Hidden Metabolic Danger In “Healthy” Adults

Feeling “fine” with normal labs can hide the earliest signs of metabolic trouble. We dive into a revealing study of young adults that compares sedentary people to those who simply meet activity guidelines, and what it uncovers inside their muscle cells is hard to ignore: lower mitochondrial respiration, poorer cardiolipin quality, higher lactate production, and a tilt toward glycolysis that predicts insulin resistance and chronic disease years before a diagnosis.

We walk through why mitochondria—not BMI or a single glucose reading—are the real engines of health. You’ll hear how cardiolipin acts like high‑grade motor oil for the electron transport chain, what happens when its quality drops, and why consistent moderate movement upgrades both the quantity and the integrity of this critical lipid. The active group in the study wasn’t elite; they just hit 150 minutes of weekly activity, yet showed superior fat oxidation, better lactate handling, and true metabolic flexibility.

We also connect the dots to food. With the dietary guidelines flipping the old pyramid, we talk about prioritizing whole foods, quality protein, whole‑fat dairy, eggs, fish, and minimizing refined grains to support resilient cell membranes and healthier mitochondria. Pair that with practical steps—brisk walking most days, a bit of resistance training, and paying attention to deeper markers like fasting insulin or HOMA‑IR—and you have a blueprint to improve energy, reduce cravings, and lower long‑term risk without chasing extreme routines.

If you’ve been waiting for a sign to start moving and simplify your plate, this is it. Subscribe, share with someone you love, and leave a review to tell us the one change you’ll make this week. Your cells will notice first—and the rest of your life will follow.

For video, open source references and PowerPoint slide deck: www.thehealthedgepodcast.com

Transcript

Setting The Stage: Metabolic Health

SPEAKER_00 0:01

Welcome to The Health Edge, translating the science of self-care. I'm Mark Pettis with my friend, colleague John Bagnerlo. John, good morning, my friend.

SPEAKER_01 0:09

Hey, good morning, Mark. Great to see you, bud.

SPEAKER_00 0:11

Great to see you. We're into the new year and have a great paper to review with our listeners today, John, that um makes some really important points, many of which that I think we we emphasize and have through the years. But one of the points that this study will emphasize is that long before disease manifests, long before we have a diagnostic test to label whatever you're going through a disease like diabetes, a high blood sugar, or a high hemoglobin A1C, long before you get to that point, you can see very significant changes in cellular function, metabolism. And we've been on this theme of metabolic health. And this paper really opened my eyes to how profound in people who are otherwise at a good body weight and have no diabetes history can have changes that clearly have them on a trajectory of chronic complex disease, particularly diabetes, insulin resistance, you know, these passports to aging and diminished quality of life. And the paper, as we'll see, makes this distinction between people who are sedentary, and these are young adults, versus people who are active as defined by meeting the current recommendation standards for activity, which we've touched on in recent podcasts, of you know, 150 minutes a week of moderate um activity. And um so so I this was a very revealing study. It'll be it'll be fun to share this. And there's some uh geek level uh biochemistry that that we always love talking about. So I'm gonna uh that sounds okay, John. I'll I'll throw out some slides here. I'm just gonna share the screen.

SPEAKER_01 2:26

Sounds sounds perfect. And I again, just for our listeners' sake, I think the you know the real startling, if you will, part of all this is that you know, you're you're talking, I think, above 20, right? There's 20, 20 subjects in the study, 10 considered moderately active and 10 considered sedentary. But to your point, Mark, the 10 that were sedentary, and the authors put the word healthy in quotes, you know, throughout the paper, they were healthy because you know, decent BMI, um, you know, no abnormal blood work, you know, no signs of pre-diabetes. And you know, these are these are subjects that would have left their annual physical, uh, being told, hey, everything looks good, you know, exactly. You know, and so I think you know, the fact that this paper is looking at quote unquote healthy adults and finding these pathological changes that we'll get into now, it's you know, this we could look back on this paper as being a landmark paper, you know, five or ten years from now.

SPEAKER_00 3:25

Absolutely. Okay, let me just bring this up. So we uh have to start, John, by just briefly uh Yeah. Absolutely.

SPEAKER_01 3:38

Absolutely.

New Dietary Guidelines Turned Upside Down

SPEAKER_00 3:39

I could not resist putting this topic up, and I apologize for for those who are listening. All of these slides will be on our website, healthedgepodcast.com. And we have a YouTube channel as well. Uh, but I think many of our listeners will know that the dietary guidelines for Americans has just been published. These are guidelines that go back to like what 1970s, John? Yeah.

