There's all sorts of evidence that if
you don't have a lot of fiber, your
microbiome is not healthy. Feed your
microbes. You know, they need to be fed.
And what they eat is fiber. Okay? That's
what you want to eating. You want them
eating fiber.
>> And if you're not feeding them fiber,
they'll eat your mucous layer. Okay? And
we already talked about how thin that
barrier is. And all of a sudden, they
start eating your mucous layer. They're
they're not producing the butyrate you
need. And the butyrates needed to
maintain the tight junctions, right? So,
there's layers to this. It's like a
snowball effect that if you're not
feeding those micro the microbiome and
keeping it healthy, you're going to run
into all sorts of all sorts of trouble.
>> Welcome to the Hubberman 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
Stanford School of Medicine. My guest
today is Dr. Chris Thompson. Dr. Dr.
Chris Thompson is a professor of
medicine at Harvard Medical School. He
is also the chief of interventional
gastroenterenterology at Mass General
Bighgam in Boston. He is a renowned
expert on the intersection of
gastroenterenterology, metabolism,
nutrition, and obesity medicine. And in
today's episode, Dr. Dr. Thompson
explains how to improve your gut health,
including the roles of your diet, gut
microbiome, and gastrointestinal
motility, as well as how your gut
communicates with the rest of your body,
which of course includes the gut
microbiome, but as you'll learn today,
much more. Dr. Chris Thompson is a guest
on this podcast because he's not just a
GI tract and obesity medicine expert.
He's also credited with having created
an entire new field of treatments and
perspectives on GI and metabolic health.
So the knowledge he shares today is
truly at the cutting edge and
applicable. Which is why by the end of
today's episode, you will have a clear
understanding of how your
gastrointestinal system works, and you
will have a set of new modern
evidence-based tools for improving and
maintaining your gut health. Before we
begin, I'd like to emphasize that this
podcast is separate from my teaching and
research roles at Stanford. It is,
however, part of my desire and effort to
bring zero cost to consumer information
about science and science related tools
to the general public. In keeping with
that theme, today's episode does include
sponsors. And now for my discussion with
Dr. Chris Thompson. Dr. Chris Thompson,
welcome.
>> Thanks so much. Good to be here.
>> A lot of us hear these days about the
gut microbiome, the gut brain axis. We
hear about GLP drugs that help people
lose immense amounts of weight and stop
feeling this food noise thing and on and
on. But could we start by just having a
conversation about this tube that is the
digestive tract and get real basic and
just educate people a bit on what
happens that stimulates them to want to
eat, why perhaps for certain periods of
day or night they don't want to eat and
then what the passage of food through us
looks like as a series of steps. This is
such a critical part of our biology and
our lives. It's becoming more and more
complex all the time, right? the gut and
it does a lot of things. So, it's
obviously involved in digestion, but
it's also an endocrine organ. You can
hear it called the second brain, right?
There's a lot of different ways we we
think about about the gut and it is
compartmentalized and each each area has
a different job. So, you first you have,
you know, the esophagus and its job is
to just kind of move the food into the
stomach safely and it's thick, right?
has different lining so it can handle
things that might be a little rougher
and uh it pushes sequentially, you know,
down into the stomach. So, it's taking
that food bolus and driving it into the
stomach and you can have all sorts of
problems in your esophagus, right? So,
each one of these organs has, you know,
things it's supposed to do and then
things that it doesn't do well.
Sometimes people don't swallow well. It
gets too tight at the bottom. There's a
condition called acalasia where it's
just the bottom of the esophagus doesn't
relax, right? And so we have procedures
we can do in my line of work where you
can tunnel down in between the layers of
that esophagus. It's very thin, you
know, a few millimeters you can tunnel
down into there and cut that muscle to
relieve the obstruction. So
>> what are the symptoms of that?
>> So inability to swallow.
>> So what do they do? They choke.
>> Yeah. They'd feel like they're choking.
So they'll they'll swallow food, it'll
get down and stop and then they'll feel
pressure. They'll feel really
uncomfortable. If they drank some fluid
with it, it might start coming back up.
It'll just stay there. And then
sometimes they'll have to, you know,
induce vomiting to remove it.
>> It's very uncomfortable for them. And
it's not a terribly common condition,
but it's coming more and more frequent.
I see it every week, right? So that
inability to swallow and you can get
that inability to swallow for other
reasons actually that are far more
common. Chronic heartburn. If someone
has reflux, you know, that burning
sensation, uh that can damage the line
of the esophagus and it can lead to
precancerous conditions called Barrett's
esophagus, which is something that, you
know, needs to be treated, looked at,
and and and uh kind of followed. But
with time, it can actually cause
scarring. So you get a stricture. So
it's kind of very firodic tissue there.
That's another reason why people might
have difficulty swallowing. There's
other reasons as well that are more
obscure, but so that's the job of that
esophagus just to move the the food down
safely and a lot of times it it doesn't
work. Then you have the stomach next,
right? First, what the stomach does is
is it stretches to accommodate and
accept a meal, right? So it stretches.
Normally it's like a tube in your, you
know, in in your abdomen. But then when
you start to smell food, it starts
stretching and becoming more like a bag.
>> Really just the the odor of food.
>> Yeah. It can it can stretch, relax to
accept that meal. And if it doesn't do
that properly, it's it causes symptoms
like nausea, right? So uh so then it
accepts the meal and uh it has to do its
job which is to break it down and pass
it on. So that the stomach now isn't
just transporting, it's breaking it
down. And it does that mechanically. So
and the the fundus the top of the
stomach is holding that meal. That's
what kind of stretched up to hold it.
And then the rest of the stomach is
working on it. So the body of the
stomach next segment is breaking it
down. It's grinding the food into
smaller bits. Acid is part of this as
well. The stomach secretes acid and then
the bottom of the stomach called the
anstrum will push the food out slowly
into the dudenum, right? That's the
first part of the small bowel. Satiety,
satiation all becomes part of this
because the stomach is what secretes
grein. We'll talk about that probably
more later, but the stomach secretes
ghrein. And so this is part of your
satiety signaling. All sorts of problems
with the stomach, right? So similar to
the esophagus, food might not leave uh
you know as it should in the right in
the right timing. So it can happen due
to ulceration in the stomach, scarring
or something called gastroparesis where
for a variety of reasons it might be
postviral, it might be due to diabetes,
uh neural hormonal um kind of origins of
this, the stomach just doesn't empty as
it should. People have nausea and
vomiting with that and other problems.
So then you get into the small bowel and
the small bowel's job now typically you
do a little digestion so early on cuz
you have pancreatic and bilary
secretions going in there but its main
job is going to be to absorb calories
right so that's absorbing calories and
moving it down it's very thin it's one
cell thick has about the surface area of
like a pickle ball court right
>> one cell thick
>> yeah one cell thick the lining is one
cell thick that's where the cell type
just to
>> interosytes
yeah must be some really sturdy cells
>> columnar epithel ium. Yeah. So, they're
pretty sturdy. Uh they they rely on more
than just the cell itself to to to
maintain that barrier. Um there's
certain cells called goblet cells that
produce mucin and that creates a nice
thick layer there uh that help as as as
another part of the barrier. They have
something called tight junctions right
between the cells which are complex
little structures that are part of that
barrier as well. And there's immune
cells in there. There's other elements
to that barrier but it is one cell layer
thick. So that's why the stomach's the
esophagus and stomach got a good job of
processing that processing that food so
that it's it's safe to go down through
the small bowel and be absorbed. All
sorts of issues with the small bowel.
Similarly you can have different
diseases that affect that you know
celiac disease uh Crohn's disease etc.
different inflammatory conditions. Um,
and uh, what we're learning now and
hopefully get get into is it plays a
central role we think in metabolic
disease. And that's kind of what's very
exciting is is its role in obesity,
diabetes, and other similar conditions.
And then eventually you have the colon
and that's where your microbiome is the
star, right? The colon uh, its job is to
usually just absorb water. Most of the
nutrients are gone by then. But it does
play an important role um as well and it
is working handinhand with your
microbiome to uh you know to to make
sure that um you producing it really
it's it's it's mostly butyrate I think
that's mostly involved there where the
microbiome is producing short chain
fatty acids and one of them the most
important probably is butyrate that has
a lot to say about your metabolism as
well that's involved in satiety
signaling and you have a lot of GLP1
produced in the colon again so you're
you're getting these kind of endocrine
function function of your colon that's
very involved and then it passes. So and
again diseases in the colon colon cancer
is a big one right so colon cancer
screening is important people typically
now I think they moved the age back to
45 everyone should start getting
screened uh to make sure you know they
don't have uh cancer you can do it
different ways there are genetic tests
you can do like colig guard and if you
do that you have to do it every every
few years but you can do that uh you can
do screening colonoscopy every 10 years
if it's normal and there's other things
you can do as well CT colonography is
not as common and other tests but those
are the two most common. It's important
important to do that.
>> How common is um colon cancer
>> in our line of work? Is the is the most
frequent cause of of cancer?
Unfortunately,
>> are more people being diagnosed because
of more diagnostic procedures and are
more people surviving colon cancer.
>> The survival rates are definitely
improving due to screening programs,
right? So that's that's important. So it
is definitely important to get screened.
Also screening earlier helps. So for
instance, starting at 45 is better than
many people who started at 50 and they
wouldn't get till 55 or 60, right? But
also if you have a family member that
has had cancer, you want to start at 40
or if they were younger, you want to
start 10 years younger than when they
were diagnosed, right? So you want to
start that screening process really.
It's very effective. Um, you know, and
uh it's important to do it. And I think
that things like colag guard and other
genetic tests are going to keep getting
better and help because you don't have
to have that kind of very uncomfortable
screening procedure. colonoscopy is not
it's not a great way to do screening,
right? You shouldn't have to have a
relatively invasive procedure to be
screened for something, you know? It
should be something you just do a blood
test or a stool study or something like
that. And I think we're getting there
with technology and that will definitely
show dividends cuz you can have the
colonoscopy to remove the lesion, which
is something that we can do. It's it's a
newer technique where we can actually go
in and remove these very early cancers
endoscopically. So, we call it organ
sparing surgery. So, you don't have to
actually remove a piece of the colon
anymore. you can just kind of, you know,
take take the lining where that
precancer is residing. It's a
complicated procedure, but it's easy for
the patient. You know, they keep their
colon, they go home the same day. And
these tests, you know, are are easy ways
to to diagnose those patients and and
get them in for proper care. So, very
important. So, that's pretty much the
quick overview of of the gut. And uh it
plays one thing we haven't touched on
too much yet is its role in in really uh
you know satiety and and kind of how
it's involved in processing of food uh
in detail and the kind of endoendocrine
system that's involved. I'd like to take
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Couple questions that uh no doubt will
resonate with people because they're
fairly common and you'll tell me if
they're of concern or not depending on
the frequency. We'll start at the the
top of the the GI tract. People will say
sometimes that they eat and some of the
food seems to go up their nose. They
know this because if they blow their
nose, they might get some food
particulate. It it sounds like something
that's not entirely uncommon based on
the number of questions I get about it.
What's going on there? Why would you
know I get asked a lot of questions some
of them truly weird and rare and some of
them um weird and less rare and I would
put it in the second category
>> that could be a variety of different
things and this is the area that I do
work in right so it can be an oral
fingial transfer problem where the the
hypoparrenx is transferring food into
the esophagus that can be you know ENT
thing it can actually be functional
medicine as well where you can work with
a speech pathologist that teaches people
how to swallow better they might have to
change the the quality of the food
they're eating to thicker food they
might have to turn a certain way to
swallow and there's ways they can
actually train people with with kind of
bio feedback to to learn how to swallow
better because that part's still under
your control a little bit.
>> They're not swallowing well.
>> Yeah. And with age that can happen,
right? With age that can happen. Now the
next thing that can contribute to that
is if they have high tension in the
first sphincter up above which is the
upper esophageal sphincter. That's the
the sphincter that separates the top of
your esophagus from your mouth
basically. And that can be have high
tension. And what I see a lot is
something called Zanker's diverticula,
which we haven't talked much about.
There's a few different little pockets
that can form high up on your esophagus
near that sphincter.
>> There's different names for how they,
you know, kind of where they where they
exactly occur.
>> And with time and with age, this this
this is like a herniation of mucosa
through the muscle and it creates a
pocket and that can actually trap food.
So when people are eating, the food goes
into the pocket and then comes back up
on can go out their nose or or sit in
there which is very uncomfortable for
them, right? That's another way you can
have problems swallowing
>> and that can be fixed very easily. We go
in through the mouth actually make a
tiny incision and just kind of take down
the septum that's part of that pocket
opening up the pocket so that the food
can leave. So it's important to do it
early too because people can actually
this it looks like an inconvenience
initially, right? It's you know you're
not swallowing well. foods, you know, is
is not where it's supposed to be
necessarily. The problem is when people
then aspirate and that food goes in the
lung and then it can lead to scarring in
the lungs and eventually it can really
cause problems. So, it is something that
should probably be taken seriously and
looked at even though it sounds funny,
you know, it is something that can be a
real problem.
>> There's a weird thing about GI tract and
bowel movements in particular, which is
the following. with babies, with puppies
and to some extent with ourselves, but
especially with babies and with uh
puppies, we sort of because they can't
speak, we have a couple of like key
readouts that we intuitively understand
reflect their health. One is the color
of their skin, the eyes, like if eyes
are looking glassy or tired, you know,
um and their and the uh quality or lack
thereof of their bowel movements,
quality, frequency, etc. But then
something happens where speech comes
online and we get uh you know uh toilet
trained and then everyone's responsible
for like understanding like their own
bowel movements, right? And then we're
never really told like what's healthy
bowel movements but we all kind of know
what's normal for us or not normal. I'd
be lying if I didn't say like these are
important metrics of health. Yeah. Well,
there's so much you can tell from bowel
movements. Okay. So the rule of thumb
is, you know, you don't want to have
more than three a day and you don't want
to go longer than three days without
having a bowel movement. So that's kind
of the general rule and you want it to
be one formed bowel movement, you know,
or a couple. You don't want little tiny
pebbles. That's called scibula stool and
that's that's a sign something's going
on. But there's a lot you can tell how
much are they taking enough fiber,
right? the World Health Organization um
uh published something in the Lancet
years ago on on fiber fiber synthesis I
think they called it and they found that
you know the vast majority of population
really doesn't especially western
countries just are not getting enough
fiber which is obviously concerning
because that that causes a lot of issues
long term right which we'll get into.
But if you're having these scibulus
stools, if you're if you are
constipated, meaning you're having a
bowel movement more than once every 3
days and they're hard stools, that's a
sign you're not getting enough fiber. So
that's one thing you really have to to
think about, right? Additionally,
there's other things you can tell after
procedures. You know, if a if a
procedure if a if a bowel movement is
very dark, tarry, and shiny, that's sign
you have blood in your GI tract, right?
So there's different things you can tell
from from from the stool that are
important to keep an eye on. But in
general, that's kind of the rule of
thumb. uh you know uh with with uh with
bal having more than three a day is
probably leaning towards being too
loose, right? And if you're not having
one every three days, you're probably
bound up and and then you really have to
think about fiber.
>> As I recall, the recommendations were
for adult men 35 grams of fiber per day
and for women 25. And obviously that's
not accounting for variations in body
weight and height and all the rest. So
um does that sound about right?
>> Yeah, that's that's about right. And it
kind of depends on the quality, too.
There's a couple other really
interesting studies that came out
recently just within the last few years
uh looking at the importance of fiber
related to certain conditions like one
was fatty liver right and fatty liver it
was a interesting interesting study they
were using resistant starch like level
two so basically raw powdered um
potatoes something like that right uh
>> um and they were supplementing it I
think it was at 40 g and they found that
when they did that they actually saw a
significant improvement in fatty liver
which is phenomenal right and it was you
know relatively weight stable. So it has
important treatment effects. Another
group actually um studied it and looked
at insulin uh sensitivity. So they did
clamp studies you know where they they
would um kind of really be able to
detect insulin resistance and kind of
try to look at um kind of glucose
utilization and clearance. And they
found that with this RS2 type, you know,
resistant starch too, they were able to
improve insulin resistance and insulin
sensitivity as well. So fiber is very
important. It's not just about the bowel
movements, right? It's also about, you
know, really just having, you know,
health.
>> It probably helps the microbiome.
There's there's all sorts of evidence
that if you don't have a lot of fiber,
your microbiome is not healthy, right?
