Zone 2 Training: The Science Behind Peak Metabolic Health | Dr Inigo San Millan | The Proof Podcast

I tested once in the laboratory on 80 81 year old gentleman thought boy you've been doing sports all your life right so man you you chose the right lifestyle right and he told me actually no actually until I was uh in the early 50s uh I was obese I was hypertensive I used to smoke uh I had a very poor lifestyle I didn't exercise a lot and one day I started to write and bike and think about life and things like that and ever since then this was an individual the early 50s uh [Music] sedentary

very poor healthy lifestyle and then you know 30 years later at 81 years old his metabolic Health was some of that of someone in their 30s who's healthy that's unbelievable hard to believe in and this is how that that person obviously 81 year old that's an example of what exercise can do for your longevity right that person was not on any medication hey friends in today's conversation I sit down with Inigo sign Milan PhD from the University of Colorado to talk about exercise specifically moderate intensity cardiovascular training otherwise known as Zone 2 training and how

this type of exercise affects metabolic health this episode is extremely detailed which is exactly what I had hoped for Dr San Milan is one of a few across the globe who is truly an expert in this field of science we're very lucky to have had this time with him so I wanted to ensure we went deep on a topic that is absolutely critical to optimizing our health span and Longevity if you do want to skip through some of the more nerdy scientific basis for Zone 2 training and jump straight to the Practical stuff fast forward

to about 90 minutes into this conversation where we begin talking about how an individual can set up Zone 2 training I will also be doing a follow-up episode with Drew Harrisburg exercise physiologist and regular guest on the proof to further summarize the Practical takeaways from today's episode on Zone 2 training so no stress if things don't land the first time it's a lot to take in over one conversation I hope you enjoy it this is me and Inigo San Milan PhD something that I think we'll talk about at various points today is metabolic health what

is what is your definition of metabolic health and and why should The Listener Care about this yeah that's a good question and I think this is this is something that we're um understand more and more right as as you know and and many people know right the traditional um definition of metabolic health is the compendium of um the multiple parameters like your lipid profile your blood pressure levels uh your glucose levels right and your body Max index or at least your uh waste uh ratio so um circumcision sorry so uh but but as as we

know more about the adaptations or what happens at the cellular level right we are getting to to an inflection point in the in the field of of medicine where um metabolism has gone from being the uh the poor brother to being the uh the Crown Prince right right I mean you look at the curriculum of medical schools um uh even steel today they barely have any courses right or Notions of metabolism at the cellular level while at the research level the advances have been immense that we can already use to help people as well as

to understand diseases at a level that we have never been right so so this is why metabolic Health implies more mitochondrial function in place also more Fitness in place longevity right so people nowadays are not happy just to have good cholesterol levels right or or good blood pressure right or good A1C or or glucose levels right people want to be feeder want to be want to live longer not necessarily per in the amounts of years because we all want more but to live better right and uh and want to be a healthier so all these

I would put it in the new basket if you will of metabolic Health a lot of your work seems to focus on how efficiently we can take the I guess potential energy in food be it carbohydrates or fat and turn that from chemical energy into a mechanical energy contract the muscle and and move the skeleton do you also consider sort of fuel partitioning you know I'm interested in some of Professor Roy Taylor's work I'm not sure if you're familiar with him and his work looking at type 2 diabetes and this concept of of personal fat

threshold being sort of integral to metabolic Health in that uh once we kind of spill over or store fat beyond our subcutaneous fat capability it starts to get in between and and within organs and that seems to also be a sort of key component of metabolic Health yeah absolutely there's no doubt about it that's a big component um abdominal fat is is highly Associated uh with a cardio metabolic disease and also uh there's more and more research one of the leading researchers is a uh I call it here at the University of Colorado Dr Brian

Bergman uh with his research in the intramuscular fat which is highly and and others right they have they've been doing research extensive research on this linking that intramuscular fat with the uh insulin resistance and type 2 diabetes as well so yeah definitely fat uh the connection between fat and and metabolic diseases is there for sure and we are doing already in our laboratory and uh yeah which we can talk in more detail later if you want sure how much of your understanding of of how exercise specifically influences metabolic Health has come from your work with

Elite athletes and and why why are Elite athletes sort of this a good model for studying metabolic Health yeah that's a good question thank you so um I always say is difficult or or or or not very you know it's difficult to understand imperfection you wouldn't know perfection in the first place right so um uh and Elite athletes are that the perfect machines they're Perfection and uh they're the Ferraris or the Lamborghinis right so from the lessons that we have learned from working with the perfect machines we can understand or have a uh um a

reference of what Perfection is so that we can understand imperfections so this is why I've been trying to bring forth for for a couple of decades into the clinical space right to push to try to understand um I mean to try to bring the lessons that we have learned working with Elite athletes so that we can understand different diseases better as well as the application of different interventions like a exercise especially and and also even nutrition how much of the sort of cardio metabolic disease burden that we see today do you feel is is explained

by sedentary Lifestyles and a lack of of specific cardiovascular training versus other things like nutrition which you just mentioned yeah so I I'm gonna wear my my uh cell physiology background writing and try to see this from from a decrease in mitochondrial function or a decay in the mitochondrial function so um the the mitochondria you know is as we know the powerhouses of the cells and this is how we have been learning about that for for decades right however not until until recently relatively relatively speaking we've been very interested in mitochondrial function and now um

what we see is like pretty much no matter which medical field you get into and you talk to Leading researchers uh in in in in multiple medical Fields everybody's stumbling upon mitochondria right in mitochondrial function now when it comes to cardiometabolic disease um uh there are two main events that happen um when it comes to nutrition one is the metabolization of uh carbohydrates and the uh and fats so um um during postprandial conditions after a meal um about 80 percent of all carbohydrates are burned or metabolized in in skeletal muscle right uh and it's time

to really call skeletal muscle and organ it's probably the largest organ in the body and it's very important to to to see these because uh within skeletal muscle um at rest carbohydrates which are turned into glucose in the blood no matter what type of carbohydrate you have whether it's good or bad carbohydrates they're all going to become glucose in the blood like fructose most of the fructose that you ingest is converted by the liver into glucose right so all that has to be metabolized and under resting conditions about 80 percent are done in in skeletal

muscle and within skeletal muscle this happens in mitochondria so if you have a dysfunctional mitochondria or or a mitochondrial that is impaired you're going to have a metabolic challenge because you're going to have to burn that glucose and if you don't do it correctly eventually you're going to have a problem because that glucose is going to be building up in the blood causing hyperglycemia high blood glucose levels and the pancreas reacts to that because it's dangerous to have high glucose levels and the pancreas reacts by releasing insulin an insulin triggers the uh uh the the

transportation of glucose inside the cell but it's not just about the transfer of glucose inside the cell which is what we've been hearing for decades right the world of type 2 diabetes has been involved more at peripheral level if you will at the level of hyperglycemia insulinemia or hyperlinsulinemia insulin resistance even glut4 which are the the Transporters of glucose that are stimulated by by insulin right but we need to start talking about pyruvate and about the Fatal being of glucose inside the cell because this is absolutely key because one thing is to transport glucose inside

the cell and the other thing is to metabolize glucose to ATP and energy in mitochondria of in inside the cell right so this is the the key aspect so there's two sort of critical things here we're talking about with regards to glucose and metabolic Health one is the ability to get glucose from circulation into the muscle cell and you sort of alluded to the fact that that's been the story for a long time and earlier you spoke about intramuscular fat and so to my understanding part of that story has been that as fat starts to

accumulate in muscle tissue it can make it harder to get glucose into the cell yeah but what you're adding and saying is that the story of metabolic health and glucose metabolism and the difference between someone with poor metabolic health and an elite athlete goes beyond that and we need to begin thinking about once that glucose is within the cell how it is being metabolized which I believe from from from your work and and it's something that we're going to discuss comes down to the function and health of the mitochondria exactly and and and and then

the problem is like if you don't metabolize that glucose in mitochond inside the cell within mitochondria then uh you have a metabolic challenge right and eventually yeah you're going to increase uh or you're going to eliciate a condition of uh hyperglycemia hyperinsulinemia eventually insulin resistance but the same thing and the same thing happens also or the same metabolic uh problem happens with fats because uh fats can only be oxidized in mitochondria as well right so when fats cannot be oxidized in mitochondria they they build up right you cannot utilize them as a energy so you

store them you store them in adipose tissue but you also store them adjacent to mitochondria in um in in the muscle right and that eventually increases their Reservoir or the deposits of of fat inside muscle right which is again as I said at the beginning right it's highly related to insulin resistance right and and that could be a connection between cardiovascular disease and type 2 diabetes we know that about 80 percent of not eight percent I don't want to say a percentage yet because we still have to learn more but a big a big number

of people will take to diabetes they also have a cardiovascular disease and vice versa and this is what's been now termed more like a cardiometabolic disease right because it's the combination of both diseases right so so this is what uh probably a big Nexus for this is uh it happens in in mitochondria let's define the term metabolize I know that term gets used a lot and it's certainly um sort of widely used within the the literature talking about mitochondrial health and energy metabolism but we may we may take it a little bit for granted and

and perhaps someone's you know wondering what does that actually mean to metabolize something yeah so it is it is too uh converting to energy right so um the food that we have we we we uh we have right we need to metabolize them to energy so uh and and we live in uh and for and that happens in mitochondria so if you cannot metabolize it correctly to energy uh you are going to pose a metabolic challenge to that cell and because it's not going to be able to convert it to energy efficiently so it it

either it's going to be building up right uh and and as in the case of fat is not good that it builds up around muscle it's indicate if it is in the case of a glucose because it's it's an immediate challenge metabolic challenge because you cannot have high blood glucose levels because it can be dangerous right um um and another thing that happens too is that when glucose cannot be metabolized correctly inside mitochondria my pyruvate pyrule pyruvate turns into lactate and lactate is a key metabolite for it's a signaling molecule it's one of the most

important singular molecule and this is that the work the 52 years of work that my colleague and Mentor George Brooks from Berkeley has been doing uh pretty much everything we know about lactate is because of him and now the implications of of lactate in health so we know that lactate is a great um seemingly molecule that is probably very important for cellular homeostasis but when it builds up and is is is too much lactate inside the cell it uh become detrimental to the function of the cell and and we have seen that in different research

that we and others have done um but that's that's the problem of not being able to metabolize nutrients efficiently and this is happening already in as a big part of Alzheimer's Alzheimer's has been historically only been focusing on um the uh the amyloid plaque uh and uh um which is there of course and is highly related to the progression of the disease but the whole thing is that every single drug against the amulet plaque has failed now that has led to many researchers to to try to look into different angles to understand Alzheimer's and one

of them has been insulin resistance in mitochondrial dysfunction in in Alzheimer's which is a it's a Hallmark before it was it was daring to to even mention that right the connection between Alzheimer's and diabetes uh or colic type 3 diabetes but it's a it's a it's now highly widely recognized as a Hallmark of diabetes insulin resistance and uh um mitochondrial dysfunction so there's a big problem for Alzheimer's patients to metabolize glucose as well I want to put a pain in lactate and come back to it once we've kind of walked through the different energy systems

that the body is using and and how this may change at sort of different exercise intensities I know there's a whole sort of lactate lactic acid story and I've heard you before sort of clarify a few things so I think it's important that we do come back to that another term I want to Define here any go at the outset that is thrown out a lot is metabolic flexibility what does metabolic flexibility actually mean yeah so uh the the yeah the term metabolic flexibility um it's not a new term uh we are starting to to

use it more right but uh it's a term that it was coined over uh of 25 years ago by uh Kelly and uh mandarino as well as good good pastor um and and and even before that in the late 1700s um um it was thanks to the work of uh Lagos here who uh started to look into aerobic [Music] um metabolism and uh um so he started everything related to uh reseller respiration but the the the the term metabolic flexibility um in a very uh simple way is is the ability of humans to to uh

burn fighting carbohydrates and to to to switch back and forth so when there is a carbohydrate availability um like Elite athletes for example or or fit individuals they can use them very rapidly to for energy purposes and they metabolize it very rapidly uh when there is not much carbohydrate availability then you switch very well and very efficiently to utilize uh fatty acids for energy purpose says or when you're fed uh fatty acids you can metabolize it very well right and all that happens in mitochondria where most of that happens in mitochondria and at rest everything

