Jay Feldman 0:12
Welcome to Episode 65 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 non alcoholic fatty liver disease, and today we will be talking about how fat burning and low carb diets contribute to fatty liver and throughout the series, we've been beginning by explaining some of the general mechanisms and physiology underlying fatty liver. And this is a really important disease process to understand, because it pretty much directly applies to almost any other chronic health issue or symptom. So because of that, we have been diving in. We've been taking some time to go through the different mechanisms, and we are including graphics. So you may want to watch this one on YouTube if you want to take a look at those graphics. But we'll also make sure to describe them verbally, and then toward the end of this series, we'll be digging into the more practical application for the concepts that they're that we're discussing, including what this means as far as diet and lifestyle and supplements in order to reverse the situation of non alcoholic fatty liver disease, and this series has been a slightly different style of podcast compared to what we normally do here on the show, where we have been digging in a little bit deeper into the mechanism. So you'll have to let me know in the comments whether you guys like that or would prefer a little bit more of a surface level format in today's episode in particular, we'll be discussing why low carb diets are not a good solution for fatty liver. We'll be talking about how fat burning and lipolysis, or the release of fat, actually contribute to fatty liver. We'll be talking about why ketone production is a sign of stress and inhibited mitochondrial respiration. We'll be talking about the role of uncoupling in non alcoholic fatty liver disease, and why aiming to increase uncoupling is a misguided approach. And then we'll be talking about why a low fat diet also doesn't directly address the root cause of non alcoholic fatty liver disease. To check out the show notes for today's episode, you can head over to Jay Feldman wellness.com/podcast we can take a look at the studies and articles and anything else that we reference throughout today's episode, and if you are struggling with fatty liver, non alcoholic, fatty liver disease or any other symptoms or conditions that we discussed throughout the series, whether that's insulin resistance or related conditions like heart disease or diabetes, or if you're dealing with any other low energy symptoms, maybe that's chronic cravings and hunger, low energy or fatigue, joint pain, brain fog, intestinal symptoms, gut issues, weight gain, poor sleep, insomnia or any hormonal imbalances, reproductive issues, low libido, 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 lack of energy. And I'll also 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 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 we've talked through basically these mechanisms as far as how mitochondrial respiration, or should say, inhibited mitochondrial respiration, is underlying the fat production in fatty liver. And this next study discusses that further, but then also talks about some of the mechanisms that might be causing that, which I think are potentially counterintuitive and are definitely helpful to go through. So I'm going to read this quote, and then I'll pull up pull up the graphic from that study and we'll talk through it. So they mentioned that approximately 1/3 of the US population has non alcoholic fatty liver disease, a condition closely associated with insulin resistance and increased risk of liver injury. Dysregulated mitochondrial metabolism is central in these disorders. Individuals with non alcoholic fatty liver disease had 50% higher rates of lipolysis, that's fat release, and 30% higher rates of gluconeogenesis. There was a positive correlation between intrahepatic triglyceride content and both mitochondrial oxidative and anaplerotic fluxes. These data indicate that mitochondrial. Today for metabolism is around twofold greater in those with non alcoholic fatty liver disease, providing a potential link between intrahepatic triglyceride content, oxidative stress and liver damage. So that's a lot there. We'll talk through it on the graphic.

Mike 5:14
No obelispaniola Jay haha

Jay Feldman 5:19
I mean, just to kind of summarize, again, what they're what they're mentioning is that, basically, you've got a lot of flux going on. You've got these metabolic issues that are leading to very high rates of things like lipolysis and gluconeogenesis, which are stress pathways. And we'll talk about that in more detail in a bit. But then they also talk about high rates of mitochondrial, oxidative, oxidative and anaplerotic fluxes, and we'll talk about that in a second, too. But what they're saying is that there is a high rate of oxidation going on, which we talk about high metabolism. So somebody reading that might think that's a good thing, but in this case, they talk about why that is and why, in this case, it's not actually efficient mitochondrial oxidation. Instead, it's very inefficient, and that's basically the major problem. Do you want to add anything before I pull the graphic up?

Mike 6:08
Now you can go ahead, just for anybody out there. Gluconeogenesis is the liver producing glucose, like literally making glucose from what it has available, and then, like, lipolysis is the release or breakdown of fatty acids from your fat tissue, and then they basically will push it into the bloodstream. And then, as far as your anaplerotic fluxes, the Spanish part of that, that statement, there is just like a buildup of intermediates in the pathway.

Jay Feldman 6:38
Right, right, yeah. And to, just to add as well, with lipolysis, you can have it from the body fat stores, but you can also have it in terms of the release of LDL or VLDL from the liver. So that's basically when you have these excess triglycerides in the liver that are that are leaving. And so what it's kind of saying is that you have high amounts of these backup pathways, which we already talked about, that these are the pathways that come about when glucose is not stored, or the fructose is not stored as glycogen. It's not oxidized to energy. Then it becomes fat. It becomes released as well. The gluconeogenesis itself is not a problem if you're just converting some fructose to glucose, but when it's under stress, it's a problem.

Mike 7:15
Well, yeah, this case is like the you have a buildup of intermediates in in the Krebs cycle, or the citric acid cycle is what we use to produce energy. And so the intermediates build up, and the cells kind of like, well, we need to get rid of them, so let's turn them back to glucose. That's kind of what's going on. And it's like, oh, we can also turn it into fat. And so that's what you're seeing. It's like, moving. It's like, you have all these the these things like, Oh, we're going to put into storage, because we can't use it right now.