SPEAKER_01 4:08

Even before then, in some ways.

SPEAKER_00 4:09

And they're updated uh every five years. And they really, perhaps more than any consensus guidelines that that we see in the public health community, uh this probably influences how people perceive what's good for them and not more than than any uh as it relates to food. And so uh this is what came out uh this week. And um it it's uh for those who can't see it, it's kind of a reverse pyramid from the old the old uh pyramid uh food uh pyramid that we can all recall. And uh I guess it's true, John, that sometimes hell does freeze over. Uh it's it's just amazing that this this uh new emphasis on uh red meats, whole fat dairy, fish, eggs, butter, and vegetables.

SPEAKER_01 5:09

And vegetables to be, you know, to be fair here. It's great. You know, they're not in the when you look at this, and what the thing I like the best really or most about this is that the whole thing got turned upside down. I think I, you know, I'm sure that was intentional to turn the pyramid upside down as it as it is, um, and to get grains down there in the you know, very limited number of servings per day, right? I mean, I that's a huge win. And I know, you know, for our listeners, I you know, again, I always say to people like you can't throw the baby out with the bathwater. So regardless of what your political affiliation, and then that's the unfortunate part about this, is it will probably become political on some level, you know, one camp versus the other. And in in rather than the science behind this, and the science behind this is it's it's massive. I would say it's you know night and day difference between the science that supports this way of eating, these recommendations, compared to the lack of science that supported the previous food guide pyramid, largely established by the big food groups, you know, and and processed food, the the processed food industry. So, yeah, Mark, this is a, I mean, like you said, I mean, we were literally seeing hell freeze over here.

Study Design: Sedentary Vs Active Adults

Normal Labs, Hidden Dysfunction

SPEAKER_00 6:27

And that that was such a great synopsis, what you just said, John. The the evidence to support this has been around for many, many years. We we talk about it on most of our podcasts. It has defined many of the nutritional principles. Uh obviously, whole foods is the emphasis, but with uh greater emphasis on protein, particularly quality bioavailable protein from animal sources, um, uh, you know, some emphasis on the need, if you're vegetarian or vegan, to be thinking about inevitable deficiencies. It it was a guideline that I think more closely approximates where the research has been, as you said, John, for a long, long time. And so uh undoubtedly there'll be uh pushback, but uh and I think it takes a lot of gonadal integrity for uh RFK Jr. and a lot of his team that they take, you know, they take a lot of shit. Yeah. Uh and and yet you know, within that um um sort of conflicted political landscape, there's very, very good science. And I think any person who uh shifts from what may have been the more traditional guidelines uh to something like this in terms of their day-to-day um uh nutritional roadmap will realize we're gonna benefit changes, and hopefully this will start to help mitigate this overwhelming fear of fat and fear of red meat. And again, the emphasis here is on whole quality foods, and and that's the bottom line. But wow, who would have thought? Yeah. So this is the study that we've been referencing here, John. It's from um University of Colorado. This was published in within the last several months. And as you noted, they took a small group of healthy uh adults, and um one group was sedentary, did not really engage in any regular activity. The other group would have been considered active by virtue of their compliance with current guidelines for recommendation. And they looked at the metabolic landscape of these individuals, particularly in their muscles. And uh, this is a uh, from my perspective, a really uh kind of a sophisticated analysis. Uh, you know, the average person, you know, won't volunteer for a muscle biopsy. Uh so they really got to at to the cellular mitochondrial level uh with very sophisticated analytics and histopathology, and and so uh it's really uh a unique data set in comparing these two groups. And uh the first thing that came up for me, John, and we alluded to this in our introduction, uh, was the uh extent to which all of these individuals would have been considered uh on this uh early end of the of this health continuum where they have no disease, uh they're considered healthy, uh, they're at a what we would consider based on BMI, that's a whole nother issue. Um BMI is probably not a very great biomarker uh in terms of metabolic health. But all of these people would have been considered uh perfectly healthy. And to your point, John, you would have come away from your visit um with a gold star. And uh and we know in the example of diabetes that uh it's your sugar, your blood sugar, or your hemoglobin A1C that will trigger the diagnosis. And we may call that early stage disease pre-diabetes in that example. We know that if if none of the factors that are driving that change, it will become established type 2 diabetes. And then we know if that trajectory fails to shift, you're looking at just horrendous uh late-stage diseases from cardiovascular disease to chronic and end-stage kidney disease to uh stroke, liver failure. Uh and so, right, the emphasis is on okay, um, if we check a blood sugar, check an A1C, we can prevent more of this and pick up people in these early stages. And what this study shows is that all those things can be normal. A blood sugar and a hemoglobin A1C can be normal. And when you look uh at a deeper level of metabolic health, you see dramatic uh disruption, uh, really setting the stage for what will be future uh clinical diagnoses and obviously clinical problems. And so I just want to remind people of this of this the importance that feeling well doesn't necessarily equate to good health. Uh absence of disease is not uh uh equivalent to good health. And um, you know, we often talk about, John, optimal function. It's really uh not whether you have disease or not, it's optimizing your biology, not just to mitigate disease risk, but to really allow you to kick ass in in life, to to thrive in a modern environment that's toxic, that's challenging, that's conflicted, that's uh, you know.