happens in mitochondria during exercise it can happen in the in the cytosol uh so while it's inside the cell but not in mitochondria right because you can use it through the uh aerobic glycolysis but uh during uh rest under resting conditions yeah everything happens in mitochondria so that's again it it's at the epicenter of metabolic flexibility so people who are you know metabolically inflexible uh there are people who cannot metabolize fatty acids or glucose properly right and therefore yeah as we mentioned earlier uh it it's going to pose a metabolic challenge because you can increase

blood glucose levels on one hand has also increased the fat deposits in the muscles as well as then in the adipose tissue Inigo is it is it those things that are driving the increased risk of conditions like fatty liver disease and type 2 diabetes and cardiovascular disease or is it the building up of lactate and and other changes that are occurring or or is it sort of a a coalescence so to speak of all of these factors yeah I think I think there's a lot of in you know multifactorial right uh in in these processes

of diseases but uh many of these elements are are are are acting or working together um I I really think and is my opinion that everything starts by a mitochondrial Decay or a medicinal dysfunction and uh where as we mentioned um it's you cannot metabolize nutrients efficiently which can lead to uh disease uh because yeah again hyperglycemia and increased fatty acid storage but the the the the the the the core question for that is like where the what causes that mitochondrial dysfunction right so um what what happens in mitochondrial dysfunction the main element that we

know besides uh infections or besides mutations that can happen right um uh at the at the level of acquired uh decay of Maracana function is like a physical activity is the main mechanism in the same manner that we know that the only thing that we know that exists to improve mitochondrial function is exercise um the same thing happens when there's lack of physical activity yeah mitochondrial function is going to Decay so when you have as we have an immense majority or immense amount of population who are not physically active to have a a lot of

mitochondrial dysfunction or Decay happen in this population combined with an excessive amount of food that we have so that's a that's a an exposure an explosive mixture right that eventually it is going to lead to disease right so if you have a poor mitochondrial function and you you add more glucose or carbohydrates that you're you're adding yeah you're just adding gasoline to the fire and likewise uh and this this you're going to see rapidly because it's an immediate metabolic challenge you need to deal with that right away right because you're going to have high glucose

blood glucose levels but with the fat it's not an immediate challenge it is stored but it keeps being stored stored in down the road it's going to lead to disease but I think everything happens by by a mitochondrial Decay due to a lack of physical activity right so for the average person in Western developed countries the current lifestyle is kind of stoking this metabolic fire in in two directions one is that that lack of stimulus to keep the mitochondria healthy and as you say leading to mitochondrial Decay and I know that your work has looked

very specifically at how can we exercise with intent how can we provide the best stimulus which we're going to to get to which is the Practical side of this conversation but then the fire is also being stoked through the consumption of a diet that is leading to excessive calorie consumption and and frankly I guess energy toxicity to an extent too many calories um beyond the person's requirements you've you've mentioned you've mentioned the word aerobic a few times and we've been speaking about mitochondria and when I hear the word aerobic I think about oxygen I think

about energy being produced in the presence of oxygen and this occurring in the mitochondria can you explain how this works I think that most people appreciate the importance of oxygen in sustaining life but but maybe do not fully appreciate how oxygen is involved in the production of energy yeah so I mean oxygen is it's it's necessary right at the in in in doing them uh what what we call oxidative phosphorylation right which is the production of ATP oxygen needs to be present right um um but that's that's at the very end spectrum of the of

that of the chain right of events of metabolizing and nutrient right uh so um that's what you know like most of the energy um uh metabolize nutrients metabolites are under aerobic conditions however we we've been having you know that this idea that when you exercise um at high intensity it's anaerobic right uh how many times we hear that oh I was doing anaerobic interval sorry I was I was I was I was anaerobic really hard today training for 20 minutes right when that that's not anaerobic right and this is what I think it's time to

to to kind of change a little bit the perception of these more formed by energetic standpoint than from oxygen standpoint because everything pretty much up until VO2 max until you reach your your maximum oxygen consumption which is almost your maximum effort is aerobic right beyond that point uh yeah it's it's it's it's um ATP cannot be synthesized right with the help of of oxygen and it needs to be the ATP that is stored in the muscles it needs to be utilized for energy purposes and that does not require an aerobic metabolism so that's why it's

called anaerobic right exercise but everything up until then it's aerobic what it changes is the types of fuels that you use So within the big range of aerobic metabolism you can use a lot of fatty acids and then not much carbohydrates or you can use a lot of carbohydrates and not much or not many fatty acids right so that that's the key point you know what is the fuel that you're using right within the whole um um aerobic room because that's going to determine um what is going to be the metabolic outcome uh as well

as uh for by energetic stimulus and cellular level what are you going to stimulate what metabolic pathway what type of bioenergetics are you going to stimulate with one exercise intensity or another right uh you're still stimulate aerobic metabolism but you might elicit different changes at the cellular level with different exercise intensities okay so let's let's step through this as intensity is increasing so the listener can appreciate what changes are happening with regards to the substrates that are being used to produce energy where that energy is being produced and indigo it may make sense here to

start introducing zones I think people have heard you know Zone one zone two zone three zone four zone five so if you think it's a good idea perhaps as we're talking about the changes that are occurring with regards to how energy is being produced and where it's being produced we can kind of pair that with the Zone slash intensity yeah so um yeah I mean again the way I see zones is from uh you know like a cellular metabolism glasses right um uh what so I see for example this is also based on the muscle

fiber recruitment pattern which is going to also um uh elicit different Fuel utilizations and fuel partitioning right so when we start exercising very easily like a very easy walk for example or a very easy bike ride for those ones who are fit on the bike the body prefers to use fat for energy purposes now that doesn't mean that we don't use glucose right because we we also use glucose uh that there is a miscon misconception that at low intensities we do not use glucose we do use glucose and this is I've been for almost two

decades uh measuring in the laboratory fighting carbohydroxidation rates at the wide range of exercising entities all the exercise intensation seen in grams per minute how much uh how many carbohydrates and and fatty acids uh you uh burn or oxidize a different intensities right which has helped me tremendously to understand the bioenergetics and metabolic map as I call of whatever the series of events of different intensities so again a different at a slow intensity we we deploy a lot of the fat um and then we use a little bit of glucose right it's very low intensity

and we we deploy we recruit the slow twitch muscle fibers that's what I called uh Zone one right uh and again when it comes to zones the multiple zones people have different uh um terminologies and and interpretation so I'm just giving you mine right um so so Dennis exercise intensity increases then the the muscle contraction gets faster right and stronger so uh it it needs a higher metabolic demand to produce ATP so that's what you start uh burning even more fat right but you also start burning more glucose also but not as much uh fluctuation

in glucose uh utilization as it is in fat right so and this this glucose at this stage is being being used to produce energy within the mitochondria all of this is still occurring in the mitochondria normally yes because it's uh the glycolytic flux as we call it allows the velocity of the glucose to be used through pyruvian mitochondria yes although some is reduced or transformed to lactate in in the cytosol of the cell and therefore uh there's a little bit of lactate production which is also coincides with this intensity little B which is about Baseline

levels or a little bit about Baseline levels right but but this is where um at this intensity that I calls on to this is where you um uh reach a point where you oxidize the highest amount of fat right um and and this is a key point because uh fight is oxidized exclusively in mitochondria right so when you reach a point where you achieve the maximum fat oxidation is that yeah you're putting those mitochondria to work at that by energetic system which is the the fatty acid oxidation and oxidative phosphorylation to to the max so

this is what I use this Zone to prescribe exercise as this is what I see that this is where you oxidize the most amount of fat so we can see in many people when we do this test in the laboratory we can see that this uh we can we can translate this into a heart rate for example or into Pace or into power so that that is the exercise intensity that releases the highest fat oxidation um then we we start we continue increasing the exercise intensity and the metabolic demand it becomes even larger right so

you need to produce ATP faster and this is where there's an inflection point where fat cannot continue producing ATP at the same rate as before so this is where glucose is um called in at a higher rate because uh ATP from glucose is produced significant significantly faster than from fat right so that's when glucose starts to be in recruited and then you see in in in the laboratory at this intention you see that fat starts to drop significantly there's a significant drop in fat oxidation and there's a significant increase in glucose oxidation or utilization and

and at the same time you see also of an inflection point also for lactate because lactating glucose go together as I was saying earlier it's about glucose flux the higher the glucose flux into the cell the higher the lactate accumulation right so so this is what's starting to happen in this zone three that I call which is a transition zone before we enter a whole different um by energetic terrain which is glycolysis right or or yeah with the glycolytic system so this is when exercise intensity is now so hard that fat can no longer provide

ATP uh or or uh you know like or be Associated for ATP production right and this is when uh you need to uh start deploying um um I mean carbohydrates and glucose and this is what we see that at this intensity fat oxidation completely disappears uh it's gone at the same time uh you see a big increase in glucose oxidation and a sharp increase in lactate uh because the glucose flux and this is also what lactate also has the uh um endocrine paracrine and auto cream functions so the the endocrine function of lactate is that

when accumulates in the cell and cannot be metabolized in mitochondria it goes to the blood and it goes to the blood it inhibits lipolysis which is the breakdown of fatty acids from adipose tissue so when inhibits lipolysis you're not going to be able in the first place to to bring the the fatty acids to to the muscles to be burned right and then secondly and we we have published this recently two years ago that we saw and we demonstrated that lactate as an autocrine um function it also inhibits the fatty acid transporter so in in

in the muscles fatty acids they they have a door which are the cpt-1 and cpt2 in my in mitochondria outside and inside mitochondria the transport fatty acids right so lactate inhibits both doors so when you have a high glycolytic flux and you use a lot of glucose the fat disappears for several reasons first because of necessity to produce ATP right at a faster rate in second because the actions of lactate on both adipose tissue and also on on the Transporters for fat so it's a way to to a feed forward mechanism right to to kind

of get fat out of the way and say Hey fat you're done your job is done now we go into glucose and this is what I call the zone four right or people call also lactate threshold although there are many interpretations of lactate threshold also of our FTP functional threshold power Etc right and then but all this is aerobic all this is 100 aerobic metabolism right although this is what I was mentioning earlier the misconception is like we're already in the anaerobic State and that's why people call it anaerobic threshold right we're still aerobic right

then we move on into the the next uh phase which is it's it's it's an intensity that this is where you reach your view to Max this is an intensity where uh uh you Max your aerobic capacity right your lactate it's off the chart your your glucose utilization in the glucose flux in in the cells of the chart there's no fat oxidation either but you're you're at the intensity where you um uh have the highest aerobic capacity uh and and this is the view to Max and I call that the zoom five right and then

lastly we call I call the zone six which is pure anaerobic uh this is when we're talking about sprinting or about efforts that last two or three minutes right where uh that oxygen that you were referring to earlier is not enough or even glucose is not enough to to maintain I mean to synthesize app and and then the muscles they need the ATP that's stored in the muscles already without the need of of oxygen okay I have a lot of questions that was beautifully explained let me let me try and summarize some of that and

you can let me know if I've got anything wrong um but at at lower intensities the body is is using the oxidative phosphorylation system this aerobic energy production system whereby energy is being produced within the mitochondria and at very low intensities that's primarily but not exclusively being being done by using fat as the substrate there is some glucose and that's fat is predominating as the substrate of choice at sort of Zone one and two and then as you start to go up above zone two you start to see an increase in the amount of aerobic

glycolysis so using glucose to produce ADP within the mitochondria and the oxidation of fat starts to go down as you go up from zone three to zone four but all of this is still aerobic and then once you go into zone five you start to get this anaerobic glycolysis so we're now able to produce ATP from glucose without the presence of oxygen um and then above that is that where the phosphocreatine system would kick in the the sort of third Energy System yeah the ATP Force are creatine yes exactly is what's stored in the muscle

already and it doesn't require oxygen for that yeah and that's the pure hydraulic uh system that we have right everything else is aerobic there there are some like uh Sparks of an anaerobic metabolism right but but yeah this is like a the predominant is always aerobic so I have a few questions the first is for a given amount of oxygen is it is it accurate that we can produce more ATP from glucose than from fat well I mean more rapidly the the the the the the important aspect and this is why there's a transition right

