Jay Feldman 0:12
Welcome to Episode 58 of the energy balance podcast, where we teach you how to live without constant hunger and cravings, fatigue, brain fog, poor sleep and other low energy symptoms by maximizing your cellular energy. I'm Jay Feldman. I'm a health coach and independent health researcher, and joining me again today is my good friend Mike Fave. Mike and I have been studying health and nutrition together for a long time now, and Mike also draws on his experiences from working within the healthcare industry. Today's episode is part three of our series discussing tissue oxygenation, cellular swelling, pH balance and other related topics. In part one and two of the series, we discuss carbon dioxide, lactate, glycolysis and pH balance and the effects of all those factors on our metabolism. So I'd highly recommend checking those out if you haven't already, because that information is going to be particularly pertinent for today's episode, where we'll be discussing altitude, panic attacks, swelling, heart failure and other related health states that are specifically related to these components that we've talked about in these last couple of episodes, and this series has been a little bit heavy on the physiology. And so if that is not your cup of tea, then I'd highly recommend going back and listening through episodes one through seven of the podcast where we took some time to build a foundation as far as the bioenergetic view of health is concerned. And in today's episode, specifically, we'll be discussing how insulin resistance and diabetes are symptoms of excess glycolysis and lactate production and how Metformin makes these conditions worse. We'll also be discussing how excess lactate production and a lack of CO two causes altitude sickness and anxiety and panic attacks. We'll be discussing the benefits of altitude and the surprising parallel effects of stormy weather. We'll be talking about the problem with 100% oxygen ventilation and critical illnesses like covid 19 as well as sepsis. And we'll be talking about how glycolytic metabolism and the swelling that results contributes to high blood pressure and heart failure. To check out the show notes for today's episode, you can head over to Jay Feldman wellness.com/podcast where I'll link to the studies and articles and anything else that we discussed throughout today's episode. And if you are struggling with any low energy symptoms, whether that is symptoms related to the topics we've been discussing today, like high blood pressure or edema or swelling or panic attacks or anxiety or insulin resistance or diabetes, or if you're dealing with any other low energy symptoms, like chronic cravings and hunger, low energy or fatigue, chronic pain, trouble sleeping or insomnia, weight gain, digestive symptoms like bloating or gut inflammation or any hormonal imbalances or any other low energy symptoms or chronic health conditions. Then head over to Jay Feldman wellness.com/energy, where you can sign up for a free energy balance mini course, where I'll walk you through the main things that you can do, from a diet and lifestyle perspective, to maximize your cellular energy, and also explain why this is the key to resolving these symptoms and conditions. So to sign up for that free energy balance mini course, head over to Jay Feldman wellness.com/energy, and with that, let's get started. All right. So part of the reason why I think it's so valuable to dig into some of these real world applications and to apply a lot of information we talked about is because some of it does end up being a little counterintuitive, where, in general, when we're seeing a lack of oxygenation, the assumption is that you just want more oxygen, and as we've talked about, carbon dioxide is really the main determinant of how oxygenated we are in many ways. And so it's, it's worth exploring how this applies to these different scenarios. And obviously it applies to various symptoms that people experience in various conditions. You know, I've alluded to altitude sickness and hyperventilation in terms of like panic disorder and panic attacks. So that stuff is, is worth talking about, for sure, although it is maybe not the most common situation, but something that occurs, you know, that's that's a lot more relevant to today and now is the whole situation regarding acute respiratory distress syndrome from respiratory illnesses like covid and how these like this directly applies to the whole idea of how ventilation occurs and the potential effects of ventilation and what can be done instead, which is obviously worth digging into. And then also, this is a like these, the set of kind of symptoms and experiences regarding lactate and carbon dioxide and swelling. Also. To affect like heart health a lot, and dysregulation of these systems is seen in heart failure and heart disease and high blood pressure and then various other situations of edema. And that's a pretty common symptom that I'll see, as well as especially in people who are relatively hypothyroid, a lot of swelling and edema in different capacities. And then there are some more, again, kind of a little more on the obscure side, like other conditions that involve a lot of these same processes, like glaucoma and epilepsy, which can involve swelling and like energy disruption in the brain or in the eyes. And yeah, it's a pretty universal process that really applies to a ton of different scenarios. So that's why I think it's worth digging into. Did you have anything to add before we jump in?

Mike 5:46
I mean, I just want to point out that under and this is something that I think Pete really gets well, or does really well with his whole hypothesis and everything, is that almost every single disorder, almost every single disease comes down to the energetic level, and so it affects all these principles. It affects what's happening at the cell. It comes down to the mitochondria in the cell and energy production and energy regulation, and then the structuring of water. So these processes, the reason they're so broadly applicable across multiple diseases is because they're all everything comes down to that key component. So if you want to, instead of, like, having 100,000 different disease categories with the set of symptoms, and then this is the disease with those symptoms, and then here's the specific reductionistic pathway, if you understand things from the context of everything is happening at the cellular level. In regards to metabolism, it gets while knowing the symptoms and the disease process and whatever, it gets rid of all the minutia BS to essentially sell drugs. And it's like, okay, so what do we have to do? We have to fix what's going on on the cellular level, energetically. And then it's like, how do we address all of those things? And it, it, it that really changes the game overall. It changes the entire model. It changes the entire treatment process for people, and it changes the it. It goes to root causes, and it goes to solving problems, instead of just managing or just manipulating one pathway, which I mean, clearly based on the current successes of modern medicine, despite what I don't know, whatever the most futuristic articles want to talk about, all the advances that we've made, like, despite all that stuff, like, we're kind of not doing so well In regards to chronic disease. So, yeah, I think it's just really important to to understand that all everything, all these processes, come down to this level that we're talking about, and that's why we're going over it, because it's fundamental.