SPEAKER_01 12:34

So And that, hey Mark, just real quickly, that you know, that's a you know great point that you're bringing up here because for many people, you know, if they don't exercise, if they're not active, they don't really see the limitation in their functionality, in their not being close to optimal health, right? If you never exercise, but you're at a decent weight and you don't have an abnormal blood sugar level, you don't have hyperlipidemia or whatever, you know, whatever is going to be the red flag with blood work, when those things don't happen, but you're sedentary, you feel like, hey, everything's going well. Until you go out for a you know a power walk, right? Until you get on the bike and you start to challenge yourself and you're like, wow, am I winded? Wow, why am I feeling all this lactic acid in my legs? I've I've only been walking for two minutes. So I I think, you know, to your point, uh, I like the way the author uh you know provides this context where exercise now is like a prescribed intervention instead of being something that people accept to be part of daily life. You know, you you always talk in such a great way about the blueprint we have for a certain way of life that our ancestors had. And you know, woven into that was movement throughout the day. You know, whether you're walking eight miles or four miles, or whether there's high intensity or low intensity, you know, we can debate about the like the nuances of that activity. But the bottom line is our ancestors moved throughout the day. It wasn't like for a half an hour here or you know, three times a week at this intensity. We moved all the time, and that's really what we have the genetic blueprint for. So the way that the author weaves that into the kind of overall summary of the paper, I found really refreshing that you know, we're in a world now where people consider exercise to be an intervention instead of a like a core component to life, like breathing or eating. It's it's fascinating, right? It's fascinating how we yeah, how we've lost an appreciation for that as a foundational component of life. And so to your point, a lot of people don't understand their limitations because they never challenge their body with a faster-paced walk or you know, more time on you know, any whatever piece of equipment it is you want to get on. If you don't push yourself, you don't know. You don't know that you have limits.

SPEAKER_00 15:04

And we are indeed a species with amnesia.

SPEAKER_01 15:07

It's amazing how you come from, you know.

SPEAKER_00 15:12

Yeah, that's great, Sean. Uh and when you look at um uh you know, just looking at this study, and again, just to sort of remind people, I use diabetes as the an example here, uh, because the the changes seen in this study that we'll we'll report in a moment um really predict future onset of diabetes, of cardiovascular disease, of uh cognitive decline, right? These are these are the early drivers. Uh you know, if you're dealing with uh you know with a huge fire, uh we've seen plenty of those in in recent years. You know, these are the sparks. This is um like ground zero of uh of that happening. And so to be able to see that uh and then ultimately intervene, um not all things that one might see uh can necessarily be modified. That's not the case here at all. This is all modifiable. So we know that diabetes is epidemic, one of ten Americans, this is type two diabetes, this is recent CDC data.

SPEAKER_01 16:24

These are really conservative, these are really conservative numbers, too.

SPEAKER_00 16:27

They're conservative numbers.

Movement As A Core Human Blueprint

SPEAKER_01 16:29

To your credit, you're yeah, to your credit, you're you're giving people a you know a picture that isn't quite as depressing as as you could, right? I mean, and a lot of this is the way, you know, just to the point of this of this entire study, you know, so many people walk around out there in society at decent weights, but they're metabolically, right? They're a train wreck.

SPEAKER_00 16:51

Yes.

