds to you know try to

test that.

>> I love that you're linking outside

environment with internal you know

>> I feel like it's a totally unexplored

area and a pretty important one.

>> Yeah. Yeah. And I think the fires in LA

among other things have sensitized

people to this notion of air quality 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. And I think the

interest and emphasis on microplastics

recently right?

>> Um, is interesting. I did an episode

about microplastics, we had Shauna Swan

on the podcast. I mean, I think

>> it's been known for a long time that

these microplastics, BPAs, and phalates,

so-called forever chemicals, have been

an issue. I think that um people are now

just shocked to learn how many of these

things we've accumulated and maintained

in our body

>> and they're all over our body too.

>> Yeah. And the health effects are still

unclear,

>> right?

>> I mean, it's really unclear.

>> They've been talked about endocrine

disruptors and things like this. Yeah.

>> I mean, I filter my water and um uh I

try not to drink out of plastic

disposable bottles. Um that seems to be

an important one. And but you know,

there was

>> I've only recently switched. I should

have done it. We should have done it

years ago, right? But there's a recent

study showing that actually the glass

bottles contain more microplastics than

plastic bottles because of the what's on

the lines, the underside of the caps. I

see.

>> But what's less discussed around that

study is that 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 can be

really really important. Um so I'm

grateful that you're commercializing so

many of these things. I I can tell you

are a data guy but the fact that you

translate things into real world tools

is so valuable. Speaking of which, um

I'm going to be very direct about this.

uh

two Stanford faculty talking about

measuring lots of biomarkers from a

single drop of blood. Screams of

Theronos, let's just call it what it is

and 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,

>> right?

>> Um

>> thousands.

>> Thousands. So that's exciting. Um

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. Like what 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.

>> First of all, we don't get measured very

often when we're healthy. Uh this idea

that we mostly practice sick care, not

health care. And why do you go to

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, fasile

ways of measuring people? Well, 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. I mean, 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 Theronos, I think, too.

uh and our you know shick 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 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. 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. Then we showed you

could actually do the kinds of things we

do the metabolomics is 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 this. 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 my case, we we

took a sample every hour for seven

straight days to try and correlate

>> around the clock.

>> Well, at night when I was sleeping, no.

But although when I did wake up, I would

take a sample sometimes. Yeah.

>> Um

>> Oh, it's just a drop.

>> Yeah. 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 like a follow

activity doing food logging all that

sort of stuff and then the end we're

trying to correlate basically people's

activities

and phys people's biochemistry and

physiology with their activities and and

heart rate and things like that and and

so we found literally thousands of

correlations It's pretty cool. A lot of

which is known right after your your

insulin goes up after your glucose. But

we can precisely measure we 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.

Alphasucine which is involved in

Parkinson's and dementia actually showed

an interesting pattern. that seem to

fluctuate with stress actually

>> goes up with stress.

>> 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, yeah. So, anyway, I'll leave it at

that because 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 have get out there to

help people in some fashion or

>> very cool.

>> So this is the kind of stuff we do and

these are what you're calling

observational trials. Take 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.

>> I love it. Well, let's go further into

what most people consider kind of

esoteric, at least in this half of the

world, but it's not really um esoteric

at all. Has tremendous precedent, which

is acupuncture.

>> Okay.

>> 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 Chufu 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. I'm down on

sabbatical at UC Irvine with Shyista

Malik who uh runs an integrative health

institute where they bring in nutrition,

exercise, and things like acupuncture

into trying 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

want to see what's going on, if there's

ways that makes sense to collaborate.

And as you point out, acupuncture has

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.

>> 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, is like, "Yep, there is

evidence acupuncture can work."

>> 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 because it

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 moderate 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 jail piece if all this works.

But anyway, the next day I measured it

the exact same time and son of a gun, it

was 25 points lower. The high teams like

118 kind of. It was unbelievable. I can

show you the data.

>> Uh and and the other went to like 72,

right? some the diastolic. So I just

with one treatment that was

electroactive puncture I should say. So

they zap you.

>> Um and they yeah had 30ome 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 11s maybe 120 uh which is

pretty good roughly where you want to 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

>> great

>> 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 I'm a responder no

question to this treatment that I love

hearing it. I haven't done acupuncture

in years. So it's and I've you have done

it.