Jay Feldman 7:52
Yeah, absolutely, yeah. The Energy failure is the deep root cause of, really, all these things, everything from cancer to Alzheimer's to autoimmune issues. And we've talked about, and we haven't talked about cancer and Alzheimer's specifically, we've talked about autoimmune issues. We did a whole series on that. But yeah, and the swelling component and tissue oxygenation in specific are seen or, like, kind of highlighted a little bit more in some of in some of these situations that we'll discuss. But yeah, it's, it's on some level happening in every condition. And the energy phase, energy failure is definitely happening in all those issues. So, yeah, extremely fundamental. And yeah. So with that in mind, I know we were talking about, just like in these last couple episodes, we've been contrasting the efficient glucose metabolism, the complete glucose oxidation, with the inefficient glucose metabolism and and the kind of forced glycolysis, basically because, for whatever reason, those pieces of respiration, of mitochondrial respiration, are blocked further further down the line. And I don't think we directly talked about the fact that this is basically the direct exhibition, like the direct, yeah, I mean the direct picture of what's going on in insulin resistance. It's like, kind of synonymous with insulin resistance, basically. So I just wanted to touch on that, just because, and again, I'll link to previous point, like previous episodes where we've talked about this, and articles discussing this, where the general idea with insulin resistance is that, for whatever reason, the cells stop being able to respond effectively to insulin, like they they have become resistant to insulins effects, and they don't respond to it anymore. And and the conventional and even alternative ideas here are basically that too much insulin causes the cells to just tired of responding to it. Yeah, they just kind of yeah, get, get kind of burnt out over time and stop. You know, they can't respond anymore. And it's like they only have a certain amount of times they can respond properly, properly to insulin. You know, just like that same wear and tear machine idea that you know, if our bodies keep running through the same systems, eventually they're going to burn out, which we've talked about that too, and why that's not the case. And I'll link to some episodes talking about that too, but, but in reality, what's happening insulin resistance is. That instead of being to being able to completely oxidize glucose, there are problems farther down that line, whether that's in the electron transport chain or the Krebs cycle. Generally, it starts the electron transport chain, and that causes, you know, it forces the cell to be running through glycolysis, and it also slows down the use of glucose. The the cell has to start to switch to oxidizing fat instead, and that causes a buildup of glucose in the cell because it's not using that glucose well. And so as that glucose builds up in the cell, there's much less room to bring more glucose in. So when insulin is trying to help allow the glucose into the cell, there's not as much room for it. And so the cell becomes, quote, unquote, insulin resistant. It really just kind of becomes glucose resistant. Becomes glucose resistant.

Mike 10:47
That's what you want in that situation. Because if you force more glucose in the cell, you either damage or you kill the cell. So, like, it's, it's a it's, it's a break on purpose. It's, so it's, it's an adaptive response to pathological situation. And it's, yeah, it's something that the cell. So the question is, is, then, why is that happening? And that's, that's essentially what, what factors causing that? Is it endotoxin? Is it nutrient deficiencies? Is it not having enough NAD plus available to function as an electron carrier? Like, what is, what exactly is going on there, and it's essentially fixing that. The thing is, you don't have to be so you don't have to get super nitty gritty in detail and go analyze your mitochondria. You sort of just have to, like, the general strategies to fix that is basically addressing lifestyle and dietary changes. That's what's beautiful about it, right? You if you have, like, this general underlying cause, you can sort of shotgun approach it and change lifestyle and dietary factors to fix the underlying cause. That's like making sure you're getting all the nutrition that you need. There's more nuance that comes into it, but that's always the foundation.

Jay Feldman 11:55
Yeah, yeah, absolutely, doing the things decreased stress hormones, which is all of those things, not just avoiding stress in your life, but if you're not eating carbohydrates consistently, that's going to cause an increase in stress hormones to maintain blood sugar and things like that. But yeah, yeah. And then, and then, just real quickly, to add on with the insulin resistance situation is Metformin also directly falls into this category, where, instead of fixing the problem, what it does is it actually further blocks the ability for complete glucose oxidation and the function of your electron transport chains, where you're almost even inhibiting fat oxidation too. And because of that, the cell is left with really only one way to produce energy, and that's glycolysis. And we talked about how inefficient that is, and how little ATP you're getting, and how much of a burden it puts on the liver. And metformin basically forces that to happen in really high amounts, and it causes you to get rid of all the glucose, because it's all running through glycolysis, and so you see drops in blood sugar. But it's not because you're using the glucose better. Instead, it's driving that stress even further and causing all of the negative effects of the lactate and causing all these and it does actually cause lactic acidosis. There's a strong association there. So it causes all these problems that we've that we've talked about, and so that's really the main way that it's lowering blood sugar. We've also talked about how it has some antimicrobial effects too, that aren't really talked about, and that could intestine, yeah, yeah. And so that could account for some of its benefits too. But for the most part, it's, it's really not working through a mechanism that we would benefit from.

Mike 13:22
Yeah, it's just insane that that it's, like, considered such a great drug, or that it extends lifespan, like and you you have an article about this, essentially where, like, it induces hormesis in what was it C elegans or yeast, and it does this by essentially forcing them into torpor because they're which is hibernation, because their metabolism isn't functioning well. And so it's it's actually a kind of, it can be kind of a dangerous drug in certain populations if you can't get rid of the lactate, because not only are you forcing the cells to go through glycolysis and produce lactate, you're also shutting down the liver's ability to turn that lactate back in the glucose to the Corey cycle, and so while so yes, this is going to lower your blood sugar, for sure, because you're going to be disposing of your you're going to be wasting the sugar that you're producing at the cellular level by pushing it through glycolysis and producing lactate and a minuscule amount of ATP compared to what you would be doing if you were doing cell respiration, and then you're gonna, when it goes back to the liver, it's not going to be converted, and to the same extent, to glucose. So yeah, your hemoglobin, a 1c is going to go down. Your blood sugar is going to go down. But this is the problem, like with with the with using these markers, they don't tell you exactly what's going on. They're proxy markers. It's like looking at TSH for thyroid. It's a proxy marker. It gives you, in a little insight into the situation, but it doesn't actually tell you what's going on with the whole system. And that's when you start to think, oh, only using t4 is a good idea, or only using Metformin to control blood sugar, or using Metformin to control blood sugar is a good idea. Yeah, and this is what happens when you don't have that foundational context. When you start looking at something like energy metabolism of the cell as the foundational context, if you don't have that, then you can think, oh, Metformin is a great idea. It lowers blood sugar. And C elegans, it, you know, they extends their lifespan. And it's like when you don't understand energy metabolism, or you don't have the context under energy metabolism, and then you don't get the nuances behind some of those things, then you you can make like those are serious errors, like you don't recognize that it's putting the body essentially into hibernation and is making the metabolic issue worse. So on paper, yeah, it can look better, but in reality, it's not better. And I just want to point out that Metformin directly shuts down the electron transport chain. Forget which complex these are complex one or two. I think I think it's one, yeah, yeah. It directly shuts it down, which is not what you want to do. You don't want to turn off the electron transport chain. That's literally completely deranging cell respiration if you're turning off one of the complexes So and then, you know, from there, then you go in, and this is where we get into the hormesis stuff, where it's like, since you've turned off proper energy metabolism, you have to rely on all these backup pathways and though. And then it's like, oh, the backup pathways are good. It's like, they're good if your energy metabolism isn't working. But that shouldn't be option number one. Option number one should be fixed energy metabolism. Option number that shouldn't like that should be the option in general, like the backup pathway comes into place, essentially as an adaptive process to protect the cell.

Jay Feldman 16:35
Yeah, yeah, they're better than dying, which is the alternative, but yeah, it's not a state you want to be entering to be encouraging. And what you were saying earlier, as far as people, you know, the life lifespan extension is, I mean, just to make this clear, people use Metformin when they don't have diabetes because of these supposed life span extension effects, like people who are trying to biohack. And, yeah, it's, I would say, definitely not a good idea.