Jay Feldman 7:40
Exactly, yeah, and kind of export it out, like get it out of here. There's, there's, you know, we've got too much, essentially, because we can't use it well. So let's pull up this graph, which basically shows that. So what we have here is a few different things to point out. Basically, they, they aren't showing here the the fructose or glucose entering in. Instead, they're focusing more on the fat side of things, because they note how there's a much greater increase in fat oxidation in the situation of non alcoholic fatty liver disease. So what we see over here on the right, we see the adipose tissue, and they're showing increased lipolysis, which is basically that that fat tissue is getting released as free fatty acids, which are then entering the blood and are then picked up by the liver. And this is key because, and I know we talked about this a little bit, as far as fat from the diet can enter the liver as a fuel, but normally, people are not considering the fat from our fat stores being released and then entering the liver. And we'll talk about this in more detail, and how this is associated with high stress. Associated with high stress hormones, and something that can happen regardless of what you're eating. Essentially, it's just not coming directly from the diet, and instead is, instead is a sign of systemic stress. So we, we have these free fatty acids that are taken up, and then those are entering into, I mean, they're doing one of a couple things, but the first thing that they would do would be to enter into the mitochondria and enter into beta oxidation, and then enter into the Krebs cycle, or the citric acid cycle, which is so we've got the beta oxidation here, and the tricot Tricarboxylic Acid Cycle, which is the Krebs cycle. And we've talked about this, you know, before, where we've got this build up here because of various reasons that we'll discuss, which one of which is just excess fat oxidation, which increases the amount of flux through complex two, and this is due to that increased FADH two to NADH ratio that we talked about a bit. And that increases reactive oxygen species, and it also slows down the production of ATP, and leads to a slowing down of the citric acid cycle, which is what leads to what they're describing as anapluss. And so, as Mike mentioned, this is a buildup of intermediates in this cycle because it's not flowing through. So you basically at every step that things are being blocked, you end up. The buildup of that intermediate. One of those main intermediates, which we've talked about a lot, is acetyl CoA, which then can leave the mitochondria and be converted to mountain Lionel CoA and then converted as fat, or it can be converted to ketones that they mentioned here, which the ketones can then be exported. And I think it's really great that they highlight this, because this is something that is known to be seen in something like diabetes, or condition like diabetes, where, which is a condition that's highlighted or or just directly illustrated by impaired, impaired mitochondrial respiration. And when that happens, that's the process that leads to ketone production. It leads to ketogenesis, which also tends to be driven by stress hormones. And so it's kind of an aside from this topic directly, but it's, I think it's so paramount to highlight that ketogenesis is not something that occurs during healthy, free flowing respiration and energy production and health. Instead, it's something that occurs under major stress when you have a huge buildup of something like acetyl CoA, because the citric acid cycle is blocked and the electron transport chain is blocked, and you're in this low energy state, that's when you start producing ketones. And this is going to happen as well when you're, you know, starving or not eating carbs, which is essentially starving, mimics starvation. It shows the exact same effect. So, yeah, I just wanted to highlight that. And I like that they mentioned that. And then they also mentioned that the other aspects of arosis could involve elevated pyruvate or precursors to pyruvate, and these can then be used to increase gluconeogenesis or other basically, they mentioned gluconeogenic substrates, that this is just all spillover, as Mike mentioned, this is all just spillover when these things are not being used properly. And then when that does happen, as we mentioned before, the free fatty acids will then be reesterified into stored triglycerides or released through VLDL and then potentially going back to the adipose tissue. And again, the same thing would happen with any substrate that's coming into the liver at this point, whether it's fructose or glucose or free fatty acids.

Mike 12:03
Yeah, because you have essentially a breakdown of energy at the at the cell. So no matter what you're putting into the system, because the energy is not flowing appropriately, it has to be moved into all these backup systems. And then we could talk later on, which I'm like, itching to get to is kind of like, what, what makes this situation worse? And what's, what's like, what are some of the root causes under it? I mean, the primary root causes is going to be your your energy failure. But like, what's causing the energy failure? Stuff like that.

