I think first and foremost it's weight

loss. So it's very satisfying to go into

a state of ketosis because you do see

the scale change pretty dramatically and

that's due in part to some fluid loss

associated with a reduction of fluid

volume. It does have a diuretic effect.

Ketosis does ketogenic diets and

obviously fasting and also a naturic

effect where you dump out some sodium.

Your blood volume will contract a little

bit. So, if you have high blood

pressure, that will likely go down. So,

if you're on blood pressure medication,

you have to think about that. But first

and foremost, it's an effective way to

get your body to lower the hormone

insulin. If you have insulin resistance

and [snorts] shift your metabolism to

burning fats, and as we burn more and

more fat, that stimulates the production

of ketones.

>> Dom, happy holidays. Nice to see you.

>> Great to see you, Tim. Thanks for

connecting.

>> Definitely. I suggested we hop on the

phone because I have been harassing

the living hell out of you with so many

questions via text message and I

thought, you know, this must be pretty

annoying. So rather than answer me once,

why don't we hop on and record a bunch

of the details because the details are

so fascinating. And for people who are

just tuning in who might not know

the good Dr. D Augustino Dominic

we should establish some basics and I at

this point have been quote unquote in

ketosis for 18 days now and we'll dig

into a lot of questions around that

tactical practical questions but before

we do why would someone and we can talk

about what it is and so on but first

let's just give some of the let's call

it establish lished

benefits

ideally in human studies but could

extend to animal models and then if

there's anything on the horizon say in

the next few years because you're at the

cutting edge if you think there's

anything that might plausibly be

established as a benefit what could that

be so what would you put on the bullet

list of benefits of intermittently or

for extended periods of time being in

ketosis

>> there are many benefits to being in

ketosis and a ketogenic diet if we're

going to go there kind of has the

benefits of fasting and there you know

for millennia we know the benefits of

fasting without the without the baggage

without the metabolic baggage you know

the muscle loss the fatigue obviously

you can't live in a you know that level

of caloric deficit but in regards to

the practical applications of it

we know that being in a state of ketosis

really quiets the mind [sighs] and I

think that has major implications and

this was you know from centuries we knew

this and now over the past decades this

has been like a term kind of used and

it's backed up by experimental data to

show that there's an elevation of GABA

obviously it's silencing a broad array

of seizures independent of the ideology

temporal lobe seizures Lennox Gustoau

syndrome dur syndrome rare forms of

epilepsy the ketogenic diet just quiets

the brain, lowers glutamate and elevates

GABA, a brain stabilizing, calming

neurotransmitter. And you know, that's

why people gravitate towards alcohol,

right? The gabaurgic effects of alcohol

and bzzoiaines.

>> So you can sort of in a very gentle way

transition your physiology to a state of

ketosis which changes the

neuropharmacology of your brain to sort

of [clears throat] quiet it down. And

that I think really echoes its broad

application for metabolic psychiatry

which is everything from major

depression to bipolar to schizophrenia

to anxiety disorders to anorexia

nervosa. So that that's a very

interesting and rapidly expanding

application of ketosis that's being

funded largely by the Bazooki group.

>> Yeah.

>> You just interviewed

>> had David on.

>> Yeah. And on the physical side, some

folks, if they're old enough, may

remember the Atkins diet. Not saying

that is what we should hold up as the

necessarily the end- all beall of any

sense, but why would someone go on this

for

benefits outside of the cognitive

psychiatric? Are there any other

benefits that you could list off?

>> I think first and foremost, it's weight

loss. So, it's very satisfying to go

into a state of ketosis because you do

see the scale change pretty dramatically

and that's due in part to some fluid

loss associated with a reduction of

fluid volume. It does have a diuretic

effect. Ketosis does ketogenic diets and

obviously fasting and also a naturic

effect where you dump out some sodium.

Your plasma volume, your blood volume

will contract a little bit. So, if you

have high blood pressure that will

likely go down. So, if you're on blood

pressure medication, you have to think

about that. But first and foremost, it's

an effective way to get your body to

lower the hormone insulin if you have

insulin resistance and [snorts] shift

your metabolism to burning fats. And as

we burn more and more fat, that

stimulates the production of ketones,

ketogenesists. And ketones have a broad

array of applications, metabolic

signaling, epigenetic,

that have real world applications. And

that's why the whole field of exogenous

ketones has developed and there's 160 or

more registered clinical trials on

exogenous ketones on clinical

trials.gov. And I could go into each of

the applications individually if we want

to go there.

>> Well, as we talked about before

recording and I have to act as a bit of

a referee for my audience because I know

you can go as deep as as we want down

the rabbit hole into the 17th dimension

of biochemistry. So, if you get

possessed by the the organic chemistry

demons and [clears throat] start

speaking in tongues, I'll rein you in a

little bit. However, let me perhaps

provide a personal example first for

folks because some of this will be

familiar to people who have listened for

a long time, maybe to other episodes of

the two of us, but a lot of it's going

to be new, but I want to establish some

priors just so people are aware of what

this might look like in practice. So, I

have experimented with the ketogenic

diet, also extended fasting. You can

arrive at some similar places, but like

you said, there can be some pretty heavy

taxes to pay with extended fasting. The

ketogenic diet I've experimented with

all the way back to the '9s. Some of you

weren't even born probably who are

listening, but some of you will remember

the '90s. And I was using it

specifically for mood stabilizing. This

was towards the end of college, but also

to lean out while building muscle on

something called the cyclical ketogenic

diet.

>> So, we're going to get to that later in

the conversation, but it was

effectively, let's call it, 6 days of

focusing on a ketogenic diet with one

day or a half to threequarters of a day

of [snorts] glycogen depletion and then

loading with more carbohydrates, lower

fat, etc. The reason that the ketogenic

diet became doubly interesting to me is

that when I had Lyme disease the second

time, which came with all sorts of co-

infections like besiosis and so on. And

this isn't

chronic fatigue or depression searching

for a diagnosis that is external. I I

feel like sometimes the cottage industry

of diagnosing and treating people for

quote unquote Lyme disease can be shady

at best. But in this case, I'm coming

from Long Island. Everybody in my family

has had tickborne disease. Wow.

>> And was credibly diagnosed. So the

second time I had lime, [snorts]

>> I got to a point because I I did not see

the bullseye rash. Assumed I did not

have it, which is a mistake because

sometimes you don't see the

dermatological response and you

nonetheless have contracted something

like Lyme disease. I ended up weeks

later slurring my speech. took me

minutes to get out of bed because my

joints hurt so much. Forgetting friends

names and my assistant said,"Tim, you

really need to see someone. This isn't

fatigue. I've seen you sick. I've seen

you tired. This is something else." And

suffice to say, that turned into several

months even post antibiotic treatment,

which I do think is important, of we

could call it pseudo dementia. I mean I

I really felt like I was operating at

10% cognitive capacity and basically at

my wit's end I said well what can I

control because a lot has not done the

job and I went into

strict ketosis. What does that mean?

That means that I'm consuming moderate

[snorts] protein, probably getting at

least 50% of my calories from fat, and

keeping my my carbohydrates to less than

20 gram a day, probably at that point.

And within 3 or 4 days, I'd probably say

around day 3 or four because I wasn't

very fat adapted at the time. My body

wasn't well trained to use fat because I

wasn't doing intermittent fasting, which

we'll come back to. And within 3 or 4

days, effectively, all of my cognitive

symptoms disappeared. And I stayed in

that state through nutritional ketosis

for a few weeks, had complete remission

of any of the cognitive symptoms plus

the joint pain symptoms, and those never

came back. And I recommended that and

this is not a randomized control trial

but over the years due to various

factors we've had ticks growing in

population also expanding to the coasts

and on the west coast that is and

elsewhere had three friends replicate

this with ketosis after suffering

various symptoms from tickborn disease.