You get less diversity in your
microbiome. the different studies that
have looked at that. It is important to
have that fiber and that constipation is
an early window into it, right? It's an
early sign that maybe you're not getting
enough enough fiber.
>> Yeah, I make it a point to eat fruits
and vegetables because I like them. But
recently, I started supplementing with a
powdered pelium husk that and some of
them actually taste pretty good and my
expectation is I was going to feel
really bloated. It was quite the
opposite. It not that I had gut issues
before. if it was normally kind of like
hypernormalized things actually it made
uh postmeal um subjectively the
sensation just like feel good feel great
um and I didn't expect that I thought
okay more fiber I think a perception
people have is like more fiber more
regularity and more bloat
>> and I think that's a that might be true
for some people but it certainly wasn't
my experience and I think that if I feel
like the messaging on fiber to the
general public is pretty lousy meaning
people are told to take it that's Great.
They're told all the time, but I think
people think, "Oh, if I have a lot of
fiber, I'm going be really gassy. I'm
going to be really bloated." But as you
point out, it's not just about
regularity and speed of digestion. It's
about creating a healthy millu for the
gut. I think if more people knew that,
they'd probably make a move to consume
more fiber.
>> Totally. It's like feed your microbes,
you know, or they're going to eat you,
right? And it's kind of true, right?
Because they need they need to be fed.
And what they eat is fiber. Okay? That's
what you want them eating. You want them
eating fiber. And if you're not feeding
them fiber, they'll eat your mucous
layer. Okay? And we already talked about
how thin that barrier is and all of a
sudden they start eating your mucous
layer, they're they're not producing the
butyrate you need. And the butyrates
needed to maintain the tight junctions,
right? So there's layers to this. It's
like a snowball effect that if you're
not feeding those micro the microbiome
and keeping it healthy, you're going to
run into all sorts of all sorts of
trouble.
>> Raises some um interesting questions
about uh intermittent fasting. I think
very few people are doing long-term
fasts of more than a day or so. I mean,
it does happen, but most people a lot of
people do sort of timerestricted feeding
or they they'll skip breakfast. You
know, I'm I'm one of those people most
days just by default. I had a a
colleague friend at Yale who studied
microbiome and I said, "Oh, so does
fasting improve the gut microbiome." And
he said, "No, actually during the
fasting period, your microbiome starts
eating up your your digestive tract,
which is what you're But then he said,
but then the rebound often is puts you
at a slightly better place afterward. So
it's tricky. Should people avoid
intermittent fasting if they're having
gut issues? I know we don't want to make
any broad recommendations. It's highly
contextual, but based on what you said,
it it seems that it stands to reason
that you might want to avoid having your
stomach empty for very long periods of
time outside of sleep.
>> I don't see it as being a major issue. I
think the benefits of intermittent or
timerestricted eating, intermittent
fasting probably would outweigh that
risk. You know, you need to give your
pancreas time to relax. You know, you
need to have insulin come down. If
you're eating frequently, your insulin
levels are already up, always up, and
that that causes problems. So, I do
think the benefit of of of the the time
restricted eating definitely outweighs
that that potential risk.
>> Yeah, great to hear. um especially as
somebody who just by default doesn't eat
breakfast or and just don't get hungry
till 11.
>> I skip breakfast as well, but there's
studies because initially they actually
used to say, well, you have a cordal
sauce spike in the morning and you know,
you know, you're more likely to star the
uh the food you take in if you if you if
you eat in the morning. Turns out maybe
that's not so true. It might be better
to actually have you know, eat earlier
and then have your fasting window start
in the afternoon, right? I think doing
is better than not doing it. I still I
still skip the breakfast. The topic of
fermented foods, low sugar fermented
foods as a possible benefit for gut
health has come up um since Justin
Sonnenberg and colleagues have published
that the study. It there's a small
number of people in that study
admittedly, but um that taking in some
low sugar fermented foods really helped
lower the inflamm. They didn't look
specifically at as I recall uh symptoms
of gut irritabil irritation or things of
that sort, but what are your thoughts on
fer low sugar fermented foods? So, we're
not talking beer. We're talking kimchi,
sauerkraut, brine.
>> I think they're they're important. Um,
and they're missing in the western diet,
which is an issue. And I think there's
the study you referred to actually, I
think they compared it to to fiber,
right? It was it was fermented foods to
fiber.
>> And with the fermented foods, you had uh
reclaimed some diversity in in the
microbiome, which was great, as well as
the reduced inflammatory markers where
the fiber didn't seem to do that. And
you saw all these benefits in these
other other fiber trials that we're
we're talking about with the resistant
starches, right? So, it stands to reason
that we'd probably see that as well as
we do more research into the fermented
foods. They're beneficial for a variety
of reasons. You know, one, they're
prebiotic, right? So, you're feeding
your microbiome things they want, which
is phenomenal. And it's already kind of
started. It's a little partially
digested, which is really helpful. And
um and they're also a little bit of a
probiotic as well because you do have
some, you know, some live cultures in
there, right? And um they usually have
bifidto bacterias for lactobles or
something like that in in them and a
variety of other things as well. So it
gets the ball rolling, right? So it's
sort of like when you're you're trying
to grow something, you want to plant the
seeds but also have the fertilizer and
whatnot. And this this is what um
fermented foods do for you. So I think
you know that that's that's very
helpful. And it's all about maintaining
this this kind of healthy microbiome
that can produce things like butyrate
which have a lot of a lot of benefits we
can talk about. You can't just take
butyrate and then it's not going to make
it to the colon, right? It needs to be
in the colon to have its to have to have
its effect. And so what these bacteria
do is they kind of they they will um
kind of crossfeed in a sense, right? So
you have those first layer of bacteria
that will take the fiber and break it
down and they create acetate and lactate
and whatnot. And then that can then be
used by other bacteria. So you're
feeding the other the other bacteria
that can then turn that into butyrate,
you know, and things like that. The
butyrate is magical, right? So that will
feed your colon cells. Your colon cells
live on that with butyrates needed for
those tight junctions. Butyrate, you
know, does all sorts of things via GLP-1
pathways and satiety pathways. So it has
a lot of different uh a lot of different
roles that it's playing. Additionally,
it keeps your bowel acidic, right? So
like these short- chain fatty acids and
you know acetate and whatnot and that's
great to to make sure you are protected
from certain pathologic organisms might
want to take take root, right? So the
aerobic organisms and the the other
organisms that you don't want don't
survive as well in an acidic
environment.
really important to to to take these
fermented foods in addition to fiber.
>> Do you make it a point to consume them?
>> I do. Yeah. I I Yeah, I like keer or
kefir and everyone say that, right? I
like I like that. I think it's
phenomenal. Yeah, it's good.
>> Kimchi is good, you know, sauerkraut.
>> Um there's all different types. Yogurt,
you know, um there there different types
I think that everyone should be able to
find. Kombucha, you know,
>> um and it's certainly missing in our
diets. So I think it's it's important to
to to to recommend that the folks do
>> cankera sores and ulcers u my
understanding for a long time is they
were caused by stress or wounds to the
mouth and then you know couple folks won
a Nobel prize for identifying a
soilbased bacterium that causes ulcers
and I loved that Nobel Prize year you
know as a scientist like some people
watch the Super Bowl like you know like
who you know who won the Nobel Prize and
it's never surprising who wins it's at
least for the scientists right um it's
often surprising who doesn't but let's
leave aside that uh that component but
that was a very surprising set of
findings right like a gut bacterium is
causing ulcers and I I love the findings
but at the same time I think many many
millions of people hundreds of millions
billions across history would say stress
gives people ulcers so there's something
going on there that's more than
soilbased bacterium right
>> yeah definitely you know and that that's
the problem with these you know the way
the media covers these findings like
it's not all that you ingested the wrong
soil. Stress can give you ulcers, right?
Or am I am I missing something?
>> Stress can play a role. Um, you know, it
is it is certainly complicated. So Barry
Marshall was phenomenal in Australia and
he found H. pylori could cause gastric
ulcers, right? And he had to consume, no
one believed him. He had to consume
himself consume it and and then he had
gastric ulcers.
>> I love it when scientists do self
experimentation.
>> That's crazy, right? So, but that was
phenomenal, right? And he he proved H
pylori and we need to treat that, right?
>> And uh and that that actually H pylori
was actually found even in AI the
iceman. I don't if you remember AI the
ice man. He was this uh
>> 5,000y old, you know, homo sapien in the
in the Italian Alps. He was found
frozen, right? So you could actually get
into his stomach and see what's in
there.
>> He died stressed. He had h pylori in his
stomach. That thing's been around a long
time. It's kind of interesting. There's
other lessons there like like a loss of
of of diversity of the microbiome,
right? with industrialization, we have
far fewer species and less genetic
diversity in our microbiome. But
regarding ulcers, so I I actually did
study this in gastric bypass patients a
good bit, right? And uh it was not a
bacterium that was causing it, right?
Sometimes it was a relative eskeeia.
Type two diabetes causes uh kind of
microvascular eskeemia. Smoking can
cause microvascular eskeeia. In gastric
bypass patients, the small bowel doesn't
uh it's it's a distal part of the small
bowel from lower down that's connected
to the stomach and it doesn't have
bicarbonate uh that's being secreted
from the pancreas in in the area. So
there's no way of neutralizing acid. So
if the pouch which you know we can get
into the anatomy here, but if the pouch
of of the gastric bypass is too large
and makes acid the douadinum now has no
the junum actually has no natural
defense against that. So acid clearly
plays a role and if you're stressed it
can produce more acid, right? So
generally there's probably multiple
hits. We don't fully understand things,
but clearly it's not just an infectious
organism and it kind of depends on
individual circumstances um and
susceptibilities, but ulcers are
certainly something that can occur short
of a bacteria.
>> So important for people to hear that,
you know, because one thing can cause
something, it doesn't mean it's the
always the case that
>> Yeah. So, let's talk about metabolic
health, hunger, obesity, weight loss.
These are areas that went, you know,
square in your wheelhouse. Can't have
this conversation without talking about
the GLPS. Um, most everyone has heard of
these things nowadays. Millions and
millions of people I've heard, I don't
know if this is true, as many as 20% of
of uh people 18 and older have taken or
are currently taking a GLP or either,
you know, Zen Picjaro soon, Red True
Tide will be out to market. What's your
thought on these compounds? are they the
perfect solution to weight loss?
>> Well, I'm grateful we have them, right?
Um, obesity is is a serious problem and
all the all the metabolic issues that
that are kind of there with obesity
uh need to be addressed and we weren't
doing much with it unfortunately until
the GLP1s came around. So, GLP1s are
fantastic from that standpoint. They're
not perfect, you know, there's
limitations, but they're it's much
better to have them than not have GLP
ones, for sure. There's issues with with
certainly um adherence, unfortunately.
Right. So, there's a there's a number
over a million people a month are coming
off GLP-1s, right? And that's for a
variety of reasons. About 30% come off
GLP-1s in the first month and then 50%
or so by by the end of the year, right?
So, and it's not specific to GLP1s. You
see that with any medicine. You see that
with with blood pressure medicines? You
see that with cholesterol medicine?
>> What's the Can we say what the primary
driving force is in the case of GLP1? Is
it the side effects? Is it they don't
like having to pin themselves?
>> I I think because the numbers so
curiously similar to all the other
medicines, maybe there's some underlying
thing where people just don't like
taking medicines frequently.
>> That might be part of it. I think that,
>> you know, sticking yourself is is a is
probably for some people they don't want
to jab themsel once a week. That might
be something. They needle fatigue.
That's probably there. I think when you
take a medicine orally every day, it
gets hard to remember to take it. And
then I think there are issues with with
how you ramp them up to the effective
dose and side effects. I think there's
ways you can do that, you know, safely
going step by step. But nausea is an
issue with some of these. You know,
muscle loss is an issue. There's
different features there. And then
additionally, you know, long-term this
this is, you know, you're taking a super
physiologic dose of something and we
don't know what the long-term
ramifications could be. So even though I
believe the benefits outweigh the costs,
right? You're treating obesity. We know
obesity is a problem. We don't know you
GP1 to be a problem long term. That does
weigh heavy on some people's minds and
that might be why they stop as well. So
in my practice where we do endoscopic
therapies, uh over 85% of people have
already been on a GLP-1 and either
they're struggling on it or they've come
off.
>> 80 85%.
>> Wow.
Yeah. Um we again we don't want to get
too far into the sociology and
psychology of of uh uh medication
adherence but it is interesting that so
many people come off meds but then there
are meds like SSRIs and things like that
which I think can benefit certain people
like people with like full-blown
clinical OCD extreme they save lives
right but but then they're
overprescribed I feel like especially in
the United States people like their
prescription drugs so if they're
stopping I feel like there's got to be a
reason. I mean, aren't we the biggest
consumer of prescription drugs in the
whole world? Like, people love their
drugs. Like, I you know, I've heard
about the nausea. I I don't
>> There are a number of people now who are
quote unquote micro doing the GLPS and
finding that they're getting some
benefits without taking the the the
prescribed amount. I'm not recommending
people do that. Uh, you know, I guess
talk to or don't talk to your doctor.
They probably won't approve. But I know
people are doing that. I think initially
it was because of cost and actually pen
sharing. Um but also people feeling like
oh I get the same effect. So is your
sense that when because the way clinical
trials are done there aren't often there
aren't like really nice dose responses
that you're just kind of comparing
they're so expensive to do these trials
that they're going you know two doses
you know moderate high versus placebo
and then the that's what the doctors
have to work from. Do you have any
knowledge of whether or not the lower
dosing brings takes people away from
side effects and then you're seeing
fewer of them?
>> I think it's actually very useful. So
that's you know the approved dosages are
kind of just an effect of our regulatory
system as as you've alluded to, right?
And it's too expensive to do different
different doses. Plus it takes it takes
away personalization. You know we're all
trying to get to precision medicine and
personalized medicine and that's what
micro dosing allows you to do. The first
time I I heard about micro dosing was
one of my patients and he was a
physician and he came in and he he said,
you know, I it's a it's too expensive,
you know, b I don't feel great on it and
c I'm doing this thing where I take the
pen and I inject it into a sterile vial
and they use a an insulin syringe and
I'll take a small amount out and I'll
give it to myself. And he said, I'm
doing great. You know, I don't feel
nauseous. My weight is staying off. and
you know he was a physician so he's he
was familiar with with you know the the
equipment if you will and that was the
first time I came across it I was like
wow that's actually that's a great idea
so a lot of my patients actually do
micro dose these things uh and you know
generally you get up to the the point
where you want to lose weight you get to
that dose you're losing weight you're
losing weight and then for maintenance
rather than just stopping it because if
you stop the jp1's there's problems
right this is not meant to to be stopped
these are kind of lifelong medicines
instead of stopping it just go to micro
dosing and you'll find a spot hopefully
you know, not everyone does, but you'll
find a spot where uh you keep the weight
off, you feel good, and you're not
you're not taking as much of the med.
Now, the problem with coming off of them
is especially with the the the original
drugs, you know, like simaglletide's an
example, right? Where when you lose
weight, about a third of the weight you
lose would be lean mass, right? So, most
muscle, right? Maybe some bone, etc. And
the problem is when you cycle on and
off, right? So, say you come off of it
and you put your weight back on. You're
not putting the lean mass back on, okay?
You're putting the fat back on. So, now
you've shifted your body composition to
be less favorable than before you run
the GLP1. And then you go on it again
and you lose weight again and you lose a
little more muscle. And then you go off
and you put more fat on, not more
muscle. So now, basically, you're taking
your your your body composition and
shifting it, you know, worse every every
cycle. So, there has to be a game plan.
If you're coming off the JLP1, you need
either to micro dose it or have a
bridging plan to a procedure or
something else which uh you know will
keep the weight off for you.
>> Are there any good studies um showing
that resistance training can offset the
muscle loss um from a standard or micro
dose of of one of these GOP drugs?
>> Yeah, resistance training definitely I
I'm not familiar with that where that
was the primary outcome of the focus,
right? But you can actually see that
that does play a major role in
maintaining muscle and that's with
anything. It's not just GLP-1
medications. It's with the first
generation medications. It's with any
surgical procedure or endoscopic weight
loss procedure. You know, you if you're
doing resistance training, you tend to
maintain your muscle because the body
realizes, hey, I need this muscle. I'm
not going to I'm not going to get rid of
it as the person's losing weight, right?