it depending on the muscle fiber recruitment pattern the way I would approach it is like how fast you can produce ATP that's going to dictate uh the fuel that you use right so ATP so from from I mean derived from fat is significantly much higher uh amount uh from of ATP derived from fat then it is from glucose however it significantly slower so that's why when you're in the lower intensities recruiting the slow twitch muscle fibers uh you um yeah you don't you don't need to oxidize or use so much glucose as at high intense

it is uh where then fat cannot be oxidized because it's not fast enough and you need to switch to a different fuel which is the glucose right which which gives you significantly less amount of ATP total right per mole oxidized but it gives you a much higher amount of ATP which is why the muscles need that fast contraction and that's why you have the fast twitch muscle fibers so why does the body prefer to use fat at lower intensities is that is that a survival adaptation just that there's more potential energy in the form of

fat available in the body and and it makes sense to conserve energy from carbohydrates for when you need to shift into a sort of higher intensity to escape predation for example yeah absolutely and and this is this is this is the the one thing you know the the way we store food right so carbohydrates are like gold right that that the body can only store about uh 500 grams you know of carbohydrates whereas uh so we're talking about that's a uh 2 000 calories you know uh where is that the the the the skinniest individual

um Can can store more than 10 000 calories from fat right because fat is everywhere right uh so uh it's kind of in a way fat is in a it's kind of an unlimited source of fuel right whereas uh carbohydrates or glycogen right that's how we stroke like carbohydrates as you know so glycogen is a very very small uh storage compared to Fat so that's why it's gold and this is why um yeah which is that as as our Evolution you know we're um aerobic creatures were slow in general creatures right we walk a lot

or we run at a low Pace right um and we can even beat horses in Long endurance you know because we're more efficient metabolically speaking the horse has a lot of um um fast twitch muscle fibers we have a lot of slow twitch muscle fibers and those mechanisms as they allow us like uh um I I cannot cite the research now but uh uh but there's been a few studies on on how and and and competitions are very long competitions like uh like a 100 miles or so where of a horse versus a human and

a human can get to beat the horse right uh obviously bigger for both but anyways that you still want to get out of a context but yeah we are born our Evolution we're born to uh to uh to burn fat uh as glucose but to be able to store a lot of fat but our Evolution has told us that a Key Energy not just for high intensity exercise when when we we have to run away from a from a bear or from a lion right or or when we have to get engaged into very high

stressful situations but also for the brain right we need your glucose and so that's why it's it's uh the storage is very small and that's gold for the body so the body is going to try to defend as much as possible the glucose or the glycogen storages uh by then try to be more efficient at burning fat yeah there's a a really nice review paper I'm sure you've come across this it was in nature metabolism by Mark Hargraves and I'll put figure two up on the screen for those that are watching on YouTube but it

speaks to the potential energy that's available in the form of fat in adipose tissue and glycogen in the liver and muscle and it sort of makes it very clear that there is this order of magnitude more potential energy in the form of fat stored in adipose tissue as you just kind of walked us through the next question I have is you you stress the importance of the point of Maximum fat oxidation quite a lot and my understanding of where you're coming from there is that during um specific exercise namely zone two at this point of

Maximum fat oxidation we're providing a very specific direct stimulus to the mitochondria which then causes it to upgrade or adapt or grow stronger which we can we can get into in a little bit as to exactly what happens but my question is why that is the best intensity to stimulate the mitochondria because you just made it clear as well that when we go into zone three and zone four this is still aerobic so even though the the contribution of fat to the production of ATP may be declining glucose is ramping up and that glucose is

being used to produce ADP within the mitochondria so why is it that we're we're chasing a stimulus to directly Target the production of ATP from fat within the mitochondria as opposed to just the total amount of ATP that's produced within the mitochondria regardless of whether it's coming from fat or glucose I'm not sure if I articulated that well yeah that's a great question and uh yeah it's it's a it's a complicated and we're we're still trying to really um uh answer it I guess you know in a more articulated way right uh and and uh

in a more scientific way if you will right so what what I have seen from 30 years of uh of work with uh with athletes with patients and research is that that's the intensity when I started using it and by no meantime I'm saying I I invent it it's on two because that that you know who knows who started I just say that my zone 2 the way I see it I started using it 30 years ago and this is what I what I first I saw looking at lactate clearance capacity that that intensity it

was the one that improved the most lactate clearance capacity uh in in performance so um um lactate is a it's a it's a mitochondrial substrate because lactate can only be oxidized in mitochondria or or be converted back to pyruvate to be actually that's in mitochondria so laxity is a great product lactate it's a great proxy or surrogate for mitochondrial function then about at 18 years ago I started to add fighting carbohydrate oxidation rates in the laboratory and to measure as a to measure as I mentioned earlier fat oxidation and I could see also that that

intensity was the one that improved fat oxidation the most right so that's what I developed this this indirect methodology to look at or or to assess mitochondrial function in a non-invasive way without doing muscle biopsies so by looking at lactate and looking at fat oxidation both are mitochondrial surrogates or mitochondrial substrates right so we can indirectly measure that so and and my colleague George Brooks and I were published in 2017 a study looking at the correlations between fat oxidation and lactate blood lactate levels denoting lactic clearance capacity and the correlations whether you were like an

elite athlete an active a moderately active individual or a person with a metabolic disease met a metabolic syndrome uh the correlation was was incredibly high so that's why we know that they both can be very good surrogates for mitochondrial function now that being said again this is why at first was a trial and error right I was saying okay which intensity of the ones I Define in my dictionary which intensities to improve mitochondrial function the most I see two ones one two three four five right so with thousands of tests that I've done all right

this is what I saw constantly constantly that this was intensity that improved uh mitochondrial function the most and also I saw that this was intensity the improved performance the most so this is what I saw this with with my athletes it was very successful to see this with results and now this is where I from the beginning I was saying from Lessons Learned From athletes uh can we use these um to to to prescribe exercise to populations with chronic diseases to stimulate mitochondrial function so again this is a way um and and I'm sorry if

I didn't do the the best way but this is my way to explain why Zone 2 is an important uh to stimulate mitochondrial function not saying that the other ones are not going to do that right but what I've seen that this is the most efficient and I've seen over 30 years for for almost 30 years this episode is proudly brought to you by inside tracker track your blood biomarkers understand your biological age and receive personalized lifestyle tips backed by evidence to optimize your health to get started with inside tracker today and get 20 off

your first purchase head to insidetracker.com forward slash Simon that's insidetracker.com forward slash Simon for 20 off okay so you're you're looking at lactate not so much as a problematic compound which it has been kind of labeled over the years but more so as a window into the mitochondria to tell you how well the mitochondria in that person is functioning so when you looked at people with metabolic syndrome what you saw compared to sort of average people and Elite athletes was that for a given sort of intensity they were producing much more lactate and so that

was telling you that their mitochondria was not as healthy and not functioning as well as the others who've at that same intensity were producing much less lactate yes exactly it's a it's a great surrogate to see what the mitochondrial functioning and it's going to become more and more uh part of the regular blood analysis that people do like when people look at blood glucose levels like what are your risks in blood glucose levels right so soon we're going to see what are your resting lactate levels because what we see in populations with that metabolic syndrome

um uh or obesity or type 2 diabetes we see that at rest they have about two to three times the level that healthy people have so if we have at rest if you look at athletes the resting levels of lactate there are 0.6 0.8 uh morally active individuals Health individuals this is kind of our standard how would we like to be we're around one millimole but we see that people with type 2 diabetes metabolic syndrome obesity uh cardiometabolic disease they have at rest many of them two to three millimoles so that that's about two to

three times that the levels that Health individuals have so imagine that your blood glucose levels are two times or three times as high as what the normal should be in health individuals right so I think that this is it's getting to be it's going to be more and more a parameter for health rest in lactate levels and yeah but that but that lactate uh yeah it's um it's uh it's a great fuel so that's the other thing to so likely we've seen as a toxic product is probably the best fuel in the body because uh

it's it's it's it's it's it's it's it's it's it's it's it's metabolized faster than glucose significantly faster than glucose so if you give uh most cells in the body the possibility of use glucose or or or or lactate they're going to prefer to use lactate the brain is a great lactate user the heart is a great lactate user the kidneys the muscles obviously but it happens in mitochondria so you need to have a good mitochondrial function and and the problem is not when it comes to exercise it's not the lactate but it is the Hydro

hydrogen ions Associated to lactate which elicit an acidic microenvironment in the muscle this is the other thing that we see in cancer the famous now uh tumor microenvironment which is the the micro environment around cancer cells which is very acidic and that's a niche for cancer growth for carcinogenesis for metastasis right that is a big deal area a big area of research now and and that tumor microenvironment and that that acidic micro environment is caused by lactate from from the tumor cells which is dysregulated in skeletal muscle is this related during exercise and uh um

or accumulating people who don't clear it correctly into energy and and those hydrogen ions accumulate and they might it's it's part of the fatigue not everything by no means there are multiple aspects of fatigue for Central fatigue peripheral fatigue local fatigue that we still are trying to understand and explain but this is a part of that where excess of hydrogen ions from lactate can impair both the speed and the force of muscle contraction okay so lactate itself is not necessarily a problem if we can clear it and we can shuttle it back in and use

it as an energy substrate but if our mitochondria are dysfunctional it can build up and along with that lactate coming for the ride are these hydrogen ions which changed the pH within the cell that then can affect perhaps contribute to fatigue and and Power yes yes and and and when it comes to disease uh it's lactate um it's it's highly related to disease you know when it's not when it accumulates chronically because during exercise lactate even in in a people in in a person who is not fit lactate is going to accumulate fast but when

the exercise ceases uh lactate levels don't accumulate return back to Baseline but in diseases like cancer or when there's a significant mitochondrial dysfunctioning people with type 2 diabetes that lactate accumulates chronically right and especially in cancer the more aggressive the cancer is the more lactate is produced and uh through our research we're showing that lactate acts as an uncle metabolite that is it's a it regulates the expression of uh sorry the irregulates the genetic expression of of the the extra version of the main are the most important genes involved in in cancer we're doing this

with a breast cancer we have published one paper we have another one in in under review now and and then we we have two more papers coming out with two types of lung cancers um and then we also see that um lactate also regulates the the transcription of the main proteins there are dysregulated in cancer and and now what we're trying to intervene and in the study that we have now under under review uh we are um with genetic engineering we're knocking out knocking Downs or the the enzyme that produces lactate which is ldha and

then in breast cancer cells we see that when we knock out that enzyme uh no lactate is produced and uh no gen no there's no protein expression of those dysregulated proteins uh coming from these regulated genes in cancer right so it's a key regulator of of cancer uh that already also Harbor a century ago proposed because now we talk a lot we hear a lot about sugar the connection of sugar and cancer right and that comes from the uh Renaissance of of the warbury effect so although water work Discovery in 1923 that cancer cells they

utilized a lot of glucose and that was the first uh metabolic transformation of a normal cell into a cancer cell characterized by that but what really struck world work was the excessive amount of lactate produced by by cancer cells now that was back in the days unfortunately he didn't have that technology that we have nowadays to understand that better and they were not the genes were not discovered right and so but um but yeah um he already he was so smart and so ahead of us that a century ago he already posited that cancer could

be a metabolic disease which is not quite entirely correct but there's no doubt that the metabolica factoring cancer is crucial but the way how he described an injury of of cellular respiration or mitochondrial function was lactate because he he already said okay wait a minute if lactate cannot be oxidized or burn in mitochondria of cancer cells is because mitochondria are not working properly so maybe there's an injury of cellular respiration so this is the main thing that he proposed a hundred years ago yeah that's fascinating and some some Cutting Edge sort of insights I guess

into where the the world of cancer research and and treatment might be headed from a metabolic Health point of view my head is sort of thinking at the moment about two two different ways of keeping lactate down and I'm sort of wondering if you've been able to elucidate this from your research looking at Elite athletes or looking at zone two training interventions is it that Elite athletes have a greater capacity to clear lactate or are they just producing less lactate because they're better at oxidizing fats that's a great question also so and it's been demonstrated

uh by different researchers and among them George Brooks that um the feeder and athlete is or a person is in fact they produce more lactate mainly because in the same manner that their mitochondrial function is is more robust and more efficient their glycolytic system which I also call you know colloquial terms the turbo right the turbo it also works better right and in fact we looked at lactate as a sign of high glycolytic function which is key for performance right so those athletes with very high lactate levels at very high intensity levels they're really good