And

you know, we were texting, maybe even

talking about this, but I never had a

great explanation for why it worked. I

said, I don't know the exact mechanism.

Maybe I have faulty glucose metabolism

that was somehow maybe something was

impaired by the ticks and therefore I'm

giving my brain this alternate fuel that

it really likes, ketones. But it didn't

explain necessarily the durability of

the changes. Right. In brief, do you

[snorts] have a theory or an explanation

for why that would work?

>> Yeah, I'm glad you brought that up

because quickly dozens if not hundreds

of people with tick born diseases,

including Lyme disease and all the tick

born diseases have communicated with me

and one of the patients is actually

Deanna Tadon who was diagnosed with ALS

and prior to 2010 and has basically been

stabilized,

given three years to live. So, I

realized that it's underdiagnosed. The

the tests to do that are kind of

controversial, you know, with the CDC

testing, the two-tier testing and

hygienics. So, I know I'm going off

track a little bit here, but I think

it's important to say that the spyroet

morelia that spyroet is essentially 100%

glycolytic.

>> And when you limit glucose availability

and glycolysis, you are targeting the

energy systems of that microbe. So,

that's one thing to think about. And

it's well established now. It wasn't

three years ago, but a ketogenic diet,

in particular, beta hydroxybutyrate

elevated in the blood, stimulates the

adaptive immune response. And that's

essentially your body's ability to

target foreign invaders and neutralize

them. And that has become a rapidly

growing area of interest. University of

Pennsylvania, you know, they're doing

CARTT therapy and and checkpoint

inhibitors because of the ketogenic

enhancement of the adaptive immune

response. So, and I think that plays a

role and situationally I have observed

that you go into ketosis if you have an

inflammatory process and Lyme disease is

is inflammatory. But people who have

shingles and herpes simplex and things

like that, I have an inbox full of

people that do that and I would like to

experimentally go down that direction to

understand why. But I think there's two

reasons. You're targeting the energy

systems and you're augmenting the immune

response to keep the spyroet in a

[clears throat] dormant stage or maybe

eradicating it in in some context.

>> It's really incredible on a whole lot of

levels and I'm just lucky that I had the

prior experience with the ketogenic diet

to even have it occur to me as a last

ditch effort. And for people if it

wasn't clear I mean you explained it

clearly but glycolytic I'm simplifying

here but it means that something needs

to eat sugar or metabolize you know

carbohydrates to survive right and there

are also Dom correct me if I'm wrong but

particular cancers that are very

sensitive to being starved of glucose as

well and for people who want more on

fasting ketosis as it relates to cancer

we may come back to it also but we've

had prior conversations about this and

the benefits some of the incredible

effects of fasting prior to cancer

treatments of of various types. So, is

it fair to say, do you think most of the

benefits that someone would derive from

fasting prior to cancer treatments, they

could also get from ketosis or is it

dialed back to

smaller percentage of effect?

>> That's a good question. I think it

requires a nuanced answer that we

probably don't have time for. But if you

are overweight and your BMI for example

is like as many cancer patients tend to

be like 28 30 32 a fasting or a

calorically restricted ketogenic diet is

the way to go. If a patient is trending

towards being lighter like a BMI you

know 20 22 something like that a U

caloric meaning like keeping stable

caloric level to maintain your weight is

going to be important and then elevating

beta hydroxybutyrate

will be important to get some of the

anti-inflammatory effects and also the

immune boosting effects and [snorts] the

neuroprotective effects going into

cancer therapy because there's people

studying ketosis for chemobrain like

reverse hemobrain and like managing

that. So, it has a broad array of

applications, not just targeting, it's

targeting the tumor growth and putting a

break on it, not it's not a cure for

cancer. And I cringe when people talk

about that online, the ketogenic diet

curing cancer. It does slow it down,

especially if it's highly glycolytic,

which 80% of cancers are. And it

enhances and augments the response to

the standard of care, that's radiation,

chemo, and immune-based therapies. We

know that now.

>> All right. So, why have I been in

ketosis for 18 days and why am I doing

it a few times a year? Well, part of how

I implement this does hinge and will

continue to hinge on some of the answers

in this conversation from Tom because

this is very self-interested. But what I

have found is that for mood

stabilization and you mentioned

metabolic psychiatry I've had and you

made the introduction I believe Chris

Palmer out of Harvard on the podcast to

discuss this but there are certain

conditions whether it's depression but

even more squirly when you're dealing

with something like schizophrenia for

instance or different types of bipolar

people who have been on dozens of

medications who go into let's call it

remission or they no longer meet the

criteria right for the diagnosis of some

of these

after being treated on a ketogenic diet

of one type or another. It is

astonishing. And so for my own mental

health, I've noticed complete

stabilization

and without subduing the highs, right?

I've never had mania necessarily. I'm

not talking about that. But I'm not

muted. I feel just calm, stable, sharp.

And that's one reason in and of itself

to do it for periods of time. But I seem

to feel a carryover effect.

Also have Alzheimer's and other neuro

degenerative diseases in my family. I

have three relatives with rapidly

advancing Alzheimer's at the moment. So

maybe we could talk also to how these

things might intersect. But my feeling

is possibly and I'd love your input

here. If I follow a ketogenic diet for a

number of weeks or maybe a month and a

half or something like that, I'd love to

know the timing you might recommend.

Let's say I do that two or three times a

year that there could be enduring

effects that have protective carryover,

right? And I also find it much easier

now that I started doing intermittent

I've been intermittent fasting pretty

much every day for the last 6 months,

which means I'm eating between typically

2:00 p.m. and like 8 or 9:00 p.m. and

having two meals a day. That's it. Not

hungry at all. Like I haven't eaten

today. It's 12:30 my time. I will not be

hungry for another 2 2 and 1/2 hours.

That by itself completely

completely revolutionized I mean that's

an overused word but completely polished

my insulin sensitivity and metabolic

health on a bunch of levels like my labs

have never been better my oral glucose

tolerance test has never been better

>> and one question I have for you which is

just for Timmy Tim but will apply to

other people is is there an argument to

be made and maybe I'm totally off base

but that if

follow a ketogenic diet and make it work

for a multi-week period of time that

you're changing your metabolic machinery

or just your body in some way that has

carryover effects even after you stop

the diet or is that me just doing some

handwavy

fancy footwork as a muggle? I just I

don't know if there's a there there but

what are your thoughts?

>> I would say absolutely. I think the

science is still working to clarify that

and make it less ambiguous the benefits

that we are deriving from that. But that

is kind of like one of the pitches for

the fasting mimicking diet by Dr. of

Walter Longo who was one of our keynote

speakers at Metabolic Health Summit and

he's presented some really compelling

research on that that opened my eyes to

that 5 days of fasting can have I think

he presented at the time even three

months of effects on sort of

cardioabolic biomarkers

>> in his case this would be the fast

mimicking diet so a few hundred calories

a day

>> yeah like 600 you know using his

protocol of various foods kind of

gravitating towards more of a

plant-based lower protein strategy and I

think that it's promoting metabolic

flexibility and ramping up fatty acid

oxidation enzymes and much like muscle

memory I think there's a metabolic

memory the more you stay in ketosis the

easier it gets and the more benefits you

derive from it and the more that you

shift your body to being more fat

adapted

just like you can build your V2 when you

build your V2 max or you build up to

like a 400 lb bench press and you take

like months off and you go back and you

can only do like 225 for a couple reps.

It only takes like two or three months

to get back, but it took you 10 years to

get there. You know, that muscle memory

snaps back quick. And everybody agrees

that there's this metabolic memory. And

I think there's a lot of things at play,

including, you know, gene programs,

epigenetic regulation that comes to

play. So, first and foremost is changing

our mitochondrial function and

mitochondrial capacity. So the number of

mitochondria increase and then when you

take a break and then get that

stimulation again that mitochondria is

kind of there and it responds very

rapidly.