Mike 17:02
Yeah. And the biohacking is essentially just, like, at least the way I see a decent amount of it. There's definitely some benefits with that, but it's like, it's the same thing as modern medicine. It's like, oh, we're gonna find out these pathways, and we're gonna take this obscure compound to alter this pathway. And it's literally what it sounds like biohacking, but it's like, when you have that reductionism without a big picture context, like you can reductionism is helpful in certain circumstances, like if you're going to understand the Corey cycle, you want to understand the steps. If you're going to go through cell metabolism or cell respiration, you want to know the steps. But you need to understand that in a larger picture. And you need to be able to integrate, instead of just Oh, amp kinase over here, and the sirtuin pathway over here. And, like, we're gonna hit all these other all these random pathways, right? Like, there's instead of, like, looking at everything is one large, holistic picture, and that that that seriously changes just that small shift changes it dramatically. So it's not that those things aren't helpful there. It needs to be put in context. And so that's why, like, while we may be going a little bit through the weeds, for some people here, in regards to like, CO two, and the bore effect and the Haldane effect and energy metabolism and like, its applications in real life, this is part of that, that big picture. We're trying to piece together the picture so and we're trying to, at our best, to make it digestible, you know, so that you understand essentially what's going on. And you can unders, like you could read Pete's articles and see the context or the topics that he's talking about, or you can read some of the research and understand the big picture, because once you get the ideas in your head and you get the definitions down, or the lingo that the researchers and everybody likes to use, then it makes it like when you have a concept of that, and it's easier to start putting things together. So we're trying to basically make it more digestible. We're trying to to, I guess, simplify it a little bit, because sometimes it can seem like a like a beast, like, I know there's times, like when I first looked at cell respiration when I was in high school, and I was just like, who needs to who? Who wants to know all this? Right? Like, who cares? I remember in high school thinking that, and then now I'm just like, Wow, it's so it's so amazing, so, and that's just the difference in understanding it.

Jay Feldman 19:15
Yeah, yeah, trying to create those shortcuts for people that would have been helpful for us to have, for sure, yeah, I wish, right, yeah. And like you talked about going through the weeds, like, it's things that we had to kind of do, like weed out and and put together, piece together, so that it was, you know, try to put it in this more clear and semi concise way.

Mike 19:35
Yeah. I mean, when you get the textbook, right, it's when you get the textbook, they don't provide any context for cell respiration, like, it's just, like, the chapter cell respiration, it's just like, oh, this how the cell makes energy. But there's, like, no larger idea around that. So when you're learning that, you're just like, Okay, this is how the cell makes energy. Like, what does that have to do with me if there's no if there's no applicable element to it? It's just like, Okay, this is, you know?

Jay Feldman 20:03
Yeah, the grass is green. Everybody learned at some point that the mitochondria is the engine of the cell, yeah.

Mike 20:09
But there's no context behind it, yeah. So we're trying to bring that, we're trying to bring that to the forefront, I guess, and in a digestible way, because there's been other people who've been doing it, like, like, I mentioned him a name drop him a lot, but very Pete, like, he's and that's that was, I guess, a part of our inspiration, that like, provided the context for us. But he's been doing that for decades. It's just he's just on another level sometimes. So we're, we're not trying to simplify his work. That's not the point. We're just trying to, like, make the concepts more applicable, so that if you were interested in his work, or just energy metabolism in general, or whatever disease process you have going on, or whatever issue you have going on, if you can understand the concept, then you can, and you can, and you know how to apply it, then you can make those differences for yourself. So just want to bring why we're doing what we're we're talking about this in case, you know, in case somebody's like, what are these guys talking about with CO two and boar effect? Like, who's boar?

Jay Feldman 20:13
Yeah. And with that in mind, let's talk about respiratory alkalosis, right?

Mike 21:19
Yeah. All right. Let's go.

Jay Feldman 21:23
So anyway, yeah, so that does bring us to one of these next situations that we see these things play out and so and that we'll start with the altitude situation, and specifically altitude sickness. And it does cause the situation that's called respiratory alkalosis. And we'll talk about basically what that is, where, when. So, just for context, when, like, altitude sickness is when somebody goes up to high altitude and they get legitimately sick for, you know, can be for a week or two weeks or even longer. And some people who are really struggling, like they just can't stay at altitude. They have to move. You know, some are lower altitude, and they get, like, flu symptoms and feel very weak and fatigued. And the physiology of it is actually really elucidating, and has, you know, has at least in part, led to, like, cleared up some of what we've talked about in the past, in the past two episodes. So in general, when somebody is in the state, they're well. So the other thing to mention is that when you're at high altitude, there's a lower partial pressure of oxygen in the air. Basically, the air is thinner. You know?

Mike 22:28
There's less oxygen, there's less percentage of oxygen in the air.

Jay Feldman 22:33
Yep. And so every time you're breathing in there's, there's less, less oxygen in that, in that inhalation. And so ideally that shouldn't be such an issue. And we'll talk about that like we've kind of talked about all these regulatory issues. But in somebody who is already semi hypometabolic and already struggling with some of these issues, maybe they're already having a tendency to produce some extra lactate and not enough CO two, and they're not offloading oxygen as well, then this puts them into a pretty deep stress state, because they're already having trouble getting oxygen from the air because the lack of CO two and the excess lactate, and then there's even less oxygen available in the air. So if before, let's say there was, I mean, obviously it's not, there's only, like, 20% oxygen in there. So I guess we'll use that. Let's say there's 20% oxygen there, and they're only able to pull out 80% for every breath. Well, now there's 10% oxygen in there, and so they're only able to pull out 80% and that's way, way less, yeah. So what that causes is, is an extreme lack of oxygen being taken up. And we talked a little bit about ventilator ventilatory drive before and last episode talking about how generally, CO two is the thing that determines how fast we breathe, but if we're very low on oxygen, that will also make us breathe faster. It's one of those Emergency.

Mike 23:54
Regulatory systems, yeah, yeah, responses.

Jay Feldman 23:58
And so this is called hypoxic ventilatory drive, and so when there is this lack of oxygen that's being taken up, then that'll increase ventilation the but there's a problem, yeah, that actually doesn't work the way that you'd want it to. Because what happens is, when you're breathing quickly and you're not taking up the oxygen very well. You don't really end up taking up all that much more oxygen, but you do end up breathing off even more CO two, and so that makes it even harder to take up more oxygen. And then there's some other factors that we talked about, as far as CO two goes, where it helps to increase vasodilation, which helps with blood flow, and it also helps the cells take up oxygen. So those things get decreased as well, because you're blowing off all this CO two and the cells then can't get any oxygen, and the blood is low in oxygen, and you end up with this kind of excessive hypoxia, and you end up with a lot of lactate production. So So you actually see lactic acidosis, or just excessive lactate in this situation, in in altitude sickness. And. And it leads to, then a lack of blood flow because of the lack of CO two and so you end up with actually decreased blood flow to the brain, which is, you know, another kind of important quality or characteristic that they see when this happens. And you also end up with swelling. You end up with edema, especially in the lungs, and then also in the brain too. And these are relatively dangerous things. And obviously, when you have this excess lactate production, you're also in basically a systemic inflammatory state and this and so that's why people have this altitude sickness. So it's this kind of vicious cycle that that continues on in this way, all due to basically a further decreasing of CO two and then this excess excess lactate. Do you want to add anything in?

