Zone 2 Training Explained: The Single Best Workout for Your Mitochondria | Dr. Inigo San Millan - Live Well Be Well with Sarah Ann Macklin | Health, Lifestyle, Nutrition

Episode Transcript
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(00:00):
That's nutrition in my humble opinion.
Reverse mitochondrial function. I don't think so.
The only way where we can improve mitochondrial function
is through exercise. If mitochondria don't work, that
cell and that organ is not goingto function very well.
Mitochondrial function and health is next level.
How can one actually measure their mitochondrial health?
By measuring fat oxidation like burning, we can indirectly have

(00:23):
a proxy for mitochondrial function.
Why is zone 2 training so important for a mitochondrial
health? Zone 2 prove the most 2
parameters of fat oxidation and lactate clearance capacity,
which both are surrogates of mitochondrial function.
Introducing Exercise Physiologist Inigo San Milan If
you have higher blood lactate levels, it's a sign that your

(00:43):
mitochondria are not processing that lactate or clearing it or
recycling it properly. A lot of people would just think
that lactate is a waste product.You know, it's kind of where you
go to the gym and your muscles hurt, and that's how people
resonate with lactate. Lactate, without a doubt.
It's an amazing biomarker that has been there in front of our
eyes. Factate is the best field for
the cells and even in cancer, weknow that it is a master

(01:05):
regulator or a carcinogenesis. So the way it's about to combine
it, as I said, if you do four days a week zone 2IN combination
with high intensity, at least 2 or so towards the end, that's
when you start hitting some sweet spot.
Is there differences between menand women when it comes to Zone
2? Well, that's a good question,
and I think things get mixed up because of.

(01:27):
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(01:47):
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(02:09):
Thank you. I want to start with VO2 Max
because it's a big buzzword, especially in the last, I would
say three to five years. It's become at the forefront of
many health conversations. It's become the gold standard of
fitness, the number one metric that every athlete wants to
improve. But you've said that VO2 Max

(02:30):
really only scratches the surface.
So why doesn't it tell us the full story?
We've been knowing about VO2 Maxfor, for decades and we've been
using it for, for decades with, especially with athletes, it
dates back more than 100 years at least since we have more
standard ways to measure it. And it's been always linked to
fitness, to performance, therefore to health.

(02:53):
And now in the in, in the times of longevity, right?
It's, it's, it's one more parameter that is plugged in
longevity, right? And it's a great measurement.
However, it doesn't tell the whole story.
There's more than that. The VO2 Max, it's a
representative of the central cardiorespiratory adaptations,

(03:16):
right? But there's more because
ultimately that oxygen is utilized by the cells and it's
utilized by the cells in mitochondria as well as fuels.
And this is where the area of Physiology in general has
evolved from VO2 Max to what happens at the cellular level.

(03:38):
And in the same manner that we've been using, you know, with
athletes being too much for decades, right?
And now it's mainstream. We have already passed that
time. We, we, we work now at the
cellular level. And this is what I see.
They are mainstream mainly in the area of longevity, getting
into, in fact, already people are talking about mitochondrial

(04:01):
function, metabolic health, right?
And this is the next level. And this is what we've been
working with athletes for performance, you need to produce
ATP energy and that's produced in mitochondria.
And for health, if mitochondria don't work, that hell, that cell

(04:21):
and that organ is not going to function very well because it
doesn't produce IITP well enoughfor longevity.
As we age, our cells age, our mitochondria age and our energy
production overall ages as well and decreases and that resides
in mitochondria. Therefore, is that mitochondrial

(04:41):
function and health is next level.
OK. So this is kind of like the next
stage of where we're exploring now with, I would say, I mean,
longevity is a buzzword, but mitochondrial health, I think
many people will have known fromGCSE biology and then forgotten
about it. But the way that I always think
about it is a powerhouse of the cells.

(05:03):
But how can one actually measuretheir mitochondrial health?
Because the VA 2 Max is, yes, a bit easier to attain and to get
to. But mitochondrial health, how do
we even measure that? Well, we can do it through a
muscle biopsy and get a chunk ofmuscle and look under the
microscope or do a bunch of things to, to that.

(05:25):
And, and but it's, I don't thinkit's, it's a very convenient way
to do because you will have a chunk of like a big scar and you
know, but that. Sounds quite painful.
Yeah, I don't think you want that.
But the other way, I, I, I developed a methodology years
ago and I've been using it with,with athletes for, for a long
time, where we, we, we have two proxies for that.

(05:48):
On one hand, with the same device that you measure via 2
Max, which it's, you know, like in a colloquial form, we call
them metabolic cards. They've been used, always use
metabolic cards. We can look at gas exchange,
right? And so when we look at gas
exchange, we look indirectly through some complicated

(06:11):
equations, we can see how much fat and carbohydrates you're
burning in grams per minute. We can see that.
Now when it comes to fat, we know that fat can only be burned
in mitochondria, OK. So by looking at fat, by
measuring fat oxidation is called fat burning, we can

(06:33):
indirectly have a proxy for mitochondrial function.
Then lactate can only be burned in mitochondria, right?
So by by pricking your finger oryour earlobe and getting a small
sample of lactate and measuring it, we can have an idea of how
well your your cells are processing glucose and which

(06:57):
under resting conditions, it happens in mitochondria.
But the fact is that if you havehigher lactate blood lactate
levels, it's a sign that your mitochondria are not processing
that lactate or clearing it or recycling it properly.
Therefore, with the two parameters, fat utilization and
lactate, you can indirectly see or or make sure mitochondria

(07:20):
function. We published that study a few
years ago and now we have already published a preprint
about an extension of that studywhere we look at muscle biopsies
and in the muscle biopsies we welook directly how they work and
we correlate them with this methodology.
So it's quite robust to do it ina non invasive way and an

(07:41):
ambulatory manner where a lot ofpeople can do it out there.
Wow, that's fascinating. So I think a lot, a lot of
people would just think that lactate is a waste product.
You know, it's kind of when you go to the gym and your muscles
hurt and that's how people resonate with lactate.
But you're saying now we can usethat as a measure to test how

(08:01):
well are mitochondrial functioning?
Is that ready available? Can people go and access that
quite easily or is it still quite hard to get our hands on?
Yeah. So to, to look at your VO2 Max,
you have to go usually to an exercise Physiology laboratory
at a, your, your local university, if they have one, or

(08:21):
your local hospital. More hospitals have those
devices then. And and that's, as I say
mentioning that's the same machine or device that measures
fat oxidation as well. But lactate, you can do it with
the pan handle device. You know, now they're very
common. It's kind of the glucose meters
by the major lactate. You can even do it yourself with

(08:42):
a little bit of technique. But the combination of both is
very accurate. But even only one alone, like in
this case, lactate, it's it's yeah, you can.
A lot more people can do it without going to a hospital or
university. Wow.
OK. So we should be maybe looking
more at our lactate levels than we have been previously.

(09:04):
Yes, lactate without a doubt, it's an amazing biomarker that
has been there in front of our eyes.
It's lactate. It, it's everywhere in the body
and, and what we know very well from the pioneer studies from
40, from over 50 years ago, fromDoctor George Brooks from the

(09:25):
University of California, Berkeley, who's my mentor and my
great friend and and a colleague.
He has been discovering everything we know pretty much
about lactate and he was swimming upstream for for
decades trying to prove that lactate was not 1st and a waste
product as a result of anaerobicmetabolism.

(09:47):
And 2nd, that lactate is the best field for the cells.
And then the lactate is a singling hormone that is needed
for the homeostasis of many cells in the body.
And yeah, he has been proving all these concepts for the years
which have been transformationalto understand cellular
metabolism, whether for exerciseor for other diseases.

(10:09):
And now we we've been taking that lactate a little bit
farther. And even in cancer, we know that
it is a master regulator for a carcinogenesis.
Some idea that we proposed in 2017 through our what we call
our lactogenesis hypothesis, that it was rejected 7 or 8
times and finally got on a because it was a crazy concept

(10:33):
and even 2 editors wrote U.S. Box and you guys are crazy.
Yeah, you know what you're doing.
And now, and I mean we're talking about 7-8 years later
now our article has about 850 citations in the literature.
So people have been paying attention entering that door.
And now, I mean, without a doubt, lactate is a major
component in cancer and it's going to be kind of just a

(10:56):
bigger one. But it's a it's, it has a
complicated role in the body andit's a great feel.
If you give a cell lactate or glucose or ketones or fat, it's
going to prefer lactate is that is the preferred fuel for the
cells. And because it's the fastest 1
to be burned and it's a similarly molecule, It's a main,

(11:18):
very important assessor for homeostasis for the good and for
the BAT. Because if you build up in the
cells and you don't have enough clearing capacity, it can become
pathological. But but and it's a great aid and
assistant to exercise. People think that the built up
of lactic acid, which doesn't doesn't exist in the 1st place

(11:38):
that the body produces lactate. But lactate, it's it's necessary
for the continuation of of energy processes in in the cell.
And in fact it removes one proton that cause acidosis.
So what happens in their musclesis that as we increase exercise

(12:00):
intensity, that burning sensation that we feel that's
not from lactate, it's from the production of ATP and what we
call the ATP hydrolysis, which is the the burning of ATP for
producing energy. And that's what liberates a lot
of acid particles called protons.
And they make the, the muscle very acidic.