>> So thank you for that and I want to

bookmark maybe we come back to this but

if people are trying to think about this

understanding that the [gasps]

the science right now is maybe

provisional or you know hypothesis worth

disproving at this point but that it

seems to make sense right from an

evolutionary perspective. Yeah. that

both muscle memory and metabolic memory

would be a thing. Otherwise,

it makes sense your body would want to

adapt to be prepared for the next famine

or whatever it might be, right? I just

want to say muscle memory is metabolic

memory. So, someone I gave the analogy

of like lifting weights, but someone who

runs marathons, it's the same same

scenario. They take time off and then

that B2 max quickly establishes again

and it's muscle but it's it's metabolic.

So I like to use the term metabolic

memory.

>> Metabolic memory. Okay. Yeah. Metabolic

memory. Just so people know where I am

at at the moment. And actually, yeah,

I'll just tell people like what I'm

doing because I know they're probably

getting itchy for some just like what

does this look like in practice? And

then I want to talk a bit about

how ketosis or the ketogenic diet may or

may not

be helpful for maybe not treating, maybe

treating. I've certainly seen some

interesting effects in some of my

relatives when I give them exogenous

ketones where suddenly their sentences

are three or four times longer 30

minutes later, which is wild to see. But

in terms of prevention or staving off

the onset of some of these diseases, I'd

love to hear your perspective. But let

me tell people what I've been doing for

the last few months and especially in

the last 18 days. So for the last

whatever it is, I think I mentioned 6

months I've been doing intermittent

fasting. And uh that was after hearing a

conversation between Dr. Dr. Ronda

Patrick, who I'm a big fan of, and Mark

Matson, M- A- T- S O N, who's done a lot

of research related to intermittent

fasting. And the key piece for me,

because you see all these different

types of intermittent fasting, all these

different ways to do timerestricted

feeding, and I am going to paraphrase

here, so Mark, I apologize if I'm

getting this wrong or oversimplifying,

but in effect, it's important that you

fast. This means no calories. Or we

could talk about pure fat, but let's

just assume you're not consuming any

calories for 16 hours because you want

to deplete your liver of glycogen. And

once you deplete your liver of glycogen,

your body experiences this metabolic

switching. And I've certainly felt this

just doing intermittent fasting where my

meals contain carbohydrates later that

around the end of that fasting period,

boom, something switches and my mind is

sharper, right? M

>> and then when I got to the point of

going into the ketogenic diet this time

and also a few months ago because I was

doing the intermittent fasting and it

takes it took me about a week and a half

for my body to to get comfortable with

that at which point it was no problem

but I was a little pissy a little

irritable for a little while a little

foggy and then when I went into the

ketogenic diet this time it was the

easiest transition I've ever had. I did

not have any foggess. I did not have low

energy. I did not have what some people

might call the kind of keto flu adaptive

period, which it seems to be pretty

remediated or or addressed with

electrolytes for a lot of people. But it

was incredibly easy just straight into

the ketogenic diet with no problem

because I was already doing the

intermittent fasting. And then for 18

days, I've been

having two meals a day. And you've

recommended a few that sound, frankly,

pretty disgusting, but that are actually

really easy. Like two cans of canned

mackerel with about 2 tablespoons, 30 ml

of MCT oil plus apple cider vinegar with

some salt and pepper. It's actually

delicious. I just love mackerel. Oh,

there it is. Yeah, you've got your apple

cider vinegar right there.

>> Cheap stuff you can get on Amazon. So

>> yeah, for people who might think, "Oh,

wow. This is what for fancy people who

can do all sorts of expensive things in

their diet." We're talking about like

how much does that meal cost? Three

bucks.

>> A dollar a can for that chicken of the

sea. And literally you get almost a

pound of mackerel. And this is like

third party tested, very low chub

mackerel, the little mackerel.

>> Yep.

>> So $150 for almost a pound of mackerel

that you can get that for. Like you

can't And the omega-3s are off the

charts. the heavy metals are low. You

know, I consume pounds of this stuff and

I've gotten my blood and my hair heavy

metals tested and it's like like super

low, like non-detective. So, I wouldn't

worry about that. People have questions

about cost and heavy metals and that's a

non-issue, you know, for me. And maybe

you could mention, I'll put links in the

show notes as well, but since we're on

the topic, any any brands that you

default to that you like and that chub

mackerel piece for folks that detail is

important cuz there are mackerel of many

different sizes.

>> Yeah, King mackerel is kind of high.

This is chicken of the sea. So, if you

want to do the budget, you buy the case,

the more you buy and then Amazon

subscription and then it goes on sale.

You can actually get it for like less

than a dollar a can. And I do the same

with chicken of the sea jack mackerel.

Just chub mackerel or jack mackerel. So

they're both small fish. And I kind of

like the King Oscar brand, too. Yeah.

>> Just a little bit more pricey. And

Season's brand is pretty good, too. But

I mean, it's like as cheap as dog food.

[laughter]

>> I mean, we buy some pretty fancy

freeze-dried. We don't buy the kibble

stuff, but when you run the numbers,

>> it's very inexpensive. We buy cases of

eggs for like 120 per, you know, if you

do like eggs, fish, beef, and also

turkey. You can get turkeys for under a

dollar a pound, the whole turkey. And

just for people who are like, "Oh my

god, I can't believe you guys are eating

mackerel mixed with oil and vinegar in a

dog bowl." That's not all you can eat.

Like, there's more that you can eat. You

can have like chicken with cheese on it.

You can have vegetables. There are

certain things you have to watch out for

so you're not whacking yourself out of

ketosis. But in my particular case, I

don't mind. And the fact of the matter

is when I wrote the 4-hour body, people

were like, "Oh my god, you want us to

repeat the same meals over and over

again?" I'm like, "What did you have for

breakfast the last 5 days?" And they ate

the same damn thing. You're just

swapping out to fall meals. So my first

meal is something typically pretty

small, like the the mackerel I

explained, and then I have a big meal. I

might have some more protein in between,

but it's like yesterday I had lamb chops

that were delicious with some vegetables

made in an air fryer. No problem, right?

And later on, I might have like a ribeye

chopped up on a big gigantic salad with

some other stuff added to it, but that's

about it. You have to be careful with

the macadamia nuts. Those things will

creep up on you. But that is in effect

the diet, right? And I'm doing my

training. I'm doing my rehab. I'm doing

my zone 2. I do find I'm a little,

let's say, lower performance when I'm

when I'm in ketosis. But what I wanted

to talk about is

maybe a false negative that I've

experienced. And I'll explain what that

is. So, how do you know if you're, and I

keep putting this in quotation marks,

like quote unquote in ketosis, right?

Because most people are, or maybe all

people are producing some level of

ketones. So, there are different

concentrations, right, that you can

measure with a finger prick, just like

you would look at glucose. And at least

with the finger prick, I think that's

measuring what you mentioned earlier as

being so beneficial in a lot of studies,

the beta hydroxybutyrate, BHB.

>> Mhm.

>> I also have because I wanted to run this

tracking, a G7 Dexcom continuous glucose

monitor on one arm and then a SI bio,

apologies, I'm not pronouncing that

correctly, continuous ketone monitor on

the other arm. And I'm wearing an Aura

ring when I sleep to see how all of this

affects my sleep architecture and

everything else. So, I'm gathering all

this, but then I notice something really

weird, which I've texted you about

because I I keep feeling like I'm

failing at keto. I feel great. I feel

sharp.