Mike 25:44
Yeah, I just want to, I want to put it into context, uh, for people, because it's like, so there's, there's two things going on. First of all, when you talk about, like, okay, at, at a sea level, where most people are generally at, or somewhere close to that, not at, like, what, 10,000 feet, whatever it is, 5000 8000 feet, however high they are, for altitude, whatever the range is to reach a certain altitude, oxygen percentage is what is 21% so there's, there's 21 liters, and every 100 liters of room air. So it doesn't, you were just giving the example, bringing it down from 20 to 10, just to make it easy. Yeah, just, just so, because that doesn't, I don't think it necessarily goes that low, but.

Jay Feldman 26:25
Yeah, I don't think so either. I'm not sure what, how low it goes, Yeah, I

Mike 26:28
don't know the specifics either. So that was just an example. But even if you're breathing, if you're if you're breathing in more oxygen by taking more breaths, if you unload your CO two and taking more breaths, like you're breathing off all your CO two, even if you had enough oxygen, you would still have a problem. And this goes, this goes back to the bore effect, or the bore and Haldane effects, where, essentially, at the cell, you want the cell to be produced. You want a high concentration of CO two. You want the cell to be producing a high concentration of CO two, because that high concentration of CO two and the low pH, the acidic environment that is created by the high concentration of CO two causes hemoglobin to unload oxygen. So if you're breathing off all of your and hemoglobin is in your red blood cells, right? So your red blood cells unload oxygen in that environment. But you're if you're breathing off all of your CO two, if you're breathing all of it out, then you start to deplete that environment of the CO two, and then you start to get a more alkaline environment with less CO two. And then the hemoglobin, even if it's carrying oxygen, is unable to deliver it to the cell. And that's, that's the kind of, the fundamental piece here with altitude sickness as well as maybe not get being able to get enough oxygen as well. So, so then the question is, well, if, and then, since we talked about CO two being a vasodilator, the question is, well, if CO two is a vasodilator and you're not, and so if you're not getting enough CO two, then how do you get swelling in the brain, right? Like, if there's not as much circulation in the brain, why is it swelling? And basically what happens is, any time that you have an energetic failure, which you would have, in this circumstance, not a complete failure, but to some extent, a failure, because you don't have enough oxygen, and oxygen is the final electron acceptor in the electron transport chain for cell respiration. If so, basically, without this oxygen, you you can't produce energy effectively. Then what happens is, is that water and the protein shape and structure starts to starts to be able to not maintain itself. It starts to loosen up. Essentially, it starts to break, break down. And then all the minerals like potassium and magnesium, which are intracellular, start to be released from the protein and move out. And then the cells structured water. Can't exclude sodium and chloride, so the sodium starts and starts to move into the cell. And where salt goes, where sodium goes, water tends to go. So then the cells start to swell. So that swelling is, it's, it's, and the swelling in most of these other conditions is, it's not necessarily because of poor circulation. I mean, it is poor circulation in the sense that the the vasculature isn't vasodilating enough in that area be via CO two because it's not being produced. But the major issue with the swelling, and the major problem with the swelling is is, or the cause of it is that energy metabolism isn't running effectively, so the water can't be structured, and then certain ions can't be retained, like like potassium and magnesium and others, like sodium and chloride can't be excluded. So you start to get essentially like, I guess a good analogy for it is like, if the cell is is a bar, and the cell is making a lot of money in the bar, it only lets certain clientele in, right? And that clientele, if that clientele is, is inside the cell. If you know they got money, they can spend it at the bar. They don't ruin the bar, whatever. But when the but when this, when the bar starts to lose money, then anybody starts coming in, and then it gets crowded, and things get broken, and then there's a whole bunch of problems, right? So that's, I guess that's kind of the way you want to see, like the flow of energy, and then the ions and whatnot, potassium, magnesium versus sodium and calcium. So in that high altitude situation, until your body adapts to this, you essentially are like you're at even if you're breathing, if you're hyperventilating enough to get enough oxygen, you're still at a cellular oxygen debt. You're still at cellular hypoxia. And that's what's most important. It doesn't matter how much, how much oxygen's in your blood, per se, right? Once you have enough oxygen in your blood, once you meet that threshold, you're good. As far as your blood's concerned, the question is, how much oxygen is actually reaching the cell, and after you meet the threshold in the blood, that is the most important, the most important piece to focus on.

Jay Feldman 31:02
yeah. And then that's why we'll talk about the problems with ventilation when it's 100% oxygen, which happens in various illnesses, is that yeah, the blood ends up with oxygen, but that doesn't mean the cells do Yeah. And just to clarify also, you mentioned vasoconstriction not being the cause of the cause of the swelling, which is true, it just exaggerates the hypoxia, because you have less oxygen, oxygen delivery because there's less circulation. Obviously it's just one piece of that. But yeah, the other thing I wanted to clarify. So two things, one, I did look up the oxygen concentration at elevation, and so it does go down from 20 21% to about 15% at 8000 feet elevation. So that's a lot. It's over, not quite the 10% I used in my my example hypothetical, not unless you're way up there. I think above Kilimanjaro would still be, you'd still be a little bit over 10% but

Mike 31:58
not unless you're an astronaut.

Jay Feldman 32:03
Haha the other thing I wanted to say so I started off by saying that this is all leading to respiratory alkalosis. And I didn't explain that the respiratory, respiratory alkalosis is just a characterization of this state when you have a lack of CO two, where we talked about CO two being acidic, and so in this respiratory alkalosis state, you end up breathing out of, you know, a huge amount of CO two. You end up with low CO two. And that's why it's called respiratory alkalosis, and that's what's seen in altitude sickness. And then it's it's also seen in in panic attacks and hyperventilation, which we'll get to in one second. But in talking about altitude sickness, there's, you know, again, just a I was saying, like, when you think there's a lack of oxygenation. You just want to give anything to ventilate someone with oxygen, but adding carbon dioxide actually helps increase oxygenation. So here's a quote from a study that was looking at that where they added a certain amount of carbon dioxide to the air, and what they found was that a 3% that 3% carbon dioxide in ambient air resulted in a rise in oxygen saturation percentage of between 24% and 40% so 24 and 40% increase. And then it said there was a nine to 28% increase in carbon dioxide in arteries and a reduction of that respiratory alkalosis that's normally seen at high altitude, and they said that symptoms of acute mountain sickness were rapidly relieved. And then in three of the six subjects, cerebral blood flow increased by 17 to 39% so that oxygen delivery to the brain would have been considerably improved, and that was just from a very small amount of CO two added to the air. And obviously, if our cells are producing enough CO two, that would help a lot as well. And somebody who's susceptible to that situation, and that's also why, and we'll talk about a how we can increase CO two at the cell. And the other thing too is That's why a drug called acetyl ace, acetylzolamide is used in this situation, which decreases the breakdown of carbon dioxide, so it then increases, basically the carbon dioxide concentration, I shouldn't say, break down, just the conversion, and so it increases carbon dioxide levels, which also helps to relieve these symptoms. So, yeah.

