But, um my my meals are mostly like

healthy protein. So, I have homemade

turkey burgers. I eat a lot of I eat a

lot of those. And then I eat chicken.

You know, I pastured raised chicken. I

do I do still eat wild Alaskan salmon.

And then I'll um also mix in some like

filet mignon. Like I like grass-fed

steak as well.

>> Yum.

>> Those are my protein sources. And always

I pair it with greens. So, or like some

sort of vegetable. Most of the times

it's it's greens cuz they're the most

most micronutrient dense. And so, these

days I'm eating a lot of sautéed collard

greens that are like pre-prepared. It

has garlic and onion. And I'll put that,

you know, have that with my meal. Or

I'll have some, you know, sautéed kale.

Sometimes I'll have a salad with it.

But, the portions are smaller. And like

I said, I I also do a little bit of

intermittent fasting. We can talk about

that as well. But, that's kind of these

days what I'm doing for my meals. I

haven't eaten as much. Sometimes I'll

eat the high protein oats. They have

this high protein oats that Have you

seen Have you seen those? They're pretty

good.

>> eat oatmeal, but I I like protein foods.

I like vegetables. I like fruit. I feel

very lucky to like those foods mainly.

Yeah. And then the starch for me has to

be very clean. I like oatmeal, rice,

homemade pastas I'll eat. Like if I go

out, I'll have Sometimes I'll have some

homemade pasta or or a sourdough bread

or something. But, I find that most

starches that are out there in the world

have a bunch of other junk in them. But,

I just feel lousy. Get kind of sleepy

afterwards. And so, I

uh so, it sounds like we eat pretty

similarly. Although, I probably eat more

starches than you do.

>> It's the more processed types of

carbohydrates that as you mentioned,

it's like you typically you don't feel

good after you eat them. And, you know,

part of that's the postprandial

inflammatory response cuz some of those

foods are a little more inflammatory. I

mean, a lot of additives and stuff that

are affecting the gut, gut

permeabilization. You're leaking

lipopolysaccharide into the bloodstream,

right? That's activating the immune

system.

>> We used to inject. I don't do any animal

experiments anymore. And I'm actually

grateful to not do them. So, I didn't

like working on animals, but it was what

we did until I decided to work on

humans. But, we used to inject LPS

um

to stimulate an inflammatory response to

kind of prime a regeneration response

that you could get through macrophages

and things like that. And so, LPS is a

very potent way to generate local or

even systemic inflammation. I think um

hearing that some starches will

stimulate LPS, that's uh interesting.

>> Well, let me clarify.

Let me clarify.

>> No, I'm not challenging. No, no, no. I'm

I'm not challenging. It squares with my

experience. I'm one of these I never get

stomach aches, I never get headaches. If

I do, something's badly wrong with my

stomach or my head. But, if I eat

certain starches, I'll be like, "Oh,

like I feel lousy." And I'm wondering if

it's this.

>> So, we have about a gram of LPS in our

gut.

>> Mhm.

>> Like that's on average cuz, you know,

lipopolysaccharide is the outer

component of a cell membrane of

gram-negative bacteria, right?

>> At least.

>> Yeah. We have a lot of bacteria in our

gut, gram-negative bacteria, right?

Trillions of bacteria in our gut. So, um

when when we eat food, typically, like

our gut epithelial cells, they have we

have a tight junction that's holding

them together. When we eat food, they

transiently open and then close. Like

it's kind of a normal response, right?

Um the the I would say the opposite end

of the spectrum of that would be like

celiac, where they eat gluten or

something, it opens up and stays open.

And so, you get like a ton of LPS

leakage into the system, which causes

massive inflammation.

It just happens with meals in general.

You do get somewhat of a LPS response

from a meal. Now, the type of meal does

matter. So, when I when I say

refined carbohydrates, it's not

necessarily like healthy,

you know, co- carbohydrates like

vegetables. It's like you're eating

something that is refined sugar,

typically with saturated fat.

So, those types of foods really cause

like LPS response.

You know, it's it's it's inflammation.

It's bad. It's hard on the gut.

But, the postprandial inflammatory

response, essentially, is that LPS

getting into the system, activating the

immune system, which draws the energy. I

mean, it's like it's very energy

consuming to activate your immune

system, right? Which why that's why when

you're sick, you're so sleepy, too,

right? Well, there's also cytokines that

are somnogenic and promoting sleep, but

like activating your immune system

requires a ton of energy. And so when

you're constantly activating the immune

system, you know, that's an energy sink,

right? And so you do feel tired, and

that's why a lot of times after a meal,

you're feeling kind of lethargic.

>> To protein foods of the sort that you

listed off before,

um do they cause less

opening of the tight junctions of the

gut?

>> I think the the big deal with the the

opening of the tight junctions in the

gut is, you know, I mean, eating eating

a big meal will do it. Eating a very

like ultra-processed food meal will do

it.

Interestingly enough, just eating a

bunch of saturated fat without a fiber

matrix, so like like butter, you're just

like eating butter. Don't ever do that,

but like if you just eat butter,

>> Got it.

>> that's been shown.

>> My niece when she was little, now she's

all grown up, but when she was little, I

taught her how to eat like a little bit

of Kerrygold butter, and she loved it.

So then we would do this thing where

we'd we'd

we'd do that. Um

we won't do that, I'm

>> I mean, a little bit's fine, but like

I'm I mean, there's there's studies

showing that it does like saturated fat

is hard on the gut.