(12:22):
And that's the acidosis that decreases the contraction.
And it feels that burning sensation lactate.
It helps by removing a proton. So it's, it's a removing
protons. It's a instead of adding.
But it's, it's a concept that it's been taking decades to
explain. And hopefully now that it's a

(12:43):
little bit more mainstream, we can get to understand it better.
Well, so, OK, so when you just said it there about the
mitochondria runs better on lactate, how do we then produce
more lactate? Is it just exercise or is there
other forms of how we can be making sure that we're feeding
ourselves to what you're tellingus?

(13:04):
But it's not that mitochondria run better on lactate.
Lactate is it's burnt in mitochondria, right?
So if you don't have a good mitochondria function, you're
not going to be burning be burning lactate very well.
Farther, yeah, farther, more. Lactate is the mandatory and
product of glucose utilisation. So when you burn glucose, you

(13:28):
always produce lactate. Always.
The higher the glucose burning, right, the more lactate you
produce. So it gets to the point that
lactate, if you want to burn it inside mitochondria and do an
exercise or even at rest first has to go glucose.
The first door that is at the entrance of the cell, OK, then

(13:51):
that glucose is transformed in asubstance called pyruvate which
ultimately has to enter the furnace of the cell to be
burning produced ATP or energy, right?
But that furnace has another door, right?
And that is the one that it has to be also working.

(14:11):
And if the flux of glucose is too much into the cell, whether
because there's very high intensity or there's a
pathological state, glucose cannot be burned, that pyruvic
cannot enter that door into Maracandra into the furnace and
be burned. And the only way they have is to

(14:31):
be transformed to lactate, right?
So when you see and that lactategoes escapes to the blood.
So when you see high lactate, high blood lactate levels, it
it's telling you that that glucose is not be fully oxidized
or burned right in mitochondria and it's been transformed to

(14:52):
lactate because otherwise you would see very low lactate
levels, meaning that the glucoseis very well oxidized or burnt.
Got you. OK.
So if people really want to makesure that how can people apart
from taking a lactate test, is there any physical signs that
one person on earth they're having good mitochondrial health
before they get to testing theirlactate levels?

(15:14):
I think that this is one of the areas we wouldn't have
biomarkers. You know, let's say people have
type 2 diabetes, for example, right?
It's, it's, it's a metabolic disease characterized by a poor
capacity to burn glucose, but not just to transport it through
the cell, but to burn it and, and resting conditions.

(15:36):
You burn in mitochondria, right?Now the biomarker that we have
is that diagnosis. We have the glucose tolerance
test or the hemoglobin A1C, right?
That's a diagnosis right there. There are no other biomarkers,
unfortunately, the same thing for Alzheimer's.
Alzheimer's, we know that beyond, you know, the amyloid

(16:01):
plaque hypothesis, we know that no drug has been able to target
that plaque and that now the newthinking in Alzheimer's is
looking at brain metabolism, right?
And that Alzheimer patients are or Alzheimer's disease is
characterized by two hallmarks, insulin resistance and
mitochondrial dysfunction, whichare the same 2 hallmarks of type

(16:25):
2 diabetes, which is now given the name or rename it, you know,
like a more colloquially type 3 diabetes or brain diabetes or
end stage type 2 diabetes, right?
But without a doubt, there's, there's a big part of that of
its pathology is a is a modern kind of dysfunction and and

(16:47):
insulin resistance. So there's a poor glucose
utilization. But again, we don't have any
biomarker, right? The biomarker that we have is
the PET scan that has been in front of us forever, right?
You've got a PET scan of a typical Alzheimer's and most of
us have been either seen one or looked at Internet how they look
like. We see the very bright images,

(17:10):
right? The, the, the very bright eye,
orange or red and yellow, especially the, the, the orange
or red. That's metabolic activity,
right, of the brain. And that specifically it is a
glucose activity in the brain. That's a normal brain, a normal
brain with early Alzheimer's. Alzheimer's has reduced

(17:31):
activity, reduced metabolic activity and it's reduced
glucose activity, an advanced Alzheimer, Alzheimer's disease.
You can see the image that is very, is very dark, is very
blue, right? There's not much medical
activity because there's not much glucose utilization.

(17:51):
But again, that's not a biomarker, it's a diagnosis.
And this is what one of the areas that we need to focus is
on developing novel biomarkers so that we can see metabolic or
cellular dysregulations at the mitochondria level a decade or
even 2 before it becomes a full disease.

(18:12):
Because then we can intervene, whether it's without lifestyle
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(19:59):
on your journey. Well, it's so interesting that
you mentioned about Alzheimer's there, because in the UK
dementia is the number one killer.
And it's interesting that I've spoken to Chris Palmer on this
show about metabolic health and and mental health and the
mitochondria is always at the centre of these conversations so

(20:20):
much. But I think so many of us are
confused about how we can improve on mitochondrial health.
So we, we started at the beginning about talking about
VO2 Max is looking as A1 predictor.
But you talk so much and you've pioneered this whole sector with
exercise to help support mitochondrial function.
So although we're in a bit of anexplosive of chronic disease

(20:44):
right now, there is a lot of things that we can do.
We've got to have hope to get our mitochondrial health like
pumping back. So you have pioneered, and I
know that you know, there's a lot more to it, but you have
pioneered Zone 2 training. So I thought it's important to
start there. Why is Zone 2 training so
important for our mitochondrial health?

(21:04):
Well, I mean, everything starts with a professional athletes,
they have taught us a lot, right?
I always say we cannot understand imperfection.
It wouldn't understand perfection in the 1st place.
Those are the, the, the Formula One cars, right?
Those are the gold standard of what a human should be, right?
Metabolically speaking, right. And This is why I've been

(21:26):
fortunate for almost 30 years to, to be able to work with
these kind of humans and be ableto understand them very well.
So they have taught us a lot in order to understand other
concepts in, in different pathologies characterized by
these functions at the metaboliccellular level, right?
So performance on one hand, right, it's about, as I

(21:47):
mentioned, about producing ATP fast, producing energy fast and,
and, and, and lasting as long asyou can.
Competition is that being as fast as you can for as long as
you can, right? That's whether whether we're
talking about swimming or rowingor cycling or football,
basketball, you need to be fast and you need to sustain that

(22:09):
effort, right? So for that, you need to produce
ATP at very high levels and havea very metabolically efficient
engine, right? Which is what happens at the
cell. And that furnace, that
powerhouse, that central part ofthat engine, the cell is
mitochondria, right? So what do we need to do with

(22:31):
athletes? Improve their mitochondrial
function? So for that, back in the days,
I, I developed these methodologies to try to
understand how we can translate what we were learning about
cellular metabolism into training.
So we know that different exercise intensities elicit
different metabolic results. It's not the same result when

(22:55):
you go for an easy spin on the bike, for example.
Then if you do a 32nd Sprint, you're mobilizing different
energy systems, right? So that's what I saw in the
laboratory with this methodologies with a metabolic
heart, with the lactate. And I start to define different
training zones because there were different metabolic events.

(23:17):
If you do a maximal, I mean an incremental exercise intensity,
you see this beautifully. And anybody who has done this
test or performed this test as an operator, you can see these
events happening in front of your eyes, right?
And therefore, we're talking about from very low intensity
all the way to maximum sprinting, right?

(23:39):
So if you, if you put together the dots, you're going to see
these metabolic events. That being said, that's why I
created different training zonesbecause I couldn't tell an
athlete, hey, you're in a high glycolytic intensity or you're
in 100% oxidity phosphorylation state.
That's what you have to train, right?

(24:01):
You cannot speak that language, right?
So I had to do something that was very easy to understand and
that's what I decided zone one through zone 6, right?
Then I started by trial and error, OK, Now let's try the
next step. OK, what is the intensity that
elicits the best effect? That's just for mitochondria,
but for other intensities, right?