So, when there's a caloric deficit, the
body is looking for what it can do to,
you know, uh, you know, to to to uh
maintain, you know, energy levels, if
you will. And you don't want it chewing
up the the muscle to do that. The side
effects that I see getting the most
coverage are um increased feelings of
apathy. Um general, you know, food noise
is down, al alcohol appetite is down,
appetite for life is down. You hear
this, but I don't know that how accurate
that is, right? Social media is a weird
place cuz certain things get amplified
it um out of proportion to the the real
data often. The other one is that GOPs
um can cause blindness. these GLP drugs,
but turns out that's in a very very rare
set of individuals that have this uh
optic nerve head kind of eskeemic
opportunity. So like so yes, the GLPS
can make certain people blind, but yes,
also it's a very small number of people.
So you want to get screened for this um
structural thing in the eye, but it's
not true that like GLPs are making
people go blind all over the place. So
what I'd like to ask is like when
patients come to you and they say like,
"I didn't like the GLP or it wasn't
working for me." Are they telling you
why? Are they saying, "Look, it made me
feel nauseous." Certainly, you know, if
it they lost their vision because of it,
but is there some resounding themes
there? There are. I think that muscle
loss honestly is is one of the bigger
ones, right? Um and it might just be
subtle like ompic face, ompic butt,
right? You're losing some muscle in
places where it's noticeable. Other
people actually truly develop
sarcopenia, I think, right? Where you
have significant loss of muscle. It's
rare, but those are people that they're
not really exercising a whole lot when
they take it and they might have had a
predisposition to it in the beginning,
right, to start with.
>> So, in people that I'm concerned about
that, it's good to get a DEXA scan
beforehand, right? Make sure you have
adequate muscle mass. And if you don't,
you really have to think twice about if
you want to do the GLP1, right? Or if
you want another another avenue to try
to lose the weight and you definitely
have to start hitting the gym. I think
that's the most common thing is is
muscle loss in obvious places or
sarcopenia developing. The other one's
nausea. A lot of folks do get nausea on
the higher doses and they will not lose
weight on the low dose, right? And if
they go on the high dose, they feel
nauseous. So that's another issue. Some
people say it stops working and that
might be because you know of of that of
that similar issue. They don't tolerate
the higher doses. Those are the primary
reasons that I that I hear. U maybe we
can move a bit towards some of the
surgical procedures. And um I always uh
like to remind people there's basically
two ways you can affect your your brain
and body. You've got chemical methods
and mechanical methods. So uh you know
um and when I think of quote unquote
stomach stapling, I think of that purely
as a mechanical thing. You're making the
stomach smaller. Make people feel full
earlier in the meal is my naive view of
this, right? But of course it stands to
reason that you're also removing tissue
and so you're going to change the
chemical millu of the environment. I'm
sure that you'll tell us that the you
know both things are involved and what
we had this thing called stomach
stapling for a long time. Why did we
need the GLPS? Now, some people say,
well, that's a surgery. But I think in
today's conversation, hopefully we'll
convince people that uh surgeries can be
done less and less invasively now and
can be done with tools that make it seem
a lot more like a a dental cleaning,
maybe a bit more than the idea that, you
know, you're cutting open the body and
taking things out, laying them out on a
table, putting back in this kind of
thing. Cuz people's minds go all sorts
of crazy places, trust me, including
mine. When we hear surgery, why did we
ever need the GLPS? We had stomach stay.
>> So surgery, it really started back in
the 50s. University of Minnesota, I
think, was the first place they did it.
And the first procedures were focusing
on malabsorption, right? So the idea was
they're going to bypass a portion of the
small bowel so that you don't absorb
your calories. Okay? And it was called a
juno ilial bypass. But this procedure
was awful, right? So the people did lose
weight, but the problem was they created
a long blind limb. So there was there
was no actual food going through the
limb. Okay. So you connected the junum
which is the kind of early small bowel
to the very bottom small bowel and the
rest of the small bowel was still in
there but it wasn't no food was going
into it.
>> So you had bacterial overgrowth in
there.
>> You had all sorts of problems. You had
the fat that was being malabsorbed was
binding calcium. And so calcium you
didn't have calcium in the bowel. So
what happens is the oxalate which
normally binds calcium gets absorbed and
then it binds calcium in the body in the
kidneys. So you're having all sorts of
renal failure issues and it was a
disaster went on for years right because
you know people were desperate but it
was a very bad procedure and it was
replaced by something called gastric
bypass and I think that came about
probably in the in the mid to late60s
and Mason I think was the was the
surgeon that came up with this. So his
goal was to avoid the problems with the
ji bypass and um you know still get a
treatment effect and he did right so he
thought of this as restriction. So when
you eat stomach stapling the stomach is
smaller so you'd have some element of
restriction and then also an element of
bypass where you're not absorbing all
your calories. Turns out that's not
really how this thing works really but
that's what he thought was going on.
>> And then from there you keep moving
forward you have all these other
procedures. lap bands, adjustable
gastric bands that was just purely
restrictive. It it worked. True stomach
stapling which was I think the VBG and
now the sleeve gasterectomy. So these
are the real surgeries and you know they
were created at the time just
conceptually thinking about either
restriction or thinking about
malabsorption but they work entirely
different than what they thought.
>> I have a question about your profession
generally. I'm guessing there are not
large-scale clinical trials of each of
these surgeries like they're doing you
know 5,000 of these surgeries comparing
to the existing surgery. So, how much
license do physic do surgeons have? Say,
you know what? I'm very familiar with
this tissue. Maybe I just like graft
these two, cut out the middle. That's
the part that absorbs stuff. Oops. Okay.
Actually, big problems and modify. And
then cuz I mean there's
>> there are other things, but there are
few things greater in terms of trophies
for a physician knowing some physicians
aside from the great feelings they get
from healing patients and saving lives.
Let's let's be fair. having a procedure
named after you that saves lives like
that seems to me like that's like the
ultimate thing. So there's got to be a
huge incentive for um physicians to do
it on that basis which might sound all
like ego but there's another facet to
this which is no and we know this from
science too like you can read about the
brain but if you get your hands on
brains record from them slice them up
look at them under a microscope
you just like a familiarity with the
tissue of interest especially in the
context of the whole person who's coming
back and saying I don't know I'm still
hungry less hungry but I got this pain
on my left side you know what that pain
could
Are there any procedures that you would
love to be able to do? Cuz you have the
sense that it could really help people,
but the red tape is just too thick that
it doesn't even make sense to try and
develop that procedure.
>> I don't think so. I think the proper
channels are workable. I do think that
there are compassionate use cases where
you need to make exceptions and then
they have expedited protocols for that.
I remember one time I had a person that
was bleeding and it was was bleeding
that was chronically going on and
couldn't be stopped and we needed
something that was not yet approved in
the United States. was approved in
Canada and the person they had no other
option right and so we were actually
able to get within you know 12 hours
approval to use it as compassionate use
and it worked for the patient so there's
even pathways for that right so I think
there's always you know there's always a
way to use that it slows it down yeah
you're excited to do something right and
it does slow things down but um but I
think it's always workable now there are
other examples of where you have a
device that's approved for one thing
that the company doesn't want to get it
approved for everything. So, it would
have no money to do that. So, you use it
off label. That happens every day in
every hospital.
>> Just like drugs are used off label.
>> Yeah. Right. Same thing, right? So, so
um like we use wires when we're when
we're accessing a bile duct to remove a
stone, right? That wire has not been
approved for that. It was approved for
some vascular indication, right? And
we've been using it that way forever
because no company ever went through and
did it. So, the whole field is based on
this, but it was never approved for
that. So, so there are examples where
you use your clinical knowledge and use
a device that's approved. it's approved
but just not approved for that
indication necessarily. And so there's
there's that. Um and that does require
medical judgment happens on a daily
basis. Um but if you're developing
something truly new, generally the
proper channels are very workable. And
actually a lot of times they give you
even better ideas like oh why don't you
think about checking these studies like
if you're doing this check this gut
hormone, right? So they have uh you know
a lot of times they they give good
feedback that helps the study um you
know improves the study.
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When it comes to the chemicals
associated with hunger and satiety, we
could just kind of like list out the the
big players. So we're talking about the
GLPS, which obviously play a role in
satiety and other things, hence the side
effects. So what are some of the big
ones that we don't hear about so so much
anymore because of the GLPS?
>> Yeah.
>> Well, it starts grein's a big one.
That's the hunger hormone, right? So
that goes up and it is produced in the
fundus of your stomach. And uh when that
>> the fundus is the uh
>> the very top of the stomach, the top
thin part of the stomach, right? The the
kind of where the esophagus comes in and
a lot of the ghre is produced there. And
when that's how you feeling hungry,
>> so it leaves the gut, travels to the
brain.
>> Yeah. and stimulates hunger. What a
beautiful mechanism. You're the top of
the gut. You're like, I haven't seen
food in a while. I'm still, you know, I
I have to say I'm proceverating in the
background about this this thing that
the gut expands in anticipation of food
and that that's odorbased. So, does that
mean that the alactory neurons are
communicating with the gut directly? Are
they talking to insulin goes up and then
the gut expands? Does
>> insulin actually does go up, too. So,
insulin is before you eat, you'll have a
little spike in insulin, too, right? So
I don't I don't know if they ever
figured out exactly that mechanism by
which uh smell you know tasting food
early on um uh triggers or seeing food
potentially right triggers this whole
process to start but before you swallow
any food right you already have insulin
coming up a little your stomach's
already starting to stretch to
accommodate the meal so maybe some of
it's learned as well I don't know but
I'm not sure those mechanisms but it's
very interesting how it's a critical
role right it certainly is involved
>> when Was it grein discovered? I I should
know this. It was this is like over 30
years ago.
>> Yeah, it was it was it was a while ago.
Yeah. So after grein that's your hunger
hormone, right? When you eat it drops
and then you know it comes back again
sometime after the meal. So grein is one
to watch cuz we actually we actually use
ghrein. We work with ghrein. It's one of
the mechanisms we we use to to um get
our treatment effects with endoscopic
procedures and with surgical procedures
too. So that's ghrein. So then after it
kind of the food leaves the stomach,
right? Then you have your CCK which goes
up, right? Which um CCK will cause the
the gallbladder to dump bile, but it
actually also will be a satiety signal
as well. And um it that that's secreted
from the the first part of the the dueum
there. And you also have peptide Y and
GLP1. Of course, they're big ones.
Before you get there, I guess G GIP from
the K cells approximately too. GIP is
like GLP-1. It's kind of similar. It's
not it's not quite as potent. um people
think of as Batman and Robin with JLP1
and GIP, right?
>> People might um be curious to know that
this drug retorew tide that the more
cavalier peptide curious folks are
already getting off from compounding and
gray market, black market reat, as I
understand promotes GLP, GIP and
glucagon
um to I think the clinical trial Lily
ran showed a 30% reduction in body
weight, which is really striking. So,
it's kind of curious that this GIP never
really took off as a drug, a druggable
thing, but you know, GLP seems to be
like the heavy gun, but now by combining
with other things, maybe you actually
get some synergistic effects.
>> It does help. I think it helps with
nausea. So, it allows you to have higher
doses potentially of GLP-1 with less
nausea. So, CIP, I think, plays that
role. It has a role in insulin
sensitivity as well. And it does some of
the same stuff JLP1 does, and it's
synergistic, I think. But what's
interesting about the glucagon is
potential muscle sparing there, right?
So glucagon among other things. So, you
know, glucagon is usually up when your
insulin is down and vice versa, right?
And its job is is is to say burn fat,
right? That's it main job. It also
causes you to to dump your your um
glycogen out of your liver a little bit,
but the main job with glucagon being up,
it says burn fat, right? It's kind of
nice that uh they're adding that as a
muscle preservation as well as as a way
of helping to burn some of the fat
potentially.
>> Yeah, these uh pharmaceutical companies,
however a bunch of people might hate
quote unquote big pharma, I mean they're
putting hundreds of millions of dollars
into the the research. There's kind of
an amazing case of the of like 20 years
ago there was nothing for for druggable
for for obesity as I understand and what
was there was mainly stimulant based
>> like the finine and like the valve
issues but you had well you had
fentamine right which was a
sympathomimedic really um and
>> speed
>> yeah basically
>> mother's little helper kind of thing
right I mean and nicotine you know
there's a whole set of conversations
there some people think that when we you
know basically abolished smoking. Um,
people started eating more and then
America got fat. Then snack foods and
highly palatable and there are a lot of
things, right? Moving more, eating more,
highly palatable foods and less fiber.
But um, now nicotine's back in oral
forms is back big time, mostly with men,
but also with women. And um, a lot of
people like it because it's an appetite
suppressant. I'm not a fan for a bunch
of reasons. Raises blood pressure,
highly addictive, and so on. But it's
interesting, right? Like people have
struggled for forever to like how can I
eat enjoy food but not eat too much
whether it's a compound that we norm you
know a drug that increases a compound we
already make like gip or we're taking
something to make us move around more
and like you said sympathy medics it's
like stimulants it's like a human
obsession why can't we just eat enough
and not too much
>> I think it's uh obviously metabolic
dysregulation and there are of it. The
processed foods which you touched on
certainly is an element to it, right?
There was a study done I believe it was
in Bethesda NH study when they had they
had like 20 subjects and they randomized
and crossed it over and they could
either have whole foods or they could
have processed foods and the people that
were eating the processed foods they
could eat at will. They were eating like
500 calories more a day. So it is
something that you do in in your normal
environment if you're eating stuff in a
wrapper and you're eating it you're
inclined to eat more of it. And not only
are you eating more of it, right? It's
easier to digest, right? You're getting
bigger glucose spikes and you have a
lower thermogenic effect of food, right?
So, it really is it's probably also not
doing great for your microbiome because
there's less fiber in it. And so, that
is playing a big role. It starts
starting the ball rolling for sure.
>> And then there's different there's
different layers to it. Then you have
your your PY and your and your GLP-1
which the GLP1 um you know it's
triggered by anything but glucose tends
to trigger more of it, right? And then
the PY, um, that's more, you know, your
proteins and your fat. And it does
something similar. You stay full longer,
I think, and with a with a big heavy fat
and protein meal, probably because of
the the PY. Um, uh, that's something
that's been very hard to drug, right?
They didn't have a Hila monster to solve
the problem that the GLP1 did, but uh,
it's it's also very potent. And they
both come from the L cells in the distal
small bowel and the colon. And, uh,
those are those are kind of all the the
major players. You also have leptin in
the background. Now, that's more of a
thermostat, if you will. It gets
involved in it set point and things like
that. And it's that's secreted from your
fat cells. Uh, and if it's in almost
proportionate to fat. So, if it's high,
you know, generally you're going to
probably eat less. If it's low, you're
going to eat more. But there's all sorts
of problems with leptin resistance and
other things like that, too, that
complicate it. I remember coming up
through science like leptin was all the
rage. um it's discovery, it's cloning,
and everyone thought, okay, there drugs
gonna are going to come along to mimic
or stimulate leptin and we're going to
solve the obesity or overweight issue,
but it didn't really pan out. Why was
that? I think leptin never panned out in
large part because of leptin resistance,
right? I think the hypothalamus and the
uh the brain itself is is just becoming
resistant to it because it's so high in
people with obesity for so long, right?
And
>> there's just saturated. They got a lot
of fat, a lot of leptin receptors are
are clogged.
>> There's low rate inflammation we know in
in in those tissues and and you
eventually just yep you don't respond to
it anymore. And so
>> so the the drugs just didn't pan out. I
think that um with with the GLP1s it's
another story, right? I think you know
incrretins in general we've talked about
incrretins we've been talking about
these these hormones that are produced
in the gut they go into the blood and
they do something. So the concept first
came about in the 1930s and it was in it
was in London and they basically were um
grinding up animal um douadinums. Okay.
And they're emulsifying it and injecting
it back into the animal in the vascular
system.
>> Science in its not crudest form history.