Like I said, it's a sliding scale. Like

meals in general do it, but it's like

you would it's it's like you would

think. The healthier foods that you're

eating, like whole foods, you're getting

less of that LPS response. And then of

course, there's gluten, and that

complicates the whole story, especially

for people that are celiac, right? Cuz

that's

>> Which is a small percentage of people

are actually celiac, right? But a lot of

people seem to believe, and I believe

them, that when they eat gluten, they

feel worse than when they don't eat

gluten.

>> I'm sure there's some people that are

sensitive to gluten that do feel worse.

And then I'm sure some of that's the

nocebo effect, right? That's been shown

with gluten in in particular. Did you

have you seen that study where people

there's been so so there were people

that

think they're you know glu- gluten

sensitive and so

they were enrolled in this study and um

these individuals were separated into

two groups. One group was getting given

the gluten bread with gluten and the

other group was given the bread without

gluten and the people that were given

the bread without gluten had a terrible

you know abdominal res- like they were

bloated, they felt terrible. I mean it

was all and there was no gluten in the

actual bread but they thought there was.

So it was thought that this is a nocebo

effect where it's like

the opposite of a placebo effect where

you just you're you're you're you've got

that phenotype where you think things

negative are going to happen and you can

make them happen. [clears throat] You

can change your immune system, you can

change your brain signaling and you

know, so probably a combination of both

with that regard. In addition to like

the lethargy, so we're talk- I was

talking about in the context, that's why

it sparked my you know, interest is like

you're talking about feeling tired after

a meal and I do think that is part of

that reason for feeling sleepy but you

know, what's interesting about LPS, you

talked about injecting it to mice and

I've also done experiments injecting LPS

into mice. There've been studies where

people have been injected with an amount

of LPS that is you know, similar to what

you would find your gut releasing into

your bloodstream

or a placebo control which in this case

was saline and individuals that were

injected with the LPS high amounts of

inflammatory markers like TNF alpha. I

mean we're talking like up to 50%

increase.

>> Ooh.

>> If o- over baseline, right? So high

amounts of inflammation which makes

sense. LPS is activating the immune your

immune system is like there's a foreign

invader, right? It's not a foreign

invader, it's just the food you ate that

caused transient gut permeability

>> [snorts]

>> and those individuals also feel

depressive symptoms and feelings of like

social withdrawal. So the inflammation

is affecting the brain, right? These

inflammatory factors are getting in

crossing the blood brain barrier, and

affecting the way we feel. And we know

now that inflammation plays a big role

in major depressive disorder and

depression. Not in all cases, but

there's a subset, right, where it's

really like it does it seems to play a

big role. In fact, interestingly,

there's been some studies showing that

people that are that don't respond to

SSRIs are have very high amounts of

C-reactive protein. So, this was a

biomarker for a classical biomarker for

inflammation. I would argue it's not

that sensitive, but nonetheless, it is a

biomarker for inflammation. And so,

people that um don't respond to SSRIs

have high amounts of inflammation, which

kind of raises this question of is there

like this subset of depression that's

really inflammatory driven, right? Um

interesting. So, so the LPS is affecting

not only our

our energy levels, but also our mood.

And then, you know, there's there's also

evidence that

so, we know that LPS

binds to LDL particles through

lipid-lipid interactions. And in fact,

it's kind of part of the adaptive

response. It's why you don't want to

ever go get your cholesterol measured

like after right after you're sick or

had a very stressful event, something

that causes inflammation, cuz you will

increase VLDL production increases, and

LDL production increases, and it's sort

of an adaptive response to bind that LPS

to prevent it from, you know, causing

more damage.

>> [snorts]

>> And so, it actually binds to LDL

particles on the apoB protein. So, apoB

is a protein that is on these

lipoproteins, and it's a a very

important protein because that is what's

used by the LDL receptors present on our

liver to recycle LDL particles. And so,

what happens is these these LPS

particles are now bound to,

you know, our our lipoproteins, and our

lipoproteins are still doing their

function, right? They're going around,

and they're they're they're giving, you

know, triglycerides and and, you know,

fatty acids and to some degree

cholesterol to our cells that need it,

right? We're constantly making new cells

and repairing and we our cells need

that.

As they donate triglycerides and fatty

acids, they get smaller in size.

The lipoproteins, you probably heard of

small dense LDL, right? Like that's a

very dangerous type of LDL particle. And

that's one that's kind of been donating

along, getting rid of triglycerides and

um whatever. If you think about a train

with cargo, it's donating the you know,

dropping off the cargo.

And so um when it's time to get recycled

back into the liver, what do you know,

the apoB protein's obscured by that LPS

and it's not recycled. And so it gets

lodged into the arterial wall. And

because there's an LPS bound to this,

you know, small dense LDL particle,

macrophages, which are as you mentioned,

it's like the first line of defense

against something like a bacterial

invader, right? Comes and chews it up,

right? Gets rid of the problem. So

macrophages come in cuz they're seeing

the signal of LPS and think it's a

foreign invader when it's actually just

a small dense LDL particle bound to LPS

that came from the gut, tries to engulf

it but it can't cuz it's not bacteria

and you get the macrophage stuck to that

lipoprotein LPS, you know, complex and

you get the formation of a foam cell.

You probably heard of a foam cell. It's

the beginning of atherosclerosis. And so

this is

where gut health and the food we eat is

sort of it's linked to cardiovascular

health, right? Gut permeability, getting

that LPS into our circulations actually

not a very good thing because you're

you're basically, you know, slow

dripping in that infla- inflammation,

that inflammatory signal and it's

wreaking havoc in our arteries, on our

brain,