(24:24):
Because we, we always have to remember that when it comes to
for athletic performance, you always win competitions at the
high intensities. I have never heard about any
athlete or seen any athlete winning a, a competition that in
the zone 2 or low intensities never happens.
So, but unfortunately, people are taking to the, to the
extremes now and all of a suddenhigh intensity is gone.

(24:45):
It's worthless. Well, it depends.
If you're an athlete, you must train high intensity.
And my athletes train very high intensities.
In fact, you know, like about 50% of all the best times that
PRS happened during training, that competition, right?
So it's very high intensity because you need to stimulate
that. So anyways, that's why you set

(25:06):
up all these training zones. And that's why I started to see
people in the responses back in the laboratory where you can
study that metabolic response very closely and see which
trainings have improved the most.
So what I saw is that, that Zone2, that was the one that
improved the most, 2 parameters that I mentioned earlier, fat

(25:27):
oxidation and lactate clearance capacity, which both are
surrogates of monochondrial function.
I was seeing this over 25 years ago.
And and then obviously working with athletes, you saw that also
in the competition. That's where you saw that the
action, right? And so that's why this one too
came along. But of course, you have higher

(25:47):
intensities from 4, some 5, which are, you know, that that
turbo you, you need to improve that, that turbo, right?
The important thing is that you also have to train the turbo,
which are like the high intensities, the zone 5, zone 4,
because you need to stimulate the tour because that's where
you're going to improve the competition as well.

(26:07):
But then you need to stimulate also the Sprint 'cause sometimes
you need to Sprint, you know, But anyways, but when it comes
to mitochondrial function, that's important.
But when it comes to VO2, right,which is the cardio respiratory
adaptations, training high intensity is very efficient.
That's probably more efficient, if if not more efficient than
training at zone 2. But as I said from the

(26:29):
beginning, that's, that's the how you express your cardio
respiratory adaptations to exercise, right?
And, and but another thing is like how well mitochondria
function works. So anyway, so this is what now
from, from the lessons that we have learned from elite
athletes, then I started workingwith people with, from different
pathologies, right, and chronic diseases, including type 2

(26:53):
diabetes, cardiac rehab patients, oncology patients and
metabolic syndrome. And that's what I saw in this,
in these people also improved mitochondrial function the most
that, that training. And also with people, yes,
that's what I was seeing. And also with people who just
wanted to get fitter. The typical person who hadn't

(27:15):
has been struggling forever because they only did heat, for
example. And at first they see results,
but eventually they get injured or they get discouraged or they
lose patience with that because it's, it's not sustainable for
many people, not for all, of course.
So I am not saying that you haveto disregard high intensity at
all, but I think that you need to reduce the amount.

(27:37):
And this is what we know very well, again, from the lessons we
learned from athletes, that you cannot sustain high intensity
training all the time. And we don't see that, I mean,
in that, well, any of us who hasbeen working with athletes at
the high level can confirm this.You know, you don't see, let's
say like very high intensity sport, you know, like swimming,

(28:01):
right? It's under a minute, OK, It's
under a minute, OK. What do we have to do to
training? What's, what's the intuition
tells you? Let's just do 4050 second
sprints all day, right? OK.
We can't be so naive to think that the best coaches in the
world and the best swimmers havethought about this, right?
Of course they have. Does it work?

(28:23):
Well, just go around any swimming pool around the world
with the best swimmers in the world.
They spend hours a day, 234 hours a day, swimming up and
down, up and down. And of course they do intervals,
but it's not sustainable. And you can take this to any
sport out there, right? So the same thing, you know,
for, for regular life, high intensity is important, but but

(28:46):
it's not sustainable. And and the zone 2, the
characteristic that has had is that it works and it's
sustainable. So when we think about zone 2
and tell me if I'm wrong but I'mthink I always think about zone
2IN training that I can just about talk but not in a
comfortable way. How can someone understand if

(29:08):
they don't have a wearable? How can they understand where
zone 2 is? Yeah, that's a good question.
And and this is, this is about, about it and it, it resembles
closely to what we see in the laboratory when we establish the
parameters for for that zone 2 and the other the rest of the
zones, right. Yes, that's an intensity where

(29:29):
definitely we cannot keep this conversation.
This would be a resting as we are, but it's a conversation
that you can't sustain. I mean, you can't sustain, but
it takes an effort, right? It's a forced conversation that
you have to breathe, you have totalk, but you can't sustain it.
But with an effort, if you can'tsustain, if you cannot sustain

(29:50):
that conversation for, for more than a few seconds, right, that
you're already in very high intensity.
And this is due to glycolysis, which is another event that you
see very well in the laboratory when, when you're working in
zone 2, you're burning glucose, but you're burning fat.

(30:11):
And that's the intensity of the one who burned the most fat,
which is another concept not getting very popular, which is
the fat Max, right? That's intensity of the one you
burn the most fat. I've been using that concept for
25 years at least and, and usingfor weight loss purposes too.
People would come to the laboratory and because they've

(30:32):
been trying to lose weight through exercise and, and they
can't. And then when you do the test,
you see that they've been, they've been exercising too high
intensities where you burn 0 fatand you show that to them
because in the laboratory you see very well when you burn the
fat, you see the grams per minute, the fat oxidation in

(30:52):
grams per minute and carbohydroxidation.
So there gets to a point that you get to your fat Max.
And then as exercise intensity increases, the fat disappears
and you burn 0 fat. And why is that is Because as
you go on to a higher exercise intensities, the, the cells, the
muscles need faster ATP, faster energy.

(31:17):
And that energy cannot be supplied by fat anymore because
while fat can give you more overall energy, it's slower.
It's like a diesel gasoline, right?
It's lower away. It takes more time to give you
that energy, which when you're at lower intensity is great,
right? This is part of the evolution,
right, of humans, because we canonly store about half a kilo,

(31:42):
500 grams, like 2 lbs of glycogen.
No, 1 LB of glycogen, sorry, which is how we store glucose,
carbohydrates, right? So the body tends to preserve
that tank very well and for thatstarts using other fuels, mainly
fat, right? But when exercise intensity is
very high, fat cannot be cannot give you energy fast enough and

(32:08):
you need to switch to carbohydrates and then and
sorry, I've been going the long way.
This is what happens is like yousuppress fat and This is why a
lot of people were not burning fat because they were always in
in carbohydrate burning. They were not burning adipose
tissue. But then through the talk test,
to your point, the fact that you're speaking fast is because

(32:32):
you're burning a lot of carbohydrates, you're producing
a lot of lactate and you start buffering that lactate and that
CO2 that's part of producing, ofbuffering the lactate and that
forces you to breathe faster, right?
So when you're breathing faster,you're at a higher metabolic
stress and you you start decreasing significantly the

(32:54):
amount of fat burning. So when you can't stop at all or
when you can't speak at all, you're not burning fat, you're
burning glucose. Wow.
OK, so sometimes people might just be doing too much high
intensity and that's why they'renot losing any weight.
Yes, we've been knowing that forfor decades as well in working
with. That, but I don't think that's a

(33:15):
normal conception in in the public.
I think a lot of people today will go to the gym to want to
sweat and burn a lot of energy and wonder why they're not
losing weight and this is the exact reason why.
So you're saying if they can balance that with more zone 2
and recovery, then mitochondrialhealth will improve?
Yes, yes, it it pays off. People would say, of course,

(33:38):
yeah. But if you do high intensity,
you increase your basal metabolic rate and you burn fat
down the road in the next 6/12/24 hours.
Sure, of course you can do that,of course.
But why not burning fat while you're exercising?
So the instead of burning fat after you exercise, relying on

(34:01):
what you think that you're goingto be burning at rest because of
the high intensity you did, right?
I think there's room for both concepts, obviously.
But again, why not burning fat during exercise?
Because you're going to burning more fat.
You're burning, it depends, right?
But you depend, it depends on your fitness level and your
mitochondrial function level. You burn between 0.20 point 3 to

(34:24):
0.8 or 9, close to 1g per minuteright of fat.
That doesn't seem quite a quite much, but day after day after
day after day, it counts, right?But during the rest, during the
rest, you burn very little fat, right?
So it might be burning 0.10.15. So why not burning 0.40 point 5g

(34:51):
half a gram for, for, for doing exercise for 60 minutes or 90
minutes, right? And it's just, you get a
calculation people can do, get acalculator, you know, it's just
plucks on numbers in. And you're going to see that if
you have about four days a week,but 5, four to five hours a week