And yet, when I look at not just the

continuous glucose monitor, but even

with the fingerprint, because you do

have to often calibrate these things,

right? Don't assume that your continuous

monitors are accurate. You want to

calibrate them. But I'm looking at the

numbers and for instance, my girlfriend

freaked out the other night because my

phone started screaming. I had earplugs

in cuz I didn't hear it and it was like

critical medical alert or whatever the

code read was because my glucose was 69.

I suppose it's gotten quite a bit lower

on ketosis, but you know, usually hovers

somewhere between like 65 and 80. And my

ketones were 0.2 millmers. Now, when

we've talked in prior conversations

about what kind of target you might aim

for, it seems like, you know, between

1.2 and 2 millmers is anxolytic, right?

Lowers anxiety. And then you're looking

for this ratio. You could talk about

this, but the GKI, there's a ratio of

glucose to ketones. And I look at those

numbers and I'm like, this makes no

sense to me because I'm not getting

enough glucose to function well. And if

I'm basing it off of the Keto Mojo

finger prick, even the precision extra

from Abbott or my continuous ketone

monitor, I'm not getting any ketones

either if you're taking it at face

value. So, how am I functioning?

[laughter]

How would you answer that? Because I

don't think I'd be the only person who

feels like they're doing something wrong

if they run into this, but how would you

interpret this? I would definitely say

you're running lean and I think what

you've done and your O GT test is really

good. I think you had messaged that.

>> And the O GT for folks is just that oral

glucose tolerance test where you drink a

bunch of dextrose water and then they

take your blood every 30 minutes for two

hours to see how you're responding to

it.

>> Yeah. The biggest metabolic lever would

be you have enhanced insulin sensitivity

and I think that has been the focus. For

example, Ben Bickman wrote a book on

this and you know doing hundreds of

podcasts on insulin resistance,

reversing insulin resistance and low

carb ketogenic, you know, being

effective for that. So that first and

foremost, your insulin sensitivity is

very high, your fat oxidation is really

high and your glucose disposal is high.

And if [snorts] you're in a caloric

deficit, your ketone uptake is very

high. We see this quite convincingly,

you know, in older rats where we like

gavage, where we tube feed the rats and

they're older, the ketones get to toxic

levels, whereas like a younger

metabolically fit rodent will dispose of

it very quickly. Same with a couch

potato human, same with an elite level

athlete. So you have very rapid. So when

you measure ketones in the blood, that's

a function of ketone production and

ketone utilization. And you could have

two to five times higher ketone

utilization, you know, with high

metabolic fitness. And that's due in

part to ketoytic enzymes. The you

upregulate the MCT transporters that

could be two or in rodents two or three

times higher. We I haven't done that

personally and we have some data in

humans we haven't published yet, but

that is a real thing and I think that

you're experiencing. Also, I if you're

in a caloric deficit, there's less

spillover. I just bought like an antique

motorcycle and it's got a carburetor and

the float sticks a little bit and it

always drips out the carburetor when I'm

running it and when I stop and it's like

kind of pouring out the carburetor so

there's spillover of fuel, right? So,

but when I'm running it, it's running

lean because I'm using I'm using the

fuel that's kind of going to the

carburetor. And kind of the same analogy

here is that, you know, for example, it

might be good to just sit in one spot

and relax and maybe eat a little bit of

surplus calories or even eat a little

bit of carbs. And what you'll see often

is like your ketones spike up. Yeah.

>> So I remember some of my highest ketone

levels ever is when I consumed

[laughter] carbohydrates after I was

fasting or in a state of keto, it like

jumped up to 5, six, seven. I was like,

what is going on here? But the glucose

in that context is ketone sparing. But

the glucose will also shut off

ketogenesis. So it'll tank you know

after but

>> afterwards. So it sounds like then

because of probably the intermittent

fasting in large part I would think if

my insulin sensitivity is high enough

that can be paired with higher ketone

utilization. So if on the assembly line

of my body right they're producing 10

units of ketones. If I didn't have good

ketone utilization and it was my first

rodeo with ketosis, let's just say, or a

ketogenic diet, the finger prick might

pick up all 10 of those units. I'm

simplifying here, right? But if I have

high ketone utilization and my body's

quickly using eight of those, especially

in a caloric deficit, then it's only

measuring two and I'm getting the false

negative that I'm not actually producing

ketones in the first place. Is that a

fair, very, very simplified description?

And you're not measuring tissue levels

of ketones, which we have done too, even

in the brain. And that can shoot up like

really high also. And I've done this

with Peter Aia too. We were measuring

blood and then breath. And it seems like

when we were in a caloric deficit

fasting, our ketones were like really

low in the blood.

>> Low is [clears throat] like one to two,

but we're like really deep into fasting,

whereas our breath ketones were maxing

out the meters. We kind of concluded

that after a lot of testing that the

breath ketones were almost a better

indicator of ketosis, a more accurate, I

guess you could say in a caloric deficit

because when you're in a caloric

deficit, you just have very high ketone

disposal uptake into the tissues.

>> It looks like a breathalyzer, right? So,

is that measuring what is it?

Accetoacetate. No, I'm just trying to

repeat words that I've heard once or

twice, but it's not BHB.

>> Acetone.

>> Acetone. God damn it. All right, I know

I was close. That was It was a 50/50.

>> Comes from the spontaneous

decarboxilation of accetoacetate. Like

we'll spit out about 20% of the

acettoacetate will kick off to acetone

and then you can measure.

>> I got it.

>> We've measured blood levels of each and

it's very tricky to do that, but we've

done it in the lab.

>> All right, here's another practical

tactical question for you because I've

gone back and forth on this and Uncle

Chad GPT has confused the out of

me. So maybe you can help resolve it.

gluconneogenesis

and protein intake, right? So, you

consume what is it between like 200 240

grams of protein a day? Something like

that. Is that roughly?

>> Yeah. On active days, on like less

active days, if I'm just behind my

computer all day, maybe closer to 180

200, but yeah, generally speaking,

>> and people might have picked up when Dom

was casually throwing around like, you

know, when you've been squatting 400 and

you take a break and then you go back

and you only could squat 300 lb. Tom's a

pretty big guy who's also deadlifted 500

lb for like 10 reps before after fasting

for a week. So, he and I [snorts] are

not the same size. But, nonetheless, I'm

trying to figure out on one hand how

much protein I can eat without my liver

taking excess protein amino acids and

turning it into glucose. Right? And

depending on what I look at and I have

looked at sources outside of chat GPT on

one hand there are folks who say don't

worry about it if you're consuming

enough fat you really don't have to

worry about it and then there are other

folks are like watch out watch out if

you consume more than x number of grams

at a given meal you can very easily

knock yourself out of ketosis which

would if that's true be maybe an

alternate explanation for why I'm

getting these low readings if I'm having

a small meal around 3 and then a

gigantic meal later on. How should I and

how should listeners think about this?

>> If you were to consume protein in the

form of liquid, for example, like whey

or something like that, then the the

rapid entry of amino acids into your

bloodstream from your small intestine

will shut off ketosis. So fat and fiber

and salt because your pyloric sphincter

will basically be pretty tight until

your stomach

>> talking dirty dumb

>> pyloric sphincter where your stomach

connects to your small intestine. If you

have a very fatty, salty, high-fiber

meal, that little that entryway, we call

that the sphincter. It's the pyloric

sphincter will remain shut until like

the contents of your stomach become

isotonic which means that your body has

to kind of give up water and it's got to

churn it and break it down. So you could

delay gastric absorption simply with

fat, fiber and salt is pretty good too.

You could do ketone salts or just salt

electrolytes. So that will delay the

entry of amino acids or protein into the

small intestine and thus amino acids

into the bloodstream. And that's the

major regulator of ketosis, you know,

having an impact on insulin and also

having impact on glucanogenesis to that

rate of entry. And if you can slow that

down, you see nothing on the CGM and

your ketosis levels can basically stay.

You could further augment that by using

MCT oil with the protein and the fiber.