Jay Feldman 12:35
Yeah, exactly. Yeah. And I know we're spending a lot of time digging through the mechanisms of what actually happens during that energy failure. So hopefully everyone's just on the edge of their seat waiting to hear what causes it. But I think it's really helpful to just illustrate these things, clear clear it up, or really take the time to build it out, step by step, because that's as I mentioned, with something like ketones. Like if you don't have this picture of what's going on, then it's really hard to understand why ketone production is a problem. You know, someone tells you that ketones are great for brain health or or just the best fuel. And how would you know any different? Or how would you have any concept of what actually is involved in producing ketones, you know? And the same could be true. As far as somebody saying that fructose causes fatty liver, it's the same idea. So I think that that's why it's so helpful to really take the time to break these things down, step by step. And that brings us to the next piece I want to highlight about this study, which is that they mentioned that because of all these processes going on, you they see elevated mitochondrial oxidative metabolism. You see and we show that it's not necessarily running efficiently, but you see higher rates of it. And normally there's a couple of hypotheses, or there's two main hypotheses, as far as what's causing that, again, like, what kind of mechanism is underlying it? It's, we're still not talking about like causes as far as what you're eating or what's in your environment, but rather, like, what is the more immediate kind of underlying cause? And the first one that they mentioned is impaired mitochondrial capacity due to increased increased lipid metabolites which cause insulin resistance. So what they're saying here is, and both of these two main hypotheses are central, centralized around excess lipids. So they say they're basically saying that you have these excess lipids, these excess fatty components that are blocking the ability for the mitochondria to work properly, and oxidized glucose, or even oxidized fats, to an extent, and this causes insulin resistance through that Randall effect, the Randall cycle, and that is why you see increased metabolism, because it's it's being blocked by these lipid metabolites. The second hypotheses that they mentioned, or hypothesis that they mentioned is that you have this lipid overload. You end up with so much of these fats coming in that this forces a lot of fat oxidation, because you just have all the substrate, and this then causes oxidative stress, and it causes damage and inflammation, and eventually you end up with non alcoholic fatty liver disease. And those things are. Both, I think helpful. I think it's helpful to acknowledge those hypotheses as far as pieces of the mechanism, but they then point out a third hypothesis, which is their own, which I think gets a little bit deeper. It basically gets at what leads to the excess lipids that are that are seen there. And the reason why it's so important is because you'll hear the hear this often, maybe in like classic low fat circles, whether it's like vegan, vegetarian or just a conventional medical view. When they're talking about fat being a problem, they talk about how fat will fat is basically the cause of fatty liver disease, and fat is the cause of heart disease, and fat is the cause of diabetes, because in these situations, you see these excess lipid, excessive amounts of lipid metabolites that are blocked that we know block glucose oxidation, we know they block insulin signaling. So they just blame it straight on the fatty acids or the fats that we're getting in our diets. And what they're not doing is questioning what is leading to like, the assumption is just that if you eat more fat, that's going to cause this. You know, all of these lipids that are just blocking up the cell, because the cells aren't meant to have fat. So of course, it's just going to be blocked, and it's not going to work, right? And instead, these, these researchers talk about their own hypothesis, which I think gets more at what's going on. And so they mentioned, basically that it comes down to an increased energy demand, that is like the main reason why you're seeing increased respiration. And when they say increased energy demand, they're basically talking about not having enough ATP. They're saying that there's a lack of ATP and that drives it. So here's a couple of quotes that they mentioned. The first one is that they say, in as much as mitochondrial TCA cycle activity is closely governed by energy demand. We interpret this finding to indicate increased energy demand during non alcoholic fatty liver disease. So that's that first piece, which they're basically saying. They know that the Krebs cycle activity is closely governed by the amount of energy available, and that must mean that there's more energy needs in non alcoholic fatty liver disease. And then they explain why that might why that might be from their hypothesis. And they say that mitochondria may simply be less efficient during non alcoholic fatty liver disease, a possibility supported by mitochondrial damage and uncoupling in the liver of non alcoholic steatohepatitis patients. So I just want to break that down real quick before I go on where they're saying that you see increased mitochondrial damage and increased uncoupling in patients with fatty liver and the mitochondrial damage, we've talked about increased oxidative stress and all of that, they also talked about uncoupling. And again, this is one of those areas where it's so helpful to be breaking down these mechanisms, because people talk so positively about uncoupling all the time, and are you good?

Mike 17:44
I'm just laughing because it's, yeah, it's like, as soon as you hear like, the buzzword, whether it's uncoupling or whether it's increased oxidation, it's like, Oh, it must be good. And right, it's a question always like, why? And it's, again, it's just like the uncoupling is like a protective mechanism. And you, I guess you could either see it from one of the three hypothesis hypotheses, as a disposal mechanism of the excess fatty acids, because, basically, the the electron transport chain isn't working very well, or doesn't have enough of the carriers and you have an excess amounts of fatty acids. Or on the other side, which kind of works in the same idea of what we're talking about, even in this first that first one, the first hypothesis I just mentioned, is that you basically have the the the electron transport chain, or the mitochondria, is damaged, and so it can't produce energy adequately, so it's going to upregulate, up uncoupling. And there's but there is showing uncoupling as like, an example of like, or like a sign indicating the mitochondrial damage. But the and to prove their hypothesis that the original point is that the mitochondria is damaged, less efficient, and so you have an increased energy demand, but you're unable to meet it, and that's what's the primary mechanism behind any FLD.

Jay Feldman 19:04
Yeah, yeah, exactly. And just to some people might not be aware of what uncoupling is, I think we mentioned a little bit in one of the previous when we're going to one of the previous graphics, but basically we've been talking about, I guess you can kind of see it in this. Here's just a I'll pull up one of the previous graphs just so there's some sort of image with what we're talking about. So this is one of those kind of complex ones. But on the left here number three, you see the Krebs cycle. And then over here, at number seven, is where you see the electron transport chain. And so these are two separate pieces of energy production, and you can actually see it a little better in this in this graph, which is a little simpler as well. Okay, so you see right here in the center the the Krebs cycle, and they're focusing specifically on the production of NADH here. But. You also have the production of FADH two, and that's mostly you're going to get some of that in cycle, and some of it in the in beta oxidation. But then those those electron carriers, then head over to the electron transport chain. Right here, they drop those electrons off. And then you see this function along the along the electron transport chain, which isn't shown directly here, but, but you basically have this kind of passing along, and then you end up producing ATP from it. And when you have an uncoupling, is basically that you have this drop off of electrons here, but you don't have you basically increase the permeability right here. So and this, you see these protons coming through at every point, and so those help to create a gradient that allows for ATP to be produced here at Complex four. And so basically what you have in uncoupling is a is like a release valve that turns that stops any ATP production and just allows for you to fully release the gradient, that's the proton gradient, and you just start dropping off all the electrons, and everything gets released basically as heat. So you're not producing energy anymore. You're just releasing heat and burning through a lot of substrate. And people say that this is good, because this is the best way to burn through all your fat. Is you just need to uncouple and not produce any energy and just burn it all as heat, and you're good to go and go. And you know, there's these studies where they use uncoupling agents like DMP, dinitrophenol, exactly, so compounds like DMP that directly cause this uncoupling, and you see a ton of weight loss, and all these other well, mostly it's centered on weight loss. And I'm sure you would see a reduction in fatty liver, and I'm sure you'd see a reduction in diabetes similar to Metformin, just because you're just causing all this substrate to be burned up. And there can be some value to that if you have just a ton of substrate laying around, but it's it's so far beside the point, and you're not getting any energy from it, and that's part of the whole problem in the first place.