(35:13):
burning fat 0.40.5, you know, every month you're going to be
losing it depends on the time, you know, and your fat burning.
But you can be losing 1K if you want to lose weight, right?
So along with the diet, you can really help, you know, but
anyways that that fat, that fat Max coincides also with some
too. That's that's a good parameter

(35:35):
to see. Wow.
OK, so I guess I. Mean, I find this really
interesting as well from a nutritional perspective, because
there's also the the argument that if you're training at high
intensity all the time, you're also going to be eating a lot
more as well. So if you are on a a fat loss
mission and you're consuming more calories and, and you're
having more of a nutrition load,that also is also quite a hard

(35:58):
one for, for losing weight as well.
So there's, I mean, and I'm not saying that's right or wrong,
but there's also eating more when exercising more.
And I do see that a lot within clinic where people are just
exhausted and they're kind of eating their way through the day
because they're doing so much HIT training.
Yes, I mean we have to also. Think that, yeah, if you do high
intensity training, you're goingto burn a lot of energy and

(36:22):
you're going to have to resynthesise it, right?
And that's important to know that you can be burning a lot of
energy and you're going to have to eat a lot more to
resynthesize it. And this is the problem.
Sometimes it's like how much youhave to eat.
Some people, they think they have to eat more than what they
need. Some people, they think they

(36:43):
have to eat less, right? Then when you have low, imagine
that you have low glycogen content because you're having a
low carbohydrate diet and you can only store about half a K1
pound. Then people with high intensity
training, you can be burning somewhere between 457 grams per

(37:05):
minute of carbohydrates, right? So you can run out of glycogen
pretty fast, especially over a few days.
And then the body tries to defend that the body does not
like to lose glycogen, right? So it starts adapting to that.
The first line of adapt of adaptation from an evolutionary
standpoint is muscle breakdown. That happens in, during in

(37:29):
athletes. We know that happens very well.
That happens to ICU patients andthen happens at cancer patients.
So the more glucose you use and and once you hit depleted
glycogen storages, the body is very wise because it can
breakdown different proteins in the muscle, converting different
amino acids in the muscles. Like the branched in amino

(37:52):
acids, they can become glucose, they can go to the liver and
become glucose and also glutamine.
It goes directly into mitochondria.
But you pay a price because those amino acids are derived
from muscles. So the muscle starts eating
itself to feed itself. It's like, it's like an oxymoron
in a way, right? But it's an evolutionary

(38:12):
mechanism. Then you move on to the next
phase, which is through using keto ketones, right, which is
much longer adaptation time, right?
But but right away in the many people is what happens.
They, they are burning all glucose when they go out, they
don't have enough, they don't have enough glycogen.
They're starting breaking down protein.

(38:33):
They don't lose weight. They get tired, fatigued and
also increase the chances of getting injured.
And I am not obviously, I am notsaying that heat is bad, but if
you do heat, you need to be very, very well monitored,
right? Otherwise it can be tricky.
So when we do heat training withathletes, we need to monitor

(38:56):
very well because they can get overtrained like that, you know,
and that's why it's very the events in a week where an after
that high intensity training arevery limited because of you can
get overtrained. So with like a normal person.
Listening to this, I say normal because you know, you do work
with elite athletes like people from Tour de France and stuff

(39:18):
that you've done with them is incredible.
But obviously the normal averageperson doesn't have the time
that an athlete has or the expense.
So I think the general like conversation online, which I was
trying to find for this conversation, is that most
people are saying four to five times a week of exercise where
how much zone 2 should that be for an average person?

(39:39):
If they're going to the gym fouror five times a week, how should
they be looking at their exercise to support
mitochondrial health? And what would you suggest an
ideal dose should? Be somewhere around 200 to 300
minutes a week, right? That's, that's somewhere,
somewhere around three, I think 3 to 4 hours a week of zone 2.

(40:03):
It works really well. And if on top of that, maybe
towards a zone two session, you do high intensity at least two
days a week. That's important.
So you can do, let's say ideallyyou do it one hour to an hour
and a half at zone 2 on the bikefor example, or one hour on the

(40:24):
rowing machine. Or you do 40 minutes to an hour
running or fast walking, right? If you that four days a week,
two days a week, you can do highintensity right towards your VO2
Max, right, to stimulate VO2 Maxalso and to stimulate what we
call the turbo that was mentioned that glycolytic

(40:45):
adaptations, right? But you just have to touch it,
right? If you can first, if you can,
can you or if you enjoy it, can you do a Sprint or can you do
2-2 minutes maximum exercise? If you're a cardiac patients,
you're not going to be able to probably do it.
If you're an oncology patient, you're not going to be able to

(41:06):
do it right. If you're a longevity person,
you might not have the the stamina or yet or you might not
enjoy it or you might enjoy it very well, right?
But I think it's important to try to stimulate the high
intensity twice a week and, and then resistance training,
obviously, yes. And then resistance training two

(41:27):
or three days a week. Two of the research shows that
if you do like a, a well-roundedstrength training program, about
two days a week is enough or should be enough at least to
maintain muscle health. Not to become, not, not to
become a bodybuilder, to have a lot of muscle, right, but to, to
maintain your muscle mass. Today's week should be

(41:49):
important. I'm interrupting for one moment.
To ask one small favour, please subscribe to the show.
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(42:10):
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Thank you. And so it's interesting because
I've had Doctor Stacey Sims on this show who talks a lot about
Women's Health and talks a lot about Zone 2 training as well.
And it's really interesting because obviously you've been
speaking about Zone 2 for such along time.

(42:32):
Is there differences between menand women when it comes to Zone
2? A lot of a lot of these studies
mostly based on men. What does the Women's Health
sector show? Do we need to be doing less or
more of Zone 2 training? I think Stacey's argued on the
show that she agrees with Zone 2, but maybe we need to be doing
a bit less of it as women. But she's still a massive

(42:54):
advocate for it. But she says it's in it's
infancy. What's like now.
I have you on. What is your view on like women
versus men in Zone 2 training? Is there any evidence that you
can like share with us or or even like that you've worked
with athletes yourself in this sector?
Well, that's a good question. And I think that I think things
get mixed up because of the, of the perception that everything

(43:19):
is on 2. And therefore, whether you're a
man or a woman, that's not it. You need to do high intensity.
And this is, this is when I, when I started with the concept
of zone 2. I, I watched the zone 4 and zone
5 also. And as I mentioned, I've never
heard anybody winning a race in soul 2 for you need to do high
intensity. Now everything comes to the

(43:40):
extreme right. That is all is on 2 and that's
not true. So maybe when Stacy refers that
you need to do less than two is because you need to do more high
intensity. I agree with that because that's
what I recommend to to my patients, whether they are men
or or or women or my athletes also.

(44:00):
So that's that's important thingthat you need to have.
And as we just talked, we need to do some like one or two times
a week. You need to you know, get those
incursions into into high intensity because are necessary
for that glycolytic capacity. The one thing too, women have a
decreased glycolytic capacity and by glycolytic capacity, I

(44:22):
mean that turbo capacity and that's the high intensity.
They have a lower muscle mass. They have a lower capacity for
those fast twitch muscles to produce ATP fast, right?
And therefore there's a reason for women, they can try to
stimulate that more. That being said, when it comes
to mitochondrial function, many women are equal or should be

(44:47):
equal, right? And therefore any exercise that
that increases, you know, mitochondrial functions should
be applied like zone 2:00. Well, it sounds very similar, so
I guess. You're saying that men and women
shouldn't have this really any differently.
We should both be prioritizing Zone 2, yet actually women will
struggle more with HIT because of these, because of these

(45:09):
muscle fibres to produce the ATP.
And that makes so much sense because I went through a phase
probably about eight years ago when HIT was, I don't know if
you remember, there was a huge surge in HIT and everybody,
every studio was opening and everyone was doing HIT.
And I felt worse than I've ever felt before, like awful.
And also what what was coming upat that time.

(45:30):
And I'd be really interested to ask you about this with exercise
and also how you train athletes and if it's different for men
and women. I was also fasting before I was
doing those sessions as well. So you can imagine I had like no
energy in me and I was going offto do these ridiculously
expensive classes for an hour and raising into Zone 4, Zone 5.
And I've never felt worse in my life.