This is 1930s folks said science is not
that old you know real science
>> right nittygritty right and the idea for
that was secretin. So someone had found
secretrretin right and that is that
that's a hormone produced in the
dueadium that goes to the pancreas and
says secrete fluids for digestion. So
extorine function of the pancreas. So
this person thought well wow if the
dueium secretes secretrretin maybe it
secretes something else. So he they did
this study and in the animal the blood
glucose fell and like holy cow right
this something in the dudenum is causing
glucose to fall phenomenal. I'll call it
Inkrretton because you have Sacretton
I'll call it Incretton. So that was that
was where it started 1930s, right? And
then there's another lab uh Sheila
Sherlock's lab in in London and she was
famous for being one of the kind of you
know founding physicians that that that
started the field of hepatology and she
was trained in some medicine and some
some internal medicine some surgery and
they had this concept but what they had
access to was this new tool which is
where you see innovation right they had
access to this way of actually detecting
and measuring insulin and so they did a
very interesting study where they gave
subjects a set amount of glucose
introvenously and then they measured the
amount of insulin that was produced.
Then they gave them the exact same
amount of glucose orally and they found
they produced much more insulin. All
right, so this was something they they
they coined the incrretin effect. But is
that based on taste? So they had no
idea, right? But they knew the insulin
was going up and they thought it
probably because the only other research
that was out there was from this this
old 1930s study where it was coming from
the dudenim. was probably due to that
inkerton. Then there's other studies
that come after that that get get closer
and closer to it. Right. So eventually
what ends up happening is uh in in the
uh um Lily Labs I believe it was there
was there's a physician named Bell who
actually he he the pre-p pro glucagon he
ends up you know cloning that and then
from that you get GLP1 and GLP GLP2
right and so he now he now we now have
GLP1 we've identified it and then there
was this a physician um uh Blossom I
believe was the name in in London again
this guy did some phenomenal work. So
what he ended up doing is now we had
GLP-1 so he could actually study it. He
found GLPM1 was in the bowel where we
thought it was. He also um found out
that when you actually gave glucose GLP1
increased in the blood and then he
actually infused GLP-1 and found that
when he infuses it insulin goes up,
glucose goes down. So now all of a
sudden we had a real sign that what what
what this incretin was and it was GLP-1.
Very exciting work. The problem was you
had to infuse it, right, for it to work
because it gets chewed up really quickly
by dipepadil peptidase. It chews it up.
There's something on the end terminus of
it that is susceptible to that. And uh
that's the part that binds the receptor
so you can't really get rid of it. Uh
and then it was in the Bronx in the '9s
when there's a Dr. Ang and he's studying
Hila Monsters and in Hila Monster he
finds this thing in the Hila Monsters
Venom that looks very much like GLP-1.
has one uh substitution like second
second uh yeah amino acid in from the
inside otherwise looks just like it'll
bind a receptor. The C is a little
longer and different but this is um you
know uh extending 4 uh and basically
this is the the molecule he he discovers
and this is what ends up becoming all
the GLP ones.
>> These healer monsters don't have to eat
very often so it makes a good candidate
to to stay.
>> So you do surgeries of various kinds. um
the people are coming to you, they have
they all tried GLPs and they don't like
them or they're not working for whatever
reason or they'll micro dose it but it's
not solving the problem and um what
sorts of surgeries were you trained to
do and then at what point did you become
the doctor I referred to earlier uh who
seeks out IRB approval to build
something better like like I'm a I guess
if there are multiple themes in today's
discussion but one of them is if the
really great physicians look at a
problem they look at the tools they've
got to solve that problem and if they're
not working for any number of patients,
they build something better or different
or they they increase the array of of
tools. So tell us that story. How does
that where where did that start and
where are we at? Where are you at now
with that?
>> Really for me it started in in um
fellowship. So I moved to Boston to to
learn interventional gastronurology,
right? So this is not you know
colonoscopy and whatnot. It's doing
procedures mostly focusing on
pancreatobilary. So pancreas and bilary
conditions and the big problem at the
time was really pancreatic cancer
diagnosis. And so I was moving there to
learn a new procedure uh that they
called endoscopic ultrasound. So you'd
be able to put a scope in the mouth into
the stomach and small bowel and then use
the ultrasound probe that's embedded in
its tip to see the structures just
outside the lumen and you could gain
access to them. You could put a needle
in them and that held a lot of promise.
You could maybe ablate lesions with it.
You
>> So you're feeding a needle through a
tube. You're watching it on a screen,
right? So you're not you're not using
the you're you're not opening up the the
abdominal cavity.
>> Yeah. So you can do it through this
through the mouth. So it's a natural
orifice. You're going through the mouth
rather than opening up which for
pancreatic cancer a lot of times that's
how they would do it. They would go to
surgery, open the belly up, and get the
biopsy, right? To see what it was. Uh
cuz it's really hard to make the
diagnosis. And so I wanted to learn this
new technique where you just the patient
goes home the same day. They don't feel
anything, right? So I thought it was
phenomenal. When I got there, I I'd done
a masters in health evaluation science
at Penn State before before going and I
thought that I would be doing
epidemiologic research. And when I got
there, the my my my uh mentor, Bill
Buggy at the time was a pioneer in this
ultrasound. And um he he he gave me a
needle and said, "Hey, this thing
doesn't work to make the diagnosis of
pancreatic cancer. I need you to try to
fix this. Right. And he was right. The
thing didn't work. Unfortunately, like
we had about a 50/50 chance of getting a
diagnosis with the needle. And it's
because it was it was designed like a
hypodermic needle. Like you get an IV
placed, right? The IV is not taking
chunks of tissue out of you. It's
designed to atroatically split the
tissue. And that's needles we were
using, right? So for
>> to deliver stuff, not take stuff.
>> Yeah. Yeah. So I kind of figured out
what the problem was. They didn't know
the solution honestly, but I gave him my
report and the company thought it'd be
too expensive to fix and we didn't
really do much with it. But it still
went on. when I was a couple years into
practice on faculty there and you know
we still had the problem of you know you
you take these FNAS final aspirations of
it and you wouldn't have an answer and
you know you'd have people that wouldn't
want to have a major surgery having
their pancreas taken out without an
answer and then they'd have worsening
cancer and then by the time you'd be
able to make the diagnosis it'd be too
late to treat them and help them. So
that's where I started kind of uh you
know entrepreneurial stuff right and so
my first um my first company I guess
you'd say was based on that and uh I
needed a team you know and one of the
engineers had the brilliant idea of how
to change that bevel design helped raise
the money I knew what the clinical
problem was and and and that and whatnot
but you needed a team to fix it. So we
hired engineers and we got together and
we came up with a needle that could bind
to the pancreas without causing
pancreatitis or any problems and it has
been wonderful because that that really
became very instrumental in helping a
lot of people to get the diagnosis
earlier. So we're saving lives with
that. But now we look forward to the the
fact we have preserved cell cellular
architecture. So you could do you know
precision medicine. You can actually uh
test different drugs on the tissue and
see what it's going to respond to. you
can do immuno staining and uh it's a lot
better than just having a few shaved
cells. So that was the first time I
really get involved in in trying to
solve a problem like you say and that
was before I started diving into
metabolic disease where I've spent
really a large part of my time but that
was what started it off. So just like
earlier I you know I was saying the
mechanical influences and chemical
influences over our health and biology
for what I call like reading from the
body like people get a sleep score or
your heart rate or blood pressure that's
reading obviously you're not writing to
the body but you have a structure and
you have functional readout so like if
you know someone goes I have a pain in
my side and you go okay well you you uh
give them an ultrasound there's a
massive thing there like you got a
structure there that doesn't belong
there then then you can decide to cut
open right What I hear biopsy, people
hear biopsy, they go, "Oh boy, you're
getting poked with a needle." this kind
of thing. But I might shock a few
people, but if you told me that I could
come into the clinic and spend one long
day under anesthesia and get completely
non-damaging biopsies of every single
one of my major organs to grab a few
cells here and there through the mouth
or heck, even if they have to make a
small incision one place and then zip me
back up and send me home and I can just
say, "Okay, like I'm let's just look at
all the cells. Let's see what's you
know, let's see if I have any issues." A
lot of people be like, "Why would you do
that?" Well, I'd rather do that than
walk into the clinic at 72 and go, "I've
got this pain or I'm not sleeping well
or I'm sweating or I have this bump
here." I mean, in the end, we end up
diagnosing ourselves. Well, we either
drop dead, diagnose ourselves, or
someone else diagnoses us, right? And
so, with a procedure like yours, I'm
kind of inclined to say like, would you
just get it? You seem healthy. Have you
done it to yourself? Can I come in and
get it just for uh checking things out?
We take blood tests now. People go,
"What's my testosterone, my estrogen, my
uh luteinizing hormone, my lipids, my,
you know, small uh, you know, LDL,
APOB." 20 years ago, if you wanted to
get a blood test 15 years ago and you
didn't have a problem to motivate that,
it was thousands of thousands of dollars
at best. It was very hard to find people
that give you these. Now, it's triv
trivially inexpensive for most people.
Um, so I feel like we're kind of going
that way with biopsy. So how soon are we
um going to just be doing biopsies with
non-damaging procedures?
>> So I think a lot of times with biopsies,
you have to be very targeted to get the
tissue of interest, right? So even in
the pancreas like like we said earlier,
you know, you could be even in the area
that looks like a lesion like a tumor
and not getting cancer cells out. So I
think that you have to be very very
targeted, but then once you do get the
tissue, you can do all these stains and
you can really figure out what's going
on. Is there a gen genetic
predisposition to it? Is there some way
it'll respond to one drug over another?
I think that's phenomenal. But I would
like to see the diagnostic studies
become less and less invasive so they
can scale easily. So the the one problem
with uh procedure-based diagnosis, I
like procedure- based treatment. I love
it. It's better than surgery. Um you
know going through the mouth and rather
than making an incision in the abdomen I
think has has benefits for the most
part. But when you get diagnostic
studies similar to colonoscopy, there's
a scaling problem,
>> right? So when when a patient has to
come in and spend an hour with a doctor
or two hours, that doctor is taking care
of one patient for two hours and he's
outnumbered, right? Everyone needs
screening and it becomes very
complicated. So, I would love to see
innovation in technology go where we
have minimally invasive ways of
diagnosing things, whether it's via your
smartphone and AI or it's via minimally
invasive scans and and uh um blood tests
are great because it it's quick and easy
to do. And we're not even doing talk
about metabolic health. You know,
there's several things we could be doing
non-invasively at home right now that
we're not doing that catch it much
earlier. So,
>> well, so an example is most of the time
we're waiting for hemoglobin A1C, right?
And that's the the marker of diabetes
and that's the going to be the thing
that you know once you have an A1C or a
high APOB which they're probably not
checking maybe you know an LDLC or
something right once those are high we
know there's a problem however there are
signs much much earlier than that and so
so metabolic dysregulation follows a a
fairly predictable sequence right first
it's calorie excess right so it's it's
in the western diet it's usually glucose
right so you have too much glucose
around you have too much saturated fat
but too much glucose and then at too
much glucose uh you could catch that by
doing a CGM right so that's one way you
could do it a continuous glucose monitor
you could then see if you have
particularly glucose spikes to certain
foods and if your glucose is shooting up
to 200 with certain meals you know
you're sensitive to that and maybe you
should change how you're eating it try
to eat it after having something fatty
maybe avoid it right so because we know
this is part of a sequence that's going
to lead to problems and this goes back
to the white hall 2 study which um to to
give relevance here so the whiteall two
White Hall 2 study was on British civil
servants. It was a prospective kind of
longitudinal thing and they found that
um they followed all sorts of metrics.
One of them was insulin. Fasting insulin
was one thing that they followed. They
followed other things as well. And they
saw that if someone had high fasting
insulin, they're more likely to get
diabetes long term. So, so and it was a
long period of time. It was like a 10 15
year time. They could detect this thing
15 years earlier. They could do
something about it, right? But no one
does because no one looks for fasting
insulin. And the other thing that's very
relevant here is there was another study
was the UNCC NHANE study. Okay. And um
that's another large database. It's more
cross-sectionally looking at at a at a
point in time. And what they found was
that less than a third of people that
are lean are are metabolically healthy.
That's crazy. 12% of the whole
population, less than a third of lean
people are metabolically healthy based
on their parameters. And the parameters
looked at waist circumference and
glucose and blood pressure and whatnot.
Right? So looking at metabolic signals.
The word there is start looking early
and don't look with the traditional
things. Okay, we have to look at other
things. Getting back to you know
metabolic syndrome ideas. So first you
could check for glucose. So glucose
spikes a CGM can do that. I wouldn't say
wear it all the time. Get one for a
month or two. Learn what spikes your
glucose. See if something spikes your
glucose and adjust it. Next you have
fasting insulin. Okay. So the next thing
that happens is first in anybody they
have the insult of excess calories. The
excess calories comes. That's what
happens. Insulin's job is to take that
sugar and push it into the cells because
glucose is really bad for the body. We
know this. If you look at endstage
diabetes where they can't control their
glucose anymore, they go blind. You
know, they have kidney failure. It's
killing the vasculature. It's sticky.
Glucose is sticky. It glycates things.
It causes problems. So, the insulin's
got to get it out of the bloodstream.
So, next in the sequence of metabolic
dysregulation is high insulin levels.
Fasting insulin goes up. So, you can get
a fasting insulin level. That's the next
thing you check, right? It's not a lot
to ask for. It's an inexpensive test and
you can see if you've if you've evolved
into that problem where now you have
chronically high insulin levels. And
part of that honestly is due to eating
too frequently and could be eating you
know certain things that are uh you know
high fructose corn syrups or things that
that basically u you know have a high
glycemic index or load that's going to
cause your sugar to spike. So and the
problem is if you're eating every few
hours insulin goes up and it spikes. It
drives the glucose out of your blood but
then the insulin stays high. Okay, it
doesn't go right back down. It stays
high for a few hours. So, if you're
eating every few hours, you always have
this high insulin. That's going to lead
to other problems. And the next thing
that happens is ectopic fat, right? So,
your fat exists in different areas. You
have subcutaneous fat. That's where it's
supposed to be. That's your depot for
energy and uh it's healthy there. Has
different ways of growing. Then you have
visceral fat, which is really in your
your momentum. You know, it's a it's in
the abdomen and uh in your mezzentary in
the abdomen that's around the bowel.
Okay, so that's that kind of your
visceral fat. Then you have your organ
associated fat. You have some fat around
the heart. You have some fat around the
kidneys, etc. It's kind of supposed to
be there. They're all adiposicides.
They're all fat cells. Their job is to
store fat and release it, right? That's
what they do. Then the last bucket is
ectopic fat. And ectopic fat is where
you have fat in cells that is not their
job to store fat, right? Like liver
cells or muscle cells or pancreas cells.
And that becomes that becomes a problem.
>> It's like Wagyu beef.
>> Yeah. It's like Wagyu beef.
>> Yeah. Those cows are over they're not
they don't move. They're overfed. It's
>> Yeah.
>> And and that that's you know that's
another problem. Right. So that's the
next phase of metabolic dysregulation.
And they've done all sorts of great
studies that have shown exactly from
each step what happens and how you get
there. Right? And so that's when you get
fat in your muscle and you get fat in
your liver and that's bad. Fatty liver
is very bad. And then that is what goes
on to insulin resistance. Okay. So for
the fat, how can you look for that?
Well, you can do a waist circumference
measurement, waist to height ratio. You
can get a DEXA scan that'll tell you if
you have visceral fat or you know if you
have a lot of subcutaneous fat, a CT
scan MRIs, other things will do it too.
Um or an ALT, look at a liver test
measurement, right? Uh that's
amotransferase in your liver. Um and
usually, you know, that'll signify some
inflammation. So you know that's the
next level, right? And then you have
insulin resistance, which that's a
little harder to check. That's a
combination of there's a formula that
you can do to look at that. It's a it's
a a fasting blood glucose and a fasting
insulin level. And you multiply those
and divide it by a constant. And if it's
greater than two, you have insulin
resistance. So that's the next next
phase of it. And then finally, you have
metabolic inflexibility. Your body is
supposed to change between calories,
right? What is burning? If you're
fasting, it's supposed to be burning
fat. And if you're eating, it's supposed
to be burning some element of carbs
depending on what you eat. But if you
have carbs in it, it should be burning
the carbs, right? And so you can develop
metabolic inflexibility as the next
phase of this once you have insulin
resistance where when you're fasting,
you're not really accessing your fat
anymore. Your fat's still there. It's
burning more your glycogen stores and
god forbid it's chewing up muscle,
right? But it's it is no longer
accessing the the fat stores is supposed
to be accessing. And then when you eat,
it doesn't shift over to burn the carbs
well either. kind of just it doesn't
know what to do. So that's a loss of
metabolic flexibility. And by then
you're getting near the time when all of
a sudden something's going to happen cuz
once you have a loss of metabolic
flexibility, they've shown in studies
that you're more likely to gain weight
and develop obesity. You're more likely
to start losing beta cells. You start
burning out your beta cells and they
became apoptic and you lose beta cell
mass and you start having all sorts of
other problems. So this is a very kind
of typical sequence that you see. It can
happen in other ways, but that's a
typical sequence that's backed by
science and different clinical trials.