at the turbo right so they produce a lot of lactate because they use a lot of glucose for Energy System uh like uh some athletes can oxidize six seven grams per per minute those intensities were very good athletes or the top ones can oxidize seven or eight right but the the the side effect of that is they're going to be producing a lot of lactate right but the virtue they have because they have a very robust mitochondrial function is that they clear that lactate from the uh fast twitch muscle fibers which is where lactate is

produced they clear it in the adjacent slow to its muscle fibers and in mitochondria of slow tooth muscle fibers and for that you need Transporters also so you need two doors Two Transporters MCT force and mct1 so mct4s are the doors that take lock it out of the fast twitch muscle fibers and you need to stimulate that intensity training not just to improve the turbo the glycolytic capacity but to improve the capacity of that door to shuttle locked it out right and then the slow twitch muscle fibers when you stimulate those you as I'm will

be mentioned in not only improve or or stimulate matter kind of function because that's where they're the most present because fast tooth muscle fibers cannot burn fat much so the mitochondrial content is much less but also the MCT ones are present in those slow twitch muscle fibers so you stimulate those as well so that that's how kind of in a nutshell like the lactate shuttle that was discovered by George Brooks in the 80s already works let me throw that back to you and and see if I've heard all of that correctly so lactate clearance can

be improved or is a product of our ability to get lactate out of these fast twitch muscle fibers which are going to be activated and utilized at higher intensities I'm thinking sprinting or resistance training for example and and so that stimulus is going to help increase the number of the mct4 transporter you mentioned that helps get lactate out of those muscle fibers or muscle cells we could call them and then the lower intensity work so zone two which is mostly stimulating the slow twitch slow to fatigue muscle fibers muscle cells is acting in a way

to increase the mct-1 transporter in those cells so you get this sort of nice Push Pull I guess lactate clearance system where if you're doing the right uh training sort of modalities or intense training at the right intensities have the right stimulus in place you can you can get the lactate out of the fast switch muscle fibers get it back into the slow twitch muscle fibers which keeps lactate levels down and also acts as an energy substrate exactly absolutely and this is why I yeah the way you see training or exercise prescription is that right

it's like a from a bioenergetic standpoint and as I always say which Energy System you want to stimulate today right so that that's where it's partitioning of of of cellular by energetics through through exercise and we're talking about two completely different systems the glycolytic system and the oxidative phosphorylation system the lactic shadowing system out of the cells and the lactate receiving um uh cells right uh the the type 1 muscle fibers and everything is different intensities of exercise are going to elicit different adaptations and different responses so therefore different adaptations but we all are talking

and all this happens within an aerobic world right so still everything that we're talking about here is aerobic right so uh you can produce plenty of lactate under aerobic conditions so so again it's just like that that that's how it's important when you prescribe exercise whether it's for an athlete or for a fitness Enthusiast or for for longevity purposes or for patients uh to really identify training zones because whatever you exercise the intensity that you exercise is going to stimulate one pathway significantly more than the other right so yeah you want to really Target and

want to know what you want to do do you want to improve your glycolytic capacity your turbo because you're very good at let's say you're very diesel you're very good at a very efficient and metabolizing fats and lactating mitochondria but you're not good at high intensity you know so you need to stimulate that by identifying your weakness but for health purposes that's more maybe for performance but although we lose like like a little capacity of as we age and we we want to kind of maintain some of that or a big part of that but

for health purposes the main problem that happens as we age for longevity purposes it's a matter of candle decay as we don't exercise as much as when we were kids some mitochondrial Decay and uh again what I've seen on my experience for almost 30 years is that that zone 2 is the one that improves mitochondrial function the most and that's because it's targeting mostly the slow twitch muscle fibers where most mitochondria are found yeah that's how I see it and and and again like the way I see is through fighting fighter oxidation in laboratory as

lactate cleans capacity that's the the area for me uh or at least from my experience is without a doubt and many others you know they've been telling me this uh this is where we see that this is the way you improve the most right uh we might be wrong and maybe in 20 years 30 years we might be talking about their different methodologies of training or different understanding sure of course right things of all but uh uh that that's that's my my experience that has been been working very successfully with Elite athletes with some of

the best athletes in the world uh as well as at a clinical level I've had a very good experiences with people with chronic diseases when it comes to exercise prescription I want to get into all of the Practical elements of of zone two and we can perhaps kind of further Define it but just quickly to close off on this conversation about lactate clearance on the mct4 side of things and the stimulus to um to activate the fast twitch muscle fibers and increase mct4 so you're better at clearing lactate from those muscle cells are we talking

about zone four slash zone five Training here exactly yeah this is where you you have to stimulate that that the turbo right that glycolated capacity right so uh that that's where you improve uh not only just the glycolytic pathway the whole glycolysis right which is faster and more efficient right therefore the turbo right but it also improve those MCT ones because I mean lactate is the mandatory obligatory byproduct of glucose utilization the more glucose you use the more likely you produce so that's where like when you stimulate that Energy System you're going to use a

lot of glucose and you're going to produce a lot of lactate and that lactate has to be shuttled out so of that fasted cell and in the way that is through the MCT force and he shuttled into the adjacent cell and as long as the and this is why it's very important I always say that for for performance right for those athletes you know you win the races or or the competitions in the high uh intensity levels obviously right but because you produce so much lactate you really need you depend on on that mitochondria of

this low twitch muscle fibers because that's where you're going to be shuttling the lactate into for lactic cleanse capacity as well as for fuel right uh and so that the toolbox keeps working better and better and better right and this is what we see that as an athlete increases performance let's say at 350 Watts which for more models it's almost impossible even to turn the pedals uh 350 Watts uh an athlete today might have a lactate of of 8mm calls and maybe one year specifically working to improve uh lactic cleaning's capacity that lactate from eight

millimoles is going to go to uh four millimoles maybe 350 Watts or that that athlete can sustain that intensity that before was only sustainable for three minutes or so now that athlete can sustain the intensity for 40 minutes for example right so that's absolutely key to Performance and at the same time for the everyday person should they do a protocol that lowers their lactate in that way for a given intensity that again is a window into mitochondrial function which which speaks to their metabolic health and risk of cardio metabolic disease so there's a benefit up

for grabs here for the athlete that's looking to race better but also for the everyday person who's just looking to sort of live better for longer I think this is really really helpful Inigo in terms of in my undergraduate I remember one of my lecturers is sort of just Bolding and underlining this statement of structure reflects function and speaking to the importance of you know specific stimuli to create a very specific adaptation so I think you've stepped us through really really nicely the different stimulus that is kind of zone two training which is mostly targeting

slow twitch muscle fibers zone five or zone four five the fast switch muscle fibers but the way that these can kind of work together to improve metabolic health and performance a lot of people speak about an 80 20 split 80 of time in zone two twenty percent of time at zone four five high intensity work and and that's commonly something said I guess within the endurance Community is that is that a kind of rule or protocol that you also recommend both for an athlete and also for the everyday person just looking to improve their metabolic

function yeah I mean that's part of the polarized training um that uh it's it's it's been trending right for for for a while and I I embrace it I particularly embrace it because this is actually what we do um uh with athletes um if you look at and this is counter-intuitive right and um but if you look at the uh percentage of a workload of an athlete throughout an entire year it doesn't matter if that athlete is a uh uh like a like a marathon runner right or or a triathlete or a cyclist who's more

pure endurance or that athlete's a swimmer right or a rower which is really high intensity uh the immense majority of the entire workload of that athlete throughout the year is in the lower intensities more in the zone two in the zone one right uh and a very small percentage is in the very high intensities right and this is something that we can see this very well nowadays we have all these platforms where we capture the information right uh where we see this in these individual athletes team sports are a little bit different because uh it's

it's high intensive all the time mixed with lower intensity but in the individual sports we see this all the time and uh um and uh yeah so that's works that works and and and and it also is necessary because if if the the conception that many people still have that Elite athletes they train hard and intervals and intervals and heart all the time uh that's not sustainable that's not sustainable and in fact we really are careful with athletes with when we prescribe intervals because um yeah it it cannot put you in a very dangerous spot

for our training and and uh decrease performance so we really need to mitigate it's not sustainable and if you keep pushing for that you're going to end up over trained so that that that's where like a uh by default um and this is again this is this is just been uh evolution of the sport right I always say we cannot be so naive to think that the best uh um uh athletes and coaches in the world uh over decades they haven't thought about these Concepts right of course they have right uh intuitively I would say

a swimmer right It's let's say 100 meter swimmer is usually under a minute right so it's super high intensity so intuitively what what what would a swimmer need just do one minute intervals right all day right but uh when you see swimmers Elite swimmers and in Australia you guys have some of the best in the world right uh great School of swimmers they're swimming hours and hours and hours and hours right at lower intensities uh what lower intensities for them for us it has unsustainable right because that's the other thing we haven't talked about the

um the the what's low intensity for an athlete and what's what's low intensity for more model right but for them relatively speaking it's a lower intensity right and this is what that's why they can sustain hours and hours and hours but uh yeah but it's counterintuitive I understand I know but that that's the way it's been evolution of of sports okay so if we come back to this idea of building your aerobic base how much of this would you say is influenced by mitochondrial function versus the amount of oxygen that we have available our VO2

max yeah that's another great question so um and this is something that we have learned a lot in in the last two or three decades so um we used to measure performance or predict Performance Based on BO2 Max right and uh and it still is it's it's a very good parameter because uh um it's it's uh it represents the cardio respiratory adaptations to exercise but um definitely and and that's for sure and this anybody could who who does a lot of testing physiological and metabolic testing can tell you that uh VO2 max is not um

it doesn't discriminate right so it gets to a point that is so well expressed uh that uh it doesn't make the difference and this is what we see all the time you you see two athletes with the same view too Max right so therefore um um yeah they're they supposedly are as good um and then one athlete is much better than the other right and then you go at the cellular level right um and then you see that yes that that that athlete at 350 Watts has eight millimoles of lactate and the other one has

three or four right despite of the same VO2 max so so this is why VO2 max it's it's uh it's a great surrogate for health of course and for Fitness no question right but um you know looking and this is from looking for from a cardiorespiratory standpoint and this has been the norm right for forever right VO2 max but uh by looking now in in the last two decades especially at the more cellular level we're seeing that that's what makes the difference and within the cellular level uh and you know everything happens or or that

the Keen of the or or of the cells uh or the queen because they come from The Mother We should say right um our mitochondria and when we're thinking about stimulating the mitochondria through Zone to training are we mostly thinking about improving the function of those mitochondria or are we also thinking about improving the number of mitochondria that are found within muscle fibers that's a good question too and and it's it's usually both right so we improve both the number and the function uh of mitochondria um uh definitely I I I I believe and this

is what we still need to do more and more research because there are different studies showing things you know but uh I think that uh in my humble opinion is more the function uh but they usually go together right uh you see mitochondrial content in type 2 diabetics or obese individuals is significantly lower than in in morally active individuals and when you put uh those um um those athletes um to uh there is this great researcher that was from Pittsburgh Toledo he started doing uh these studies where with Mother Control Function that was 20 years

ago uh but not many people listen to him but he was looking at people with obesity and looking at the mitochondrial content in the muscle and after I believe it was like for God six months or five months of aerobic training back in the days they still talk about aerobic training uh what we still do right they improve their uh they they triple the number of mitochondria so in the same way that you reduce the number by being sedentary you can increase the number of mitochondria in the size the triple the number and the size

of mitochondria and and the function also will significantly improved so all things come together yeah so that's worth sort of unders underlining that we're not born with a set number of mitochondria that's fixed for life we can do something about this and if I heard correctly if we've lived one two three decades living a very sedentary lifestyle and lost a bunch of mitochondria if we then commence exercise particularly specific exercise and do the right dose and frequency which we'll get into we can actually build new mitochondria and bring some of these back yeah absolutely and

you know and this comes within the plasticity of skeletal muscle I mean we're still focusing on skeletal muscle right although it happens also in the heart and in the brain too but uh the the plasticity of skeletal muscle is extraordinary so uh yeah yeah it can deteriorate over time for sure and it will if you don't do exercise and something that we see on the outside of of people who don't exercise but uh also it can improve significantly over time as we see also you know from the outside of people you know but imagine what