(45:52):
Yeah, you're, you're totally right.
And this is one, one of the things that, yeah, I mean, HIT
was, was a hype and, you know, it was very popular 10 years
ago. But you know, very few people
from 10 years ago, they're stilldoing it or not, not that many
people because or at least people who were pursuing health

(46:13):
benefits through HIT, you know, it's not sustainable and it can
lead to injuries. Again, I am not saying that heat
is bad for you, but any exerciseprogram based on heat, right, is
not sustainable. There are no athletes in the
world who who all that training they do is HIT.
It doesn't exist. And believe me, I know a little

(46:35):
bit about what athletes train, but it doesn't exist.
And in fact now and I'm not saying if it's a tendency or
not, but what we we have seen ithistorically is that 8020,
whereas the proportions of of ofthe time or not, not the time,
the sessions, not the time because that you know the, the

(46:56):
sessions that, that you dedicated to different
intensities. About 80% is lower intensity,
call it zone 2 maybe and about 20% is higher intensity.
This is the approach that we've been using with athletes forever
and it has worked. Any other approach of doing 2080

(47:17):
like 20% lower intention, 80% hit, it doesn't tend to work.
It causes overtraining, fatigue.And I was mentioned earlier, but
that's kind of what we do with athletes.
So that the whole thing of now the 8020 it comes from from
again like like as many conceptscome from what we have learned
with athletes, they're now becoming mainstream, right?

(47:37):
But at 8020 is not about minutesor percentage of minutes.
Because in fact, if we go by theminutes, it's even less.
If you look at that volume, justobservationally, if you look at
the volume of any athlete, whether it's a a very high
intensity of athlete like a swimmer, 100 meter swimmer or a
roar or a marathon runner, about5 to 10% of the entire minutes

(48:04):
per season are in high intensity, right?
So, but we need to think more about sessions.
So it's about 80% of the sessions who contemplate maybe
Zone 2 and about 20% of the sessions who content should
contemplate high intensity. And the way we break it down is
to yes, so many times we isolatea session because they have more

(48:28):
time to specifically do high intensity because of the demands
of competition. Other sessions specifically is
high Zone 2 training and they can be four or five hours, but
more models don't have four or five hours or they even can do
four or five hours at that for Zone 2 or high intensity.
So the way is about to come combining as I, as I said, but

(48:49):
if you do four days a week Zone 2IN combination with high
intensity, at least 2 or so, that towards the end, that's
when you start hitting some sweet spot.
And then that was like the, the,the, the, the distribution,
right? It's more like 8020.
But then again, like, you know, hit, it's something that, yeah,

(49:12):
it's just a lot of people, you know, did it.
But it's just many people don't enjoy it.
Didn't enjoy it. Have you had to change a lot?
Of these athletes mindsets on this approach to more an 80%
like lower intensity and the 20%high intensity like have you
seen them have some resistance to that because obviously you've
seen these insane changes. I'd love for you to share some

(49:34):
of these stories for for our listeners, but how is the
mindset approach when you're working with with athletes in
the sector? Not much to be honest, because
that's. Been the mentality always like
that. In fact, you know, for as I
mentioned earlier, right, if youwatch what swimmers do and have
done forever and they continue breaking records, is that you go

(49:57):
to a swimming and you see the world class swimmers, they swim
up and down, up and down and then eventually, obviously they
do some intensities, right, But it's not the other way around.
So you don't have to convince them to hey, you can't do 1000
sprints a day. It's bad for you do 5 or do 10,

(50:17):
right? Well, they're already, they're
already there, right? In fact, what I had to convince
him more is that the zone 2 is amuch harder intensity than just
cruising, which was what a lot of people were doing because
that 8020, they didn't know it by 20, but you know, that's what
they were doing was like more aerobic training, long endurance

(50:41):
run or ride. It was too easy, right?
And it was too easy. It was close to a recovery
intensity and that doesn't stimulate that by energetics of
mitochondrial function as much. So it was about convincing them
that they had to go faster. And if you look at what you look
at, if you talk to some other people that I've been working

(51:02):
with that Zone 2, especially at high at high level athletes,
it's really, really, really demanding, very demanding.
And until they get used to that,but it's not an easy training at
all for that. We have recovery days, OK.
And what does the recovery days?Look like nothing.
No, I'm not active. Recovery, I mean you yeah, you
have to do nothing. It's important to that's what I

(51:24):
figured. I remember when I introduced
also the concepts or off days in, you know, like a long time
ago to to the athletes I was working with, it was a crazy
idea to have an off day or even a recovery week, like an active
recovery, right? But now everybody does an off
day completely and, and at leasta recovering active recovery

(51:46):
day, which is, you know, like a light run with friends to, to,
to grab a coffee, right. Or a light bike ride, you know,
to grab another coffee with friends and come back.
You know, it's something that ismore to me.
Yeah. There's no, there's no
difference between an active recovery day than just do
nothing, right? Because when you do nothing, you

(52:08):
just rest. And we do active recovery days,
maybe more psychological becauseto break down the to break out
of the routine of training hard,because you need to train by
yourself many times in individual sports.
So that day where you're going to have fun and just gather with
some friends, that's your recovery day for a coffee,
right, for example, or a coffee run.

(52:30):
But yeah, you need. You need those too, to make sure
you're performing but also. To make sure I get your immune
system and everything you need recovery for so many different
dimensions. You know, your immune system
plays such a big role in and exercise.
Yeah. And this is something.
That to me it's, it's a, it's anarea of, of importance because I
have seen a lot of people, let'snot talk about athletes now, but

(52:54):
obviously you see that overtraining, but you see a lot
of people there, you know, whether it's for longevity or
for fitness, they are completelycrushed and they don't know it.
You know, people who have, as you were saying, on top of doing
one routine of exercise, they're, they're, they're going
through extreme diet, they're struggling through and that has

(53:17):
consequences. You can pay for those.
And that has consequences in thelong term, for example.
And I've seen looking at biomarkers, I do a lot of
biomarkers to look at how athletes are assimilating
training and competition. But again, we can use these
biomarkers for people, you know,for longevity purposes, people
with different diseases and how they are simulating that dose of

(53:38):
training. Is it too much or is the right
one right? So I see biomarkers and we see a
lot of muscle damage, for example, in people and low, I
mean low grade inflammation, chronic low grade inflammation.
When you have muscle damage or when you are working so hard and
not enough nutrients and not enough rest, the body fights it

(54:02):
because you're it's an aggression to the body.
It's an insult. The body cannot recover fast
enough and therefore it starts breaking down like muscle mass.
And one of the the ways that thebody has to heal is
inflammation. It's a physiological process,
but that inflammation usually should be acute according to the

(54:24):
damage. When that damage is chronic,
that inflammation becomes chronic.
And that's what you start seeingalso, you know, some biomarkers
of telling you that that person has chronic low grade
inflammation, which as we know from epidemiological studies,
it's it's important because it'sbeen related to multiple

(54:45):
diseases. Yeah.
I mean, inflammation is the start.
Of, of every chronic disease, right?
And I, I think like when we, we don't sometimes always are aware
of how much pressure our immune system is under, but it's not
just exercise, it's all the other things in the day.
And like, I know if I'm doing anintense session and then I've
got an intense work day and I'venot slept well and then my

(55:06):
nutrition is not great, I'm not going to get the outcome of that
session that I want, which is really important to think about.
And I mean, I want to make sure that we touch on metabolic
flexibility because this might also be connected to this as
well. You were saying just earlier
before this that it's quite a new term.
Can you explain metabolic flexibility?

(55:26):
Because my understanding is how you can how easily you can
switch from fats to carbohydrates, which feel like
women do pretty well in their menstrual cycle phases.
But can you talk to us a little bit about this term and get us
to understand it better? Yeah, so metabolic flexibility.
Is it's, it's not a new term necessarily, but it's been,
we've been known for maybe 2025 years.

(55:49):
But yeah, now it's mainstream like a lot of things.
And, but yeah, it's, it's about that, right?
I mean, in a simple way, it's about the ability, you know, to
switch back and forth between fuels, mainly fats and
carbohydrates. Absolutely.
And, and, and where does it happen?
Where do you burn fuels? In mitochondria, right.

(56:11):
You burn the fuels because you have to produce ATP and that ATP
happens in mitochondria. And when you burn those fields,
sorry, in, in mitochondria and, and, and yes, this is, This is
why metabolic flexibility and mitochondrial function are
pretty much identical terms, at least in my view, right?
Because if you have a good mitochondrial function, like

(56:31):
athletes, you're going to be switching back and forth fields
very well. You want to burn fat now?
OK, let's burn fat. You want to burn high amounts of
glucose? OK, let's do that.
That's being metabolically flexible, right?
And that's pretty much what what, what is the the same terms
of metabolic flexibility and mitochondrial function are for

(56:52):
these purposes of bioenergetics are very important.
And when mitochondrial dysfunction happens or
mitochondrial decay happens, thefirst thing that you start
seeing is a decrease in the capacity to burn those fuels,
right? And that's you start become
inflexible and we can talk aboutthat in more detail.