Mike 34:12
Yeah. I mean, it's just essentially, what's going on is when they add the CO two to the air, and this is the air that a person's receiving, right? So if they put a nasal Canyon on, which is just like a little tube that goes in the nose, it they just added 3% CO two to whatever mixture they were giving them. And so just adding the CO two allowed their cells to oxygenate better and increase the perfusion of the brain. And it was by, not by a small amount, by cerebral blood flow, is between between 17 and 40% or 39% and 39% Yeah. And then the rise in and it's pa o2 which is arterial oxygen concentration, and basically the amount of oxygen that's that's dissolved. In the arterial blood, because that's really the main that's really the main blood that you want to you want to have higher oxygen concentration in, because that that blood is is basically carrying the oxygen to the cells, whereas your venous oxygen concentration is or your venous blood is carrying carbon dioxide away. So your venous ball will have higher CO two. Your pulmonary blood, or your arterial blood, will have higher o2 but it increased it it says in here between 24 and 40% which is not a small amount, especially if you're considering they just added 3% CO two.

Jay Feldman 35:37
Right.With the same amount of oxygen.

Mike 35:39
Yeah the same amount of oxygen, and this with acetylzolemide. This is doing the same thing, essentially just keeping CO two as CO two. And there's an enzyme in your body, I think it's carbonic anhydrase, that will convert CO two into bicarbonate and carbonic acid. And so you basically, you're inhibiting that enzyme. So the CO two remains as CO two, and then with that CO two remaining in that state, it allows the oxygen that's on your red blood cells to actually be unloaded to the cell. So it's the drug is enhancing that process, or adding some CO to the air that you're breathing will enhance that process. And this is this, and for everyone that, in case they got a little confused, mountain sickness. Here is the same thing as altitude sickness. It's the same it's just a different name for it.

Jay Feldman 36:27
Yeah and in a very parallel way, this is the exact same process that happens in panic attacks, when people tend to hyperventilate, and this is part of the reason also why bag breathing has been something that's always been talked about for using those acute scenarios, because bag breathing causes you to rebreathe the carbon dioxide because you're breathing off carbon dioxide, so the air that you breathe in has that same higher percentage of carbon dioxide, which helps, in the same way, to reduce the respiratory alkalosis and to increase oxygenation. So when you hyperventilate, you basically altitude sickness is just hyperventilation that occurs due to your body perceiving the lower oxygen availability, whereas in a panic attack, the hyperventilation is just brought down by excess stress. And there's a great quote from another study that was also talking about how patients who are prone to panic attacks tend to already they tend to respond to hyperventilation with a greater increase in lactate. And they say that this is probably because some panic disorder patients have a chronic, subtle respiratory alkalosis, and they acutely increase respiration when they're stressed. Therefore acute or chronic respiratory alkalosis may be one of the main, maybe one of the mechanisms for the exaggerated lactic acid production which is seen in this situation. So what they're saying is kind of the same thing as altitude sickness, where somebody who is already tending towards lactic acid production, already not producing enough CO two and is therefore very susceptible to stress, because they basically have a lack of energy, they're going to be more prone to hyperventilation, and then when they do hyperventilate, they're going to have much more trouble oxygenating, and that's going to cause the the whole panic attack response. So, yeah.

Mike 38:06
I want to, I just want to and to break that down a little bit with somebody who's predisposed to panic attacks. What the study is essentially saying is that they, or implying at least, is that they aren't oxidizing glucose fully through cell respiration to produce CO two. They're actually running more strongly on glycolysis, so they're not producing a lot of CO two. So essentially, anytime they get stressed out, or they have to increase their respiration, whatever little CO two they're they're producing, they're blowing it off. And then, essentially, their cell is at a debt for oxygen because they're not producing enough CO two, and they're they're not unloading that oxygen to the cell. And so they're already in the glycolytic state that they're already in. They're forcing it further. And so then they basically can get an increase in lactate, and it's basically pushing them further into the system. And their body, their body, is essentially panicking when it's going there, because the oxygen is they have like a cellular hypoxia, because the oxygen isn't reaching the cell because there's not enough CO two, and then they are in alkalosis because they don't have enough CO two. But they also have a high amount of lactate being produced because they don't have the oxygen being unloaded because they're not producing enough CO two. So it's like the whole situation is like a feed forward reaction in a negative direction. And so what it's essentially saying is this prone to panic attacks, is already a compromised metabolic state. And that's, I think that's important to talk about here, is like your ability to adapt to different situations and different stresses depending on your metabolic state. And this is a direct example of this, because essentially what it's saying is, if you get pushed into a little bit of stress and you have an increased energy requirement, which would and essentially anytime you have an increased breath rate or breathing rate, it's generally an increased energy requirement, or it's got to alter your acid base balance. But that's still coming down to the energy requirement. So. Essentially what's going on is you have an increased energy requirement, and you can't meet it. Your cells cannot energetically meet it. So the current pathway of of dysfunction that you're in gets exacerbated. And then your body, literally, your whole body, is in panic. Your whole body, your cells are like, it's kind of like OCEAN, Ocean. And that's essentially you're while you're saying that mentally, that's because your cells are saying that as well. So that's, like a real world applicable example of this Metabolic stuff. And like, in like, an everyday person's life, you know, not everybody's gonna go up to 8000 feet. You know, that's not the vast majority of people, but there are quite a few people who do get panic attacks, or who do get that anxiety, and then this is, this could be that underlying cause could be a metabolic issue,

Jay Feldman 40:48
Yeah. And part of the reason for explaining the the altitude sickness, I mean, when we're doing the progression of this podcast is kind of backwards, but that was something that makes it very like it helps to elucidate the mechanisms that are happening even at non altitude when somebody is not producing energy well, and what's going on with going on with the carbon dioxide. And so it's kind of like support for some of that earlier, those earlier ideas. But along with talking about altitude, there's also the benefits of adapting to altitude. And one of the things there's there's a few different things that happen when somebody adapts. But one of the interesting things that they talk about is what's called a lactate paradox, which is basically that for the same amount of work, of the same amount of I mean, work is just another way to say exercise or or activity or energy use. It's really there's a reduced production of lactate. And they talk about one of the, I mean, one of the mechanisms for this is because the body naturally tends toward retaining more carbon dioxide as an adaptation to help with oxygenation. Oxygenation, so you become even more effective at oxygenating your cells just because you have the increased carbon dioxide, and that's despite the reduced oxygen available in the environment. And so that's why it's called a paradox, because the assumption would be, oh, if there's less oxygen available, then you're going to be going towards anaerobic glycolysis even faster, because oxygen is supposed to be that limiting factor. But this is actually a bit of evidence that it's not really the limiting factor so much as the excessive demands. And when you're already used to retaining more carbon dioxide, you don't have to go to the lactic acid fermentation, or the production of lactic acid so quickly. So yeah, it's just, you know, kind of another side note, and part of where those benefits of altitude come from, and we'll talk about that a little bit more later on. But, and again, that's benefits, assuming that somebody has been able to adapt, not somebody who's in an altitude sickness state.