SPEAKER_01 16:51

But because they don't have the the body weight issue, they don't have the blood sugar levels, and then you know, we're still using fasting glucose or at best an A1C, if we were using fasting insulin or a HOMA IR score, you'd have two to three times the number of Americans that would be diagnosed as as we do.

SPEAKER_00 17:08

Yeah, I mean, that is such a great point, John. And it's one thing that I didn't see was included in the study, because I I think you and I would both predict that for those with a normal blood sugar, those with a normal A1C who would have met criteria for this study because they didn't have evidence of diabetes or or prediabetes. If you were to look at their insulin levels, uh you might find you might find some smoke. This is on that pre-disease part, you would definitely see some smoke. And there's good research um um going back quite a few years, looking at insulin patterns which far precede alterations in glycemic or glucose um uh uh management and and measures. So um uh the HOMA IR is definitely a great test to be getting, particularly if you have a uh um a little more weight around the midsection, right? Um family history, if you are a sedentary, um don't feel you have to wait for a high blood sugar because um chances are your insulin levels are going to be high, and that is a big red flag. And that, in my experience, John, that can be really motivating. Uh people who might otherwise confront inertia, uh, when they begin to see that, it's like, wow, um, that is getting my attention. And we connect insulin with virtually every chronic complex and accelerated aging. So it this is not a trivial um factor by any means. So uh what the study ultimately uh they took the sedentary folks and those that were moderately active, and they did muscle biopsies of the you know, quadricep muscles, and they looked at um uh how well the the mitochondria were burning oxygen, right? This efficiency, mitochondrial efficiency. They looked at uh what's called cardiolipin. This is uh uh like a phospholipid uh that uh makes up uh the membrane, the cell membrane, but in the in the mitochondria um there there's an inner membrane uh that uh cardiolipin tends to be more rich. And and we know cardiolipin, that that type of fat in those inner mitochondrial membranes are incredibly health promoting and protective against oxidative stress, and they enhance insulin sensitivity, and they they provide kind of a scaffolding for our electron transport chain, right? This flow of electrons that's really the flow of life. It guides everything. Right. So they look at um protein expression in the in the muscle, protein synthesis, which is so critical. How well are uh you know glucose uh uh transporters function?

SPEAKER_01 20:16

Very sophisticated and just on this slide here, Mark, one thing that is important because when you see sedentary versus moderately active, I mean the first thing that came to mind when I was reading through the paper, well, you know, I want to define moderately active. And I want to make sure that I'm not comparing sedentary to highly trained.

SPEAKER_00 20:36

Yes.

Inside The Muscle: Biopsy And Mitochondria

SPEAKER_01 20:37

And the reason that we know these folks were in fact just, I use the word just moderately active to your point, whether it's two hours a week or 150 minutes, um, you know, the bottom line is their lact, basically their lactate dehydrogenase levels were the same. So for our listeners' sake, if if the moderately active, if the subjects in this study were highly trained, the researchers would have seen differences in the lactate dehydrogenase LDH levels, right? Because those change when someone is at their anaerobic threshold, right? If if if that moderately active population, if they were, if we're talking about like Olympic caliber, even collegiate runners, let's say, if these people were training an hour a day, seven days a week, with you know, 15 to 20 percent of that approaching their anaerobic threshold, then the LDH levels would have been significantly different between these two, these two groups. So I think that's really encouraging, is where I'm going with this is that you know, for someone listening to this or someone trying to appreciate this study and the potential for it to improve the health of their mitochondria and overall their metabolic health, it's a moderate amount of exercise we're talking about. It's just not being sedentary. You don't have to, you don't have to be in that, you know, real high intensity window for you know 10 or 15 or 20 percent of whatever duration of exercise you have. You can just go out for a brisk walk, right? You do that 30 minutes a day, and it takes you out of this sedentary or more, you know, this path pathology state. So I just think that was really noteworthy that the LDH levels were similar. Because again, I it'd be easy for someone to look at this and say, well, I'll never, I'm never gonna be, you know, I'm never gonna be a highly trained athlete. That's okay. You don't have to be.