(57:13):
That's the study that we that it's actually what what we were
talking about the other day about that transporter that we
have identified that that's the it's the root or one of the
roots of the issues. This is the glass floor.
Right. The transporter that we were
talking about in the study, Yes,yes, yeah.
So. So you just mentioned.
There, which we should definitely understand, but you

(57:34):
just mentioned there before thatmitochondrial decay sounds
obviously cellular death terrifying, but it happens all
the time. So let's like how do people know
if they're getting mitochondrialdecay?
Well, that's a good. Point so mitochondrial decay is
like, you don't know, you know, that's no, you, you don't know.

(57:55):
I mean, so a mitochondrial decayis going to lead down the road
to some from dysfunction. And, and I think we talk about
mitochondrial dysfunction quite lightly, me included, because
we, we try to talk, you know, like a in, in, in, you know, in
immense terms. But mitochondrial dysfunction
means that the, that mitochondria don't work, you
know, or they're aberrant, right?

(58:17):
I, I, I like to call it more mitochondria decay, right?
As we age, for example, our mitochondria are not as solid as
when we were younger or as we become sedentary, our
mitochondria don't work as well and we become more and more
inflexible, metabolically inflexible.
And this is, this is one of the things that at this point we, I

(58:40):
mentioned that the methodology that I developed looking at
fatting, and I mean fat oxidation and lactate, it tells
you, because when you have a mitochondrial decay that is not
pathological, you see a decreasein the function of, of oxidation
or burning fats and, and also lactate.
And, and that's a signature, right?

(59:02):
But again, it's not you, you don't wake up one day and like,
oh, I think I have my kind of decay, right?
No, you wake up one day and, andyou go like, hmm, that's
something funky. I don't, I don't know, I've been
feeling strange for a while. I don't know what's going on.
You go to your doctor, you get blood analysis.
Your, your blood glucose is 150 and your A1C is, is 7 1/2 or 8,

(59:23):
right? Like boom, you, you have, you
have pre diabetes or you have diabetes, right.
But yeah, it's, and it's part ofthat matter kind of decades.
As I said earlier, if we were able to identify biomarkers 1015
years because it's a decay, right, then we should be able to
intervene much faster and efficiently.

(59:45):
Yeah. So talk to me about.
This paper that that we were talking about before.
Tell me about what you did. Well, not you've just found
you're we're kind of rewriting it again.
But tell everyone about the new discovery.
Yeah. So what we we?
Saw we, we, we wanted to see what are the, you know,
metabolic responses of sedentaryhealth individuals, right,

(01:00:09):
versus people who are morally active, that is, they do
exercise. But at least 150 minutes a week,
right? Which are the recommendations
right out there? So we wanted to see if there are
differences. So what we did in this study, we
we looked at mitochondrial function of both groups through
muscle biopsies. So we looked at muscle biopsies

(01:00:31):
in skeletal muscle and we were looking at how the Smarter
Kindle were working. So we, we looked at a wide range
of areas from like how well theyburned fats and carbohydrates,
how well they transported carbohydrates and how well the
electron transport chain, which is the apparatus where central

(01:00:53):
apparatus to mitochondria to thefurnace where you produce the
ATP works and how well they theyprint how much they produce ATP,
right. So what we saw is that they have
a significant reduction in the mitochondrial function compared
to active individuals, morally active, nonlinear, that's the

(01:01:14):
sedentary healthy. And this is what I call the
inside out hypothesis that I'm starting to develop from that
and that originated the study. When it comes to pre diabetes or
type 2 diabetes, we clinically and at the research level, we
see this or contemplate this as a peripheral.

(01:01:35):
At a peripheral level that is, is everything about glucose
transport uptake into the cell, it's about insulin signaling the
cell, the receptor hyperglycemia, hyperinsulinemia
from the from the pancreas, right?
Everything what happens at the, at the surface, but that's the

(01:01:56):
first part of the trip of glucose being burned in
mitochondria, right? And there's the assumption that
once the glucose enters the cell, it's going to be burnt.
No, no, no, no, no, that's only the first part of the trip.
And the glucose, as we know, enters through the cell through
these transporters, that door that is called the glad force or
glute force. And there's they're, they're

(01:02:18):
signaled by insulin, right? But then once glucose enters the
cell, it has to be broken down through pyruvate.
It's another component through 10 steps.
That's the second part of the trip.
The third part of the trip is that Pyruvate needs to enter the
furnace through another door, right?

(01:02:38):
We call it the NPC, don't worry about the name, but it's another
door. And then once Pyruvate enters
through another door, that's the4th part of the trip that
Pyruvate has to be converted, has to enter the the Krebs
cycle. The the famous thing that we
know from biology, the lovely Krebs.
Cycle. You take me back to my
biochemistry days. Thank you for that.
Yeah, well, that's the that's the 4th part of the trip.

(01:03:02):
And the fifth part of the trip is that then eventually you need
to reproduce the ATP in the electron transport chain, right.
So it's a long trip. So what we were looking is at
all these different parts of thetrips.
And what we saw is that every everywhere you looked except for
the entrance, everything is dysregulated in the sedentary

(01:03:23):
individuals in the. Sedentary, so you.
See, the first thing is dysregulated is the entrance of
pyruvate into the furnace, right?
So sorry, the, the entrance of glucose is normal because the,
the number of of the OR the expression of that door at the
cell surface for glucose, that glute force, they're the same,

(01:03:45):
they have the same amount of expression.
But then that door of the secondpart, the door of Pyrrovir
entering mitochondria is decreased by about 50%,
significantly decreased. And then the, the, the that's
the door and the entry of pyruvate into mitochondria is
about 38%, something like that decreased.

(01:04:08):
And then the, the capacity for the electron transport chain to
produce ATP is about 35 to 38% decrease.
So it's a significant decrease in the production of energy,
right, just for glucose, right. And then that's, that's where is
we call the inside out these, these, these people already they

(01:04:29):
have a very strong signature of mitochondrial decay that not
dysfunction, mitochondrial decayprobably 10/15/20 years before
they're going to show at the surface levels that glucose
cannot get in, which is what we see nowadays as a diagnosis.
That's an and one hand regardingglucose, can I just ask how

(01:04:51):
sedentary? These individuals were that you
saw in these like they just didn't do any exercise at all.
Exactly. Well.
Maybe they worked in the supermarket right by the typical
person that that you we see in alot of our today's societies,
right. They they get in the car, go to
work office go back to the car, maybe go to the supermarket and

(01:05:13):
walk that's yeah, that's sedentary people yeah.
So, but the, the paradox of thatis that health, they're healthy,
they don't have any clinical symptoms.
But you know, like historically in, in biomedical research, the
control has been that group, thehealthy sedentary individuals

(01:05:33):
who metabolically are a disastercompared to the real control,
right? And this is what even at the
university, when I needed to clear this, the, the, all the
permissions to get this, the OK to give this data.
I, I, I told them that the sedentary individuals are the
intervention group and the control, are they the, the more

(01:05:55):
active individual that at first was, no, no, we're not going to
let you go with this study at the University of Colorado.
This is crazy idea, but actuallyis the reality because, and this
is what I want to be provocativeon purpose for this, because our
genes are made to be active, right?