And each each step of that way, you have
a study you could do to find out about
it. The last one, the metabolic
flexibility is a little harder because
you you have to do kind of go and do a
breath study for that where you're
looking at gas exchange and it's very
accurate actually because we know that
there's a respiratory exchange ratio.
Um, athletes do this to optimize
performance. You can do this where you
get a DEXA scan. A lot of places they'll
tell you how many calories you're
burning or what you're burning. And
basically it's you know first law of
thermodynamics and you're burning
calories but it's a ratio of a volume of
carbon dioxide divided by volume of
oxygen. When you eat carbohydrates
carbohydrates have an equal number of
carbon and oxygen. So it doesn't require
much oxygen to to burn the
carbohydrates. But when you burn fat it
requires more oxygen. So if that ratio
is like 7 uh so it's it's carbon dioxide
oxygen that means you're using more
oxygen. That means you're burning fats,
right? And if it's one, you're burning
carbs. And then there's an in between.
And so this is a great way to see if
you're metabolically flexible. Eat fat,
see what happens. Eat carbs, see what
happens. Do it fast, see what happens.
Right? And you sit in a chair, and you
breathe for half an hour. There's
companies that are actually developing
at home method that's doing this, too.
There's a few of them. And actually, one
of them recently, I think, now has one
that does both the oxygen and the carbon
dioxide.
>> I've seen this like a little box that
you breathe in, too.
>> So, I mean, you can do everything,
right? So, and then or you can just wait
until you have diabetes and your A1C
goes up. And so, yeah, there's a lot of
things we should be doing before we do
the standard test of looking at your
fasting glucose and looking at your
hemoglobin A1C.
>> I'd like to take a quick break and
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It's gratifying to hear that you put the
CGM uh pretty early on that list. Very
early, in fact. I mean, I I don't I want
to be clear. I'm neither complaining
about nor am I um trying to turn you
against your colleagues. But I'm going
to just be really blunt from and these
are my words and my words only. I want
people to understand this. Like I mean,
I've gone public many times saying,
"Hey, like as the cost of blood testing
comes down, this is awesome. you get a
window into uh lipids, hormones, things
that can be very informative whether you
have issues or not. And the push back on
that from the medical community, not all
cuz I have friends in the medical
community who will quietly say, "Yeah, I
totally do that test. I take that test,
you know, but many of them just say,
"Oh, great. Now patients are going to be
coming to me saying like, I need to do I
need to be worried about this? Do I need
to be worried about this?" I said I
actually put a post out recently that as
the cost of of whole body MRI comes out.
It's going to be interesting to see what
happens. I have neurosurgeon friends who
tell me about life-saving procedures
they they do all the time. The
neurosurgery community was super angry.
It generated some press this week.
Actually, uh this is how the the tables
kind of turn. There's a celebrity, I
forget their name, who took a one of
these types of scans from a company I
have no affiliation with, by the way. I
took a POVO scan and um identified a a
malignant issue that could be cut out
and very likely saved their life or at
least extended it. So, I get it on the
one hand why a lot of physicians are
worried about people walking around with
a lot of data. I heard the same about
CGMs. Okay, I'm gonna try not to rant
here. It was like, "Oh gosh, who needs
to know their glucose goes up, glucose
comes down in the absence of diabetes or
pre-diabetes?" Like, you can have a
glucose spike. We don't want people
walking around neurotically worried
about eating a grape, which I totally
understand. Your body can manage these
things. But now that CGMs have been out
for a couple of years, I don't hear much
push back. Yeah, somebody wants to use a
CGM for a couple weeks and see how they
react to different foods post exercise,
post poor sleep, etc. Cool. So, it's
kind of wild to me that physicians don't
want patients to have data. But here,
I'm hearing something very different.
You're saying, "Yeah, it's I think
people should pay attention to how
they're regulating their blood glucose."
The problem with medicine is it moves
very slow, right? So, a lot of people
are going to want you randomized control
trial, another randomized control trial,
maybe a few more, and then a meta
analysis, and maybe understandably, but
from a patient perspective, people want
data now. if they can get it
inexpensively. And by the way, these are
are they called elective or elected
>> procedures? They're elective. If they're
elective procedures, so no one's saying
you have to get this done.
>> It's an option.
>> Yeah.
>> I don't get it. Can't wrap my head
unfortunate. It's it's it's unfortunate
that um there's there's a reason for it.
Obviously, do no harm, right? There's a
reason for it. But by the same token, it
does not necessarily
um do the patient any favors by waiting
for something that's that that is
logical and makes sense, right? And
there's enough evidence for this
sequence of events, if you will, for
metabolic illness all the way back to
syndrome max in the 80s, right? We know
there's this constellation of things.
And we also know that if you don't act
early, you're much less likely to have a
good treatment effect. If you start
treating someone once they have
diabetes, it's much harder to get them
back to healthy and normal. They've
already lost beta cell mass
>> or peripheral nerve. I mean they could
have loss of their fingertips and toes
or sensation, excuse me, in their
fingertips and toes.
>> And now before I mean we might not have
had access to things. We had access to
fasting insulin, right? But think about
this. So say you don't get the CGM and
you have fasting insulin, right? And the
fasting insulin is normal. You don't
know if step before that is a problem
and you're going to have problems with
fasting insulin or if it's abnormal, you
need the CGM to learn how to eat, right?
Because that fasting insulin is high for
a reason. you're spiking your insulin or
you got to figure out why you're spiking
it, right? So, so then you go back to
the CGM and you learn and I don't I
don't have any stock in the CGM company
either. You got to learn how to eat to
not spike your insulin in that case.
Now, if you're taking a bunch of, you
know, saturated fat, that's not great
either. You can't be on super high
saturated fat with an Ape B through the
roof. But, you know, either way, it's
not good, right? So, most of the time in
Western countries is it's the glucose
and insulin that are the problem. And
it's the very beginning of it. So, why
not learn about yourself? take some
responsibility, right? Learn and and
prevent these diseases from from going
on. And I do hope physicians are are
more open to kind of encourage this as
well. Um where we start acting earlier.
It's going to it's going to be better
for the, you know, for the population in
general.
>> Yeah. Because I could see why physicians
would be very reluctant towards
self-directed interventions. I get it.
But here we're just talking about
getting data and it's voluntary. The
costs are coming down. And as you point
out, having data early is better than
having data late when it comes to um
physician guided interventions. So what
I've what I've heard in this regard is
um you know I with in conversations is
well the problem is a patient's going to
then figure out they can eat junk food
like like a like something that's really
bad for them. you know, some greasy
fatty thing that's unhealthy for them,
going to, you know, put their, you know,
APOB through the roof and they'll think
it's okay cuz it's not showing up in
their CGM. I think it's not giving the
patients enough credit because generally
if you're getting a CGM, you probably
are are trying to do the right thing.
So, I think it's how will they use the
information? Could they accidentally not
be informed enough to to use that
information appropriately and could they
do the wrong thing? But again, I think
more information is better almost in all
circumstances with diagnostic stuff.
Now, I agree with this MRI thing being
concerning because you might have a lot
of little lumps and bumps there that now
you're doing diagnostic studies for that
could increase risk,
>> right? So, because diagnostic studies
could increase risk and also could be a
burden on the health care system, but
>> more information I still think more
information is better. We just have to
find better ways of doing the followup
confirmatory diagnosis. there might be
other ways we can do it. Looking for
metabolic activity of tissue like PET
scans or what doing other things rather
than a biopsy and and something that
would increase risk.
>> Okay. Well, thank you. I wasn't asking
you to take my side in the argument, but
since you threw out CGMs first, I just
kind of took that as an opportunity. I
think uh my um I won't name names, but
let me put it this way. Whenever I get
that sort of push back, I'll go to
people I know in the field and I and
I'll say I'm not looking for
confirmation that I was right and they
were wrong. to tell me what what I'm
hearing here. What what's beneath what's
the layer beneath what I'm seeing? And
almost inevitably they say the same
thing. Give it 20 months. This will be
standard. And that happened with CGMs.
No one bulks at the idea of a CGM. Yeah,
you want to put that thing on, you can
afford, you want to get some data. Like
most people, most physicians I know now
are comfy, but at the beginning it was
like all the push back in the world.
That's really wild how. So wait 20
months and and this will be a non-issue
is what I keep hearing again and again.
Well, even when you have procedures that
have gone through rigorous, you know,
evaluations and they have FDA approval
and, you know, they're they're ready.
You have so many people that are
reluctant to send patients for them,
right?
>> Why is that?
>> Yeah, I think it's it's in the culture.
>> Are they afraid they'll do it wrong?
It's like a new skill to learn.
>> That could be. So, some of these
procedures, you can't learn them in a
weekend course. You know, you have to
spend a year or or longer learning some
of these things. And so for a physician
who wants to add something to their
practice, that's they're not going to
dedicate a year to it. They might do a
weekend course and realize it's it's too
hard and then they don't they don't
adopt it. The problem is the people that
do adopt it and they're not ready. So
then doctors that are referring go,
"Huh, this procedure's been around for 6
months or a year. It really has great
data in the clinical trials, but does
the guy down the street know how to do
this after doing a weekend course?" And
so they were reluctant maybe for that
reason. So just give it time. and wait
until it's maybe insurance not covering
it yet, right? Wait to see if the
insurance companies think it's it's it's
a good idea, then maybe we'll start
sending patients. So, it just it's it
moves slowly.
>> Yeah. Well, I don't want to you hover on
this too long, but I have a friend who's
really into cars and uh he told me that
in the mechanic and automobile
community, a similar thing like as
things became more and more
computerized, there was a lot of push
back because it makes it hard for auto
shops to do their um their work. You
know it changes the the field changes
and you need more tools. Sometimes those
tools are expensive. You need training
and people like to hold on to the way
they were trained. This is absolutely
true of most every field. Adapt or die
or your patients die there. Um that's my
you know if you don't adapt your
patients will die. I have to imagine
that there are good surgeons there are
mediocre surgeons and there are
exceptional surgeons. Are there places
where you've brought in devices or
machines that could offset the mediocre
and um lousy surgeons or surgeons by day
sleep a little sleep deprivation? So I'm
not just saying like bad surgeon good
surgeon but there so what has come into
the field that's allowed you to do your
work more effectively and others to do
the work more effectively.
>> Most devices we see are kind of
incremental improvements. a little bit
of better wire, you know, devices a
little more ergonomic. But what I see
kind of happening more recently is AI
starting to have an impact where it can
actually coach you through procedures,
which is kind of work. You have an
earbud in or something
>> uh on the screen itself, it's like a
heads-up display, right? On that
heads-up display, uh it will actually
give you information so you're not just
seeing the images you're working on. It
can actually highlight certain
structures you want to work on. It can
actually point to something where you
want to put your stitch, right? And it
can count the stitches as you're placing
them and tell you if they're close
enough together. It can change the shape
of the stomach as you're working on the
stomach to let you know if you're having
a good treatment effect. This is
something that we we never could have
have done before in real time.
>> Real time. Yeah. Which is phenomenal.
Right now it's not widely available yet.
This is in research centers, right? But
you actually can see this happening in
real time and um it's it's phenomenal.
So you see that in more and more it's
happening in different surgical
procedures where AI is kind of real-time
coaching you and in endoscop endoscopic
procedures. Additionally there's the
hope for robotics to help as well and
we've done a lot of research in our lab
on robotics and how it can take trainees
that are learning a new very complicated
procedure and shorten the learning curve
dramatically. And we'll randomize the
trainees and have them do the
traditional way like this is usually
resecting a tumor from the colon leaving
the colon in place. That's a very
complicated procedure and or from
somewhere else in the in the stomach or
whatnot. And the fellows will learn
they'll spend a couple of weeks training
in both modalities and then they will
struggle horribly with the original way.
That's why it takes two or three years
to learn how to do it. They'll sit down
with the robot and be almost good as an
expert. So robotics are very interesting
and now in the future we haven't done it
yet. But when you start layering on AI
and automation with the robots, now you
might have a big win. And we we've seen
this before with different surgeries as
well with the with you know intuitive
surgicals robots when they first came
out years ago. It democratized the
field. It took mediocre surgeon it made
them excellent and the excellent
surgeons were still excellent right but
it really helped the ones that were
struggling.
>> How the excellent surgeons feel about it
in keeping with our previous discussion.
>> Seriously like are is it is it is part
of it's like is it like athletics like
it people want to be they want a
hierarchy of performance um for
themselves. they don't want patients
dying at the hands of poor surgeons. But
I would think that um if do no harm is
really the the uh the true um central
cord of medicine, then every person in a
field would want more people being
healed independent of their own stature
as a physician. Yeah, I think they're um
supportive of robots, but I think that a
truly exceptional surgeon is probably
just going to be better without the
robot and just, you know, the robot is
just it's going to it's going to make
you worse.
>> How do I know if I'm getting a truly
exceptional surgeon?
>> That's a good question.
>> Understanding do am I getting the best
physician for this thing is really hard
to determine.
>> Yeah, that's common across all medicine,
right? And even as I'm looking for a
doctor for something, it's hard to find
the right person. I'm in a massive
medical center, you know, and have great
connectivity. But knowing who truly is
the best is complicated, right? So some
things we rely on are volume, case
volume, and historic case volume. So how
many procedures do they do? That's
important. And probably more important,
how many have they done over the course
of their career. So if you're having a
procedure, you want to know volume
because volume is important. It's not
the whole story, but volume is
important, right? And we need in
medicine honestly to move more towards
objective metrics. And this is one thing
AI can do for us. Right? I'm involved in
a um a healthcare delivery platform.
It's called Everself. And what it does
basically is the doctors that are doing
these procedures are held to a certain
metric. Right? So it starts with just
collecting the data, you know, finding
out what their weight loss outcomes are,
finding out how many stitches they place
per procedure, looking at their
procedure time, looking at their
complications. So, you're grading all
that, but the next layer is putting this
AI on top of it where the AI, not only
can it coach you through the procedure,
it can give you a grade at the end of
the procedure. It can be very specific
and it can tell you you placed this many
full thickness sutures versus this many.
You want 100% of your stitches to be
full thickness. Maybe the doctor's
putting in 70. They're full thickness.
That's not good. This number of sutures
were close enough together. Some were
too far apart. It will give you a grade.
This is the pattern used. This is the
volume of stomach you reduce it by.
It'll give you a grade at the end of
that procedure. And that grade is
incredibly important. And then the the
idea next would be is to share that data
so people know kind of what grade you're
getting. It'd be great to share that
with governing bodies that do
credentiing. So people that are truly
underperforming, maybe they should get
refresher, right? It would be nice for
patients to be able to select, you know,
who they're going to go to based on
objective metrics. And AI can do this
probably across the board with other
things as well. So that's part of it.
We've seen this a little bit with ADR,
edenoma detection rates in colonoscopy
where they used to publish that and they
stopped doing it. So doctors were
expected to have a certain number of
polyps they'd see per colonoscopy and
they'd report that. That was something
that was another way. But then the
problem was all the patients wanted to
go to the one or two doctors that had
the highs and their weight times became
enormous,
>> right? And then patients couldn't get
access to them. That's a problem as
well. But there should be a reasonable
cut off where a certain level of
expertise is required and um you know I
think AI you know hopefully will help us
get there. I'm excited by what you told
me about how AI can um provide real time
data and perspective data about how the
stomach will change shape in with the
opportunity to make the adjustments as
you go as opposed to having the patient
heal up and have to have to come back in
for another surgery. years ago, I saw
something amazing. A a neuroopthmologist
um friend allowed me to sit in on a on
something. He said, you know, people
forget that surgeons wear microscopes on
their eyes, right? They they wear these
like um uh optics that allow them to see
things bigger obviously, but then there
are all these new tools that you know
like a little drop of florosine, a
little bit of like innocuous uh liquid
that creates a contrast for the for the
surgeon or for the eye doctor to see
what what is what and not cut the wrong
tissue. It seems like a like such an
obvious thing, but I was told that for
you know a hundred years the same
procedure had been done without that.