Mike 22:00
So you have an energy failure with the on, with the uncoupling, because you're not producing ATP, which is your main energy source, so, right? You're basically just taking it's like, if you put a whole bunch of gas in your car and you just turn the heat up really, really high inside the car to burn all your gas, but you didn't, you didn't like drive anywhere, and that's kind of what's going on with the cell. You're just, you're just because you have so much you have basically what's happening in the cells. The engine's broken, but you still have all this gas coming in, so the cell needs to do something with that gas so it doesn't completely flood the broken engine. So you the you just turn the heat up inside the cell. That's That's what uncoupling is doing, and but you're still not solving the problem of the energetic failure. So you're still not producing ATP. And then one thing that was on that graph that they showed is that when the ATP decreases to, I guess, to a certain threshold, that's when you see mitelphag which is literally the destruction of the mitochondria. As soon as you see destruction of the mitochondria, then you will start to see destruction of the cell if it releases cytochrome c, I'm pretty sure, which is one of the enzymes in the electron transport chain. I'm pretty sure that's like the cardinal signal for cellular apoptosis. And so in non alcoholic fatty liver disease, you basically have this state where you have too much substrate and your body's trying to adapt. And then when you go to non alcoholic, steal hepatitis or Nash, which is basically like inflammation, then you start to see the cells actually are like dying. And then you go to after that, you go to hepatic cirrhosis, which is the fibrosis or the liver is becoming fibrotic like this, the ones functional liver cells that died are now becoming fibrotic collagen, and then eventually cancer. So it's like, that's the progression, and it's just that's what happens with energy failure, and by the way, that happens with every other tissue in the body. That's literally the progression you see, even in heart disease.

Jay Feldman 23:54
Yeah, and just to to adjust the analogy a little bit with the car, because I think we, we've got a good option. We've got a good one here. So it's like, you have this problem where the engine's working really inefficiently. So you're trying to go, you're trying to get from A to B, and you're really not going very far, and the engine's not using the fuel very well. So you keep pouring in more and more fuel, and the fuel is overflowing. And you're like, we've got this huge problem here. And so to burn off all the fuel, you just throw it into neutral and rev the engine really fast. And so you're not actually going anywhere. You're still not getting to be you're just getting rid of all the fuel. You're still not actually moving forward. You're still not actually producing energy. You've just completely uncoupled the the revving of the engine, or like the the using of the usage of the substrate from the buy, from the end product, from the energy, or if you're running, you know, if you're using car from the power to turn the wheels and make the car move. And so you so and so you see this, as you mentioned, you see this in these degenerative states with a lot of oxidative stress and a lot of reactive oxygen species. Because what happens. Is when you're not producing energy efficiently, you've got all these reactive oxygen species being produced that causes a lot of damage in the cell. And so in order to prevent that from continuing, you start to uncouple and so you stop producing those reactive oxygen species. And as you said, if those things, if these adaptive mechanisms, continue and don't work out, then you end up with something like mitophagy, which is just destruction of Helen. Yeah. Or on a larger level, you'd see apoptosis. And this doesn't mean that these processes are harmful. For one, they're helpful for adaptation and for in the second point is that they can be activated in different contexts. So the other context where you see increases in uncoupling are is when you have a lot of energy, but, and that's and you basically when you have a ton of ATP, it's another signal to say, hey, we don't really need to be producing much more energy. We're all right. So you have a lot of ATP, and that starts to back things up the electron transport chain, and you have this reactive oxygen species production again, this time, you have uncoupling to burn off the extra substrate as heat, like we talked about. But you don't need any more energy. You're already you actually got from A to B, and you just had all this extra gas. So you figured, all right, at that point, I'll just rev the engine extra and get rid of this gas so my car's lighter or something.

Mike 26:20
Tickets to all the girls around that you have a nice car with a fast engine or something.

Jay Feldman 26:25
Yeah, exactly. And so at that point that uncoupling is is actually helpful, right? It's just getting rid of extra substrate, and you already have the energy. But when you're trying to encourage uncoupling without the energy there, you're just causing essentially more problems at you know, but you get to get rid of the Get rid of the substrate. And so that's what you see as one of those immediate adaptive mechanisms in non alcoholic fatty liver disease. And you see it in other conditions as well, these elevated rates of things like autophagy and uncoupling these adaptive responses. And to circle back to that study, they then went on a little bit further in that quote, and they mentioned that the oxidative stress associated with elevated hydride production in the citric acid cycle may be sufficient to damage the electron transport chain during chronic steatosis, a condition functionally manifest by impaired ATP synthesis in people with non alcoholic steatohepatitis or diabetes. So they say this would result in a degenerative spiral, whereby damaged electron transport chain, in turn requires elevated Tricarboxylic Acid Cycle activity to produce sufficient reducing equivalents for normal ATP and cellular homeostasis. And so I know that was a lot as well. Again, these studies can be a little dense for someone who's not used to them, but they're basically the first part. They're just saying that the oxidative stress damages the electron transport chain, and this causes this impaired ATP synthesis. And they said that this then causes this degenerative spiral, causes this vicious cycle where you can't produce enough energy so you end up running through basically the Krebs cycle at a really high rate, to produce, to make up the difference, yeah, to make up the difference, to try to restore some semblance of of enough ATP. And that's like the first again, it's all part of these adaptive mechanisms. And so, yeah, it's in many ways more of the same of what we've been discussing. But I think digging a little deeper as far as what is really the cause here, uh, as you know, those previous studies were just looking at what is happening, and then here they're talking about it's a lack of ATP first, and that's causing these other problems. And that lack of ATP is due to the damage of the electron transport chain and and oxidative stress, as opposed to the other hypotheses, which are just saying you've got all these lipids floating around, and that's, um, that's, that's what's leading to to these issues.