happens in the inside right at the cellular level yeah there's an incredible amount of improvements that happened at the cellular level so yeah and it comes because yeah the the body at the end of the day is very wise and uh we uh humans we haven't evolved to become sedentary uh we are our genes uh are still um you know made to be active right and the bean sedentary has been um a byproduct of progress as opposed to be the norm but uh unfortunately we've been growing uh know with this notion then then and then

being sedentary or healthy sedentary has been the norm and and doing physical and being Physically Active is is is being a control right or it's it's an intervention right with that the real intervention uh for for us humans as part of the evolution has been to become sedentary which is leading to disease you know so this is what I got yeah a lot of uh research data in medical research for decades they've been using asset to control the healthy sedentary individuals when we know that the immense majority of those healthy sedentary um they they are

going to become um uh populations with diseases and we already we have a a very interesting study that uh we we are putting the manuscript together with a really cool findings of sedentary people who are healthy and they don't have any clinical conditions and they already have significant metabolic dysregulations compared to people who are active uh moderately active not Elite athletes so we're already seeing that uh uh 15 20 years probably before they have some disease uh we already see signatures markers of metabolic dysfunction and mitochondrial decay right and one of those I'm assuming being

lactate as an early predictor of disease yeah yeah lactate is never a predictor uh we're looking doing this by looking different markers in the muscle doing muscle biopsies right uh and and metabolomics we'll look at a lot of metabolites that are happening in mitochondria and look in itself at mitochondrial function right where we where we uh where we do is like we get a muscle biopsy and we inject it uh we hope we homogenize the mitochondria of of those subjects and we directly inject in mitochondria different substrates we inject fatty acids we injector carbohydrates amino

acids and we see how mitochondria metabolize those right so we see their significant differences already in uh um in sedentary individuals and then also some Transporters that I cannot say yet until it wouldn't polish it but there's a key transporter that uh um is significantly down regulate it that that can be 10 years 15 years ahead of type 2 diabetes that is already a signature and could be a Hallmark of this population who are sedentary that's exciting sounds very promising I look forward to reading about that what you were talking about earlier about the sedentary

Lifestyles we're living in the deterioration that occur that occurs with that reminds me of a quote from Frank Booth I'm sure you you know him or have come across his work uh he said that the current Human Genome requires and expects us to be physically active for normal functioning and I think a pride guest Paul Taylor shared that with me on my show and it's kind of stuck in my mind we have already a great examples of our very primitive civilizations that still exist in our world and there there's uh so they're they're especially two

populations that the hasda hunter-gatherers in Tanzania and also that simani uh hunter-gatherer population in Bolivia right so the very primitive populations uh they they don't have any contact or they haven't had any contact Forever Without uh with civilization they haven't even evolved they have the same uh um uh tools and the same dresses as they had you know like a thousand years ago two thousand years ago right um uh so and and then um um there are a few researchers um they're they're two especially uh uh um uh punter uh uh and uh and Kaplan

who just went into these tribes and started to study the incidence of diseases as well as obesity uh body fat percentage uh their their habits uh how much time they were exercising a day and as well as what is what was their nutrition so those were the real primitive civilizations right so um the rate of obesity among these populations was about two percent we're talking about now uh or overweight or obesity in our in our western or not not western or civilized world right is uh it's somewhere between 50 and 70 percent right type 2

diabetes in this population was one percent we're talking that in the U.S alone 52 of of adults are pre-diabetic or diabetic already right um uh and a and I always say that being pre-diabetic you know uh is you already have the disease there's no terms such as being pre-pregnant or pregnant you're pregnant or you're not right so the same thing with pre-diabetes they also have the lowest cardiovascular disease in atherosclerosis plaque percentage observed in any humans in the world right so the and the life expectancy is in fact similar to the US the problem that

they have is that um like the majority of fatalities that they have about 70 percent of fatalities are due to infections they don't have medications they don't have antibiotics right uh and then they have a lot of fatalities due to trauma accidents right uh but only about 10 percent of their deaths are due to non-communicable diseases whereas in our population there's about 70 percent right uh due to uh non-communicable diseases so and then the habits of these people uh they they're they're walking between 110 and 135 140 minutes a day so uh you know the

American Heart Association American Medical Association American I mean all these associations there they're saying about the females 150 minutes a week right that's pretty much what they do a day right um and then we look at their diet and they're they're pretty much plant-based diet they they they're a hundred gathered populations they hunt whenever they can probably like the the people in the Paleolithic right we have the idea the people in the Paleolithic all the worst sick I mean 180 meters or six foot tall and uh and super strong you know and uh and they

were good hold up or bear with one hand and a lion with the other one in in and eat them alive right that's probably not true right they were probably very slim very fragile people who were to survive in and didn't have the strength to overtake a lion or a burr or a bear right but uh yeah there were hunter-gatherers they would hunt whenever they good but in the meantime hey they had a plant-based diet and the diet in these people is uh somewhere between 65 and 70 percent in carbohydrates right which is about 34

33 30 to 35 percent higher than the US in carbohydrates and they have about 15 25 protein and only about 10 14 fat so um this is this is the the the the Paradox right of these populations who have uh almost a non-existent levels of obesity of type 2 diabetes of cardiovascular disease and uh yet they have very high concentration of carbohydrates in their diets yeah it sort of puts to rest this idea that carbohydrates or glucose are inherently bad for metabolic Health that must be something that you as someone who is so close with

the research in this area and conducting your own studies you must shake your head when you come across those sort of claims yeah and I always go back to to the same thing and it's just like yeah if you don't have good functioning mitochondria and if you have carbohydrates that's bad that's that's that's as I said earlier that's adding gas to the fire that's going to make your condition worse because you need to metabolize it and and therefore yes for for someone with a poor mitochondrial function maybe a a more protein uh based diet and

carbohydrate reducing it it's needed um right but if you are a healthy individual you're you exercise you're good you know like this these populations that I described right they they do in one day what is the recommended for uh in our civilization for one week which by the way very few individuals get to meet the 150 minutes required per week right so these people I would love at some point to travel to these areas and do a muscle biopsy of these populations and see their mitochondrial function because I'm very sure it's going to resemble a

lot to to those that we see in in in uh in in in you know very individuals who exercise a lot and they have the same eating habits right eating a high carbohydrate diet low fat and moderating protein I'm glad that you brought up that point about pre-diabetes and I think that's another one worth kind of underlining that metabolic health or metabolic disease and dysfunction I should say is it's more of a spectrum would you agree so it's not as though you go from being metabolically healthy to the next moment being diagnosed with type 2

diabetes so if someone's listening today and is thinking well I live a pretty sedentary lifestyle but I don't have type 2 diabetes what you're saying is despite the fact that you haven't been diagnosed with a metabolic condition if we were to take out the microscope we took a biopsy of your muscle tissue we would be I'd be able to identify that there is Decay deterioration occurring mitochondrial dysfunction and you are on the path to metabolic disease despite not currently having it yes without a doubt and and and yeah and uh exactly and and this is

why yeah it's a sedentary individuals even you know they're healthy now they're they're the majority are going to encounter cardiometabolic disease in the forms of type 2 diabetes cardiovascular disease both they're going to have a higher chances of developing cancers uh there's more and more data around cancer at this point there's a lot of epidemiological data more than scientific cellular data of what being sedentary does to you um uh or obese right so uh being obese or being a sedentary uh it can increase about 50 chances of many cancers right so that's absolutely astronomical right

um but we're still trying to find out that more right but yes we know that um also Alzheimer's people who are sedentary uh they have higher um um risk for Alzheimer's in in Old Time disease you know and this is also uh you know you were you tell me yesterday an article right about a cardiorespiratory Fitness right and cardiac respiratory Fitness is it's it's highly Associated to a higher risk of forecast mortality uh more than any other disease yeah in that paper that I sent you there was a bunch of really interesting findings some that

stood out to me were the fact that the higher the subject's cardio respiratory Fitness in that that paper and that paper was looking at I believe over 700 000 U.S veterans but the higher their Fitness level was all the way up to Elite the lower their risk of death during that follow-up period but one of the really interesting things that kind of stuck out to me was the author's sort of calculated um what someone could achieve if they went from low Fitness so essentially the most sedentary people just to moderate Fitness what would that do

to their risk of of death and and they found that that would half someone's risk of premature death just again just going from low Fitness to just moderate and that that could probably be achieved with 150 minutes of moderate intensity cardiovascular training a week or zone two training yeah absolutely and this and I've seen I'll tell you like an example that I it's incredibly inspiring and it was even hard it was very hard to believe but it's true so the um um I tested once in the laboratory on 80 81 year old gentleman who was

world champion cycling world champion of the 80 to 85 year old bracket which believe me it exists right which is great to see right so anyways I was fascinated because his metabolism he's metabolic efficiency uh during the test that I do was that of someone in their 30s or 40s healthy and active right I it was unbelievable I I I keep that test like a treasure right because it's an absolute treasure to to see those adaptations right so anyways I right away I thought well you've been doing sports all your life right so man you

you chose the right lifestyle right and he's only actually no actually until I was uh in the early 50s I was obese I was hypertensive I used to smoke uh I had a very poor lifestyle I didn't exercise at all and one day I started to ride and bike and think about life and things like that and ever since then so so uh to your point what you said right this was our individual the early 50s uh sedentary very poor healthy lifestyle and then you know 30 years later at 81 years old his metabolic Health

was out of that of someone in their 30s or whose Health that's unbelievable hard to believe in and this is how that that person obviously 81 year old that's an example of what exercise can do for your longevity right that person was not on any medication at 81 years old that and it was a fit slim individual it was hard to believe so but hey this is uh how uh the magic of exercise right is if we were able to put exercise in the pill right and take it every day it would be the most

sold uh medication in in the history right but that's another Point that's a a very hopeful promising message story for for people to hear and and I guess speaks to the incredible capacity for the human body to adapt should you provide the right stimulus at any point in time and that it's never too late to to get started so and and sorry to your point it's in our genes right and what we say it's embedded in our genes so we have the genes humans are genes maybe in in 10 000 years our genes will evolve

to be sedentary I don't think we'll be around in 10 000 years because we're so dumb in the first place right but if we were around maybe our genes are they they adapt to become sedentary but at this point we're too too young as as uh as a race as a species for our genes to to adapt to become sedentary so they're ready to to to to to get the ball rolling with exercise anytime I have mixed feelings about that because I love moving my body hey friends if you'd like to stay connected and reinforce

the valuable insights from this show so let's connect on Instagram you can find me at Simon Hill that's at Simon Hill I look forward to seeing you there alright let's dive back into the episode I think it would be a good point now for us to sort of double click on on zone two and explain to people how they can set this up in their own life how they can know that they're in zone two and how much zone two training they should be sort of targeting or working towards on a weekly basis in order

to provide enough stimulus to get these adaptations happening that we've been talking about and then reap the benefits from improved metabolic health just quickly before we we get there you mentioned Herman Ponce or just as a reminder to listeners Herman Ponce was on the show a little while back so you can go back and listen to that episode and hear all about the hearts and for sure yeah so that was great that you mentioned him and his book Burn is a really good read for for anyone that wants to kind of Deep dive his work

with the with the hards are zone two Inigo let's let's define it I know we probably have earlier in the conversation but simple definition what does zone two actually mean so again they're they're probably different definitions some some of them are closer other ones are a little bit more separate I I just have my own definition right um um that I've been using for 30 years and and for me that that's yeah that's the exercise intensity where um uh someone can improve uh mitochondrial function the most not the only one not the only Zone because

other zones are going to always be beneficial any Zone will be beneficial but uh from what I've seen is uh looking at fat oxidation in the laboratory in lactate cleans capacity as mitochondrial surrogates and Asthma mitochondrial sisters and therefore surrogates for function that's what I see um and uh yeah that's that's that's how I cannot Define uh in a nutshell zone two I think many of the listeners will be thinking how do I know that I'm in zone two and there are a lot of different calculations online there are running tests there are lab tests