Mike 42:35
Yeah, if you go to 8000 feet and you're feeling like crap, I mean, there may be a point where you may get better, but it's also can be, like, a very serious issue. So just keep, we're not saying to go today 1000 feet and just, you know, rough it out.

Jay Feldman 42:53
Yeah, although, I mean, a lot of people do feel fine after a few days or a week or so. And yeah, just want to monitor it but...

Mike 42:59
You see to make sure that your body adapts to it.

Jay Feldman 43:02
Yeah, exactly. And interestingly, another situation where the same effect of altitude comes about is during like, stormy weather. So a lot of people feel inclined like they like when it's cloudy out and stormy out, and they just feel good in some way. And part of that could be because it has a similar effect to high altitude, where, generally it's like a low pressure system. So normally, when you see, like, if you watch the weather, I don't know if people still do that, like, show the different pressure systems that are moving around. And like, stormy weather tends to be like a low pressure and that's basically decreasing oxygen availability, more or less. And so it kind of has similar effects to mild altitude, and so in that same way, it can cause those same beneficial adaptations. And this was something that was actually brought to my attention by Marco, Marco Esposito, who's been in the repeat space. I don't know if he's still creating content, but anyway, just wanted to shout out to him.

Mike 43:56
Yeah, shout out to Marco. So then I guess the next piece that we could talk about here that is, like, pretty similar to altitude sickness in mechanism is high flow oxygen or mechanical ventilation in cases of ARDS or like, Basically extreme lung damage, or sepsis, or anything along those lines. And this is, this is very relevant, because this is some of the stuff that was going on and what they were talking about with covid. And there's actually some articles to talk about, like issues or I and a couple people like even Pete, I think, is theorized about the issues with basically getting high flow oxygen, or getting pure oxygen via mechanical ventilation to the lungs or like, directly into the system. And essentially, the problem with this is just like what we talked about with altitude sickness, that when you put in pure oxygen and you don't have CO two and you're already at. An energetic failure. So like, if you're need to go on a vent, or you need high flow oxygen because of covid or because of sepsis, or because you're an ARDS, or because of whatever the situation is, um, whether it's some type of cardiogenic shock, whatever it is, at that point you already are in, like, a systemic energetic issue, and that's why you're in the straights that you're in physically.

Jay Feldman 45:23
That's why there's a lack of oxygenation in the first place, which is why that would go towards requires the ventilation.

Mike 45:28
So you're already not doing it. You're not already not doing well. So you're already not producing enough CO two at the cellular level. You're you're like, you're beyond that point that you're producing adequate CO two and that. And then a lot of these states, they're characterized by high lactate levels. And that's the body those the cells are essentially in a state where it's like we can't produce energy, so with through cell respiration, so we have to glycolysis quick. Do glycolysis so they just all the or not all, but the majority of the cells start undergoing glycolysis, pushing out large amounts of lactate. And that's why this is a marker that a lot of er physicians or ICU physicians will look at in these states. But when you start running high flow oxygen into these situations, since you don't have a lot of CO two being produced at the cell, even though there's ample amounts of oxygen being produced or reaching the red blood cells, they're not that oxygen isn't able to be unloaded to the cell, so it actually you have enough oxygen in the blood, but you're still hypoxic at the tissue. And like we talked about before, if you are hypoxic at the tissue, it doesn't really matter how much oxygen you have in the blood, as like, as long as the blood oxygenation isn't the limiting factor, then it doesn't it doesn't matter anymore. Once you reach that threshold where you have enough oxygen in the blood, the the next question is, is it oxygenating the tissue? Is the oxygen being unloaded? So in these states, when you're pushing pure oxygen into the system, into the into this person's body, and they're not producing enough CO two, they can still be hypoxic at the cellular level, which is a huge issue, and it drives the pathology even in an even worse direction, because when you're on what, especially when you're under mechanical ventilation, the ventilator is breathing for you, is pushing air in and pulling air out for you. So it could be creating a state where you have low CO two at the cell level, because it's not adjusting for however much you're producing at the cell level, and so you basically get, like, exacerbation of the problem.

Jay Feldman 47:25
Yeah. And that's why, like, when you look at the as you were saying, a lot of people were warning about this, and when you look at the fatality rate, or or survival rate, once, by the time somebody gets on the ventilator in covid, it's not good.

Mike 47:40
Well, ventilation in general is really poor. The mortality rates are pretty high. What, even if it's just sepsis, if you're on a vent, the mortality rate goes up, like, pretty seriously.

Jay Feldman 47:52
Yeah, yeah. And it's because, in a lot of ways, it's, it's basically forcing this hyperventilation in a way which is pretty harmful. And interestingly, specifically specifically with covid, they talk about how a lot of the symptoms and the physiology mimics altitude sickness, and they show low CO two and high lactate dehydrogenase, which is the enzyme that converts pyruvate to lactate, so high lactate as well. And they've actually found that some of those drugs that help with CO two production improve symptoms, so, and that would be something like Acetazolamide. So along with these ideas, they have, like, people have acknowledged this. It's still so it's really surprising how little attention this has gotten, just the whole idea of the harm that's created when you're forcing ventilation with just oxygen, and how beneficial it can be to add some CO two. And there's a lot of research talking about it. So here's in this study they're talking about it. I say hyperoxia results in paradoxically, increased ventilation, which leads to hypocapnia, which is low CO two, diminishing cerebral blood flow and hindering oxygen delivery. So what they're saying here is that ventilation with oxygen, which is hyperoxia, increases ventilation causes hyperventilation, which leads to a decrease in CO two which decreases the blood flow through the brain and decreases oxygen delivery. Then they go on to say that hyperoxic delivery induces other systemic changes, including increased plasma insulin and glucagon levels and reduced myocardial contractility and relaxation, which may derive partially from neurally mediated hormonal and sympathetic outflow. So basically, what it's saying here is that you have an increased sympathetic activity, increased stress activity, and you also have decreased ability for the heart to actually pump. And I know I alluded to heart failure before, but generally, heart failure is a situation where the heart is basically swollen and edematous, and he has edema, and it's not able to effectively contract, because what happens when a cell is swollen is it can't produce energy effectively. And. A cell that's forced into that state ends up contracted. So you basically have a heart that's semi contracted, and so it can't relax enough to allow blood to come in and then get a full contraction to force the blood out, more or less. So it decreases heart contractility, which obviously is not something that you want, either. And so there's a couple of these, other of these studies that we're showing that in this one is showing that liberal oxygen administration increased mortality rates by around 20% compared to conservative oxygen administration that was in patients with chronic respiratory disease. There's another one showing that hyperoxia worsens outcomes after cardiac arrest, cardiac arrest and traumatic brain injury and stroke and another couple that are talking about adding carbon dioxide being protective. So one showing that 100% oxygen being administered harms the brain by activating the sympathetic nervous system and reducing blood flow to the heart in the brain, but adding in 5% carbon dioxide prevented this effect. And then there's another one showing that hypercapnia, which is increasing the carbon dioxide levels, minimized lung injury and suppressed inflammation. And so they were talking about adding CO two to any sort of inspired gas, like any time there's ventilation going on.