>> Yeah. Years ago when I was a posttock a

stressful time in my life and then a

junior professor also stressful time in

my life you know a lot of uncertainty

right in grants and things of that sort.

Um

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 not captions

but I'll also send you these papers from

Chufu Ma's lab that I mentioned a few

moments ago. 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 sure

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 Chufu 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 cytoines. Whereas if you

change that combination, you get a

decrease in inflammatory cytoines. But

what's really beautiful about these

papers is he maps it to um specific

output from the spleen

>> 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. So I'm 100%

a believer that there's a mechanistic

basis that it's not just all placebo.

some of it might be placebo much like

>> some of the GLP appetite suppression

might be be placebo but a lot of it

probably isn't. So um in any case I'm a

I'm a fan of the rigorous exploration of

things that have been thought to work

for many many years and it's always

gratifying when you see ah like here's a

mechanism

>> it really does work I mean I go into the

stuff completely open it may not work

>> and I don't know I didn't even she said

oh because first of all she said well

just try acupuncture I wasn't even sure

what kind she was going to 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.

>> You don't seem stressed.

>> 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 you 24 hours later. Is it going to

work or I don't know. But the data, I

mean, that was a pretty big jump, right?

Speaking of fun and uh things that are

at least on the face of them kind of out

there. Uh I have one final question um

which is

my understanding is a few years ago your

laboratory was involved in looking at

big data sets genomics proteomics etc

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

postoc or a student in your lab had

reached out about some protocols uh that

we had going in my lab in collaboration

with uh the psychiatry department. Um

could you describe the contour of this

study and 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 anti-depressant

treatments and they actually measure up

pretty well in terms of 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?

>> Maybe to put it in context. So this all

started when a posttock joined my lab

was very interested in mental health and

knowing that we're good at measurements

and the idea and and I thought about 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 got to be a

lot of physiology around this thing this

this biochemistry do a lot of micro

sampling mentioned earlier where you can

now profile deeply so we thought we

could bring this kind of stuff maybe and

we're still is an it's a growing area in

the lab I'm very interested in this

because I I feel like there's a lot

going on in the mental health space it's

just unexplored 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 micro

sampling 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

Katy, who runs one of these immersive

programs,

>> and I don't know any about this stuff.

And so, I basically said, "All right, if

we're going to do this, let's bring in

first." brought a colleague George

Slavich who you may or may not know he's

he's uh basically an average childhood

exp but knows a lot more than I do about

the childhood and I met met him and he's

very very bright guy so he you know we

came up with some surveys because we

have to compare up against something we

put smartwatches the one on Byron Katy

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 way

and then We so we ran that study and

then shortly thereafter we ran a pilot

one with Tony Robbins where we had a

smalish 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 that point

I think that study was done out for

several months um and then I'll tell you

about the larger 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 improve

their markers,

>> their mental health.

>> Their mental health. Yeah. By the

surveys. So that first and that was true

for the Byron Katy one. It was true for

the Tony Robbins one. and the Byron Katy

one. We now have some of the OMIX data

back and they're they do seem to improve

in their inflammatory markers as well.

So, we have some data there that's not

yet published.

>> Her stuff for people that aren't

familiar and I'm this is a very top

contour thing is a lot of reframing

>> um as I understand through language,

testing assumptions, counter, you know,

uh challenging internal beliefs,

external beliefs. Uh I I'm I'm again I'm

just scratching the surface and I'm

probably getting some of it wrong, but

just for those that don't know who Byron

Katy is, whereas Tony Robbins I think

more people are familiar with those are

very immersive events. There's a lot of

high energy activity. Also some breath

work stuff done. Um some uh

>> must be very intense. I've never done a

>> almost like um h self-hypnosis type

stuff where people direct themselves

down a a memory that's very painful,

memory that's very positive. a lot of

somatic um stuff. I mean, you know,

there's a wide pallet there. But anyway,

that hopefully that gives a little more

context for people.