Etc how do you encourage people to think about this yeah that's a great point so I think that as as we're starting to look at exercise prescription for for the mass market and for for many people are supposed to just two lead athletes right we're going to see more and more exercise physiology or metabolic Laboratories around the world right uh and in fact it's happening right until recently uh there were very few Laboratories around the world who would who did this test to specifically find out your training intensities right based on heart rate or power

output right and they were only for the elite athletes right and and uh and and then then now more and more are popping up around the world and uh and people are not so scared to go to a laboratory because I remember when I started doing this um in the U.S for health purposes uh with patients 15 years ago people were scared because uh they said oh I'm not I'm not an elite athlete right or they would see a cycling Jersey or of a runner Cersei and the one say I'm not one of those right

no but this is not about that right this is about you and so anyways that that those Laboratories and those testing they're becoming more sophisticated and people running those tests uh that they're all more and more professionals before they're not that many professionals working in this area and people would go to their local University and with all the respects to graduating undergrad students you know they were seen and and tested by them right now you see a lot of professionals who they were undergrad or graduate students and become into this field right um so that's

on one hand but um but there are people out there that they cannot find the place right uh there's not a laboratory in their town or maybe it's too expensive and they cannot afford it right so for those um and from my experience right uh I think that um the the the breathing and talk test it's a great way and and I'll explain it so like like when you and I talk like this now when you can um maintain a conversation like this you're in your Zone one you're recovering you're you're not stimulating much right

zone two uh it would be um like a um a hard conversation to to maintain right if you if you if you imagine yourself exercising with someone else you could maintain a conversation but it will be costly right you will be talking with some difficulty but you could maintain it right not for a long time not not for one hour because it would be off to to fastidious right but you could maintain it that would be kind of what we see the results in the laboratory and it kind of corresponds to that right and then

zone three would be a an exercise intensity where it's it's very difficult to maintain a conversation very difficult just just exchange a few uh phrases or a few words right um then so for no conversation that's it you know uh maybe one word you can say you know and then some five and so on six yeah there's no there's no possibility right but I think that and I honestly and and I know it might sound old school but we have now uh watches and and all these uh algorithms you know that gives us zones you

know that the immense majority are are are far away from from from uh giving you the right intensities because the the those algorithms are are not individualized yet it look it'll happen at some point right but at this point I really think that that that the talk and uh test is much more accurate than the immense algorithms that you find out there in in all these Brands telling you the training zones so and it's easy to do and again from my experience in the data the hardcore data from laboratory it's not that matches perfectly but

it it it it corresponds quite well yeah and I think you know it's just Worth US remembering that there are so many people living in sedentary lifestyle so trying to remove barriers to just get people moving is is a great thing and and what you've just described there is really accessible to people are you a little bit puffy perhaps you have a little bit of sweat happening but you can you can carry that conversation if you were on the phone to someone they would know you're exercising but they could still have a bit of a

conversation with you without it being uh sort of too interruptive and the good thing with that too is that as you get feeder you can you can be displacing that intensity right so now maybe someone is sedentary and obese overweight and maybe just just walking around the block right it might be tiring right but that might be the zone 2 for example but maybe in one year that person can do like a a brisk walk right and be at that same intensity right so that's what uh you can guide yourself through this simple test right

which at the same time this one to intensity is it's something is sustainable for life you know and and again I I I also say that any intensity will help and you need as we discuss higher intensity to maintain your Fitness and your glycolytic capacity and obviously we haven't talked about um uh resistance exercise which is very important right and you know more than than I do uh uh but the thing is like yeah it is when when it comes to both exercise and diets you know I I always ask people who do these extremes

extremes exercise routines and extreme diets and they have great results the men's majority are just temporary because they miss major go back to where they were and when you ask them can you do this for the rest of your life the answer is no so if you cannot do a diet or an exercise for the rest of your life it's not going to work so you need to have some sustainability both in your nutrition and both in your exercising when it comes to exercise zone two is something that anybody can can do for the rest

of their lives you mentioned some of those algorithms and I think the most crude sort of calculations that are out there are using max heart rate 220 minus age and then kind of just multiplying that out by the various intensities of the different zones and perhaps a step better there's calculations like the carbon and formula which I'm sure you're familiar with that uses heart rate Reserve if if someone is going to go out and use a calculation out there is the carbonen sort of formula or a formula that's using heart rate Reserve better than than

one that just uses max heart rate probably but still the thing is and this is what I've also learned working with athletes and also regular people is that the heart rate response to exercise is so individual you can have someone with the same age and uh once maximum heart rate might be 180 and the one one might be 200 right or 160 and 200 right um so and and regarding the cardio Reserve that could very significantly also among individuals so I think it's probably more accurate right but uh um but I don't think there were

not there yet uh looking into into these algorithms when it comes to heart rate uh because it varies a lot and I think that again it's one of the things it doesn't represent necessarily what happens at a sillier level I think that um uh the the future is going to come in the uh um biosensors where we're going to be uh we're working with one company with one biosensor already that we think is going to be a big deal at some point but the biosensors that they're you know kind of people have now some glucose

that if your type 1 diabetes it's a game changer if you're not it's cool to to see how your glucose goes up and down eventually it's physiology and Metabolism 101 and eventually yeah you just uh you can get some education but eventually you will not using it much because you're you're not type one but the more sophisticated by bias sensors are coming with more metabolites to come directly from your cells and that's where you're going to be guiding um exercise in a much specific way what do you think about the devices I sent you a

few on on email that you breathe into that sort of supposedly tell you what type of fuel you're using to produce ADP um yes so those are a very good um uh that's a that's a very good question uh out there and uh without a doubt it's it's it's it's a um it's a starting of of of a movement of trying to understand better uh your how your metabolism works right um but uh one of the things is that their you know they need to be very well calibrated and this is this is my my

problem that I have right and this is my my experience from um uh for 30 years working with all these metabolic cards so we we're using the laboratory metabolic Hearts who are like thirty thousand dollars uh worth very expensive very delicate and those are the state of the art and they really need to be very calibrated so they have CO2 sensors and and oxygen sensors as well so um and they believe me they get decalibrated all the time they're very sensitive so and if they're not correctly calibrated or they get the calibrated they're going to

give you false readings which happens all the time and in fact that there's a brand I don't want to name any Brands but there's a brand that I've been using to do my research and to get this calculated all these years which to me is the best how there is the most accurate and you can see the accuracy very well um but the problem is is that it's not as fancy or has these graphs uh or hasn't evolved in 30 years as other brands right other brands they have these nice and fancy graphs but maybe

they're not as accurate as did you sell their brand right but anyways but we're still talking about equipments that are Thirty thirty thousand dollars worth right but these devices are like 200 300 400 uh sure so some of them they have CO2 sensors right in O2 sensors but how do you know uh first that they're how do you calibrate them right and uh therefore how do you know that the readings are right and second how do you know when they stop functioning and because we know from these very expensive cards that you need to replace

the sensors often sometimes every year sometimes every two years three years right and that's the thing you know like I see that the concentration to calibrate them you need to to really put our oxygen and CO2 and the way they do this when you do the calibration from ambient air right the metabolic card gets oxygen and it has to read 20.94 which is the oxygen concentration and then CO2 is usually the one that is the most problematic it has to read 0.03 percent right so when you calibrate those manually or automatically uh multiple times you

see that the CO2 concentration is 0.05 or 0.06 or 0.01 in the cart metabolic card allows you to proceed with the test right so without a doubt you're going to have false readings and again we're talking about a thirty thousand dollar very sophisticated piece of equipment now how do I know in these small devices that the reading that I have is the actual one right so that that's and and again I'm not criticizing necessarily right those devices because I think that uh they can give you like a Trends in where you are you know and

and if you're burning more fat or less but I think that um yes uh I I I don't know if I don't know the calibration the precise calibration I I don't I don't trust and much you know and then you go to some of the websites of not all but some of these devices and when you when you go to a website you see hack your metabolism or own your metabolism you know or the most advanced metabolic machinery I it's it's a red flag right because there's not such thing right uh now you see greens

right that um they go to their website and you can all the more sophisticated piece of metabolic measurement you can have it like come on it's just it's a ring for B6 that reminds me of the way kind of zoned to or training at Max fat oxidation is often conflated with this magical fat burning Zone and and fat loss or body fat loss is that is that something that you could clarify for the listeners yes and and the thing too is like when we talk about this is that's an excellent question too and I like

to address because when we talk about fat marks and fat oxidation we're talking about very very very small amounts of fat that someone oxidises you know so we're talking about like for example if you're a a an okay fit individual your fat Max is going to be 0.4 grams per minute around that you know amount if you're a world-class athlete we're talking about 0.8 uh if you're a moderately moderately healthy individual your fat Max is going to be about 0.3 grams per minute so I just do the math right if you are exercising UH 60

Minutes at your fat Max and let's say you're 0.35 you're actually losing 21 grams of fat that's it right in one hour right so there's no magic like oh wow yeah I just I just burned so much fat today no it's not such a thing like that you know you you burn a little bit but a little bit every day right if you if you then also match this with proper nutrition right and and stay uh at some caloric deficit then yeah those 21 grams of fat right times uh uh if you do this five

days a week right times uh four weeks per month yeah yeah that's half a kilo right so let's have a kilos it's not bad you put that in 12 months in that six kilos that you lose right and that's again that's exercising one hour if you exercise an hour and a half we're talking about uh uh nine kilos which is could be incredibly beneficial for your health right so this is what I think that there's no magic bullet that oh wow your your fat Max people sometimes think oh I'm losing so much fat therefore I

can have a burger uh a Cheesy greasy burger because I exercise you know and that's the other thing too of of many of these machines or even watches or so like you burn 700 calories today yeah but they're not telling you the partitioning right you you could have burned 100 of those 700 calories derived from carbohydrates and zero from fat because your exercise mode or dosage was not the right one right or you might have a 50 50 or 70 30. so that's gonna obviously impact right how much progress you make when it comes to

lose weight and this is one of the reasons why a lot of people who exercise regularly they cannot lose weight and uh because they say man I'm burning 700 calories or 1 000 calories every time I exercise and I can't lose weight well first you're probably overeating uh for how much you burn and second you're not burning much fat if that at all when you exercise so this is why it's it's a tricky concept and it's about patience patience also doesn't it just come back to energy balance at the end of the day so in

your in your workout if you burn or expend 400 calories from Mostly fat versus someone else who works out for a shorter duration but also expense 400 calories mostly from glucose isn't the net effect on their body weight going to be the same despite the difference in substrates being used to produce energy I don't think necessarily that's my opinion um that there's like a there's energy balance is very important for sure but it's also an um Energy Efficiency and the type of substrate so if you want to lose fat you want to burn more fat

than glucose because that comes from adipose tissue right the thing is that um we're used to also seeing a lot of people doing high intensity exercise and who already already very fit to start with right so they have a good probably because they they they haven't achieved America Decay because since they were kids they've been fit and doing exercise and moving a lot right um but and and they you see these people doing this high intensity exercises and they're very fit uh and they don't have much fat um and uh yeah that's uh and that's

maybe the the calorie balance is more important for them but maybe for people who are overweight or obese um uh the energy balance should be more towards uh burning more fat and restricting also calories from your diet to achieve that Balor calorie balance as well as to improve mitochondrial deficiency through specific targeting of uh training intensities I guess I'd always just looked at the the kind of how the the dietary intervention trials looking at low carb diets that are high in fat versus high carb diets low in fat and at least at the 12 month