And so if you have longchain fats from

like a fatty steak and MCT oil and then

fiber and that could be insoluble fiber

is pretty good to soluble and insoluble

that can slow the entry of amino acids

and essentially buffer the glucanogenic

response.

>> So let's say I was stuck in San

Francisco late. I'm just taking a rare

trip over here.

which is pretty exciting time to be here

with all of the mania with AI going on.

Everyone's kind of drunk on the

Kool-Aid, but that's a separate story. I

got trapped downtown because didn't want

to deal with traffic and blah blah blah

blah blah. So, I ended up having a huge

bunless double cheeseburger, like

gigantic. This thing, I did not expect

it to be as big as it was, right? And so

I go online to try to figure out what

the protein content of this thing might

be. And it's like 80 gram of protein,

[clears throat]

>> but plenty of fat, certainly tons of

fat, salty AF, plenty of salt, not a lot

of fiber. We'll give that one a pass.

Should I be worried about something like

that knocking me out of ketosis?

>> I think you need to measure. So, I'm

kind of default back to like everybody's

a unique metabolic entity. But if you

eat that and kind of your activity level

is high and you're in a bit of a caloric

deficit and you were to have that and

sort of not overdo it on the total

calories, I know my body. I know my

body. I could stay in ketosis.

But if you have that oversatiated

feeling, so we have we have neurons, we

have neuronal pathways to and from the

liver and to and from the gut. We call

that apherant and epherent signaling,

right? and the entic nervous system and

a big meal will basically tell your

brain that you had a big meal and

independent I talked about the amino

acids going into the bloodstream kind of

kicking you out of ketosis but there's

also like this when you have stretch

receptors and you have a big full meal

in your gut then that could actually

tell your brain to activate the

sympathetic nervous system and then that

by virtue of spilling out catakolamines

can basically like we're talking adrenal

epinephrine, things like that that can

further augment and enhance

glucanogenesis. So,

>> okay, let me just translate that for a

second. So, people wake up, cortisol's

developed this like bad reputation among

a lot of like online influencers, but

it's like you really need cortisol,

right? So, when you wake up in the

morning and you see a bit of a glucose

spike, like it's actually important to

get your ass up and moving. If you're in

ketosis, it's a different thing, right?

So, if I'm hearing you correctly, right,

outside of how people think about

digestion,

blood sugar, insulin, etc., that just

based on stretching your stomach, etc.,

right, with these mechano receptors

taking the inputs that that signals to

the brain, it's go time. So, let's

basically get things moving with with

these hormones. And that could in and of

itself then trigger the liver to produce

more glucose or liberate more glycogen.

I guess

>> it can if it's above and beyond what you

normally eat.

>> Yeah. Yeah,

>> if you train your body to that size

meal, but it also activates other gut

hormones like choleiccytoinine that's

called CCK and other things that can

then activate the parasympathetic

nervous system that comes in a little

bit after. At the same time, it sort of

kind of bifurcates, but then the

parasympathetic nervous system is sort

of relax, digest, rest and relax,

digest. So that kind of comes in after.

So you might see a blip and sort of

might feel kind of stimulated. Also all

the salt if it's a salty meal, it's

going to expand your plasma volume. Your

blood volume will increase and that can

increase your blood pressure a little

bit and that can activate your

sympathetic nervous system. So it's

always good to go take a walk after a

big meal.

>> Yeah, I do that. Not like a strenuous,

not like go squat and deadlift, but just

yeah, even a 10, 15, ideally like a 20

minute brisk walk is really good after a

big meal.

>> Let me ask you this on the walk timing.

So when I have a big meal and I will say

I think I have trained my body to have

big meals and what the exact response

is. I can only give you subjectively

what I feel and I can give you what the

monitors show. But I typically feel

pretty good. However, if I have a big

meal, whether this is in ketosis or

otherwise, I don't see the biggest spike

until something like depends on the

meal, right? But 60 to 90 minutes later,

that's when I see the spike. So, should

I do the walk at 60 to 90 minutes or

should I do the walk right after the

meal? When should I actually time the

walk?

>> So, you eat a meal, you go walk, and

then you see the rise 60 to 90 minutes

after, or is that independent of the

walk?

>> Independent of the walk.

>> Okay. So, you're not walking, but you

see the rise 60 to 90 minutes later. So,

I'm I'm saying that you might not see

that rise 60 or 90 minutes later

>> if you did it right after the meal.

>> Yeah. Just because a little bit goes a

long way. So, just like walking actually

doing like some stretching and walking

too, it activates the glucose 4, the

glut 4 transporters.

>> Yep.

>> That's insulin independent. So, less

insulin is dumped, greater glucose

uptake. And you're also using sort of

the sympathetic nervous system

mobilization of glucose through

glucanogenesis during that walk. So it

then attenuates the buffering of

ketogenesis. A very short walk can go a

long way.

>> Okay, cool. Yeah, the is it glut? How do

you pronounce that? I don't know. How do

people say that?

>> I say glute. I say glute for.

>> All right. Glute for

>> people say glut.

>> Yeah. For the OGs in the audience, go

back and look for glute for in the for

our body. It's in there. So the other

measurement question I want to ask you

about which is you know these continuous

glucose and ketone monitors are not

designed for someone like me, right?

They're developed presumably I don't

know about the keto monitor but in the

case of glucose to help people with

serious conditions not end up in very

serious situations. So when I am looking

at my ketone levels right like right now

I feel very sharp. I had some keto

start. You know this well. Exogenous

ketone saltbased

product not too long ago just in hot

water with a little bit of MCT oil. This

was I guess an hour hour and a half ago.

But I'm at 0.4 millmers. And I guess

what I'm saying is whether I have a huge

meal or I'm fasting as I am right now my

range is basically 0.1 to 0.4 4 95% of

the time. There are a few outlier cases.

If I'm just doing like a yolo, you know,

as many grams as possible

exogenous ketone party, then maybe I

could goose it. But we can talk about

this. Like once it gets past a certain

point, then I might spike insulin and

have a subsequent crash. But I guess

what I'm trying to say in brief is my

range for the most part is 0.1 to 0.4

for regardless of whether I'm fasting or

eating a gigantic double cheeseburger.

So, I'm not really sure how to determine

what effect it's having. I can watch the

glucose, but you know, right now I'm 0.4

millmers of concentration on the side

bio. And as we've talked about, maybe

maybe the precision extra would give me

an extra.1 or two, but they've been

pretty close so far. And then ever since

my cheat meal, we had this experiment,

right? I wanted to see if I did a

workout and then had one or two cheat

meals last Saturday. It is now Thursday,

but my glucose right now is is 103,

right? Which is which is higher than the

week prior.

>> Mhm.

>> But it goes [clears throat] around. It

moves around. Last night it was probably

70 something. Do you have any

suggestions for how to read the tea

leaves or is it mostly just subjective

feel? I mean, still thinking about the

size of the meal. I guess what I'm

saying is if my device is telling me as

it is right now, right? 0.4 fat not

burning. You're almost not burning fat

at the moment. Not in ketone. Like, it's

very chastising. So, if I'm to believe

this by the letter of the law on the

screen, I'm failing at ketosis. Any

thoughts on how to kind of read the tea

leaves here?

>> I would kind of ignore that. I think

that's sort of an app in the process of

being sort of developed the fat simul.