>> 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

follow-up and um well, I should say

actually for uh the first one, they

actually went out even further. Now they

have some additional data points but in

the followup 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 they see they wore smart watches

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 as ahead of time but

we do did do the micro sampling we did

do all the surveys and we have a a

battery of wellness surveys it be

official depression scores and things,

but they're things about, you know, are

are you depressed and anxiety and

burnout and all kinds of stuff. So, we

we it's a series of questionnaires. They

they did it before, they did 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

caveat is they're not randomly assigned

because there people who did it did it

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 all

like virtually all these things anxiety

depression significantly. Yeah.

>> Uh and we have just put together a paper

on the psychological part now.

Uh and then on the we're still doing the

OMIX stuff. So we actually did the micro

sampling 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

micro sampling 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 bioarchchive which is

this preprint thing uh or can even send

you a copy.

uh say 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 lot not

everybody's in the so-called depressed

state or whatever. It's it kind of

worked out half and half. Uh and their

values all improve. Not again not 100%

but

pretty darn most of them. It sort of

surprised me and we didn't obviously in

the control group we didn't see anything

so it looks pretty good.

>> Wow. Well, I love how you are willing to

explore these sorts of things. Um

>> people are have asking 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 do this

stuff. Shouldn't somebody look at this?

I think the answer is yes. I know people

um who I would characterize as highly

motivated generally toward their health

and careers etc 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

reported and it does seem from the

outside as well to be positively

transformed right?

>> They continue to do

>> the work on their own. Um that's

correct.

>> You know, they continue to do practices

that that they learned there on their

own,

>> right?

>> 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

5 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 breath work long exhales slow

your heart rate we know that the

respiratory sinus rhythmia increases HRV

we know that right um I asked you about

meditation you don't meditate but uh but

exercise

>> I used to but and I'd like to get back

to it.

>> And certainly there are data to support

it.

>> Absolutely.

>> 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. Everyone should weight

train. Women should weight train. Men

should weight train,

>> especially as you get old, right? Um

>> Byron Katy, 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've, you know,

been thinking more and more as I've read

your work and and certainly after

today's conversation, which is that 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 seek, 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

people's needs. Um I think it's truly

important slashh heroic work because it

really would take somebody in your

position you know at least until very

recently you were chair of the

department of genetics but you're

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 there seems to be

basically no limit to what um you're

willing to explore using these highly

rigorous tools. So, I just want to

really extend my gratitude and I know

the gratitude that people who listen to

this and have watched this are surely

feeling because

things have been very siloed up until

recently and 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 we need to be less siloed. So,

thank you for doing that.

>> Oh, sure. I think you bring up a good

point. I think we're trained to be

siloed. That's part of the problem as

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 because everybody on my father's

side has died of heart problems and I

used to have high cholesterol until I

went on sat on PCSK9 inhibitors and

they're amazing. Uh and you know um my

heart guy would tell me, "Well, you need

to raise your sins." 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 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

some of these other things. And I just

don't think that's the right way you

want to 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

underststudied also like it from the

academic side because when you go into

these areas where you don't know

anything you're even when you stumble

around you're going to learn something.

So that's kind of how I view our work

and mental health and now socialization

I hope. Uh so I just hope that we can

learn some kind of cool stuff that will

be useful and then I think now we're in

an amazing position right where we the

tools with AI because no one person can

do this right you don't want a doctor

who doesn't use AI now that 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 has this they call it

mirror that builds kind of like it'll

take all your data your genomics data

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 although 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 CD8T 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. I don't know if

that's right, but I'm going to look into

it more. It can make suggestions that no

doctor is going to figure out with all

this stuff. So, you do need these new

systems, and that is the future. We're

all going to 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 going to be true. Again, those

are specific examples for me. But I

think that's you're every one of your

doctors of the future is going to have

to do this stuff. Otherwise, you're not

going to get full value out of all these

measurements, which we should be doing

that will better improve our health.

>> 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 scan 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. Correct. 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, I think um it's

important uh important because after

all, people can't forget the physicians

work for you, not the other way around.

So

>> 100% agree. Yeah.

>> Well, thanks so much for the work that

you're doing. I 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.

>> Thanks so much for having me here. It's

been a blast. Thank you for joining me

for today's discussion with Dr. Michael

Snyder. To learn more about his research

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