Mike 28:45
Well, and I think this tail will, it can trail in nicely, but essentially, when you don't have enough energy production at the cell, then you're going to start sending out a particularly at the liver, which is kind of regulating everything that's going on in the body. Then you're going to start to see signals for the stress hormones to increase. And once you see that, then you're going to start to see the increase in fat, free fatty acids being released from the tissues, or specifically fat, which is what you what you see in these states. And then after that, you're going to see those free fatty acids being shuttled into the liver, and then kind of clogging up the process with already, already, I guess, damaged cells to some extent, right? Because it's like the cells don't have enough ATP. They're not producing enough at the electron transport chain. The electron transport chain is then sending signals to the citric acid Acid Cycle, which is there, that's the same process, right? The citric acid cycle and the and the electron transport chain are part of the same process. They're just two steps. So the electron transport chain takes the products from the citric acid cycle and turns them into energy. But if the eight, if there's not enough ATP being generated at this at the electron transport chain, then the citric acid. Acid, then the electron transport chain is saying, hey, citric acid cycle, we need more product so that we can burn it into energy. We need more firewood, because the fire, like, when our fire isn't burning well enough to give us enough energy. So we just need more. So keep pushing more. The problem is, is as it's as it's like not burning efficiently. Um, that it starts to damage the electron transport chain to to such an extent that then the electron transport chain is like, whoa, and then it starts, instead of burning the firewood to produce energy, then it's just kind of like, just like, just letting the fire burn on the side over here, and getting rid of some of the firewood with heat, but that also sends a signal that to the body, and essentially, where the body's going to be like, Okay, we're going to give you more energetic resources. And so it's going to release free fatty acids from your fat tissue, and it's going to divert them to the liver, and then when or into the bloodstream, then the liver will pick them up when the liver picks it up, and now it has a lot of fatty acids, and then it also has this energetic dysfunction at the cell, and it also has whatever's coming in with food. And it's kind of like we have all this substrate that you're calling for, but our oxidative capability is impaired, so we can't run all of it through. We can't use all of this firewood. We don't know what to do with it. So then it starts, you know, packing the firewood up and and sending it back to the fat, so putting it back in the shed. And then it starts taking some other firewood, and it starts make turning it back into glucose, or, in this case, it's, you're it's taking whatever's running through the pieces that it already cut. It's just packaging them back up, that's turning it back into glucose. And then it's burning some extra with the uncoupling proteins. But the problem with all of this is that you have this excessive you have this damage or or, I guess, inability to produce ATP correctly, first at the cell, and particularly at the electron transport chain, at least based on this model here. And then, like, start sending out signals, and then you start getting this influx in to make up the difference. But since it's not working, it's like, oh, what do we do with all this stuff? But I bought too much firewood. I don't know what to do with it. Let's just put some here and put some here and put some here, and then eventually, as the fire continues to rage, and as it's like, going through the electron transport chain, it damages the electron transport chain, and it starts producing reactive oxygen species. So basically, it starts building up large amounts of smoke. That smoke damages all the inside of the cell. And then this the part, first the mitochondria, with it damages the inside of the mitochondria and the electron transport chain. Then even less energy can be produced, the mitochondria kind of just like explodes on itself with all this smoke. And then after that, the cell is just like, well, we're screwed, too. And it that's, that's kind of the end. So just the cell goes with it. So it's like, this the the first step though that, and I think this is what you're really trying to get at. The most important piece here is that that destruction or that impairment of the energy to start, and so with fixing it, that's what we want to address directly as well getting the energy to fix instead of trying to up regulate all these other backup pathways, like using high amounts of uncoupling, so that we still never fix the energetic problem at the cell, but we burn through all of our substrate anyway. So like, now we don't have the substrate build up, but we still don't have energy. It's like you need to, you need to, you need to fix the energy of the cell, and then also, in that same process, start that'll help to adjust how the energy is moving through the cell and the rest of the body's coordinated response. But everything that's happening in the body, the increase of fat in the liver, the increased gluconeogenesis, the release of free fatty acids from the fat tissue and to go to the liver, all of that is a backup process. Those are adaptive processes to help deal with what's going on at the cell. It's not just like, oh, this is a this is a problem. That's a problem like the body's just trying to hurt itself,

Jay Feldman 34:01
yeah. And and with those adaptive processes, we another reason why we definitely don't want to be like encouraging them is because they're not enough, like you see increases in uncoupling, for example, in this situation, but that's after. There's already a lot of spillover into fat production at the liver, and a lot of gluconeogenesis. And, you know, from from the liver being under stress, like the uncoupling in these contexts is not, is still not enough to prevent that sort of spillover and and that's why you're still seeing it in these disease states. It's, you know, and again, it would probably be enough initially, at first, when it's just a little bit of extra substrate, but it just continues and continues because you're not actually fixing the underlying problem.