(01:06:16):
This is ingrained in our, in ourbrains, you know, I mean in our
genes being active, right? We haven't evolved to become
sedentary yet, right? Our control status, except for
the last 200 years or so has been to be active always, right?
And, and that's how our genes are.
But the perception that exerciseis the intervention is new to

(01:06:42):
humans and is wrong, because thereal intervention was to become
sedentary as a result of progress, and that sedentarism
is what's causing a lot of diseases, right?
So I wanted to provoke with that.
The real control are people who are moderately active.
They have the good well functioning mitochondria where
people who are sedentary, they already have a decay,

(01:07:05):
significant decay at the mitochondrial level, which down
the road is going to let them, it's going to take them to
different diseases. I mean, it's so interesting.
That you put it like that because that's everything about
our health system. We're not preventative in any
way. So the fact that we're having to
look at sedentary as our, as ourcontrol group is actually a

(01:07:26):
little bit frightening. I mean, it's interesting, you
know, exercises is part of who we are, the DNA, but we all pay
to go and pay to do exercise in gyms.
I mean, I'm one of them, but it's, it's like kind of taking
us out of our normal environments.
Like obviously that's such an obvious thing, but just hearing
you say it makes it even more obvious, which I which is just

(01:07:50):
quite funny. And the fact that we're studying
people who aren't moving their bodies, who aren't eating well
and calling them the controls. Yes, you're.
Right. And that's why it's I don't
think it's a real control, right?
I think that morally active people are the control in the
same way that if we want to understand perfection, the

(01:08:10):
Formula Ones are the perfect cars and those are the elite
athletes, right? I think it's, it's a paradox
that we still call sedentary people healthy when they're not.
And we know down the road, you know, now more and more
epidemiological studies, we knowthat people would send in who
are sedentary. The majority, the vast majority

(01:08:31):
end up having some diseases. Where do you think our health?
Status is going to go from wherewe are now.
Like what are you most interested in with within this
area of research? Because we're in an interesting
time. I think that we're already in a
you. Know we're in in deep shit as it
is already and that, yeah, I think there's a good movement

(01:08:54):
of, of definitely trying to be conscious about exercise, right.
More people are exercising probably more than in the last
100 years or 50 years at least, right?
There's a conscious, there's a science to that.
There's still a lot of movementsif it's hit or if it's zone 2 or
if it's 8020 or whatever, right?I think the important thing is
to get going and to be supervised.

(01:09:15):
That's important. But what I'm more concerned now
and it's about Alzheimer's. And the thing that frightens me
is that I mentioned earlier we was trying to call it type 3
diabetes or brain diabetes or end stage type 2 diabetes.
And as most of the non communicable diseases in our

(01:09:36):
society, whether it's cardiovascular disease, type 2
diabetes, cancer, it takes 20 to25 years to develop, right?
You don't wake up one day and and oh, I have a heart attack.
No, you've been having starting to have that heart attack 20
years ago. The same thing with type 2
diabetes. And there's even the same thing

(01:09:58):
with cancer. Cancer, we know it's a disease
that progresses over time and ittakes 20 to 25 years for most
cancers, right? That first aberrant cell that
becomes then an irregular cell and then starts mutating some
more genes and eventually becomes and adenoma.
And then that's, that's eventually how the evolution,

(01:10:19):
you know, cancer, it takes 2025 years.
But my worry is that so our generations and our parents in
previous generations, right, were diagnosed with type 2
diabetes, right, or protected protect 2 diabetes or type 2
diabetes in their 50s or 60s, right?

(01:10:41):
That's, you know, epidemiologically speaking, that
was the norm. And people were diagnosed with
Alzheimer's when they were in the high 70s, low 80s, something
like that, right? Yeah.
So that was my grandmother so. Yeah, yeah, exactly that age.
Yeah. So.
But we know more from epidemiological studies the the

(01:11:03):
relationship between type 2 diabetes and Alzheimer's is just
getting stronger and stronger. Mayo Clinic using all this big
data from medical records, right, about 80% of their
Alzheimer's patients, they had problems with either diabetes or
pre diabetes, right? So there's a very strong

(01:11:25):
correlation. And as I mentioned earlier,
looking at the brain of Alzheimer's, they have insulin
resistance and minor kind of dysfunction and a big problem to
utilize glucose, right. So that The thing is like we
know if there, there's a correlation between Alzheimer's
and type 2 diabetes and that goes beyond a correlation

(01:11:47):
because it seems to be very strong at this point in getting
strong and stronger. And, and there's a causality in
reality, right? The problem is that we might be,
we might be in big trouble because if it takes about 20 to
25 years for a person with type 2 diabetes to develop

(01:12:07):
Alzheimer's, right? That's kind of when I
chronologically speaking, in the50s, sixties, people are
diagnosed with pre diabetes or type 2 diabetes.
Seventies, 80s, they develop Alzheimer's for the first time
in human history or humankind. We're seeing teenagers or
younger than teenagers with pre type 2 diabetes or type 2

(01:12:29):
diabetes, full blown type 2 diabetes when they're 15 or 20
years old, right? If the evolution is 2025 years,
are we going to see a a lot of people in the millions with
Alzheimer's in their 40s or their 50s if chronologic is
picking? It keeps making sense and I I

(01:12:51):
hope I'm orally wrong but, and Idon't think I'm the only one
thinking this, although not manypeople are talking about it and
I think it's time to have a conversation.
But if it's true, it's the end of societies as we know it,
because people in their 70s and 80s, they already have retired.
There's money allocated to that.They have produced when they

(01:13:13):
were 40s or 50s. But if they get Alzheimer's in
their 40s or 50s, we don't have money allocated for them.
They're not producing and contributing to society.
It's the end. It's the end of everything.
So that's what that's what the thing that worries me in the
next decade or two, because thisis coming to us quite soon.
Yeah, well, I mean, there's already.

(01:13:34):
Children in America and, and in the, in the UK, but more so in
the States that are being diagnosed with it from the age
of 5. So, I mean, it's, it's young and
it's interesting because I listened to that.
My grandmother had Alzheimer's and, and she lived with it for
years and she died very late in her 80s, but she was diagnosed
with it late 70s, early 80s. So she'd had a dominant most of

(01:13:56):
her life without having this condition.
Think about my father who's beendiagnosed with type 2 diabetes
in his 50s and we've been luckily stored as a
nutritionist. So she's got it under control
and we've reversed it. But there's, you know, now I
look at that situation and that's the thing.
It is reversible. But I think the conversations

(01:14:17):
that we're having in public health aren't the correct ones
to help reverse it. It's just to maintain it.
And then it just professionally gets the worse and we go on
Metformin and you know, that's, that's kind of the end.
But children as young as 5 now, it's completely a new whole era.
And there's also, and some of this is genetic, but gestational

(01:14:38):
diabetes as well is on the rise.And there's also a link.
We don't know for sure, but there's also a lot of research
connecting to autism. And so all of this is connected
to metabolic health and mitochondrial function.
But it's so interesting that there's all of these sectors and
it's now affecting from in uteroto children of five to, you

(01:14:59):
know, up to my parents age and beyond.
Yeah. We still can't seem to kind of
all collectively come together on this.
As in what they're all still treated so differently.
Like, how do you think we get past that?
Because for me, a lot of it is about our food systems.
It's the bigger picture, the food systems you see.

(01:15:19):
Yeah, yeah, I, I, I get definitely nutrition is very
important. But again, I, I insist, as I
mentioned here, where do we burnfood mitochondria?
And that's the only place that we burn it during postprandially
after a meal under a glycemic clamp, about 80% of glucose

(01:15:45):
derived from carbohydrates is burnt in skeletal muscle and
during skeletal muscle is burning mitochondria.
This is why we're also talking about muscle health nowadays,
right? And we, we tend, I mean, I was
the other day talking to, I've been giving a bunch of talks
lately to medical students, to medical specialists from

(01:16:08):
oncology to to endocrinology to internal medicine, pulmonology.
None of them told me when I asked the question, what is that
largest organ in the body? Everybody set the skin, you'll
say skeletal muscle. Won't you the the the muscle?
Is the largest organ in the body, not only the largest, but

(01:16:28):
the most active metabolically speaking.
And as I mentioned, about 80% ofthe glucose under glycemic clamp
is oxidizing skeletal muscle within mitochondria.
So it's the it's the largest disposal for for for foodstuff
because it's very active metabolically speaking.
So This is why it comes the other paradox of the world class

(01:16:51):
athletes, for example, the cyclists are through the
friends, right? If you look at their diet,
right, it's they have somewhere between 6:00 to 9000 calories a
day for 21 days. Yeah, around 2000.
And that's because they need to to exist.
It's not because I want to eat. No, no, no.
If you don't have that either through the friends, you're dead

(01:17:14):
meat, right? And they have tried it before,
believe me. And it's and it's so hard for.
Them isn't it it's like the one thing where they're they're
forcing to get this food down them yeah and and eventually
they adapt because they're. Professionals, right?
And they have an amazing stomachin intestinal, I mean tract and
they have an amazing microbiota as well because you have to

(01:17:34):
right? But the The thing is that their
average intake of simple sugars is about 2000 calories a day.
So imagine someone you give to to like a big bowl of sugar
worth 2000 calories a day and you have to eat that for 21
days. How many people will die or be

(01:17:56):
end up in the hospital? Your only source of food 2000
calories is cane sugar, right? It's crazy.
Well, that's what these guys have for 21 straight days.
And metabolically, they're healthiest very few people in
the planet, right? And that's metabolic
flexibility. They can switch back and forth
wherever they want to, right? But what I mean about, and this