Mark and some of this could be adherence there doesn't seem to be a big difference in in body fat and the way that I've reconciled that is that the people in the high fat diet although they're born burning more fat or oxidizing more fat it's dietary fat not necessarily stored body fat but that's that's interesting for for us for me to kind of think about further coming back to to to zone two so you've got the talk test um being a little bit puffy a little bit sweaty we spoke about those different formulas that are

out there and it sounds like that if someone is using any of those algorithms or formulas they're they're still going to want to come back to the talk test and and pair the two together um I I recently did a VO2 max test in a lab and through that VO2 max test they calculated my zones I know that's different to lactate testing per se I noted that there was there's an upper and a lower bound so for me zone two came out at 129 to 142 beats per minute let's just pretend that it that is

my accurate zone two and you might say that we need to do lactate testing to get very accurate but my question to you is when I am going out and doing zone two training sessions does it matter where I'm sitting in that range do I need to get right up to 142 beats per minute at the upper sort of bound in order to get the the stimulus that we need to drive these adaptations yeah that's a great question too and and it's good that you have like relatively like a small range right I've seen people

getting a range of 30 beats per minute you know first one two and I guarantee you that there's not such a big range you know we usually the range is somewhere between 5 and 10 beats per minute right um um at least with my calculations and and and how they work with for me um but yeah absolutely um I think that you want to go more towards in the middle right uh to be more conservative towards the high end um of zone two that's when you're going to push those uh by energetics the most right

and and drive into fat Max before you start engaging more uh the fast twitch muscle fibers and and switching more towards increasing glucose as energy fuel um but uh but yeah but you need to be very sure that the zone 2 is that zone two if you go in the high end otherwise I would stay more in the middle so if we are dipping in and out of zone two does that make that training session somewhat redundant or diminish the the sort of returns that you're going to get so if you're doing say 60 Minutes

on a stationary bike but 45 minutes of that was zone two sporadically throughout that session you were dipping down back to Zone one and then at some points you were going into zone three and this is something that I think people who go out and do rucking or hiking face because they're going up and down Hills is is that a problem if we're doing zone two training do we really need to get into zone two and then stay in that zone that's a great question too and I think that um and this is my humble

opinion I think that it comes to the uh the timing that you spend at your Zone too um and and and and like as you said some people who are doing sporadic leads or once or threes on two um if they're only doing these for 45 minutes um maybe that the actual portion of Sun Tzu might be 30 minutes and and what I have seen is that um and is one of the three pillars that I see is one to identify the training zones the intensity that's right second is the frequency how many days you

do this and and the third one is the the duration right of each of which a session right so I see great results with people when they reach around one hour right so like if you do one hour uh purely a zone two you're gonna get good benefits but if you go and go a little bit above them and Below or or even to zoom four here and there yeah you might want to have a longer session which is an hour and a half for example whereas those 30 minutes is like when you oscillate uh

but the pure Zone 2 is in that one hour right so uh that's where you have the stimulation within one section that that's kind of how I see it and it also depends on your form and your Peak let's say that you do like a high intensity interval in the middle of the session and you only do one hour so if you do a high intensity interval you can have a lot of lactate and it's going to be there for uh it's gonna be there for about 15 minutes and as we saw lactate is going

to inhibit like policies it's going to inhibit my um transportation so you might lose about 10-15 minutes of the session which uh again if you do an hour and a half it's no big deal like I do that you know when when I go on the bike I do usually an hour and a half an hour 45 minutes so I don't have much time but that's enough for me but yeah here and there I I do glycolytic uh intervals because I love to do them and they're good and um and now with with applications like

Strava you want to see where you're fit in with the rest and they're dangerous but anyways I see that um I mean and I love this you know this side of trying to compete with your uh with yourself right but yeah I do this for maybe seven ten minutes like a Zone 4 interval and then I'm in a relatively good form within in 10 minutes I'm gonna go back to normal level so yeah I sacrifice you know 15 minutes out of my an hour and 40 minutes so I'm good I'm still doing hour and 20

minutes or so that's on two right so but yeah I think it's about duration at zone two um that you can afford and ideally ideally with in a session that is consecutive minutes in zone two yeah that that yes that's that's the thing yeah like if people do a lot of intervals into an intervals into intervals no I mean you're you're it's not going to be your zone two you're going to be recovering from the interval right and you're going to be still going through a lot of glucose right um so I think that again

like I like to to to have it more towards the end of the session or if you have like a good hour and a half hour or 40 minutes you can have one interval in the middle of the session or two hours and uh yeah if you can allow any viewer moderate moderately fit yeah in 10 minutes on the downhill or so you can come down to like uh zone two right but if you're not very fit and uh you want to do several intervals you're going to be up there it's going to be taking

time to come back to zone two towards the end which is what I do so I tend to do 60 Minutes of zone two on a stationary bike and then at the end of that session not every session but at least a couple times a week I'll do a hit and get into zone four or five out the back of it and and I sort of treat the zone two as a warm-up yeah um in in that so in that session so dose wise across a week we've mentioned 150 minutes a few times in this

conversation is 150 minutes of zone two per week is that the minimum dose that would be required to build healthy mitochondria I don't know I I personally question those numbers right I mean I think I think that we as humans in our health we gotten so low right that um the recommendations of 150 minutes you know are in my that's my opinion you know they're they're probably not enough I would do more um and I think that more research is coming out right that if you do more minutes you know your your health is going

to be better in your longevity it's going to be better beyond x amount of minutes which I forgot how many now you're not going to see much benefit but I think that uh 150 is kind of borderline uh especially for for people who want to uh delay many diseases and for longevity 150 minutes like uh at the end of the day uh yeah it's just if you do I mean yeah it's I don't think it's enough I think that some some of them were more in the 300 to 400 minutes a week it's ideal which

is twice yeah I think I've seen some research suggesting that there's continued benefits up to 10 hours a week and maybe it's diminishing returns after that maybe there's just not enough subjects doing more than 10 hours to get to get a good amount of of data you mentioned 60 Minutes in a session being perhaps ideal I know a number of people will be thinking okay let's say I do 300 minutes per week can I can I split that up into 10 30 minute sessions um or does each session really need to be at least 60

Minutes in duration yeah yeah I think that it comes to to your schedule right if you can do that boom and get out of the way in my in my opinion doing it continuously it's better than to uh to break it apart uh but sometimes people yeah and and I I have a clients and patients all the time right they ask me hey I just don't have I can do 30 minutes uh walking to work or or brisk walking or before work and then 30 minutes afterwards or something like that right if that's the case

it is what it is right but I just want to go back to what you were saying real quick about that the benefits uh because it just came up to my mind I see people uh um who are in the late 50s early 60s who've been for years uh doing 150 minutes uh 200 struggling with time right but maintaining being fit right because they're moderately active right but being fit but always struggling with work family Etc and then they they re they retire early earlier uh if they're like those who are lucky right or pre-retired

or they work you know like 20 hours a week or part-time or something like that and then they start exercising and training in a more serious way doing 10 hours a week for example right or eight hours a week right uh we're talking about 500 minutes 600 minutes and in one year within one year their metabolic uh Fitness increases dramatically right their mitochondrial function their fat burning capacity lactogenes capacity and and then you see data in people in their 60s that it resembles the metabolic data of people in their 30s right so this this is

kind of not as Extreme as like the example of the 81 year old person that I told you but I see this all the time and it's incredibly inspiring to see that you can get a metabolic Fitness of someone in their 30s when you're 65 right it's attainable for for those ones who can afford the time but also I think it speaks a lot uh in the in the about that probably we need more minutes than 150 to to be better you know for longevity for metabolic Health than 150 minutes we can do better that's

maybe the the right way to put it yeah I want to speak to you about the best modalities uh that that someone can use for their Zone to training and you you've mentioned walking a few times here and you spoke about the hearts are doing 150 minutes of walking per day I'm sure there are people thinking well I I go for a walk every day I walk down to the shops so when it comes to walking what sort of counters zone two training and and perhaps what doesn't count so yeah that's a good point so

I think that for for most people if the if the exercise is working it's going to be a breeze walk right like a slow walk might not be enough to recover or improve that decay you know it might it might be good to maintain and this is what we see in in blue zones and areas in Europe for example in the Mediterranean countries right where people live longer and healthier than for example here in the US and they're always walking to work working to shop right or even within here in the US in in cities

like New York right in New York uh people don't have big pickup trucks to go and buy food for two weeks right people have to live in small apartments small refrigerators 85 percent of people in Manhattan for example they don't even own a car so that means they have to walk all the time to the store um and keeps them walking you know and if if if uh before that you've been uh you've been exercising for years that yeah that walking alone might maintain uh uh or or slow down the Decay significantly right but if

you already have a Decay and you want to improve it there's no walking might not do much for you uh you might want to do a priest walk right um and then eventually improve improve and you might end up maybe slow jogging and maybe a faster jogging or something like that you know or um yeah or if you're on the bike you might start very easy on the bike and uh but again this talk test I was mentioning I think they can guide a lot of people ideally ideally you want to go to a laboratory

and get your specific training zones and wear a hybrid monitor or something like that or now this this these watches can give it to you but ideally is that but if not the talk test can help you yeah and you mentioned the the blue zones there that gets me thinking about the enjoyment yeah that comes with the way that you're moving your body you spoke before also about consistency right so we could over complicate this to the point where someone ends up choosing a form of exercise that they hate because it gives them the best

sort of time in zone two um but there is rucking there's cycling there could be stationary it could be outdoors there's jogging that could be on a treadmill in a gym or it could be outdoors there's swimming laps there's all these different modalities and I guess enjoyment has to be a big part of this so that you keep showing up day in Day Out exactly and this was part of the sustainability that we're talking about right and it depends on your Fitness level that you have to start up with if you have a very high

Fitness level as the people we were talking about who do more high intensity right in all kinds of exercise but that might be good but if you're someone who's been sedentary for 20 years uh maybe just walking around the block it's going to be quite tasking right so then you don't want to take on jogging or swimming if you don't have a good swimming technique uh swimming it can be really really hard exercise for you right um or or cycling yeah if you live in a mountain mountain Zone and and you haven't cycle in a

long time and you're overweight or obese probably not not your sport right but you might be doing a stationary bike so I think that is important to when you engage in an exercise program to know as you said very well what do you enjoy what do you think sustainable and also for that you need to be what fits me the most is it running is it is it uh for my niece also I have knee problems for someone might say I have any problems so I cannot run or you know but I prefer swimming because

I used to be a swimmer for example a long time ago in school so I have good technique I don't know so I think it's important to fit the type of exercise and individualize it yeah there's some really important takeaways here for people one you sort of emphasize the importance of trying to get up to 300 to 400 minutes a week ideally of zone two which is a bit above the kind of 150 minute recommendations or that's the lower end of the recommendations anyway and then this idea of of the exercise you're doing being relative

to your Baseline Fitness so the commonality among everyone that's doing zone two training is that the perceived exertion is going to be same the same and you're going to be in that same position of being able to have a conversation but being a bit puffy it's just that the fitter person will be doing more work so they might be out jogging at a much faster Pace or swimming laps much faster and someone else might be at that same level of perceives exertion the same puffiness and the same ability to have a conversation just taking a

little stroll down to their shops and over time that talk test is still going to be what you're going to use to guide your zone two but you're going to be able to do more and more as you get more aerobically fit and the mitochondria are being upgraded so to speak yeah I agree I agree and this is this is what we see with many with many people who start exercising this is exactly what they tell you you know like wow I can go faster at the same Pursuit effort right and I can talk like

you know I can still talk before I at this I used to go with my partner whatever and I couldn't talk past this walking speed now I can talk no problem right so that that those are the things that are important to keep in mind yeah I regularly do resistance training for sort of 60 to 90 minutes and I wear a a whoop sort of wearable Fitness tracker and within that it it breaks down the time that you're in different zones during your workout and something that I've observed is that during that 60 to 90

minute resistance training session about 45 minutes of of that are are in zone two or it tells me they're in zone two would that count towards my weekly Zone 2 Target I don't think so I think that what it picks up is like when you're recovering from lifting right uh it picks up let's say your zones now you you enter with the test that you did 129 to 140 right so it picks up when you get there in between sets or intervals right boom yeah you might be in that zone right so that's why yeah

you might see the majority of the time actually you're in zone two but but it's a recovery phase right uh it's not a metabolic phase where you specifically stimulating that mitochondria function right because yeah as you know like when you when you do resistance exercise it's it's more the ATP fossil creating uh system that you engage uh which is quite tasking and then you need to replenish that ATP and you do that usually by increasing glycolysis um and and then uh one of the things that um that happens he's like yeah it's just but obviously

the heart rate decreases and it might be perceived by the the watch or the heart rate monitor that you're in zone two simply by the five that you're um um decreasing but I think that in my humble opinion that that um that resistance days obviously is are really important to do um uh but I think there is something that you need to isolate right so it's okay this is my days for resistance training or I'm just going to isolate this session completely from the rest or I'm going to do zone two as as a warm-up

for example and at the end I'm going to do resistance training or I'm going to do a resistance three in the morning and soon in the afternoon whatever but yeah I think they need to be isolated in a perfect world where would we position zone two training I know there's some discussion around are you able to stress the mitochondria more if you're doing your zone two training in a fasted state or perhaps you're following a high fat low carb diet are these strategies that would allow you to increase fat oxidation and sort of further stress