Mike 34:48
Yes, which is that energy failure? Exactly?

Jay Feldman 34:50
Yeah, yeah. So you, you talked a little bit about the about how, in this, this situation, we're seeing low ATP, and that's causing the. Released to stress hormones, and that that's those stress hormones drive free fatty acid release, and they also drive fat oxidation. And so that is another thing that you see in non alcoholic fatty liver disease. And I think it's also really important to highlight this, because normally when you're looking at Fat production, the assumption is that the opposite of producing a lot of fat for, like, in the liver, let's say, to produce, or to cause fatty liver. The assumption is that the opposite of that is burning a lot of fat. So if you're burning a lot of fat, then you can't be storing a lot of fat. And they say the same thing about, like, general body fat, not even just the liver, right? Where the idea is that if you want to be insulin resistant in the body fat, so that you can be burning fat there. And if you're as long as you're burning fat there and everywhere else, then you can't store it. But that's not what you find in these conditions. For one we and we talked about this in terms of diabetes, you see elevated rates of fat oxidation, impaired glucose oxidation, and yet you see fat storage as body fat increasing, yeah, yeah, exactly. And just in general, awaken as well. You see that a lot, and you also see that in non alcoholic fatty liver disease. So here's a study where they where they point that out, and they mentioned that there's a strong association between intrahepatic triglyceride content, which is fat in the liver, and hepatic oxidative and anaplerotic TCA cycle activity. And then they say that this demonstrates the induction of mitochondrial fat metabolism in response to lipid overload during non alcoholic fatty liver disease. Simultaneous induction of pathways of lipid accretion, oxidation and gluconeogenesis heralds oxidative stress, loss of glycemic control and potential damage to the liver during chronic hepatic steatosis. And so what I like that they're pointing out here is that they say lipid accretion, which is the increase of fat storage. Lipid oxidation and gluconeogenesis are all happening at the same time, and that this is a recipe that involves oxidative stress, loss of glycemic control, and damage to the liver, and that's exactly what you see. And so to be making the argument that you just want to be burning fat so that you not storing fat. I mean, that's not what's seen in this condition. You're seeing, in many ways, the opposite, and people will also talk, you know, kind of another piece of the flip side here is that you don't want to be favoring carboxidation. You don't want to be producing insulin, because insulin is the other major thing that drives, that's going to drive fat storage. But again, in these states, what you're really seeing. But even if you take insulin resistance and diabetes, where you might see a high level of insulin, what you're seeing that overrides the insulin is elevated levels of stress hormones, extremely high levels of glucagon, cortisol, adrenaline, cortisol, adrenaline, adrenocorticotropin hormone

Mike 37:38
With insulin.

Jay Feldman 37:39
Right, exactly

Mike 37:40
And sugar and fatty acids.

Jay Feldman 37:42
Exactly, yeah. And a lot of fat oxidation and a lot of lipolysis and a lot of fat storage. So you're seeing these overriding signals, where the ones that tend to override are the stress induced ones that are driven by energy. And again, this is why it's so important to come down to what's to come back to what's happening on that fundamental level is you're seeing a lack of energy, and the presence of insulin is not causing that. The stress hormones, instead, are a response to that. And all of the fat oxidizing pathways and the fat releasing pathways are responses to a lack of energy. You don't get those without a lack of energy. So when you are on a low carb diet, you are causing a lack of energy, and that's what's shifting you into that fat metabolism. And that's what you're seeing in these in these chronic health conditions. That is the more or less exact mechanism that you're seeing come about. And the question The only potential difference is, what's causing it? In one case, you have a lack of carbs causing it, whereas in the case of diabetes or non alcoholic fatty liver disease, lack of carbs could be part of it. Generally, you have other things that are more involved, that are blocking that energy production, things like endotoxin and PUFA

Mike 38:48
And actually direct blocks on oxidizing glucose appropriately in the pathologic states. And whereas in the ketogenic or low carb states, you have a physiologically induced state of insulin resistance because you don't have a high amount of carbohydrate coming in. So your body is essentially shifting gears and saying, Look, I'm going to switch to the most of my tissues, or a large part of my tissues are going to oxidize fats, and then I'm going to prioritize the carbohydrates that my liver is capable of producing for my nervous system. So you have, like, a chronic state of subsistence. I forget who's who call who called it that was like, you're at a you're literally at chronic subsistence. So there is a, there's parallels between them, but they're also like, one is an actual damage and failure at the cellular level, and the other one is you're just running at a sub optimal state to a large extent.

Jay Feldman 39:41
Yeah, I mean, it's the equivalent of trying to just focus on increasing, uncoupling, you know, it's that same forcing of the adaptive process.