And so eye surgeons had to essentially
guess based on their intuition, their
training of what was tissue to uh
preserve what was healthy, what was
unhealthy tissue. I mean these what seem
like kind of simple to us now
technologies have improved the margins
of safety have improved the you know
outcomes tremendously. And so the idea
that you would have AI combined with
really good microscopes either worn on
the eyes or you're looking down a
microscope better surgical tools to me
it just seems obvious like yes yes and
yes
>> but a lot of people hear AI they hear
robot and they hear surgery and they go
oh my goodness like what if the they go
to the extreme I think with AI people
think it can go rogue has a mind of its
own so I don't want you to give false
assurance that that's not going to
happen but when you sit down to do a
procedure and you're getting information
from AI where does your trust come from
that um it's giving you good information
as opposed to faulty information.
>> Yeah. So the AI is is trained on
thousands and thousands of procedures,
right? So more than I' I've done, right?
So
>> which is good and so it recognizes
patterns. So you have to use your
clinical judgment and you're not doing
you're not using this AI kind of
blindly. You're using your clinical
judgment and you might ignore it
sometimes. You don't have to follow it.
Now, if it becomes the time where you're
automating
operative robots using AI,
>> like suture placement,
>> that'd be different. If it's doing it
itself, that's different. But for this,
where it's just suggesting where you put
a stitch or showing where a blood vessel
is, I think it's a huge advantage. So,
we do these procedures that are very
technical where where you tunnel, you
know, you're creating a potential space
in the esophagus. So, back to that
earlier um person that couldn't swallow,
right? They had trouble swallowing
because they had acalasia. So the
procedure how we do that is we go in
through the mouth. We inject a little
fluid under the mucosal layer to to lift
it with a with a pocket of fluid. We
make an incision in that and we take the
endoscope. We slide under in between the
mucosal layer and the muscle. We dig all
the way down to the bottom of the
esophagus and then we cut through the
muscle. When you're doing that, there's
vessels in there and they're hard to
see. AI can actually see those vessels
because it's got pattern recognition and
color them for you so you don't hit the
vessels as you go, reducing your chances
of hitting a blood vessel. Right.
Beautiful. So that's just one example of
something that's a very complicated
procedure and you're certain you're
you're you're making certain aspects of
it a little easier. We think that
>> physicians are looking at the equivalent
of a medical textbook with coloring, but
it's not. It's black and white and gray
and beige and there are certain
structures that look different that are
contrasty and look different. So now
with with endoscopic ultrasound, it's
not even color. It's all gray. So when
we're doing endoscopic ultrasound, we
talked about looking for a pancreas
tumor. It's all gray. It's just
different shades of gray. There's no
coloring to it. Now, you can you can
turn on a button to see if there's blood
flow, right? But it's all gray. So, I
years ago in my lab, I was trying to use
image registration. So, I could take a
CT PET scan and I could link it to the
the angle of the probe and you could see
a CT scan fluctuating in the probe of
the ultrasound and lay the overound the
ultrasound over it and then you get an
idea of the tumor you're looking for,
the leion you want to biopsy or
whatever, right?
>> It was too hard to do. it would take
three hours of preparation to be able to
set that up. You could never scale that.
Now with AI, other groups are doing
similar work now and it's it's almost
automated. So I'm hoping that we'll see
image registration with these very
advanced imaging tools that are being
used help us with diagnosis and
hopefully even with therapy too. They're
they're doing something now called
hyperspectral imaging and they're doing
it in surgery as well. There's several
groups doing this. One group in Lond is
doing phenomenal work. They're using all
these narrow bands of wavelengths, just
tons of wavelengths, and they're finding
out that each tissue actually has a
fingerprint. So, you can actually use
this this hyperspectral imaging to
fingerprint tissue, and you can actually
see margins of tumors with this. And
it's very interesting without giving a
die anymore. So, you still might want to
give it for lymph node testing or
whatever. Sometimes they'll inject
something into a tumor and then look to
see if it gets into lymph nodes. That's
different. But this is for actually
looking for margins or for lesions. And
it's just with light technology, it's
amazing. So that's what LEDs are doing,
right? In different kind of cameras,
right? So instead of CCD chips, you have
CMOS, right? And so with newer
technology, even though it seems
incremental, with LEDs being able to flu
kind of fluctuate the wavelengths of
light and your chips being able to read
it faster and better, we're able to make
better diagnosis.
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like uh one structure that we could um
conceptual structure that we could put
on things. I'm realizing today is
medicine has a couple of different ways
to determine what's going on, for better
or worse. One is the stuff that comes
out of the body. And we do this with
babies, like, oh, their their mucus
looks really green. We do this maybe I
have a sinus infection it comes out of
the body or with bowel movements or
we're not so good at gauging the color
of blood kind of things or then we have
surface of the body power of skin how
the eyes look do we see you know uh
stuff that we don't normally see and
then you know the age-old story where
like was like phronology which was like
you know complete bogus but it was like
oh can we figure things out from the way
things are changing at the level of the
the shape of the skull is complete
nonsense right but as we go in. We're
still trying to do this, right? X-rays
let us see, you know, fractures and
things with, you know, you don't want
too much X-ray uh radiation, but the the
goal has always been to get more
information with with less uh in
invasive procedures. And I feel like now
we have blood tests so you can pull
stuff out of the body. And it's kind of
wild that in 2026,
this is where we're at. I think it's
super exciting, but you know, hasn't I
mean, 50 years ago, the tools were
really crude there, but I think they
might still be kind of crude now
compared to where they are in 10 years.
Are you hopeful that in 10 years you can
go into a tube, 20 minutes later, walk
out, and we might be able to scan with
good enough resolution. Do you have any
tumors anywhere? Compare that to a blood
test and um you're good to go.
>> I don't know if we'll get there. Um I'm
hoping right because we are seeing
capsule technology improve. We're seeing
imaging technology improve and blood
tests improve and there's all sorts of
things you can do with with kind of
genotyping things and whatnot. I think
that's exciting but where we are seeing
improvements I think are in learning
about physiology and how things work and
then being able to do a targeted
approach. So you're not just doing that
with drugs where GLP1 is actually GLP1
isn't really targeting a deficit
necessarily. There's different ways you
can treat things. You can either find a
pathology and treat the pathology,
right? Like cutting a tumor out. It's
kind of like treating a pathology. It's
not supposed to be there. Or you can
take normal physiology and augment it,
right? And that's what they're doing
with GLP1. There's not like some
horrible GLP1 deficit. That's that's
totally clear, right?
>> But they're ramping things up
thousandfold over what they would be
even the healthiest person. Most people
don't know that, by the way. They think
that like the GLPs are bumping things up
like two or four fold. It's like no,
never before in human history, at least
to my knowledge, have people walked
around with this level of GLP-1
circulating in their blood.
>> Yeah. You're supposed to have a little
tiny amount that's produced in response
to a meal, right? And then it goes away,
you know, and it's kind of like, you
know, relatively speaking, not this is
super physiologic doses. You're bathing
the area postrea in this chemical,
right? And it's like it's not
functioning like in a physiologic way.
Our GLP1 is secret. It's nutrient
responsive. It's secreted from L cells,
right? And then it does its job. It goes
to the pancreas, says produce insulin.
It goes to the stomach, it says slow
emptying. It goes to the brain, it says
you're full. It does things like that,
right? And it does it in response to a
meal and it's in much smaller doses like
you've said. So medicines have done this
for a while where they kind of see
something as a mechanism they can
augment or they see a pathology they can
treat. But that augmenting is very
interesting. And surgery for a long time
wasn't doing that. They were just
thinking, "Oh, I'm going to make you
malabsorb calories. I'm gonna make this
tight so you feel full quicker. But now
that we're understanding mechanisms and
there's some great research that have
gone into this, we can actually develop
targeted therapies. And I think that's
what's very excited. It's more so even
than than a new device. It's being able
to do targeted therapies and get better
outcomes with that. And where I started
with this is um in fellowship. So I saw
you know I saw a patient with a gastric
bypass. So they have a gastric bypass
anatomy. They have a small gastric pouch
like I mentioned and a bigger stomach.
And a patient was sent to me that had
bad reflux. They had weight gain after
the gastric bypass. And their diabetes
came back. Their diabetes was gone, but
now it come back. So the surgeon
basically said, "Hey, take a look at
this patient. See if they have an ulcer.
What's going on? They're having all this
pain and heartburn. Find out what's
going on." So I went and looked and
there's this little hole between the
pouch, the new stomach and the old
stomach. And I thought, well, maybe the
acid is produced in the other side.
Maybe the acid's coming up through that
fistula. And we had a new device. It was
a suturing device that you could
actually put in through the mouth and
put stitches in. I thought maybe the
suturing device I could use it to close
that hole, right? So I waited until I
was on faculty a few months and I talked
to the surgeon. He was supportive. So
again, this is kind of that thing. Are
you inventing something? The procedure
is FDA approved. The device is FDA
approved. The procedure is not. No one's
closed official with us. But we talked
to the patient, you know, we told them
we weren't sure if it was going to help
or not. We tried to do it. They were
willing and we did the procedure, closed
the fistula. And so I was hoping the
reflux would stop. The reflux stopped,
but the person started losing weight and
their diabetes went away almost
immediately again. And that was for me,
and this is 2003, 2004, 2003. I was like
>> flabbergasted, you know, was it a
coincidence? What the heck was that? Why
is closing that little hole so
important? Right? So that's what got me
involved in understanding these the gut
hormones honestly and because we we were
able to now if I learned about the gut
hormones and why we saw this treatment
effect we could potentially manipulate
them to get a to get better results.
Right. So that was the beginning of it
for me and uh there was shortly after
that uh one of my friends and colleagues
actually did some uh animal work. He had
a rat model and they're called GK rats
and they're rats with diabetes that
don't have obesity. Okay. And they were
a great model for this because you
didn't want weight loss to confound
things. And so he did two surgeries for
gut and hind gut method, right? So the
the one surgery he basically excluded
the for gut. So he excluded the
douadinum and the very first part of the
digunum. Okay? And he did he did a
little bypass surgery there so no food
could get in the dueum. Went from the
stomach and it went to the the very
first part of the dudenum and then boom
down into the junum. Not touching that
for gauging that bowel. The other one he
did a gastroadunal anesmosis. So stomach
two small bowel but he left the rest
open. So food could go either way. He
could go into the douadum like it
normally would in the fore gut or go to
the hind gut dropping down into the
distal bowel.
What he found was these were diabetic
rats. He did glucose uh tolerance tests
on them and he found that the ones that
had the exclusion, their diabetes got
much much better. The ones that didn't
have exclusion didn't get better at all
even though you were dumping stuff into
the distal gut. Very interesting. So he
thought there was something very
important about for gut exclusion and he
hypothesized there was something called
an anti-incretin in that bowel that
would maybe protect against hypoglycemia
but there was something in there that if
you exclude it you got a better
treatment effect. So that was, you know,
my fish work and then his his very
interesting animal work got us going
down that path. And it kind of fed well
into something that actually was done uh
in the 1980s that that was from uh a
continuation of that work that Sherlock
had done looking at incurrins and this
famous publication by no and uh what he
did is he looked at the same the same
study that that Sherlock did in London
where they were giving glucose to look
at the insulin response but he did it in
diabetics and he did in a normal
population normal healthy population.
The normal population had that exact
same incrretin response where you gave a
certain amount of glucose introvenously
little spike same amount of glucose
orally big spike. Diabetics didn't do
that and they had already tied it maybe
to GLP1 and maybe in the in the in the
bowel. So very exciting. So maybe by
excluding this for gut you're playing a
role you're having something to do with
that or maybe not. So that was the
beginning of trying to understand the
procedures for me. And um with that I
then did another study where I closed
those fistulas right and uh and where we
closed the fistulas 60% of people had
resolution of their diabetes. If we
didn't close it no one got resolution of
diabetes. So okay that's a good thing.
So we learned there's some important
element to to for gut exclusion. Then
there's various device companies that
start getting involved in the space
because there's this there's this
information out there that excluding the
for might be important and a company
comes up with the idea of putting a
liner in endoscopically. So it's like a
little sleeve you anchor it has a little
dent that springs open you anchor it in
the first part of the small bottle. It
covers the dueum protects it. It's
implant so it has to come out right at
some point in time maybe a year later.
But it was very interesting because uh I
was I was part of those those those
clinical trials and we found you had a
one point in diabetics you have a
onepoint drop in A1C that's fantastic
and you lose weight about seven 7% total
weight loss. So clearly it's doing
something and it's it's important. The
problem is it's an implant. It's got to
come out but it's exploiting this
mechanism potentially.
>> So you're essentially um cinching down
this compartment of the the gut or
you're create you're creating more
compartmentalization along the the tube.
>> Yeah. the douadinum, right? And then
there's a liner that you place in it.
So, this is like a stent. So, it springs
open and holds its form inside it. And
then it's a sleeve that kind of goes
down. So, you can still get all your
secretions that go on the outside of the
sleeve and track down, but it's right
after the pyloris, the outlet of the
stomach. So, all the food is going in
the tube. So, the food is inside the
sleeve. The digestive enzymes are
outside the sleeve and they don't mix
for a few feet down. So, that's very
interesting and it worked. The problem
is it's it's still in clinical trials,
been around for a while, but it's an
implant. So, it's just like taking a
drug. Eventually, it has to come out.
>> But then there was a there was a
brilliant idea that came about one of my
colleagues at at the Bighgam. He's a
cardiologist, right? And he knew I was
trying to do something that was so I
traveled to Brazil, right? And I was
doing surgery endoscopic procedures in
Brazil and there was a doctor in a room
nearby and that doctor was doing a very
novel experimental surgery called ilial
interposition. And what he was doing,
this was a lean diabetic. So they they
weren't suffering from from obesity.
They had type two diabetes. And he was
taking this the small bowel, the distal
small bowel, kind of the opposite a
little bit of what Rabbino had done.
Took the distal small bowel and he moved
it up, kept it on his mezzentan blood
flow. He resected it out of the out of
the out of the distal small bowel near
the colon and he moved it up and he put
it near the dudinum. And his idea was,
you know, the concept was that GLP was
denser in that part of the bowel and it
was also denser, you know, down lower.
And if you moved that up higher, you'd
get a more immediate icon effect from
GLP-1. So you'd hit GIP and then
immediately GLP-1 and you'd have this
amazing effect. And he did. It was
incredible. Right? These people, their
diabetes went away and they didn't lose
any weight cuz he didn't actually have
any blind areas. The food, he didn't
change anything. There's no restriction.
There no absorptive change. He just
moved that part of the bowel up. That
was phenomenal. So I was trying to do
that endoscopically by harvesting uh
tissue from the illium via colonoscopy
creating stem cells and then injecting
it in the fore and getting him to take
and hopefully getting an effect that
wasn't successful but one of my
colleagues is a cardiologist and he
actually said why don't you just burn
the douadinum you know ablate the
douadinum there's different ways you
could do it you could do it with steam
hot water um etc just ablate it and see
if you can reset those stem cells
because the duadinum is sick Okay. And
this is very interesting research to
prove the dudim is sick. We should
probably talk about but you know the
dunium is sick. If you can reset the
duodum it might work. And I said why
don't you do it and he did and he
started a company and it's been great.
So and that that that is something that
we're studying more and more of. And now
you don't have a sleeve in place. You
don't reroute any bowel. You just ablate
the douadinum. Okay. And what happens is
your A1C drops by over a point. You
don't lose a lot of weight by just
ablating the douad, right? But your A1C
corrects. That's a a potent a potential
treatment for diabetes. They've also
done some studies. Uh I don't believe
these are published yet, but I think
that is showing that when someone comes
off a GLP1, if you use this treatment,
it keeps them from regaining their
weight. So, you can take a GLP-1 and
then have your douad kind of reset, if
you will, the stem cells come back and
uh you've maybe heal those tight
junction and other problems that you're
having. So,
>> so it regenerates.
>> It regenerates. Yeah. It comes back more
healthy and more normal.
>> And the rationale for that comes from a
lot of very good research. Right. So
there were studies that showed uh in
mice that if you feed mice, you overfeed
them, an overfeeding study and you have
a control group, you don't overfeed.