(01:18:18):
is an extreme case, of course, but nutrition is completely
related to mitochondrial function because that's where
you burn. And this is I think when you
have a problem, whether at that glute 4 level or as I described
at the inside out model, right, which is the NPC in

(01:18:38):
mitochondria, you're not going to be able to to burn glucose
efficiently. It's you're going to make the
problem worse, right? That's why nutrition works very
well. That's nutrition in my humble
opinion. Does nutrition reverse
mitochondrial function? I don't think so.
The only, the only way where we can improve mitochondrial

(01:19:00):
function is through exercise. Can nutrition reverse the
severity of the problem? Right, Of course, because you're
not making it worse. And if you have a minor kind of
dysfunction, you need to decrease carbohydrates for sure,
because you already have a decay, as we have shown, right?
And we were talking about this study and but yes, I think that

(01:19:22):
both need to be under control. Exercise and nutrition.
Yeah, I think it's. I think it's.
Kind of a, it's a, it's a chicken and an egg in, in my
brain because I think people will go to the gym and exercise,
but then we're surrounded and, you know, with so many ultra
processed foods and not real foods.
And so it then kind of has a compounding effect unless you're

(01:19:44):
literally spending your entire day, which 90% or 95% of the
population aren't exercising. They're surviving, going to
work, stressed out, all of the things of hierarchy of needs.
And then we just slowed ourselves with, you know, what's
on offer because that is, you know, that's the most easy,
convenient foods. And so I think, you know, it

(01:20:06):
must have some impact on mitochondrial health, right?
Your diet. That's from my understanding and
kind of biology and as a nutritionist that the food that
you eat does impact on a cellular mechanism, the health
of a cell. Yeah, we're in a society.
I think you're right. But yeah, I think we are in
society also that, you know, these these foods have a lot of

(01:20:27):
conservatives additives, tolerance.
And and as you look at, you know, both European Union, which
is much more strict than the USAD, you know, they're they
regulate a lot of these conservatives or colorants that
might be carcinogens, right, in large amounts, but you can only

(01:20:51):
have per food an X amount of level per food, but you have
many of these foods with the same color.
And so you have a lot of that those carcinogens entering
through your body, through your body every day.
And that's, that's where like wesee it, for example, colorectal
cancer among young people, it's,it's increasing like I has never

(01:21:15):
done before. And in 1520 years, it's
calculated to be the number one cause of mortality of cancer of,
of, yeah, of all cancers among the people who are young now, by
the time they're older, it's going to be considered the
number one cancer because colorectal cancer numbers are
off the chart. It's already very, very

(01:21:37):
prevalent among these people. And why something is happening
in maybe what they eat those, those ultra processed foods,
these carcinogens, meat or, or who knows, you know, plastics,
etcetera. And and that's the thing, you
know, like how many things can mutate or cause mutations,

(01:21:59):
right? A lot of things from what we,
what we breathe, what we eat, our stress levels, our sleep,
right, can definitely have an impact on our metabolic health
for sure. And I think, you know, like not
many people talk about sleep, although more and more, right,
but a sleep is the pillar of everything, right?

(01:22:19):
I think that if you don't sleep,you can't exercise because
you're too tired and you're eating, you're going to eat in
survival mode, right? Because you don't have energy
and you end up eating whatever. So exercise is is, and you're
going to be more stressed. So exercise is a pill.

(01:22:40):
I mean, sleeping is a pillar. And I think we're in society
where we need to sleep way more,don't you think?
I agree? No, I believe that is.
Like 1 of and has a nutritionist.
Nutritionist is one of my core pillars.
But sleep, I think is the foundation.
If you don't get sleep, everything in your day is a
little bit harder. The food choices that you make

(01:23:00):
because your grenaline levels, which is your hunger hormones
higher. You don't have the energy and
motivation to want to go and exercise.
You're a bit crueler to yourself.
All of it's like compounding effects on your, your lifestyle
decisions, which we know is the like predisposing factor of
health because if we have good lifestyle decisions, then we

(01:23:21):
have a better health outcome. Basically at the end of the day,
we're more likely to go and do our exercise.
So I guess like I'm leaving this, the one thing that you
would say to everyone, listen tothis to help improve their
mitochondrial health is to get exercising 6 * a week, five
times a week if they can. From what I'm hearing, having a

(01:23:42):
good recovery day, a couple of zone twos, resistance training
one to two times have hit roughly through the week.
That's kind of your, I would saymy leaving statement from this
conversation to get people to connect to their mitochondrial
health. Would you say?
That's right. Yes, that's the only.
Way we know that the only medicine that works for

(01:24:03):
mitochondrial function is exercise because it's the
stimulus that we have since we humans were conceived.
But yeah, exercise, yeah, just 4-5 days a week, 203 hundred
minutes. And yeah, a combination of zone
2-3 to four days a week, one or two days a week intensity, which

(01:24:27):
you can combine within a sessionof zone 2 and then two days a
week resistance training. That doesn't have to be full
hour and a half. There are many routines that you
can do in 20, I mean, in 30-40 minutes, right?
But I think it all puts togetherabout 4-5 hours, maybe closer to
five hours, 300 minutes. I think that we all should

(01:24:48):
thrive for that. And we're living in very
stressful times. And, but at the same time, you
know, how much time we dedicate to our Instagram or our phones
or, you know, Whatsapps or so right, People say maybe I can't
exercise, I don't have time. We do have time.
At least we can get 150 to 100 minutes a week.

(01:25:11):
You know, it's not easy, but we can another.
Yeah. So I think that it's important
to focus on that and, and have alog into this.
I, I, I force myself. I am very, super busy at work
and especially in the last two years.
So my, my ability to exercise has decreased significantly, but

(01:25:32):
I really, really try to push myself right.
And I try to do a minimum of about 200 minutes a week and I
annotate it every week, week oneweek, two, week 3 of the year.
And I need to meet that, you know, hit of 200 minutes a week.
I force myself. But anyway, I think we, and I'm

(01:25:53):
not saying I do everything rightby no means, but I think that
exercise is important. It's key for metabolic health
and for mental health, which is a whole different area, right?
I'm not an expert, but definitely mental health and
exercise are so important. I completely agree.
I also. I now take exercise this time
for me. And actually you say about the

(01:26:14):
phone, it's the it's the one time.
I think that we can all agree that we get away from that as
well, which is why, I mean, there's many reasons why it's
also good for mental health, butthat's just one reason of
putting your phone in a locker and not being on your phone for
45 minutes. That feels like the ultimate
self-care in my brain. And so even when I'm exhausted,

(01:26:34):
knowing that I have that 45 minutes away from my away from
my phone, it's kind of a really compassionate act as well.
So I think there's always these times if we can.
It's also carving it out for yourself, which I think when
you're busy and stressed is, is is hard, but it's essential.
It is. I agree 100.
Percent couldn't agree more. I'm in to that.

(01:26:57):
So Nigo. I've absolutely loved having you
on. Thank you for coming on.
I know how busy you are. And I always have one last
question, which is obviously thename of the show.
Live well, be well. So what does live well be well
mean to you? For me, live well be.
Well, is to be first happy with yourself.

(01:27:18):
It's it's important to have metabolic health, mental health,
socialize, have friends, have family and have interior peace
and yes, and be able to to enjoylife and be simple, I guess,
which is super difficult to do right.

(01:27:39):
It takes time. Simplicity in the slalage is.
A very hard concept to to get our heads around, but but yeah,
Da Vinci said. Simplicity.
Is the ultimate art. I mean, is the ultimate
simplicity. Is the ultimate act of
sophistication? I couldn't agree with that more.
Absolutely. We need more simplicity in our

(01:28:00):
life for sure. I'm sure that's also quite good
for mitochondrial health at the same time.
Any good? Thank you so much.
It's been, I feel like I've learned a lot about
mitochondrial health and function and Zone 2 and
Alzheimer's 3, all of it. So thank you so much for coming
on. I'll put everything in the show
notes. I'd love if you could send us

(01:28:20):
that paper when it's out and we will show all of our all of our
listeners. But thank you so much.
Yeah, thank you so much, Sarah. I really.
Appreciate your time and your invitation.
And yeah, just had a great time as well.
Thank you very much.

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.css-14f5ked{margin:0;word-break:break-word;display:-webkit-box;-webkit-box-orient:vertical;box-orient:vertical;-webkit-line-clamp:2;overflow:hidden;}Zone 2 Training Explained: The Single Best Workout for Your Mitochondria | Dr. Inigo San Millan