um the mitochondria to get those adaptations that we're trying to achieve or unlock possibly possibly I am I'm definitely open to that but I think we need to be careful because when you tell people to fast and exercise it can be a double edged sword right where people can overdo it and become catabolic so they really have to manage their intensity and their frequency very well but uh yeah it could it could simulate my kind of fat oxidation although yeah we we have to be careful with that I I think that uh the truly way

to improve fat oxidation is to improve mitochondrial function first rather than doing in a fasting state or restricting carbohydrates uh there there are a lot of you know anecdotal data and even some scientific articles showing how fasting increases fat oxidation in the laboratory right um well that that's an artifact in in my my humble opinion from 30 years doing this testing because one of the things that happens if you are fasted and or you you have you've been restricting carbohydrates you don't have much glycogen so when you do this metabolic testing and people do now

substrate utilization to see how much carbohydrates and fat you do or you are or even your rer then you see yeah this person is burning more fat under this stage but yeah it's not in fact in many cases because you know you don't have as many as much glycogen so you cannot burn or utilize as many as many carbohydrates and then this uh metabolic cards function through what's called stoichometric equations right so in order to burn uh one gram of fat you need x amount of VO2 and you produce x amount of CO2 and the

same thing for fat therefore these equations can be can be equivocal because if you don't have enough glycogen you're not going to engage glycolysis so much therefore your CO2 production is going to be less also you're going to be producing less lactate and that's going to fool the machine interpreting that oh boy he's not he's narrow she's not burning so much uh uh carbohydrate therefore must be burning a lot of fat right so uh it could be equivocal and then we we have seen that um yeah you know Allah you've improved your fat oxidation tremendously

with this diet and blah blah and then uh two days later just in two days that person goes to a normal carbohydrate diet and fat oxidation decreases half right and and that doesn't mean that the mitochondria in two days all of a sudden whoa I am not burning fat now is this that it's probably an artifact from the uh from the test itself so if I wake up in the morning and make a big bowl of Oats rich in carbohydrates and have some banana in there and some other fruit and then I go and do

so I have a lot of carbohydrates on board and I go and do my zone two training session an hour after that is that in any way going to impair that's that zone two session it depends on how feeling how metabolically flexible you are I would say right if you're normally flexible you should not impair much I'd still with a low 30 to 40 minutes right uh for those carbohydrates to be metabolized and then via or via a stored as glycogen right uh and then you can burn more fat but uh but still you know

the intensity is going to override that that high hyperglycemia uh so uh one of the things that you do when you start exercising um is uh increased cortisol levels as well and in catecholamines and those are important for lipolysis so you're going to bring down more fat and that is going to override uh in in many instances that the possible slight hyperglycemia that you might have which by the way it's also be a managed by insulin right and uh but there's there's a threshold that we still don't know very well like uh it's called Canada

the cortisol threshold because cortisol is necessary for lipolysis right for breaking down the fat to use it but uh past X and um like uh exercise intensity cortisol is absolutely needed to uh break down glycogen for energy right and in cortisol then at least it's vasoconstriction to the adipose tissue and catecholamines and therefore shut down lipolysis so it's a paradox that it opens up like policies but it also shuts it down right so but I think that in early exercise intensities I mean low exercise intensities you can override the effects of having a banana for

example are there any nutritional or supplementation recommendations that are evidence-based that can help improve someone's Zone to Pace or the adaptations that they derive from Zone 2 training I I'm I'm not aware of you know of uh science based that I that at least I believe you know I think that the best way to improve is exercise um but uh yeah that's that's that's that's what I think um yeah have you heard of a compound called urolithin a I've seen some some marketing in just the recent months but maybe over the last year or so

and I quickly researched it ahead of today's conversation I really didn't know much about it but it seems to be a compound that we or our bacteria in our gut naturally produce from certain polyphenols found in berries and pomegranates Etc and I looked up online some of the the sort of more popular brands and I won't mention Brands here that are promoting this product and you know some of the claims of that this postbiotic will energize cells increase muscle strength that it's a molecule that will activate mitophy which we haven't spoken about but to my

knowledge is kind of the clearance of dysfunctional mitochondria is do you have a view on your listen a is it something that you've you've sort of looked at at all well not not a whole lot but I but I think like yeah I just I I I I yeah I don't have much knowledge about it to tell you but uh but I I I'll be ah still uh I will doubt about the the big benefits of of these supplements right I I really yeah I I don't buy the whole idea that one supplement is going

to really make a difference in in um mitochondrial function or or it's going to alter uh you know the epigenetics you know like I I really I really I really doubt it you know um uh you know like there's like one recent one that is now the the big deal although yeah I think it's it's now on the slope down that is uh um um uh any men right or anymore like uh yeah nicotine mononucleotide right which is a um uh like a precursor of uh nah NAD right uh because as as we age NAD

levels in the cells they tend to decrease um and therefore the supplement uh is going to it's a preclusive for of NAD and it's going to increase and therefore the cellular function etc etc right um I don't know I I've seen people seen saying my gosh since this I I am the strongest person in the world uh I I've been in all the records I feel amazingly strong and one month or two months later they don't tell you that anymore or six months later right so I think there's a lot of placebo involved in many

of these things and in fact we we haven't published it because it's a small sample but um for cancer we have seen that uh NAD for example um can accelerate glycolysis because Ned it's it's a big part of the glycolytic pathway that is utilized by cancer cells right so we did this experiment with mice where we are we implanted aggressive tumors it was like a um triple negative breast cancer tumor and uh one group of mice we didn't we give them Placebo right and the other one we're given the uh any men and uh yeah

within within 21 days the the growth of the tumor was 15 higher uh in the uh in the uh in in the group with the supplement right so I'll be cautious about this because can that fuel uh tumor growth if you have a small tumor can you feel with that we don't know I think we need our evidence more um is like people taking also this longevity drugs to improve uh from mitochondrial function to liver 20 years longer and and and or get rid of diabetes right which is rapamycin right so forthropomyosin it's a it's

a key uh it's part of a key pathway um um for cell growth and proliferation right and um there are a lot of uh negative and and positive feedbacks in those Pathways and I always like to say don't don't mess up with Mother Nature and biology if you're healthy right uh because why did you take in this uh supplement and this is going to dysregulate another one that is going to take to a complete this regulation of that pathway and lead to a disease down the road like could be the case of NAD supplementation right

this regulates even more probably could could do that I'm not saying this because yeah we need a lot of research on both sides right so uh yeah I'm I can I can uh yeah I I think that we have to be careful with with some of these supplements which more and more are sophisticated and can get to can really do biological actions more than just having like the typical vitamin C or you know or or vitamin uh uh a or even d right I think that now some supplements can be very targeted you know specific

yeah I'm glad that you flagged that it's a reminder to kind of remain cautious when new supplements enter the the market and there's not a lot of long-term data on them is it frustrating for you that the longevity sort of science Community um I mean clearly mitochondrial dysfunction has been identified as one of the Hallmarks of Aging but a lot of the focus on addressing that has been through the use of various compounds and I certainly haven't seen many scientists from this field talking about the enormous benefits that are up for grabs with very specific

exercise namely zone two do you wish that was more front center or prime time yeah I I definitely think that um exercise is is definitely a way much more powerful than any of these supplements or combos right um and uh and it's very healthy uh the effects of uh exercise they're like more and more research showing at the molecular cellular level and the extra kinds uh which are little vesicles produced by skeletal muscles that they go to many organs and they can they can keep disease at Bay this is something that no other supplement can

do and as I was mentioning some supplements there are so species they're so the targets on Pathways they're very important for cellular cycle and cellular growth that we might not want to touch if we're healthy you know because that my my dysregulate the whole pathway or other Pathways you know and and there's a lot of money involved with this there's there's weak science uh there's science done with a mice who tend to live two years only and they say oh they leave three three months more there are four could be 10 years more for a

human is it's a different Ballpark and I remember one of the supplements that came out uh Resveratrol right that uh it came up 30 years ago or something like that uh life right because it was shown that mice who were taking Resveratrol every day they would live longer and therefore this is going to be the best import or most important longevity that's when kind of the first longevity supplements start to come out right now the people who were 50 years old 30 years ago taking Resveratrol they haven't lived 20 30 40 years more I guarantee

you right and it faded away you know and like the same way that most supplements will fade away but exercise will continue but again that's what I was saying if we could encapsulate the benefits of exercising appeal yeah that would be the most uh sole drug ever in history everybody would jump on it okay to summarize things here for the listeners before we let them go I think two of the the most important things that we've spoken about when it comes to metabolic health is firstly being good at converting chemical energy from our food into

mechanical energy which requires healthy mitochondria and the best stimulus for building healthy mitochondria being this zone two training that we've spoken about and trying to get to sort of three to four hundred minutes of that per week and then another important part of metabolic Health being the storage of energy particularly fat in the right place which means storing fat subcutaneously rather than sort of between or within organs which comes back to partly someone's personal fat threshold but really will be achieved by finding a way of eating that leaves you feeling satisfied for without needing excessive

calories beyond your energy requirements so that you don't get into that state of energy toxicity um and that the zone 2 training um doesn't mean or shouldn't get in the way of other important forms of training so you still want some zone five four five high intensity work we spoke about how the two of those kind of work together to help you better clear lactate and of course resistance training as well was there anything that we didn't discuss today or perhaps that we we spoke about briefly that you kind of wanted to add to so

no I think yeah you summarize things very well I did you did a great job at uh summarizing and everything that we've been discussing too and and breaking down every single aspect of our podcast um and uh and I appreciate it um I just think that maybe just the thing that would add is is like uh there's a lot of hype around soon too that maybe people are getting like because in our society how societies people taking things to the extremes and uh that now for some people everything is on too when it's not right

uh and and believe me I've been doing zone two for for 30 years with my athletes and and patients as well but uh they're more than that and as you said very well you know there are other intensities are necessary to do and uh um all the forms of exercise like resistance training right that zone two is another Panacea of of health and everything you know it's a very important part I think and I I believe it strongly um but yeah it's just like we we have to still be on track that there are other

things you know that you can do um it's like in nutrition we cannot say that when nutrition is the best and that's it now I think that you know could be better than others right but I think that um yeah we need to do things in moderation also we didn't discuss this but it kind of comes to mind now zone three and zone four are often considered or said to be no man's land or or junk volume is that an oversimplification and do Zone 3 and zone four have a place within someone's cardiovascular training sort

of regime I don't think so I think that uh they both are going to be good zones right and again it depends on how much time you have you know for example with my athletes that the world-class cyclists for example that they train you know a 20 2 to 27 hours a week right so they have a lot of sessions of zone two but they also have a lot of time they spend not as much as one two obviously but they spend sessions specifically at zone four and even so three right uh which are necessary

also for for performance to improve those especially so far as we discussed those glycolytic Pathways and the mct4s for people who don't have more than uh five hours six hours a week um you know I I I would recommend more to focus on the zone two and uh and and on the zone four um you know either at the end of a zone two session or maybe dedicating if you exercise four days a week uh you can do another two days on your own or one day and all out right but uh but I I

would maybe isolate those two points those two zones on two and so forth I think they're quite important uh one for the glycolytic capacity which is the turbo and the other one for more the mitochondrial function there you go this has been incredibly informative thank you so much thank you for all of your work your research your contribution to to science I think we'll have to get you back on to to continue the conversation I'm sure the community is going to come come back to me with a number of of questions so perhaps next time

I'm in Colorado um I might actually be there later this year I have some friends that live at in Boulder so perhaps we could uh continue the conversation yeah absolutely yeah let's meet whenever you're here let me know I'll be happy to uh to me for lunch or coffee absolutely and let me know and yeah it's it's uh thank you thank you for inviting me to your show uh your podcast I'm uh yeah it's been a pleasure and thank you also for your uh contributions uh because it is very important that people like you are

uh really uh sending the message you know and that which is huge and really really important then from you know something that uh scientists and clinicians are not great are doing that right uh but uh people like you you're with your science background of course uh your understanding and your research it's it's it's important that that your contributions uh are are well well noted for sure thank you there you have it friends I hope you enjoyed this episode if you did and want to stay up to date with future episodes be sure to hit that

subscribe button on YouTube and follow on Apple or Spotify finally thank you for showing up and the effort that you're making to take control of your health I look forward to hanging out with you again in the next episode