Yeah. So you would need like whole body

metabolomics to really answer that

question if you're in fat burning or do

metabolic cart and look at respiratory

quotient or whatever. But

>> subjectively if you feel good we have

seen like in athletes especially more

advanced athletes that and we do a very

strict keto macros and everything that

basically with a bunch of athletes 0.8 8

is about as high as we get and that's

the average across sometimes you get

guys like 2.5 2.6 six like every day and

the same guy with the same you know

essentially metabolic phenotype will be

running 4.3 he could potentially just

have greater ketone

>> utilization

>> utilization so I think it would be

important to measure your blood so a

continuous ketone monitor measures

interstitial

>> ketones that can be different the bio I

think it's a great device it's very

versatile I can kind of you know jump in

and out of salt water the thing stays is

on me. It's I almost like more reliable

than a CGM. But I did notice and I

probably used about 50 of these devices

that the first week is pretty accurate

and then it tapers off the sensitivity.

And this is a known limitation of the

technology is that essentially the the

enzymebased sensor system tends to just

de and you could get around that

conceivably just by having the ability

in the app to calibrate it. Mhm.

>> So, if you were to measure it and the

continuous ketone monitor is measuring

1.0, but your blood ketones is 2.0, that

you should be able to calibrate it like

you can with a Dexcom.

>> So, they acknowledged that at the

company and they said, "Yes, we realize

that would fix the problem, but that's

not a feature of the app yet."

>> They do have in events they have blood

ketone on the bottom right. I don't know

if it actually calibrates it. It may

just record the blood ketone at this

point. It does not have the ability to

calibrate it to my knowledge.

>> I inputed one measurement on the the

Keto Mojo and it didn't seem to change

it, right? The number stayed the same.

No.

>> So, I think it's just logging it

>> because you can do that with a

glucometer.

>> Well, you can do it with Dexcom.

>> Dexcom,

>> but not Abbott.

>> Yeah. Okay.

>> So, that's a problem with the Abbott

Freestyle, too. And that's a feedback I

gave them because I put these devices

on, it's reading me like 130. Yeah.

>> But I measure I'm like 80. It's

literally like 50 because

>> Wow. If you are lean and it's stuck in

your muscle instead of your atapost

tissue,

>> oh, [groaning]

>> the glucose levels are going to be

higher, especially like when you work

out and stuff.

>> So, I've noticed this and that's why the

Dexcom is very nice because I can

calibrate it too. Yeah.

>> And I consistently show that and that

was a major issue I had. Let me hop in

also and just tell folks this is not

going to be very quantifiable, but for

what it's worth, part of my reason I

avoided intermittent fasting for so long

is that I thought I would not be able to

get sufficient protein or caloric intake

and that I would lose a bunch of muscle

mass. I was dead wrong about that. I was

very very wrong. If anything, it seems

to have enhanced my ability to put on

muscle kind of per calorie or per gram

of protein ingested. And so, I admit I

was totally wrong about that.

Furthermore, on this ketogenic diet

where I've historically found it pretty

hard to put on muscle or I shouldn't say

keep muscle because I'm only doing it

for a few weeks, but I have been

astonished by having one small meal.

Like I'll have some oxtail soup after

this with some veggies and and obviously

oxtail.

It's a whole separate story. And

[laughter] then I'll go out and have

another meal probably in like 3 or 4

hours which will be a much bigger meal.

And just with that, and I am watching

some of the grams of protein intake and

so on, but I have not looking in the

mirror and looking at the weights that

I'm putting up in the gym, I don't feel

like I have lost any muscle and I feel

like I have leaned out. Some of that's

losing fluid, but I've been really

impressed with how little relative to

what I used to do in college, like

taking weight gainers and just all this

garbage. like how little it actually

takes to at least maintain muscle mass.

But I do have a question for you which

I've never really been able to answer to

my satisfaction and it kind of relates

to rabbit starvation.

For people who don't know what that is,

you could probably give a better

description. But if you've ever watched

the show Alone, Alone is probably the

only reality TV show that I love to

watch. Seasons six and seven in

particular are outstanding for folks.

But what you will notice is that if

people are trying to survive in the

wilderness to outlast everyone else,

that's what the show is. You get to pick

a handful of items, you get dropped off,

you don't get to choose where you're

dropped, and then you just need to

survive for as long as possible.

Sometimes it's 100 days, sometimes it's

last man or woman standing. If somebody

is only eating lean protein like

rabbits, they will waste away. They will

not last. They will have to get yanked

out for medical reasons. And that might

seem strange to people. My question

though is on a ketogenic diet

specifically, can you just consume

leaner protein and then rely on body fat

for the fat? And some people are like,

"Yeah, everybody knows that doesn't

work." But I really want to understand

why that's the case, right? Because I

understand dietary fat sort of dampens

insulin response, or at least that's my

understanding. Maybe there's a rate

limiting step in how much body fat you

can break down and use, right? And who

knows if [clears throat] that's mediated

by the kidneys or who the hell liver, I

don't know, right? I guess it would

probably be liver. But I'd love to hear

your take on it, right? Because

certainly in the past, I and lots of

people reading the 4-hour body have been

able to lose more body fat than they are

told they are capable of losing as

measured through DEXA scans and other

things. Can you do a like moderate fat

or low-fat proteinbased

keto diet if your goal in part is to

lose body fat or does that backfire?

>> Yeah, just not indefinitely. So, when I

was did the ketogenic diet for a year, I

was cruising about 300 to 320 gram of

fat, sometimes 350 grams of fat per day.

And then just experimenting, I would

throw in two days per week of protein

veggies

>> with about 50 to 100 grams of fat. And

in those days of dropping to 300 plus

grams of fat to 50 to 100 grams of fat

after two days like I swore like I lost

like a 2% body fat like in that and I

would just transition back. So I would

just periodically throw in protein

veggie days. I would cruise on keto and

then periodically titrate in the protein

veggie days to assist body composition

alterations. And if I kept that going, I

could get pretty dramatic like almost

scary lean to where it happened very

fast. It's almost keto trains your fat

metabolism. And then if you just start

titrating in, it's just pulling fat out.

And I think my body really liked

throwing in the veggies with the fiber

seemed to help with gut health. And I

would do that twice a week and it's

pretty dramatic.

>> Why not do it seven days a week? What

happens when you try to do it for more?

>> If the idea is to stay in ketosis, it

was really hard for me to stay in

ketosis if I do protein veggies. Like

after 2 days, I would kind of be out,

but my metabolism would be cranking.

>> Mechanistically, why is that the case?

Why doesn't your body just break down

more body fat?

>> Well, it's taking body fat exogenously

and endogenously. And I think the more

fat going to the liver, you know, and

the more fat that's in circulation gets

sort of shuttled to the liver and then

that's sort of stimulating

beta oxidation in the liver. You just

have a greater fat pool. But actually, I

think the day that I would do protein

veggie days and then the day I would

jump back into ketosis, I would see this

big ramp up in ketones like that day.

Whereas, if I did like a cheat day and

just ate a lot of carbohydrates, it took

me like two or three days to get back

into ketosis. But if I just did like

protein and veggies

>> and cruise back into ketosis, then I

would rapidly get back into ketosis and

just gave my body a break from from the

fat. But I think just that short amount

of time really stimulates mobilization

of fat from your body because your body

is used to getting it exogenously and

then you're pulling more fat off. But

yeah, I think on the protein veggie

days, I'm getting higher amounts of

calories from protein. So that has a bit

of an anti- ketogenic effect. Yeah. And

then shifting back into ketosis on that

third day, I always had probably the

best, you know, ketone numbers for the

week. I don't want to beat this dead

horse too long, but I'd love to just

hear you riff on this a little bit more

because I guess in my mind I'm thinking,

well, on your protein veggie only days,

if you're getting not enough protein to

satisfy all of your resting metabolic

rate, right? Like you're hypoc caloric,

but you're getting enough protein to not

lose muscle. Why wouldn't the body just

break down the fat that it needs to

continue producing ketones? Right? So,

I'm trying to avoid the gluconneogenesis

problem where you're having like 200 g

at a meal with no fat to offset it. But

if you're having smaller amounts that

are slowly digested, but it's just

enough to keep you from losing muscle

mass, maybe you're doing some weight

training to help with that, you know, or

whatever, then I guess what I'm trying

to figure out is why the dietary fat is

so important because I think of the

body, right? It's like each pound of

stored body fat is what?