Mike 51:15
And just a small percentage too. Like that was what 5% Yeah,

Jay Feldman 51:19
And earlier is 3% in the LGBT Studies.

Mike 51:23
Yeah, so just a small amount of CO two rescues the system. And the basic effect is vasodilation at the cellular level to allow basically blood flow, but more importantly, the allows the unloading of oxygen from red blood cells. And the other thing that I think is really important here to point out is that high flow or high concentration oxygen is actually damaging itself to the different tissues, just just because of the oxidation effects that it causes. So the CO two is actually protective In all these situations. And this, this, this should eliminate the idea that CO two is just a waste product from the cell, if anything, if you want to oxygenate your cell, if you want any level of oxygenation to any of your tissues, in general, you need CO two. So it's, it's kind of like the dance between oxygen and CO two that allows us to effectively produce energy, right? Because everything, the only reason we need oxygen, the only reason that that all of us breathe is because we need oxygen for the electron transport chain. If we didn't need oxygen for the electron transport chain, we wouldn't need, necessarily need to breathe, right? That's the entire basis. That's why our lungs were created. That's That's why, that's why we have our red blood cells. All this is based around this, this interplay between oxygen and CO two. The cell creates oxygen, or the cell creates CO two. Excuse me, that CO two allows the cell to take up more oxygen to create more CO two, if there's sugar and whatever else that you need to basically do cell respiration. So that's, that's the and I think that's kind of central that is that we need to breathe just for oxygen to produce energy, like that's the entire basis of the system, and at the large basis of of the circulatory system, as well as set up to deliver those nutrients, whether that's oxygen, whether that's glucose, whether that's specific vitamins and minerals to the cell, so that the cell can produce energy effectively and then grow, divide, whatever it needs to do, but the core component is to produce energy, and that requires all those aspects. So when you like CO two is not the waste product. CO two is just as important as oh two in this system, and it's in a lot of these circumstances, what we're seeing is that it's actually very protective, not only from the damage of oxygen, but also from from, like an energetic issue. It basically is supplying that CO two can help correct, or can at least, I guess, mitigate the issue for whatever period of time that's there to allow you to oxygenate effectively.

Jay Feldman 54:07
Yeah, yeah. And so when we're producing our own CO two, it's a way to protect against all of these issues and more.

Mike 54:14
Well, that's the goal, right? And that's everybody wants to know how to increase CO two, and or not. You know, everybody in the piece, people on the street, don't want to, don't want to increase CO two. They're like, what am I gonna have more Sprite? Like, more bubbles in my sprite. The the real way to increase CO two, like, the most direct and important way to increase CO two is going to be through properly oxidizing sugar to CO two, through the cell through cell respiration. That's how we want to be producing CO two.

Jay Feldman 54:49
But before we get there, though, I want to talk about a couple other a couple other situations relative to this kind of dysfunctional situation when we're not producing. Of CO two. So I know I mentioned a little bit of what's going on at the at the heart, during heart failure and during swelling and everything. And the same thing ends up happening at the lungs too. So when the lungs, and this is in pulmonary, pulmonary edema, we talked about this in like ARDS, for example, but it's going to happen anytime there's impaired respiration, and especially when you have excess lactate there and everything is that then you end up basically getting hypoxia at the lungs as well. And then they can't expand and contract in the same way, just like the heart. And so then they have trouble actually breathing too. And so that's another, you know, another interesting thing when you're talking about hyperventilation is that the you end up with rapid breaths, but they're also pretty shallow, and that's, that's part of the reason too. But yeah, so that's, that's like, a very important feature of a lot of these degenerative states. And then another factor as well, which you talked about earlier, is that then it decreases the sodium in well, it increases the sodium inside the cell. When it causes that swelling, allows the sodium to come in, but then that ends up decreasing the sodium in the blood. And we've talked about this in the episodes, talking about water and high blood pressure and salt. But when you have a decreased level of sodium in the blood, it activates another stress system called the RAS system, which, which we've talked about as well. Yeah, we talked about this whole pathway, and that's also something that gets activated extensively during covid, like a covid infection. And so there's a lot of things that can be done to help prevent against this. And again, I'll link back to all those episodes. But yeah, the activation of that RAS cascade, and that RAS system is a whole other stress system that gets activated, and further ends up causing vasoconstriction, so it further decreases blood flow and oxygenation and causes the loss of potassium and magnesium, not only from the cell, but basically, basically you have this whole switch where the cell is losing potassium and magnesium that's going into the blood, and then, because the sodium is going basically from the blood into the cells, you then end up switching The exchange at the kidneys, where normally the kidneys are excreting sodium and holding on to potassium and magnesium. But because you activate this RAS system and increase aldosterone, then you have an opposite effect there too, where the kidneys start retaining sodium and getting rid of potassium and magnesium. So it's like this direct flow out from the cells, like all your tissues, directly out through your urine, and then vice versa with the sodium, like, everything's just kind of directly switching, and you end up, you know, swollen and the demon is and nothing's working right. And serotonin is a big part of that, as well, that whole edema situation and the rest system, it's essentially

Mike 57:33
Like all the good clients are leaving the bar, like they're bee lining for the door, and also, like all the rowdy clients, like, who don't care about the bar or anything like that. Or like, making their way in, like, just barging their way in, like a mob going in, and then the like, because the body's the kidneys, the kidney is trying to maintain the concentrations in the blood right, the concentrations of sodium and potassium and whatever in the blood. And these different hormones change that. And the hormone is basically sensing. The aldosterone is is basically released when the body starts to sense, oh crap, we don't have enough sodium. Or we or the other situation is, oh crap, we don't have enough we don't have enough fluid in the vasculature. And and the reason this happens because where the sodium moves. So if the sodium starts moving into the cell, the water is going to flow with it. And so essentially, you can get the you can get very waterlogged cells. And so that's where you get the edema is the cells, and the water around the cells are is being expanded and not being structured. And then the sodium basically, is moving with it. And so then you're getting, like, you're getting a shift, you're getting a shift of fluid. You're getting a shift over electrolytes, and not the direction that you want to go, right?

Jay Feldman 58:50
Yeah, and you're losing that from the blood, like, as you were saying, just to clarify, like the water is going from the blood, like that makes up the blood volume into the cells. So you end up with a lack of blood which decreases blood pressure, and that's why you have the vasoconstriction and response to try to make vasoconstriction and response to try to maintain blood pressure, and it's going into the cells, making them all swollen, so everything's going in the wrong place.

Mike 59:07
Yeah, And you can see this. You can see this in people.