SPEAKER_00 22:30

Great points, John. And really, this is you might, from a public health perspective, this is really, this would be um uh just the best benchmark for anyone who is sedentary to be moving toward. And uh, as we know, that's doable for the overwhelming majority of people who find themselves just sort of locked into these sedentary lifestyles. This was something that um I just wanted to share briefly uh that looks at this cardioly, uh, which doesn't get a lot of attention in in clinical medicine. Uh but these these phospholipids uh in the inner mitochondrial membrane really are kind of the scaffolding for the the this is you know the electron transport chain. And uh the more active we become, the the more uh efficient our turnover and stabilization of cardiolipin is, we produce more energy. And as we age, um uh, and particularly in sedentary states, the whole point of this of this research paper, we have a drop-off in cardiolipin, which which they measured will show that. Uh, and you see dramatic drops in energy, bioenergetics, energy production, and that can manifest in many ways from fatigue, diminished activity tolerance, uh, poor cardiopulmonary health and conditioning. Uh, it can manifest as pain, uh, you know, musculoskeletal pain. And and so um, this is such a uh a great uh uh distinction uh and and something that they looked at.

Cardiolipin: The Mitochondrial “Motor Oil”

SPEAKER_01 24:18

Yeah, and in both the the quantity of cardiolipin in the in between these two groups, both the quantity and the quality of the cardiolipin was very very different between the sedentary and the moderately active. The sedentary had less cardiolipin, you know, which is to your point, that contributes to the leakiness of the the leakiness of the mitochondria, right? And I you know, I one of the best analogies I've I've heard of for cardiolipin, because I it can be a like you know, I think for some of our listeners, this might be like a somewhat of an abstract term. You know, what what is this molecule in our mitochondria? Well, the I I've always heard that like if you think about the mitochondria like an engine, right? Well, you want to have that's an engine that burn, can burn really hot, the mitochondria. It's producing, you know, all of the energy for our body for the most part. You're gonna get a little bit from glycolysis, and we can talk about that in a minute why you don't want to be dependent on that. But you need to have some type of cooling agent that's gonna keep everything under control in those engines and not let them get old let them overheat and become leaky. And so you want to have really like high viscosity, high quality motor oil in those. And that's kind of what cardiolipin is, right? And there's different versions of it. There's a really cheap, really cheap kind of low viscosity. It's not gonna hold up under high temperatures, and that's the cardiolipin that starts to appear when people are sedentary, uh, when they're producing more of the fat in their body as opposed to acquiring healthier, healthier sources of dietary fat. And so you end up with more like palmitic acid in that cardiolipin as opposed to the fats that would come from your diet, um, and just less cardiolipin overall. And again, I just I think it's so remarkable to see these pathological changes in what you and I always talk about as the, you know, if we had to bring it down to what's the most fundamental unit of a person's metabolism that determines whether they're healthy or unhealthy, it's the mitochondria, right? If your mitochondria are leaky, if they're not quick to be turned on, meaning you don't burn fat at any given intensity, you tend to be reliant on carbohydrate metabolism, you don't have that metabolic flexibility, you know, everything goes down the wrong road. And to see that these mitochondria had lower levels of cardiolipin in the sedentary population, and then to look at the molecules of cardiolipin under that electron microscope and see that there's less turnover, there's less of the, you know, the the one that's based more on linoleic acid, and there's one that's you know, the the sedentary folks had had cardiolipin molecules that were more based on the palmitic acid that their bodies were producing because their insulin levels were probably higher throughout throughout the day. You just everything comes together. It's um, you know, it's just like you know, that mitochondrial impact, so to speak, it's at the confluence of all these different inputs with sedentary, with a sedentary lifestyle, maybe being, you know, from what this paper would suggest, the biggest driving factor for that pathology. So yeah, I think cardiolipin is unbelievable. You shared some stuff with me earlier about autoimmune disorders and you know what kind of has brought cardiolipin to the forefront of research, but I I feel like it's it's gonna be the way of the future because of so much appreciation for mitochondria in cancer and heart disease and every aspect of chronic disease. We keep coming back to mitochondrial health.