Mike 39:50
Well, it's even it's kind of misguided, though, right? Because the sense is like, and I don't mean that in like, I mean that from like, the actual physiologic perspective. Where it's like, well, since insulin is high in all of these states and drives growth and yada yada yada, since it's associated with all these different states, therefore I want insulin to be low, so I'm going to then lower carbohydrates, because carbohydrates increase insulin acutely. And it's like, those are, those are a series of associative arguments being made, and without even discussing the underlying mechanisms of what's going on, and just looking at like chronic carbohydrate consumption doesn't decrease insulin sensitivity over the long term. So like, just that piece alone destroys the entire chain of arguments that are created for the low carb, higher fat state. You see increased insulin sensitivity with increased carbohydrate intake, as long as you don't have damage going on at the cellular level. And so what we're trying to put it pull into focus here, and it the reason we're discussing diabetes and everything else is because there, there, it's the same dysfunctional pattern happening at the cells and but it's, it's just in different they're called different disease states. And in a lot of diabetics you, you're, I suppose, like, I think a study was showing like, 80% or something, had fatty liver disease. Like, they all go hand in hand. You have similar dysfunction going on across the board. Um, and they can be for different reasons. Some diabetics can have high amounts of have endotoxin, some diabetics can have energetic issues with their mitochondria for whatever reason. Some could have, and that could be from like excess incorporation of polyunsaturated fatty acids, perhaps. Or it can be from rank vitamin and mineral deficiencies, or can be from heavy metal exposure or or up regulations of stress hormones over an extended period of time, like cortisol and adrenaline and and what have you like for me, a chronic stress, whatever it is, there's, there's, and it's usually not just one factor. It's usually a multitude of factors. But the whole process comes down to is you have an energetic failure in these pathologic states, not the not the induced physiologic states, like, like ketosis and whatnot. There's still stress pathways, but you can, you can reverse those by switching off of your high your low carb, high fat diet, and the diabetic and non alcoholic fatty liver disease states you have, like, a direct impairment at the cell itself, at the mitochondria itself, with the production of energy that you have to repair in order to reverse the dysfunction. And so you're seeing the upregulation of all these hormones simultaneously that would in a normal, healthy person. Should not be seen together. You're not going to see high insulin, high cortisol, high glucagon, high blood sugar and high free fatty acid simultaneously, in a in a normal, healthy individual, you're basically seeing a breakdown of the of those pathways. And the body is like trying to compensate in every way it can. It has the glucose available, it can't use it appropriately. So you're getting an energetic signal that, look, we don't have enough energy at the cellular level, so we need to in. We're going to start putting out fatty acids, and then it's going to raise the fatty acids. The fatty acids are going to continue, are are going to start being oxidized over the glucose. But you're still have the energetic deficit, and the cortisol is still elevated, so it's going to increase the liver output of glucose with gluconeogenesis, and then you also with the increased signaling for glucose, for in the blood, you're going to have your insulin elevated as well, trying to move that glucose into the cell, but the cell is not responding to it. And so I think what you see with with diabetics and different people, with the met with metabolic dysfunction, is the insulin is driving the glucose into fat tissues and the cells your muscles, whatever the different cells your body, are oxidizing primarily fatty acids, and with the elevated cortisol. And so the glucose is coming, being shunted to fat, and then the fat is releasing fatty acids, and the cells are oxidizing their fatty acids. Then these are under the actions of stress hormones. And so one thing that you notice with diabetics in general, and the diabetic state is very analogous to the non alcoholic fatty liver disease state. But with diabetics, when they start injecting higher amounts of insulin, they actually one of the side effects is weight gain. Because just because you force the insulin into the body and then you have higher amounts of insulin, doesn't mean that the insulin isn't going to be able to force all of that glucose inside all of your cells. So I would say a large percentage actually has to get rerouted to fat storage because the cell is unable to actually use the glucose. And then the other thing they'll use is different drugs like Metformin, which is still relying on backup pathways where I'm just going to burn all my sugar through glycolysis, I'm not going to move it to the to the electron transport chain and the Krebs cycle, because they're not working. So you're still you're disposing of the sugar in the blood, but you're not correcting the underlying pathology, and that's why most people, even insulin dependent diabetics, tend to get worse. And that's why, like, you can hop on insulin and you can control your blood sugar and your hemoglobin a one scene, whatever. What else have you may come down, and you may see decrease the oxidative stress in the blood and whatnot, but you don't actually fix the diabetic state. Plus, most people progress and get worse, even on insulin dependent diabetes, unless they actually make lifestyle changes. And the lifestyle changes are what affect what's going on at the cellular level. And that's diet, that's sleep, that stress, that's exercise, that's whatever else, all these other factors, those are what really fix the cellular the cellular energy deficit. I don't know if I went too long with that, but...

Jay Feldman 45:38
No, no, it's fine. I mean, those are all it's helpful to go through all those things, and they're all connected. I did want to touch on the low carb ketogenic diet not being pathologic. And again, you think it's important to recognize that what we're doing there is we're still driving those adaptive backup pathways. And as you're saying, and this is what you're pointing out, it's not like those are those adaptive pathways are being forced by, uh, inhibited energy production for some, you know, due to endotoxin, for example, but they are being forced by a basically a suboptimal environment. Does that doesn't include carbs, and that'll happen whether it doesn't include any food at all, like starvation, or if you're just avoiding carbs, so you're still like the whole reason why those pathways are activated and why you see a stress response when that happens is because they are still leading to a depletion of energy and then a reliance on fat oxidation for energy. Now it's much easier to do that and function than it is to be in a state of severe, you know, fatty liver or severe diabetes and function through the adaptive pathways. Because what you're seeing in diabetes and fatty livers is that you keep having to drive down these layers and layers and layers of adaptive Pathways because they aren't responding well enough. Like the first layer of adaptation is not enough to get by. So you have to keep going deeper, deeper and deeper. That will happen on a low carb or ketogenic diet, but it will take longer for that to happen, because this is a situation where you're, there's, there's not necessarily other things preventing that adaptive pathway from functioning. It's like that first line of defense is working out fine, whereas when you have diabetes or insulin resistance, all these other issues, there are a lot of other things that happen to be driving that state, and along the another important piece here is when you're on that low carb diet, you tend to remove one of the biggest factors that does cause that pathologic state, which is the toxic components from the gut bacteria, whether it's endotoxin or others. So yeah, I just want to clarify that that doesn't because, because when you say that that's not pathologic, you can then it almost like, it's almost like you're giving credence to the argument that you should be on a low carb diet.