Jay Feldman 59:13
Yeah, yeah, in severe health states, yeah. And then that's also what's happening in high blood pressure, and we talked about that in the high blood pressure episodes. I'll link back to those two. But yeah, that's what's going on in high blood pressure. Is you have the water leaving the leaving the blood and going into the cells. And then some of those cells also involve the actual blood vessels, which are then waterlogged and in that partial contracted state where they can't expand. And that also increases the vasoconstriction, in addition to the aldosterone and serotonin and everything else. And so you end up with constricted blood vessels, lack of circulation, excess excess blood pressure, a lack of magnesium, potassium, excess sodium in the cells, which is where you don't want it, lack of energy, yeah, and excess calcium. Calcium is with a contraction. Yeah, right, right, which also ends up leaving. Leading to calcification in the long run. So, yeah, I mean, we talk about this all the time. Is so as far as how everything's this, like wonderful organized system, and it's, it's, it's cool to put all those pieces together and see it all as as one system in that way. And there's a couple of great studies looking at this too, talking about the process of swelling as a result of energy failure and what happens with the minerals. So I'm going to read a couple quotes from these studies. They're just and I'll link to them too in the show notes. They're just great studies to take a look at as far as support for all this. So first one says that when the metabolism of a tissue is inhibited by toxins, cold, anoxia, which is like hypoxia, lack of oxygen, or when the cell membrane is made so permeable to sodium that the extrusion process can no longer keep pace with the rate of entry of sodium into the cells, and sodium accumulates within the cells. So that's the first part. But the important part here is that either when the cell is under a lot of stress or it's just not producing energy, and that's basically what's going on with the cell membrane permeability, which there doesn't really have to be a membrane there for this to be happening, that then the sodium is coming in, and then it says, later on, it says that the accumulation of sodium and then chloride, which is coming in as well, will exceed the loss of potassium. So there's a net gain of intracellular solute which osmotically draws water into the cells, and as a result, the cells swell. And this next study is talking about this, specifically in the brain happening, where it says that when an insult to the brain results in ischemia or hypoxia, very little new ATP can be produced due to abrogation of oxidative phosphorylation, which is mitochondrial respiration. So it's saying that when there's a lack of oxygen, you can't produce new ATP or a lack of blood flow, right? Or yeah, both, both, yeah, yeah. Which is the ischemia part? Yeah. Thank you. And then the cells quickly use up their reserves of ATP. And unless normoxia is restored, the deranged cellular machinery loses its ability to sustain homeostasis. And then cellular survival requires that sodium be continuously extruded from the intracellular compartment, because this is critical to maintaining normal cell volume. Depletion of ATP is accompanied by unchecked influx of extracellular ions, primarily sodium down there electrochemical gradients, and sodium ion influx, in turn, drives calcium chloride influx via chloride channels, and the resultant increase in intracellular osmolarity drives inflow of water. So it's just kind of a more in depth explanation, and come a little bit more complex with all the terminology explaining that, basically, when there's a lack of ATP production, the cell loses its structure. It can't exclude the sodium, like it normally would. The sodium comes in, potassium comes out. You end up with the swollen cell that's then basically unable to function.

Mike 1:02:43
Yeah. It's, it's, and that's what we described with altitude sickness too, with the brain. It's just, it, it's, and you the thing I was trying to what I was saying before, was that you can see this in people. If you ever see grandma's legs and they're super swollen and there's a ton of water in there, it's, it's this process going on. This is the, this is largely the process that's happening. And when in heart failure, is essentially that process that's happening at these people's feet and legs. Is what's happening at their heart and and this is also why, why you see this with diabetics. When you get diabetic people's feet, if they're if they're swollen, oftentimes they're very swollen. That swelling is this process. And then in heart failure and diabetes, you get non healing wounds. That's because those cells aren't producing adequate energy to heal that wound. It's and then basically, the infection sets in, or infection set in because you have this chronically open tissue, you don't have immune function, and you don't have any energy production, essentially protecting the tissue, because the most protective effect is that energy production. And so you have, like, all of these states are basically just energy failure at the cellular level, and then the symptoms that you see from them is whatever that person's predisposition or their weakest link was in their body, and it manifests as that. But it all comes down to swelling. You're gonna have the swelling, and this what the researchers are describing here, and what we talked about is that swelling is a direct effect of the failed energy metabolism. So as soon as energy metabolism fails, the cell can't maintain its structured water. It can't maintain, it can't maintain the balance of electrolytes, and so, and we this is, this is essentially, rather than the membrane. That's where you start talking about Gerald Pollock, fourth phase of water, and then Gilbert Ling's Association induction hypothesis, where the production of energy in the cell, the production of ATP changes the shape of the proteins and allows them to bind potassium and magnesium and exclude sodium and chloride, and then also basically hold water in a particular structure. So when the cell's producing energy every the proteins are in a certain way that every. Thing is, like, it's like, in a crystalline structure, a gel state is what, is what Gerald Pollock is showing in his work. They're in a gel state, and that that gel state is maintaining the cell as, basically, this, this, this individual entity, per se, right? It's in its own particular shape. Once that energetic failure starts to happen, then the water doesn't the proteins lose their shape. The sodium and or the potassium and the magnesium start to be unbound from the proteins and start to escape. The water stops being structured to that gel state and starts moving more towards that watery state. And then sodium and chloride, since are they're not being excluded, they're not being kept out of the structure. Start to stream into the cell, and they bring water with it, and so then the cell is now extremely waterlogged and it's non functional. And then that's essentially what you're seeing in these diseases, is metabolic failure with swelling and water logged cells.

Jay Feldman 1:05:59
All right, I hope you enjoyed that episode, and if you did, make sure to tune in for part four of this series, where we'll be discussing how to increase carbon dioxide and also how to avoid glycolysis and excess lactate production. If you did enjoy today's episode, then please leave a like or comment if you're watching on YouTube and if you're listening elsewhere, please leave a review or a five star rating on iTunes. All of those things do a lot to help support the podcast and are very much appreciated. To check out the show notes for today's episode, head over to Jay Feldman wellness.com/podcast where you can take a look at these studies and articles and anything else that we discussed throughout today's episode. And if you are struggling with any low energy symptoms, including the different low energy symptoms that we've discussed today, involving this situation of a lack of carbon dioxide or excess lactate or glycolysis, whether that's high blood pressure or heart failure or edema of various sorts, or whether that's altitude sickness or anxiety or panic disorder or any other low energy symptoms, whether that's chronic pain, fatigue, weight gain, digestive symptoms like bloating or inflammation, brain fog, poor sleep, hormonal imbalances, or any other low energy symptoms or chronic health conditions. Then head over to Jay Feldman wellness.com/energy where you can sign up for a free energy balance mini course, where I'll explain how these different symptoms and conditions are really caused by a lack of energy, and I'll walk you through the main things that you can do from a diet and lifestyle perspective to maximize your cellular energy and resolve these symptoms and conditions. So to sign up to that free energy balance mini course. Head over to Jay Feldman, wellness.com/energy, and with that, I'll see you in the next episode.