>> 3600 calories,

>> right? So 3,600 calories,

that's a decent amount of calories,

right? And for for somebody who's let's

just say you're 150 lb 10% body fat.

Okay, you got 15 time 3600 you got

plenty of body fat to go around. So it

would seem to be enough to do a few

weeks of ketosis

that is low fat, higher protein, but not

enough protein to necessarily be

hammering your liver with

gluconneogenesis if you're dividing it

up slowly digested protein. Some people

are going to be really annoyed with me

dragging this out so long, but why is

dietary fat so important?

>> Because I mean that's the fuel that that

you are using. You coax your body into

using. And I should probably add a

little bit of context to my protein

veggie days. So I would go from like 125

grams of protein to like 300 grams of

protein.

>> Right. Right.

>> That's a pretty big bolus of protein.

>> That's a lot. Yeah. And if one was to go

100 grams of protein or whatever and

then bump it up to like 170 or 200 or

something, they may not, you know, kick

out of ketosis, but I remember just

lower ketones, but not out of I was

still in ketosis. Yeah.

>> But typically how I think I did it my

protein veggie days were following like

a heavy deadlift or squat workout. So

the thinking was that I'm recovering for

those two days and the extra amino acids

and proteins and mTor activation is sort

of assisting in recovery and

regeneration and skeletal muscle protein

synthesis and then I would kind of go

back I calculated it in that way. So

yeah I like doubled the protein on the

protein veggie days but my calories were

about the same or maybe a little bit

lower. Yeah, I need Sibio, if you're

listening, please allow me to calibrate

this with a finger prick because I need

a little more range. [laughter]

I need a little more range than 01 to 04

for me to be able to read this type of

thing effectively, right? Because

technically, if I'm reading this as it

is, like I'm never in ketosis. I

shouldn't say never. That's not true.

But in any case, it would be nice to be

able to calibrate. Let's come back to

something I promised that I would ask

about which is neurodeenerative disease,

Alzheimer's, etc. Could the ketogenic

diet benefit people with these

conditions? And just as important,

certainly for me personally, is it

plausible there's a mechanism by which

the ketogenic diet regularly done could

help delay the onset of any of these

diseases or am I just polyiana hoping

for a pie in the sky? I think that's a

question we don't have an unambiguous

answer to, but I think all the science

points into the direction that if you

improve upon and optimize your

cardabolic I like to say cardioimuno

metabolic biomarkers instead of cardio

metabolic biomarkers because if you can

lower for example your insulin and keep

that between 2 to six and if you lower

your HSCP

below 0.6 6 and then optimize your

hemoglobin A1C, your glucose. And I

think also, and I've talked about this

with Rhonda Patrick and other people,

too, that if you measure your omega-3

fatty acids and look at your omega 3 to6

ratio, I think that's going to be a

biioarker that's probably going to end

up in standard blood work because it's

so compelling, the data behind it.

>> And you also measure your B12, too. I

think that's important. people coming

into the Alzheimer's center that can

present as flatout Alzheimer's disease

and then you correct their B12, a B12

deficiency will cause brain atrophy. So,

and that could be reversed with B12. So,

the things that if you're following

ketone metabolic therapy, it's impacting

the things that we know are driving age

related chronic diseases and then you

know obviously one of them is

Alzheimer's. So the level of

inflammation HSCRP now is probably more

aogenic than LDL. Like there's probably

people selling statins that don't want

to hear that, but we know that the data

is emerging on that now. So lower

insulin, lower inflammation,

>> and that's an inflammatory marker,

right? The C reactive protein. What does

the HS stand for? Or what is that?

>> High sensitivity. C reactive protein.

>> High sensitivity.

>> So it measures in that lower range.

And I used to trend to like two to two

to three. Like my early CRP, HSCRP, when

I was like on a high carb, I only had it

measured twice when I was on a high carb

diet. But, you know, since I've been

keto, it's either non-detectable or like

0.2 or when I did extreme environment

research on myself, you know, then I

could bump it up a little bit. And when

I had

>> a bacterial or viral gastroenterteritis,

it shot through the roof. So because it

activated your immune system but

generally that HSCP

>> is a big driver. I used to laugh at it

and be like ah it's this nonsensitive

thing but now like all the data is

pointing to the direction that we need

to add that to that and your omega-3

status your B12 make sure you don't have

any deficiencies because that could lead

to sort of rapid progression

>> to Alzheimer's disease your magnesium

levels

>> but also just in general like exercise.

>> Yeah. the biggest metabolic lever and

your body weight, body composition. Get

Dexa scans. I know it might be good for

you to do a DEXA scan with your keto

experiments, too. So,

>> yep.

>> I was doing once a year, but now I end

up doing like three or four times a year

because I do these many experiments to

see how acutely some of the things are

impacting my body composition

>> because I I just get antsy for like an

answer to that. Mhm.

>> It's a long-winded explanation to just

basically say that your your metabolic

health is tightly linked to your brain

health and can dramatically delay the

onset of Alzheimer's disease. Not that

you're going to get it or reverse it

altogether before something else gets

you in the end.

>> The metabolic health piece, just to

underscore that, I mean, one of my

relatives in question, ApoE3, I

understand that's not the only risk

factor, but there something just seemed

to be missing, right? Because the

decline was so precipitous, it didn't

map to any

patient data or clinical data that a

number of doctors who are also

researchers I was working with had seen.

Also, because this person, this relative

had been assessed four or five years

prior and did not show any indication of

predisposition to a rapid decline. I'm a

boy E34. again recognizing there are

other factors at play but when she just

kind of disintegrated a few things there

are a few things that came to light

number one is her local GP had basically

missed severe metabolic dysfunction for

years and I can't remember the reference

range but like insulin let's let's call

it upper bound of 12 I'm making this up

but you'll get the idea and she was like

43 right it was just absolutely

atrocious

>> and her body weight and just general

like composition.

>> Poor body composition. Yeah. Poor body

composition. Very little exercise

despite my best efforts. Misbehaves

horribly dietarily. Not morbidly obese,

but certainly

>> smoking, alcohol, other drugs.

>> No smoking or alcohol.

>> Okay.

>> But here's the other piece. So she had

been diagnosed stage one breast cancer

had a lumpctomy was removed late7s was

put on an estrogen I think it's an

estrogen blocker called let

looked at this and I spoke to a friend

of mine who was a radoncologist and she

said it is very poorly tolerated by most

women from a cognitive perspective like

they get smashed by and large

>> guys too by the way guys. Yeah, guys,

too.

>> Guys that take aromaticase inhibitors,

you know, for like TRT and things like

that. It's it's not a good thing to do.