When you take them to the necropsy and
you look at their their bowels, the
bowels in the in the the overfed mice
are longer. They're heavier. The vill
are longer. They've adapted. They've
adapted. They've upregulated the ability
to absorb calories. And then these
studies have been repeated in humans
where people getting gastric bypass,
they're already going to be doing
surgery on them. So they resect part of
their small bowel and someone getting
cancer surgery is a control patient that
resect their small B. They look at the
differences and there's extreme
differences, right? The villa are
longer, it's thicker, there's more
inflammation in people with obesity or
type two diabetes. A lot more
inflammatory cells. The natural killer
cells are up eightfold. Uh macrofasages
up 1.5fold in these studies, right? So
you have more inflammatory activity
going on in these patients. The only
thing that's different is really
obesity, right? Additionally, if you
look at those patients and you you do uh
amuno staining for like zonula including
like tight junction protein, scaffolding
proteins and proteins, you'll see that
those are much lower and they're
disorganized. Two questions. So, if I
understand correctly, if people overeat,
the villi, like basically little
finger-like protrusions inside the gut
that can sense things but also collect
nutrients, right? They're growing to
adapt to the elevated levels of
calories. And so then essentially,
you've changed the digestive tract in a
way that yes, they can make more use of
of those calories, but that also creates
a more pro-inflammatory environment. Do
I have that correct?
>> That's absolutely correct. Also because
they're changing in configuration and
you're using that energy, the cells are
using energy to do other things, your
tight junctions are dep prioritized.
>> Okay. Right. So then there's this um
secondary uh or parallel effect of the
the tight junctions. We haven't really
talked too much about tight junctions
here, but um I'm not by no means an
expert, but I'm familiar with them from
the bloodb brain barrier. Like like
cells need to stick together. And some
tissues you want things sticky but not
too sticky. Some tissues you want them
really sticky. And my understanding is
that the tight, as the name uh suggests,
tight junctions, the goal is to keep
stuff inside the gut, not let bacteria
out.
Is leaky gut a real thing or is leaky
gut? Because I've heard it's sort of
like chronic fatigue syndrome that a lot
of the standard medical community, they
hear a chronic fatigue syndrome and they
go, "Okay, that was made up by people in
the Bay Area." I'm only half kidding
here. I'm from the Bay Area. But that's
how a lot of physicians react online to
this phrase leaky gut. But we've had a
fair number of people come on here and
talk about tight junction deficits,
bacteria getting out of the gut. This
isn't good for the body, inflammation
going up, bacteria circulating places
they shouldn't be is not good. So, is
leaky gut real?
>> Well, increased gut permeability is 100%
real.
>> But that's I mean, I'm not pushing back
on you. That sounds like like that
sounds like a different language for
leaky gut.
>> Yeah. So it is.
>> So why so why is this phrase leaky gut
so um no pun intended so irritating to
the medical community?
>> So I think if you say leaky gut it could
have other connotations that you don't
know what it means to the person.
Someone might think that leaky gut means
that it's responsible for a certain
constellation of symptoms potentially
>> like irritable bowel or Alzheimer's like
they can take a leak.
>> Yeah. Yeah. cuz cuz you see in in in lay
literature, right, they'll in other
literature they say leaky gut is
associated with XYZ, right? And it's not
clear that that that phrase leaky gut is
is is really talking the same thing I'm
talking about. Now, is leaky gut the
same thing? Yes, I'm still talking about
leaky gut in a sense, right? But the
danger is calling something leaky gut
when people already might have a
definition for leaky gut in mind like
it's responsible for for all these other
problems, right? But let me tell you
what leaky gut is to me or what
increased gut permeability is. And I'll
tell you that it's very real and it is
actually tied to metabolic illness. Uh
we can start with a study that used uh
small bile biopsies, right? And this was
recent just last year and they did small
bile biopsies and then they they
actually were able to from the stem
cells grow little or organoids, right?
And then organoids are like
threedimensional cultures that they they
behave as they should. as this the cells
kind of populate out of there they take
their normal form and structure and they
had a control group and they had a group
with MASH obesity and MASH right so
which is a metabolically associated uh
stat hepatitis so these two groups they
looked at the organoids and they found
that the tight junctions were far less
well-developed and more disorganized in
the mash patients compared to the
control patients additionally they did
transcripttoics on it and they found
that they weren't even producing a you
know the the the proteins. They weren't
even making the RNA to produce the the
tight junction proteins. So clearly at
transcriptional level, they were
downregulating the the the tight
junction proteins.
So with the imunoshistochemical staining
and then transcrytoics, they found that
the tight junctions just weren't weren't
functioning as they should in people
with MASH. So if you don't have tight
junctions, it stands to reason you might
have quote unquote leaky gut. So another
group actually looked at something
similar, right? They had same population
patients with MASH and they actually
studied they can there's different test
tests you can do to look for a leaky
gut. You can give something that's very
small but it should not get through
those tight junctions, right? There's
different tracers you can use. 51
chromium EDTA is one that they use and
that's one that was used in this study
and so they give it. It's not supposed
to get into the blood bloodstream. in
patients with MASH, zipped right in,
much higher levels than there should be.
And in patients without MASH, it wasn't
getting in. Additionally, in patients
with celiac disease that was treated, it
wasn't getting in. But in patients with
with fatty liver disease, it was getting
in and it's probably playing a role,
right? So, if you think about it, the
gut, the first place it goes is the
liver. There's a portal circulation and
the gut goes to that portal circulation.
Everything that goes through there has
to stop by the liver with the exception
of fat. Fat gets into the lymphatics and
dumps out of the thoracic duct. doesn't
have to actually go to the liver. So if
you have bacterial products uh uh LPS,
lipopolysaccharide,
it's a portion of gram negative
bacterial cell membrane, right? If that
gets through these tight junctions, it
causes all sorts of problems. It is
going directly they're inflammatory.
They interact with um to receptor 4 and
uh you know that that goes um you know
starts all sorts of inflammatory
cascades. So um it goes via NFC B
signaling etc. That can be problematic.
Another group proved that was
problematic but actually this was done
in Duke. They actually took LPS and they
injected it into healthy people and they
found that their inflammatory markers
went through the roof and they found all
sorts of other problems out including
they did clamp studies in these
patients. They found it induced insulin
resistance. So yes, I think leaky gut
can be involved in all this stuff. And
that gets back to our very early
discussion about fiber and about, you
know, fermented beverages and how
important it is to keep your microbiome
healthy because that microbiome and that
butyrate is critical to producing
healthy intercases. That's first and
foremost, right? As well as healthy
tight junctions, a healthy mucin layer.
All the and and and actually it also
works together. Butyrate and and the the
microbes and the byproducts of the
microbes work with your immune system,
your innate immune system and it tells
them what to recognize and what not to
recognize which is just as important
because your your your bowel is full of
bacteria, right? So absolutely very
important and you do see where this
increased gut permeability is associated
hardcore good science evidence with real
illness. So absolutely is a problem.
It's just I don't want to blame it for
everything.
>> Right. Right. I get it. I I think that
the you know earlier we were talking
about CGMs and there's sort of a kind of
a common theme here which is the general
public now because of online health
information good and bad is starting to
um create their own nomenclature and I
could see why that would scare
physicians but I think that a more
symbiotic relationship between like the
public's under like knowledge of their
own data questions about like maybe it's
leaky gut you know um and being able to
approach their physician with with these
things in mind and still acknowledging
that the physician is the physician,
right, could be really helpful. I have a
couple of questions that feel free to
pass if these are aren't meaningful. Um,
I get a lot of questions about
artificial sweeteners and negative
effects on the gut microbiome. Seems
like they're marginal to zero effect on
insulin and resting uh blood glucose
from artificial uh lowc calorie
sweeteners in a way that like would lead
people to say these are bad. There's no
reason to run out and use them if you
don't want to. But the weight loss data
say people who drink diet sodas instead
of w water actually lose more weight.
I've seen those data, but this is not an
incentive for people to start drinking
diet sodas.
>> It sounds like, you know, saccharine and
Splenda are probably worse for you than
stevia and aspartame. Like where are you
at with these things in terms of their
potential negative effects? And if you
know of any positive effects, I'd be
curious.
>> I think they're better than high
fructose corn syrup for sure. Right. I
mean that I think we should be treating
like alcohol, right? Yeah. I think
fructose and fruit is fine. I'm not
worried about fructose and fruit
fructose in general because it comes
with a matrix around it. It's not it's
not like a rush of c of of of fructose
into your liver. But fructose can only
be processed by the liver, right? And so
it's busy as it is now. It's got to take
the burden out of of uh you know a
beverage which is absorbed very rapidly
goes directly to the liver and it has to
be has to be dealt with. um and you know
it gets trapped in the liver very
quickly and that's the only place I can
really process it. So I think that
fructose is something to watch. Um again
not if it's in fruit even in juices it
can be kind of juices are processed
fruit right so it's similar just
minimally processed stuff is better I
think the problem with sweeteners
artificial sweeteners is they come in
foods that are uh that are highly
processed as it is right and you can't
separate the two I think that's for a
while why people were so down on on
polyunsaturated fats right because
they'll come in a in a bar full of a
bunch of other stuff that's not good for
So well I guess the polyunsaturated fat
is also bad for you in some way right
that was like a recent phenomenon. Well,
no, the food that it's in is bad for
you, but the polyunsaturated fat has
been shown to reduce LDL and has as has
health
>> benefits or essentially translation for
people like seed oils basically
>> that yeah, there's some still debate
about whether or not the processing of
them can make them worse, but um yeah,
it's it it's hard to uh Well, I know did
you see this recent avocado uh oils
thing out of UC Davis? Uh this is wild.
UC Davis went and analyzed like all
these avocado oil containing products
are supposed to be like healthier. You
know how much avocado oil these products
contain?
>> Zero.
>> Oh no.
>> And the push back has been that maybe
they're looking at the wrong metabolites
of of of avocados. I don't know how this
is going to play out, but if it this
could this could potentially do more
damage to the I just call the non olive
oil uh community, right? Because in my
mind, like the safest thing is you just
use olive oil, a little bit of butter if
you here and there, right? Like, okay,
no one debates olive oil. It's kind of
wild. No one debates. Everyone knows
it's good for you. No one thinks it's
bad for you. But the seed oil lard
thing, they go back and forth and it's
kind of like professional wrestling. I
feel like it's all kind of made up for
entertainment, but both sides are really
adamant. It's just kind of stupid. Olive
oil, butter, right? Or you're the
physician. Tell me, am I thinking about
this wrong?
>> I do the same. No, Olive oil is the
best, obviously. Then small amounts of
butter. I don't think, you know, large,
bad, and small amounts. I think the
problem is it's overall amount of
saturated fat, right? Um, but
polyunsaturated fats have a lot of proof
that they're very safe. Where you get
into problems is if you have a big
container of it, like a huge container,
you're not going to use it in a
reasonable amount of time and sitting in
the sun or something and you get oxid,
you know, it oxidizes. That's a problem.
You don't want to take an oxidized oil
into your body, right? Or you're deep
frying with it and you're frying over
and over again, you start generating
trans fats.
>> That's a different story.
>> But in general, I think, you know, I
think they're fine. Um, and and I don't
even think you need this omega 3 to
omega 6 ratio people used to worry
about, right? I think you need a certain
minimal amount of omega-3s, right? You
know, if you eat fish once in a while,
you're getting all you need.
>> Do you strive to get like some fatty
fish in your diet?
>> I do. Yeah. I love I love fatty fish.
It's It's good for you. Try to do it a
couple times a week.
>> I take Lavaza, the highdosese omega-3
>> pharmaceutical, because I don't want the
mercury. It's cleaned of mercury. I
don't know. My blood markers are where I
want them to be, but I'm I'm curious.
What's your read of the data on omega-3s
for metabolic health and cardio uh
cardiovascular?
>> It's mixed. I mean, it's probably better
for Alzheimer's, right? If someone's
starting to show signs of Alzheimer's, I
think it's it's better for that. The
data I think the problem is universally
supplementing is not necessarily the way
to go. You want to find a deficit and
then supplement, right? So, even with
vitamin D, you know, most people
probably are deficient, so they benefit
from it, but there's no point in really
doing it unless you're deficient for
most things. And I think with omega-3s
is it's similar. You want to get your
daily allowance if you will. And again,
if if you're a vegetarian, you can do it
from algae, the original source. The
fish are just consolidating, right? Um,
so, you know, you don't have to eat the
fish, but uh that or get that in some
kind of, you know, supplement form.
>> You heard it here from Chris Thompson.
Fish are just consolidated algae. I'm
just kidding. I put those words in your
mouth. I love that. For all the people
who are like, "No, you can't get
omega-3s from non-animal sources." I
mean, I think you put it beautifully. I
don't like eating fish, so I take the
lavaza. Yeah, I don't like I don't like
that. But I'm not on the east coast. You
guys tend to have better seafood. It's
delicious. Yeah, I know. I got to get
out. But it's too cold out there. Then
you have to take vitamin D out here. You
don't I'm just kidding. Um what else do
you recommend to your patients as they
start to move away from obesity? So
obviously fiber, some fermented foods.
Um uh it sounds like resistance training
might be in the list given that they're
they're they're at risk of uh re
becoming um thin but more jelly tissue
than uh lean lean mass. Do you do you
prescribe resistance training?
>> Absolutely. So all my patients I ask
them to do resistance training um even
you know before they start losing weight
before they go through a procedure. It's
essential. Uh zone 2 cardio is great
right? It's good for fat burning. you're
in that zone where you're burning fat
and you know not you know carbs as much
right HIT is great. So highintensity
interval training is great for
mobilizing visceral fat because your
visceral fat we haven't talked a whole
lot about it but it has betadronurgic
receptors on it. It also has
gonadotropic hormone receptors on it as
well. So um it's responsive to to stress
like acute stress. So it will mobilize
when you're going you know through the
stress of of of high you know high
intensity interval training. So, it'll
mobilize. It won't be burned right away,
right? Because you're burning carbs at
the time. You're burning your your liver
glycogen and uh and your muscle
glycogen. You're burning that, but you
mobilize the fat at least. And that's
kind of what it's designed for. That's
why you have some visceral fat there.
Um, so I included I I I try to have them
do those things. Hit little zone 2 and
then resistance training. I think those
are the most important things long term.
Do they do it?
>> This is very interesting. So, I think
they try and depending on how they lost
the weight determines if it's effective,
right? So it's it's theory of set point,
right? Which is something that's very
important. Back to back to metabolic
health. So it's it's not a point
necessarily. It's a defended range if
you will, right? So you have this
defended range of what you think your
weight's supposed to be. And that's set
by a variety of things. Leptin is part
of it, right? And your thyroid hormones
and whatnot. And you think you're
supposed to be a certain weight. And
then what you do is you do a crash diet.
You lose a bunch of weight. Like the big
biggest loser was a great example of
this, right? You lose a bunch of weight.
So now you're fighting several factors,
right? So, one factor is your body is
smaller, so it burns less weight. Okay?
So, you have to eat less to just
maintain the same weight you're at now,
this lower weight. That's a bit of a
problem. You downregulate your gut
hormones. We talked about a bunch of gut
hormones. You're producing less GLP-1.
You're producing less P Y. You're
producing GIP is here neither here or
there. Little less CCK. So, your satiety
hormones are being produced less. Your
grein goes through the roof. If you do
this with diet and exercise, your
grillin goes through the roof, right? So
that in addition to the fact that your
muscles become more efficient, I think
they become 25% more efficient in doing
a similar task. They're going to burn
less fuel to do the same task. It's
amazing, right? Your kind of non
exercise energy expenditure, right? So
just kind of daily activity, your basil
malbach rate as well, they all kind of
go down. So you're burning less calories
at rest. So we've shown this study study
after study. So, your whole body is
fighting you, okay? It wants to go back
to that weight, whatever it thought it
was supposed to be at. The biggest loser
was a great there was a kind of an NIH
follow-up study to that, and they found
that they were burning 500 fewer
calories per day after that. So, and
there's other studies that have shown
this as well if you lose weight that
way. So, that's why it's so important.
GLP1's helped fight part of that, right?
You're replacing the GLP1 that's you're
not you're not addressing the ghrein or
other things. So, time will tell if we
can have long-term weight loss, but it
does it does. So ground isn't the whole
story, right? So like with with our
procedures, so we're addressing these
very targeted with procedures and one
bridge into that is is the ESG
procedure. So this is the procedure I I
I developed in 2012. So you go in
through the mouth, someone's sleeping
obviously with a little scope and you
fold the stomach on itself. Now the goal
of that was to do two things, you know.