SPEAKER_00 27:46

Absolutely. There's no escaping it. Uh and we often talk about this concept of the oil change, Sean. I love that, I love that analogy. Uh, and uh when when it it's most people think about fat that they eat um ending up being fat in their blood, ending up being fat in their arteries, uh, when in fact, you know, most of the fat in our body is in our cell membranes. Uh, certainly the brain uh has a very disproportionate amount of fat. And uh when you are able to, it sort of brings us back to this new and improved food pyramid, when you start looking at whole healthy fat sources, many of which will be saturated, uh, and the extent to which they're gonna be more resistant to oxidative stress, uh, you you're gonna improve the the health, the the uh resilience uh function of all of your cell membranes, and and the inner membrane of the mitochondria is a pretty special place. Uh it's you know, it's got two membranes, right? Uh and um it it the the by every time I look at mitochondrial function, John, I I'm brought to my knees with reverence for just how remarkable that biology is. And uh you know, this this uh quantum level uh tunneling of electrons and and production of energy. It it's just such a refined um uh musical. Yeah, it really is pretty impressive. I I love the the the the race car uh analogy. The uh uh just to um wind down here on uh a few more of the findings, these were uh some of the measures that we we've talked about already, John. You you touched on uh you know, they they measured, got these folks on a metabolic testing, measuring their oxygen consumption and their uh carbon dioxide production, looking uh in the muscle uh and and body wide, how how they were burning fat and carbohydrate. We we talk a lot about metabolic flexibility, the ability of mitochondria to switch uh quickly from a carbohydrate-based to a fat-based fuel source, and um uh uh how this importance of lactate being able to clear lactate that is produced from glycolytic uh level activity. And and so they you know they measured all of these things.

Glycolysis, Lactate, And Energy Bottlenecks

SPEAKER_01 30:44

And uh it's a bit of a And I just want to make sure, Mark, I don't confuse our listeners. I that you know, again, the the two groups had the same levels of this lactic acid, lactate dehydrogenase. So in theory, in theory, if that's all you knew about these two groups, you would say, okay, they're both equally equipped to clear lactic acid from their blood. But obviously the researchers found that was not the case. And that is because of one group, the sedentary group, was producing lactic acid at three to fourfold compared to the active group. So they're producing so much more because they're not using their mitochondria as much as they are glycolysis. So again, for our listeners' sake, I just want to make sure I I don't uh you know lead to any confusion here when I said that. It's if if you're using glycolysis, if you're using glycolysis as the predominant source of energy for the body, it produces massive amounts of lactic acid because it's a dead end street. And some of that pyruvate that gets generated goes back to lactic acid. It's a it's a multi, it's a bi-directional pathway. So you know, your body's gonna take pyruvate that's accumulating, that's not being run through the Krebs cycle or that's not being processed for energy in the mitochondria, and it's gonna it's gonna convert that back to lactic acid. So the lactic acid pool in the body, it grows quickly, even at moderate intensity exercise when you're when your mitochondria aren't being used. And I think that's really the you know, the take-home here from the differences in these blood lactate levels is that the sedentary group just weren't converting any of that pyruvate or any of that, you know, it was a dead end street with their glycolysis. They're producing a small amount of energy by burning sugar outside of the mitochondria compared to the active group that was readily burning much more of that through their mitochondria, as well as burning much more fat at any given intensity. So, again, the lactic acid is huge. It's a it's a fundamental part of this discussion. I just want to make sure our listeners understand that it's not because one group had an increased ability to clear it with a particular enzyme, it's about the massive difference in how much lactic acid was being produced, you know, by the sedentary group compared to the active group. So just thanks. I just want to make sure I didn't create confusion.

SPEAKER_00 33:16

Perfect summary of this graphic and um really feeds in nicely to the high-level findings uh that certainly uh compared to those who were sedentary, um uh those those who are more active, sedentary folks had much less mitochondrial respiration uh as evidenced by these higher lactates, not getting into the Krebs cycle and producing uh greater amounts of energy, uh, this pyruvate oxidation, again, coming back to your point, John, uh, about um the this sort of cycling uh because you you just cannot uh engage more effective um um uh respiration, mitochondrial respiration. They don't burn fat as as as well, and and we know that uh when you measure beta oxidation of free fatty acids, sedentary people just aren't able to do that. Um lactate clearance goes down, you see more reactive oxygen species.

SPEAKER_01 34:26

Um then it starts to snowball, right, Mark? Because you've got less cardiolipin. You've got cardiolipin that's made out of the wrong fatty acids, so to speak. You've got the low viscosity oil, going back to that analogy. So the mitochondria between the higher levels of reactive oxygen species being generated, poor quality cardiolipin, less of it, the mitochondria, it gets worse, right? And you end up with that mitochondrial myopathy that you might not, you know, you might not have an extreme case of it where it gets diagnosed, but nevertheless, it's it's it's a pathology of the mitochondria and it's affecting someone's health.