>> So, I was looking at it and I mean it's

upsetting that I'm the one who has to

kind of find these things. But it's

like, okay, well, we think about the

oncologist role. It's to prevent my mom

from dying of cancer. That's the

directive, right? But if she were 30 and

had later stage cancer that was really

aggressive, it's one thing. But she's

late 70s, stage one, all cancer removed.

and so got her off of the letol with the

cooperation and after discussions with

doctors and almost saw an immediate

turnaround within a handful of weeks

after the wash out period and everything

but it seems to I mean look I'm not an

MD I don't play one on the internet but

it seems to have done some real damage I

mean there's the metabolic piece that is

very non-trivial but the the

acceleration of decline was just so

absurd over the course of a handful of

months. Terrifying to see. But I guess

I'm laying this all in not necessarily

to explore this particular case because

I've got a lot of people on it for all

of my relatives, but it's just to say

that I am not going quietly into the

night with something like Alzheimer's,

right? And so what I'm trying to figure

out for myself, I'd be curious to hear

your perspective. I will be honest, I

find keto pretty goddamn boring. like I

don't find it to be the most diverse

diet in the world. I don't really want

to do it all year round. I also have

some maybe compromising

cardiac elements. Uh I'm a cholesterol

hyperabsor so I do I use again guys talk

to your doc. Don't just copy me but it's

like I'm using rapatha taking a zetto. I

have been also taking nexet but that

might end up being redundant the bidolic

acid with the rapatha. That is a a long

way of saying like I got to keep an eye

on the heart stuff because

neurodeenerative disease and

cardiovascular disease is what's kills

everybody in my family. So, for a lot of

reasons, I don't want to do keto all

year, but I'm trying to figure out like

what is the sort of minimal effective

dose

that [clears throat]

and I know we're going to have to

probably take a couple of speculative

leaps here, but just as a working

hypothesis, right? What does a minimum

effective dose of following a strict

ketogenic diet look like for me?

assuming the rest of the time I'm still

doing intermittent fasting. I'm not

eating a lot of refined carbohydrates.

But how might you suggest that I think

about that? Because I don't know what

the durability of kind of keto memory

like metabolic memory is. So, I'm trying

to figure out like can I get away with

two three to four week periods a year

where there's some carryover of like

cancer protective

you know our last conversation we kind

of talked about thinking about ketones

as hormones but in terms of

neuroprotective anti-inflammatory yada

yada yada what are your thoughts

>> well I think in your context it's hard

to say like you know to give absolutes

but I would say you can get 80% of the

benefits

with a low carb diet. Low carb meaning,

you know, 100 grams a day, just fibrous,

non- starch, non- sugar carbs, low carb,

Mediterranean, if you want to call it

that. And then periodically, maybe one

one week out of a month, get into a

deeper state of ketosis and higher is

not better. We know that from the

research. When ketones get into that

two, three, four, five millmer range,

that creates energy toxicity and

something we call reductive stress. And

that that is not good. I did not know

this before getting into this kind of

research. But the sweet spot seems to be

between one and two for therapeutic

ketosis. Unless you're metabolically

managing a disorder that's highly

responsive to a ketogenic diet, like you

know, neuromabolic diseases and and some

of the things that we actually study

need to be in the two to three millolar

and and oxygen toxicity needs to be like

four to five because it's a very

powerful seizures. [snorts] But one to

two seems to be the sweet spots for

metabolic management of many different

things. and also just general metabolic

health. And I think what you'd be doing

just doing low carb and periodic ketosis

is just enhancing your metabolic

flexibility and maybe increasing the

diversity of food that you're eating to

prevent micronutrient deficiencies too.

I am of the opinion that plants are good

for you to eat. broccoli, asparagus,

salads, you know, colorful vegetables,

things like that that kind of fit into a

pattern of eating that we've known. Even

things like lentils are probably good.

Lentils actually have like zero CGM

response to me.

>> Really?

>> Yeah. Lentils seems to like skyrocket

other people that I know. I'm like

completely flat.

>> I'm like somewhere in between. Yeah, I'm

somewhere in between.

>> Like completely flat. I don't know.

Maybe it's the time of day that I have

them at dinner. Then I always go take a

walk, but it's like no bump at all

>> in my CGM. And I think that's where CGM

comes into play. And we can do a

personal precision

engineered diet, if you will. And it

gives us insight into the types of foods

and the amount of foods that we can eat.

And I think that's going to be really

important information. And I know

there's a lot of people harping on

because another study came out on CGMs

provide no benefit at all to the

non-diabetic. Yeah. And I've had this

conversation with people actually at a

big event and people that were type two

diabetics and I asked them just flat

out. I just went around the around the

table and just saying if you're type two

diabetic when you were diagnosed what

like three years ago if you were to be

giving a CGM

five years before that or even one year

before that do you think you would have

been diagnosed with type two diabetes?

And they said no.

>> They said once they got type two

diabetes and got a CGM it gave them the

awareness. I mean, you can ask anyone

who has flat out overt type two diabetes

and just ask them the question, hey, if

you were given a CGM a year or two in

advance and you understood the impact of

foods. So, so I think a CGM is going to

be important for delaying Alzheimer's

disease. And if you have loved ones,

Tim, and your family, that I think you

would encourage them to slap on a CGM

and get some insight into what they're

eating. But it's also forcing them to

exercise because, you know, we're

talking about diet here. Yeah,

>> but just getting out and doing a brisk

walk 20, 30 minutes a day can go a long

way. Resistance exercise, I'm a little

biased towards that, but muscle is like

an endocrine organ that produces, you

know, hormones and various molecules

that are neuroprotective and muscle is

tightly linked to brain size

>> and of course your your waist and your

visceral fat. I would also encourage

them to get a DEXA scan and gify it and

say every year I'm going to get a DEXA

scan and every year like I do I just

kind of like it create like a lot of

stress for myself to like beat my DEXA

scan every year and get their friends

involved. Make it like a social event.

Everybody goes and gets their DEXA and

then every year you go back and just try

to beat

>> beat your scores.

>> Yeah, these are lowhanging fruit kind of

things people should be doing.

>> Yeah, I think probably fair to say make

sure you consistently hydrate for any of

these things.

>> Yep. like a DEXA scan. I do I do have a

follow-up question. So, also in the

exercise piece, people can look up

something called Clotho, K L O T H O.

There's a lot more that comes of

exercise like BDNF and all these various

things. There's a book called Spark that

covers some of it, but it's very

outdated. But check out cloth. There are

a lot of good reasons to exercise.

Thinking of muscle like an endocrin

organ. That's a really good way to put

it. My question to you was you mentioned

say one week per month going to more of

a lower carb or katotic state. How would

you think about the benefits of one week

per month assuming that the rest of the

time I'm behaving right most of the time

with a like lower carbohydrate

Mediterranean diet. Let's just say,

okay, one week per month,

every 3 months, or 3 weeks,

contiguous weeks,

once a quarter. Do you feel like one of

those is superior to the other?

>> Not really. I think whatever pattern

works best, I think you would gain

benefits for both. That would be an

interesting experiment to do. I'm just

thinking about the lead time to get into

a like a properly ketogenic state if I'm

going from some carbohydrate to ketosis.

We could talk about things that might

accelerate it, but like if it takes me 2

days to get there or 3 days and then I

only have kind of 4 days in the sweet

spot.

>> Mhm.

>> These are things running through my

mind. I'm just curious to get your take.

>> The one week intervention for the month,

my kind of opinion is that it could be

pretty aggressive. like you cut calories

50% the first two days and then cruise

into it so you're really cranking

ketones by the end of the week

>> and then you're also cruising into it

from what should be like a low carb

diet. So you should have that metabolic

flexibility to kind of seamlessly

transition into that ketosis state and

>> you could do intermittent fasting with

mild caloric restriction for the first

two days to to ramp up ketones.

Alternatively, if your schedule permits

and like you know your work and you have

like three weeks where you need to

really dig deep into a research project

or something and ketosis seems to give

you that cognitive flow or boost, then

that might situationally fit into your

schedule. And I definitely have periods

of time where I do that, especially like

if my wife is traveling or something

like that or on a research project or

something. I just like, okay, I clean

the house of certain foods and then I

just prepare. I mean, simple things like

that, too. I know just from the clinical

ketogenic world is that if you have a

family member that stocks the shelves

with certain foods that can trigger and

cause food noise, then that can really,

you know, hamper your compliance to

that. But you want to prepare the house

before if you're going into a oneweek or

you're going to a 3-week, prepare the

house and just make sure that you could

do, of course, you could just call Uber

Eats and get anything delivered, but you

want to kind of have the house prepared

for that and mentally prepare for it. So

for you personally, if you had some

hereditary gnarliness, right, if you