Uh one was to augment the stretch
receptor so it's a smaller pocket. So
when food hits that the stomach
stretches quicker and you have the
veagal aerence now that go up to the
noto's ganglia and then you know uh NTS
and then you know boom into the um
hypothalamic area
>> you tell the brain we're full. Yeah,
exactly. We're full, right? Stretch
fast. Boom. So when you stretch, you get
that signal. Boom. And you're full.
That's part of it, right? That's
phenomenal. The other part of it is you
suppress ghrein because food stays in
the stomach longer, right? And so it's
suppressing grein. So it's doing two
different things. Now, when those people
lose weight, they don't have to worry
about their ghrein going up because it's
been suppressed. So it's easier to keep
the weight off for 10 years or longer
because you're not fighting that part uh
you know of of the counter measures that
the body will do to defend this
potential you know potential range.
We're not doing anything with that
necessarily to to GLP GLP1 and other
another dudal hormones but you'll see it
actually it actually you have ways of
dealing with this. So how do you augment
weight loss? You have all these
different targets right? So one thing
we're doing now is we talked about how
grein resides in the fundus. Now, in
addition to that ESG where we tighten
the stomach, someone developed an idea,
I think they were in Germany where you
can actually ablate those fundal ghrelin
cells because they live in the mucosal
layers. You can get to them. So, you can
they use argon plasma coagulation.
There's different ways to ablate it. You
just kind of spray this over the fundus
and it kills off the grein producing
cells. They grow back and there's not
much of them, right? So, now all of a
sudden, you can suppress ghrelin as
well. So the weight loss goes from about
18% with DSG alone in a in a top center
goes up to way over 20% maybe 25% if you
start ablating the gre
inhibit ghrein.
>> No not not effectively. Yeah. So and
then you add to it right. So now if
you've delayed gastric emptying your CCK
is not spiking as much as it was etc. So
but you're not getting which which is is
a subtle countermeasure potentially
right? It will still spike but GLP1's an
issue. So now what if you combine that
with a small bowel procedure right? And
there's different small bowel procedures
that we've come up with using magnet
magnetic anastmosis is one we published
about 10 years ago. We did it in the
Czech Republic where we used endoscopes.
It was a hard way to do it. Went from
below a colonoscopy. My partner did
that. I went from above. It released
these two magnets and we connected the
jigunum the first part of the jigunum to
the the lower part of the illium.
>> We should probably tell people what anos
is is basically uh when you connect two
tubes.
>> Exactly.
>> Right. Is that right? You're basically
just So you're basically like liating a
tube. Y we're using more nomenclature.
You're you're bridging in two tubes.
>> Bridging them, right? Yeah. And they did
it originally with sutures. You cut a
hole and you suture the tubes together,
right? And then they did staplers and
staplers that do it, but they're big and
bulky and hard to position. So So our
lab developed magnets, right? And these
are ring magnets. So they come out,
they're they're magnets encased in nit
so they can take a certain shape. So you
put them through a tube. In this case,
it's an endoscope. You could put them
through a laparoscope or whatever else
you want to put it through. And they
come out and they form a ring. Right? So
we went from the top endoscope we formed
a ring in the junum and the bottom we
formed one in the illium way downstream
and then we had an anastmosis that would
allow the food to directly pass there
and what we found is you get these big
spikes in GLP1. So now what people are
doing I'm conflicted and can't do this
part of the procedure but what they're
doing is they're doing that in aosis and
they're doing uh suturing procedure
endoscopically and together you're
really replicating a full gastric
bypass. You're having a GLP-1 hind gut
spikes. you're getting that sense of
restriction and the veagal aerant
signaling. You're getting uh you know
ghrein to be suppressed and you're
getting really amazing weight loss. So
what we can do now is take a procedure
that was really big. It started off as a
big open procedure that had certain
risks to it. We didn't know how it was
working and it did a bunch of different
things and we're targeting different
aspects of it. And the goal moving
forward is to even be more precise and
find out what someone is going to be
more responsive to and then just do the
least you need to do. Maybe they just
have ghrein that's driving them just
ablate the ghrein, right? Maybe they
need something more. And people are
actively studying that. Um they're
studying the phenotyping of obesity.
It's quite exciting.
>> I'm sensing another theme here. Um this
procedure that you co-developed or
developed,
>> which one?
>> This this uh bridging of um
>> So that was my lab. So yeah, that was my
lab. I'm the PI, but I have a whole team
obviously. Yeah.
>> Yeah. So, it's increasing GLP, but I'm
guessing it's not increasing it
thousandsfold like a GLP drug would.
It's got some other positive
consequences that help cure the obesity.
I'm I'm kind of sensing a theme here,
right? Like we have this these drugs
like Ompic, Monaro, etc. that blasted
GLP's through the roof, helped a lot of
people that needed help, but there were
a lot of side effect issues. Then along
comes this other drug reatride which is
like okay well let's increase GLP but
let's also kind of bump up the GIP
system a nudge or two let's also bump up
the glucagon system and lo and behold we
get a much better effect muscle sparing
and actually better weight loss so kind
of a perhaps a lesson to us that like
you don't really want to push really
hard on one lever in biology or take any
one thing out maybe the more
combinatorial approach is the better
approach
speculating here but there seems to be a
you know parallel theme.
>> Oh definitely. I think that um you can
mitigate risk by doing that by not
giving too much of one thing and I think
it's it's it's hitting again using
multiple levers is definitely a way to
get a treatment effect without exposing
the body to potentially the harms of
going too too big on one thing.
>> So that'd be the argument for these kind
of multimodal approaches. Then you can
also combine these procedures with the
drugs, right? So you do an endoscopic
procedure like a tighten tighten the
stomach and then give a drug and see if
you get much more weight loss
>> or at a lower dose and get the
>> lower dose. Right.
>> Yeah. This was what years ago on this
podcast we looked at the whole ADHD
thing and the effects of these drugs on
ADHD and you know like parents who get a
great effect of a of a you know an
Adderall or a Vivance for their kid that
couldn't focus. It's I have friends with
a kid like this and you know they're
just like it's remarkable but they're
worried about the reduced uh growth
effects. They're worried about the sleep
effects and and you know so they're in
this trade-off and and that's where I
think you it doesn't it's not always an
eitheror. We forget it could be well
maybe this child could get by with a
lower dose of medicine if they're also
doing some things behaviorally if
they're also doing some things with
nutrition etc. Obviously, the
constellation of things will differ, but
we we don't often think like that.
Americans want the drug that fixes the
problem. We love that. And then we get
all pissed off when we're like, we had a
generation of kids raised on
amphetamines. Well, it's like maybe kids
just been a little
and more exercise, right? And so it's
it's gratifying to hear that you're
doing these multi-pronged approaches and
um and that you do recommend exercise
including resistance training, right?
And it, you know, they do all these
studies that show diet and exercise
alone don't work because of the set
point. Like look ahead was a great
study, right? That was
>> that's running, right? It's like
treadmill
>> look ahead. Yeah, it was it was a lot of
that and it was a lot of um uh just
diet, heavy diet, too. And they found
they got like a 6% total weight loss or
something like that at 10 years and no
improvement in heart disease and stuff
like that, right? So there's other
studies that show it's hard to do it
alone just like the Biggest Loser
version and there's several other
versions of that where it's hard to do
it alone because you're not addressing
the countermeasures the bodies throw at
you, right? The body throws at you. But
that doesn't mean it's irrelevant,
right? So when you do a procedure like
say a gastric bypass surgery, right? Or
you go on a GLP1, you still got to fix
the fundamentals that got you in the
problem to begin with, right? You need
to start getting more fiber. You need
to, you know, have uh a better diet. You
know, try to avoid the insulin spikes.
Do what you can to treat those things.
You got to start moving. You got to
start exercising. Otherwise, it's going
to fail. The treatments will fail. The
endoscopic procedures, the surgeries,
the medicines will fail unless you
really address those underlying
problems. So, even though alone they
don't do it because the body has
adapted, they're still important to the
ultimate treatment.
So given where things are at now, the
treatments uh that you and colleagues
have have developed and when I say
colleagues, I mean people with in your
laboratory and clinic, but you know
clearly is like a international thing
going on trying to solve these issues.
Where are things headed next? You
mentioned AI. What's the potential role
of other technologies to improve um
health and outcomes?
>> Well, I think one uh thing that's very
exciting is is gene therapy, right? So,
we talked about GLP-1s and how it's mega
dosing, super physiologic. Um, it's not
nutrient responsive.
There's a new a company working on a new
approach which is a gene therapy and I
was involved in the very early work for
this. And basically what they're doing
is they've they've developed a a viral
vector, right, that has the gene for
GLP1 in it and they're using the
promoter for uh the beta cell insulin
gene, right? So basically when a a
patient would uh secrete insulin in a
nutrient responsive way, this
simultaneously be secretreting GLP-1.
These viral vectors are um they're
beautiful tool of of um biology where
you can put some genetic cargo into a
virus that doesn't cause any problems
but allows for stable expression of and
the production of certain proteins in a
cell. So how are you getting into the
pancreas? You injecting it through the
skin? No. So we actually using
endoscopic ultrasound. So you know that
same device we developed to actually you
know biopsy the pancreas. We're now
using something similar to actually
treat and you can you can ablate tumors
with energy as well. Uh people are using
electroporation to cause apoptosis.
They're using thermal means but you can
also inject something fineal injection
right. So and we're injecting the the
the viruses basically into the tail of
the pancreas. Now you wouldn't want to
just take this introvenously because
they end up in other tissue. Right?
We've done a lot of work to make sure
those things stay in the tail of the
pancreas too. Right? We've done a lot of
animal studies where we've injected it
and we make sure we use, you know, green
fluorescent protein. Make sure it
doesn't end up in areas it's not
supposed to be. Is this so we're getting
technical here, but is there a pancreas
specific promoter translation this would
allow even if some got out it could I
wouldn't get expressed elsewhere. Is
there a way to make it only expressed by
pancreatic eyelet?
>> Very very close. Yeah. But it still you
just don't want it getting anywhere else
anywhere. But it the only place it
becomes active is in the beta cells.
Doesn't become active in the alpha
cells, right? The pancreas, right? So
you're really just active in beta cells.
And and it again you you secrete insulin
into these little vesicles, right? And
so you're secreting GLP1 into those same
vesicles. So then when you have your
meal, the vesicles release GLP1 and
insulin together.
>> Oh, that's clever.
>> Nutrient. You're making the drug. I
mean, we were already making the drug,
but now you're making it an elevated
rate.
>> Not only that, you're not making it in
the L cells where it has to go all the
way up through, go to the liver, go
around, do its thing, right? you're
making it at the place where it's
needed, right at the pancreas. So, it
has an urine function, paracrine, you
know, and it can and it's it's much
faster.
>> How often are these cells turned over?
Because it it, you know, um if it were
brain, no problem because brain cells
don't turn over, but how often does
pancreas turn over?
>> Very important. Why you can't do it in
the bowel is because they're not
terminally differentiated, right? You're
turning over your whole bowel every 5
days or whatever.
>> Pancreas terminate terminally
differentiated. So, they're not going to
be changing. So, it's a it's a permanent
the episomal DNA stays in there. doesn't
integrate into the host DNA stays next
to it and transcribe with it process.
>> But they're they're not going to, you
know, not going to have to turn over.
>> I feel like there's a here's another
theme emerging like we're hearing about
drugs that you can get one injection to
permanently lower your LDL. We're now
hearing about gene therapy to um chronic
chronically elevate GLP at exactly the
place and time that you want in order to
offset excess calorie consumption and
obesity. Is this what we're going to
see? Like instead of people taking
drugs, they're going to take a one-time
injection.
>> That's what I'm hoping, right? It's very
exciting. They actually just entered
clinical trials in uh I think the
Netherlands. So, it's very exciting. So,
we'll see how that goes. But it looks
like it'd be very promising, right? So,
one time GLP1 injection that could be
nice. Additionally, you could use it to
augment other therapies. You can use it
to augment the gastric procedure or the
small bowel procedures. It might be
another tool in your armamentarium.
It might be more use for diabetes than
it is for weight loss. We don't know,
right? So, uh it's so early right now,
but it's certainly very encouraging.
>> Really glad you're doing this work
because I'm aware of a few conditions,
but they're rare, fortunately, but
they're not exceedingly rare where
hyperphasia is an issue. Um Prader
Willie syndrome and other syndromes
where these kids just can't stop eating
because they lack of hypothamic signals
and I don't know my read is that the G
the traditional GLP drugs are are not
really working there. um this would be
amazing
>> and I mean in road models it's
phenomenal because we did these trials
where you randomize mice to get
saggotide high dose simaglletide much
higher than you get for a human and then
the trans gene right and both groups
lose weight trans gene lose a little
more then they stop losing so they don't
keep losing weight forever right which
is good and then you took the group
that's simagide and you randomize them
further to get nothing or to get the
trans gene they get the trans gene and
they go back right down to the same
settling point which is great and the
ones that were randomized to nothing put
all the way back gone.
>> Phenomenal, right? So, it seems to be
getting really good results from a
weight loss standpoint as well. I want
to take too much more of your time, but
if you're willing, we could just briefly
talk about you for a second. Um, we
won't go into deep layers. Uh, that's
not the purpose here, but you're an
interesting person. Um, whether uh you
realize it or not, I hope you do,
because it occurs to me that you you had
certain solutions in hand, but you
decided to make search for better
solutions. And so I'm just curious like
was that always you are you have you
always been a tool builder like in
medical school and residency or even
prior like high school? Are you are you
the person who like sees like okay like
the reason you have to keep I'm dating
myself here like like fix the antenna on
the TV is cuz actually the antenna
sucks. Let's let's do something to the
antenna. Were you that kid?
>> Yeah. My my mother would attest to that
unfortunately. I I took my motorcycle
apart in high school. Couldn't get it
back together. had to uh have it flatbed
away and fixed and I fixed uh I fixed
some parts in my car that ended up
bursting into flames. So I'm much better
at dealing with with patience than with
Could have been the other direction.
Right.
>> Exactly. So no I always I always would
tinker with things for sure and I needed
to do things with my hands. So that's
why in medical school I couldn't be kind
of a general internist. I think I needed
to I needed to solve problems with my
hands and I think that's fulfilling to
me is to I don't I don't like managing a
slow demise right and I felt like
internal medicine we were giving people
a reason to to continue with their
current life right and instead of
addressing problems like their blood
pressure is high well instead of finding
a way to really help them address that
is well take this medicine your LDL is
high instead of finding a way to address
it you give them a medicine and you see
what that gets us into these situations
where we treat HD we we treat a high LDL
APOB really effectively but we're not
and we reduce mortality from that
specific thing but we took our eye off
the ball and fatty liver is up and
diabetes is up and people are still
dying in greater numbers right so I feel
like we need to address the underlying
problem and that's very important but
aside from that I just like doing things
with my hands and I think that was a
large part why I was going to go into
cardiology or going to interventional
gastro
so grateful that you're a tinkerer. It's
a unique thing to find these qualities
and expertise woven into the same
person. The fact that you clearly have
immense compassion for your patients and
you're willing to come here and share
information publicly. You have many many
important roles in your daily life. Um
so the fact that you take the time out
of your uh schedule to um educate the
public is uh I and everyone listening
have immense gratitude for that and that
you're thinking about what could be done
better. That's like the ultimate quality
in my opinion of a of an excellent
physician or scientist or engineer. But
when it comes to physicians and the
general public, we need people who are
thinking about how things Yes, there are
some solutions for some people, but we
need to broaden the the treatments to
help many more people. So, I'm just very
grateful to you and and thanks for
coming here today and sharing this info.
>> Well, thanks so much for having me. Very
kind. It's definitely always a team
effort as you know, right? As as well as
anyone. Everything is a is a is a team
effort and I think innovation is never
the result of one person's you know
work. It's it's a it's a whole group and
I've been very fortunate to be
surrounded by a bunch of amazing people
that help help us move things forward.
So
>> well throughout today's discussion your
reflex to give proper attribution is
more a testament to what what you just
said. It's not lost on me when uh and
and nor the people listening people who
give credit where credit's due it it
says a lot about them. So thank you. uh
come back again maybe in a couple years
when you've solved everything or close
to it. Just joking. I'm sure you guys
are making uh tremendous strides, but
these things take time. Once again,
thank you very much. This was very very
informative and has enriched my thinking
a tremendous amount. I'm sure everyone
listening as well.
>> Thank you.
>> Thank you for joining me for today's
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