SPEAKER_00 35:02

And when you look at the the uh sort of the phenotype, right, right, individuals uh with this um uh uh level of metabolic or mitochondrial disruption uh consuming often abundant calories, because their energy production is down, they're going to be more hungry. And uh, you know, we know that'll affect their leptin uh sensitivity. Uh they'll tend to eat more. Uh it it's it's an inability to produce energy even though you're consuming more quote unquote food.

SPEAKER_01 35:40

Well said.

unknown 35:41

Right.

SPEAKER_01 35:41

Very well said.

Metabolic Flexibility And Fat Oxidation

SPEAKER_00 35:42

So um, you know, the big picture is one where you're hungry all the time, you're tired all the time, uh, you know, your brain isn't isn't locked in, and and this becomes a way of life for so many that that the assumption is that you know this is who I am, and I'm kind of stuck here, and uh and and just not a very good quality of life. And this, I think, is the last slide, John, with respect to uh uh showing that in mitochondrial respiration, we we you know you've talked a lot here about glycolysis and this lactate uh pathway, which is so inefficient, yet where the the um metabolic driver is in people who are sedentary. Uh and when you measure uh the the Krebs cycle oxidative metabolism uh with all of these byproducts, not surprisingly, uh from what we've been sharing here, uh those who are active will tend to have higher levels of these Krebs cycle metabolites because they're getting more fuel into the inner mitochondrial membrane, burning it more effectively compared to those who are sedentary who will tend to produce less of those metabolic uh intermediaries. So these are, I think, all ways of uh demonstrating just an uh inability to cycle appropriately. And so you know, these were just the conclusions of the study. Secondary individuals had significant decreases in mitochondrial respiration, um, as well as you know, their ability to produce energy during resting conditions uh compared to those who were moderately active. Uh, you know, they um they had similar uh glucose function here, but um they uh you know sedentary individuals just cannot um uh leverage uh glucose getting into their mitochondria. It'll tend to get shunted into that anaerobic glycolytic pathway. Uh we know that burning fat is a real problem when carbohydrate uh is your predominant fuel source, and again, your ability to clear lactate uh is is impaired. And so these are uh signatures of decreased mitochondrial function bioenergetics that uh in otherwise healthy people with no other markers of disease uh should give us some pause with respect to uh you know how how we diagnose and uh uh and the importance, of course, of activity as really the holy grail of metabolic health.

SPEAKER_01 38:48

Yeah, I mean I think it it uh should provide, it certainly did myself, um, just a new way of looking at movement and it being something that contributes to the strength of your body uh in a different way, right? Something that's gonna change the the architecture of your most basic cellular component in asking your body to handle or to metabolize more fat and in a in a safer way, that's what you're doing with your mitochondria. You're you're you're really trying to create a much a much uh more structurally uh integral you know form of of energy production that you would be otherwise. And so I just think it's a it's a real profound study, and I yeah, it's awesome. I really appreciate the you know your conversation with us this morning, buddy.

SPEAKER_00 39:45

Yeah, yeah, me as well, John. And it and it and it mechanistically it it provides a window into why it is that someone who has yet to be diagnosed with pre diabetes uh uh or someone who Has been diagnosed with pre-diabetes can reverse that uh by incorporating more activity into a healthy lifestyle. I mean, this it works profoundly well. Uh, and this is just more mechanistic evidence that at every stage of the life continuum, uh we we need to remember where we've come from and and how we are designed to function in relationship to the environments that we're in. So uh comes back to sort of the same blocking and tackling. Uh and and it and it also helps, I think, to motivate uh the this perception that that uh not having uh uh uh an asterisk next to your blood work does not necessarily mean you're exactly where you want to be. So uh those are good uh points of of emphasis.

SPEAKER_01 40:58

Absolutely.

SPEAKER_00 41:00

John, pleasure as always to connect. Uh in in the near future, we've talked about um looking at this importance of uh acid loading in our in our diets and our ability to manage those acid loads and why that's important in terms of disease risk, disease management, quality of life, et cetera. And so uh it'll be fun to have that discussion, John.

SPEAKER_01 41:24

Yeah, that'll be great. I look forward to it.

SPEAKER_00 41:27

Uh for listeners, uh all of this will be on our website, thehealthededgepodcast.com, or on all the other sort of podcast media outlets. We greatly appreciate your your tuning in. And if this is information of value, please share with those you love. And don't forget to love yourself. And uh, John and I will see you very soon.

SPEAKER_01 41:50

See you later, Mark. Love you, brother.

SPEAKER_00 41:53

Love you too, John.