Mike 47:55
No, I just strong distinction between, for me, it's the strong distinction between the mechanisms, because like and that's purely from like a It's purely from a mechanism stance. It's not from like a ideologic stance about the diet. It's about one is you literally have a dysfunction at cellular energy production. That is not like it's it's not under your control, like you can't just reverse it right away by switching back to eating carbs, whereas the other is you're just not eating carbs. So, like, both states are a are a pathology, right? Like, you're still inducing stress. But it to delineate them, it's easier to, I think, to divide one is like, you literally have a severe dysfunction, and then the other one is like, you don't have a severe dysfunction yet, but you're kind of on your way. Yeah. And the one thing I want to say about like, the other thing with, like, ketogenic diets and all this type of stuff is when most people go on low carb keto, like, when they when they switch their diet, they're going into, like, like to Mo. It's usually like, low carb, Paleo keto, like, kind of go together. So you also have, like, an entirely change in in like, choices of food consumption, besides lowering endotoxin, like most people like, When they go low carb keto, it's like, there's no more grains, there's no more packaged foods, although now everybody's doing all this, these Bs keto foods, right? Like all the Keto pops and yada yada yada. But when it comes down to it, it's like, you're also like removing a lot of problematic issues. And I don't know if I've ever seen anybody advocate for a high polyunsaturated fatty acid keto diet. I haven't, I haven't seen that, but I think that that would be even worse situation. But most people will will do like the spat. Sources that they'll use will be like olive oil and butter and coconut oil and chocolate and maybe avocados and avocado oil, which is like a very significant difference in running your traditional American Standard American Diet of high amounts of refined grain products and granulated sugar and vegetable oil. Animals with additives and added iron, creating rank nutrient deficiencies and high amounts of oxidative stress in the cell and incorporating high amounts of polyunsaturated fatty acids into the structure and damaging its function like that, is an entirely different story than running on a lower carb diet with a high lots of like, cooked broccoli and spinach and blueberries occasionally, and dark chocolate and organ meats and eggs and like, those are entirely different dietary paradigms. Carbs are not and so like, the changes, I think, are coming from quite a few different areas, from in the low carb, keto, keto, Paleo stuff, where you're like, excluding a lot of junk and adding in a lot of benefit, even though you don't have the carbs. Like, I don't doubt that people this is not saying that people don't get quality results in some of their situations with that stuff, and that's because I've gotten them myself, and I know that, but at the same time, like, there also is issues associated with it. So, and that's where we're that's what we're getting into now. And that's what the up regulation of stress hormones with that. But the as far as, like, the conflation between insulin and and whatnot with carbs and then that, trying to compare that to, oh, if I eat carbs, non alcoholic, fatty liver disease and diabetes and whatnot, like it's not the cause, like there's some there's the energy, just dysfunction inside the cells, the actual cause, and it's we're saying that it's not related to the carbohydrate intake. And then, like the excess free fatty acids in these states is that are going to the liver is actually coming from the dysfunction itself. Because in the one study that we talked about, we talked about Off, off air. But I guess we'll put it up some point, is like the fatty acids were actually coming from people's fat stores, the bulk majority and, and de novo lipogenesis, so increase of fat in the liver, it wasn't actually coming in from the diet, which is, which characterizes the dysfunction, is actually going on at the cell and actually going on at the liver, and, and, and that's what we That's what needs to be fixed.

Jay Feldman 51:59
Yeah. Yeah. Absolutely. So I did want to mention that I have seen you mentioned a high PUFA keto diet, and I have seen keto vegan diets that are high PUFA. Oh, boy, they do exist. And that's probably, you know, one hand, I would say it's a lot worse. But in that case, when you you know PUFA are really good for shifting toward that hibernation, decreasing your metabolic needs. That might be better if you're not having carbs. It might slow the process of degeneration a little bit in some ways. But yeah, you know one of those short term benefits long term harm sort of deals. Oh, my God. Let's circle back to I wanted to mention one other thing, as far as seeing the upregulation of fat oxidation in non alcoholic fatty liver disease. There's another study that was just highlighting this, and I also wanted to mention so we were talking before about that study with the different hypotheses that they were sharing as far as why they thought this was going on. And so this is one of the studies where they're talking about one of those earlier hypotheses, that is just the excess lipids that are the problem. So they say in non alcoholic fatty liver disease, both lipid oxidation and the citric acid cycle are enhanced, suggesting that hepatocytes try to counteract excess lipid by increasing oxidation. The higher production of reducing equivalents by lipid oxidation causes an overflow of electrons through the mitochondrial respiratory chain, resulting in higher free radical generation. This may lead, in turn, to mitochondrial dysfunction, with consequent progression of liver pathology. And so just to touch on that real quick, I think so I do kind of disagree with like, two of these pieces here. So one, the important thing is that you're seeing increased lipid oxidation as what we're talking about that that you will see this Despite the increased fat production, the increased fat accumulation. So that's important, but they mentioned, first off, the higher production of reducing equivalents by lipid oxidation is what causes the overflow of electrons. And it's, I'm not exactly sure if they're just saying all reducing equivalents. But the important part there is the increased FADH two compared to NADH. And that's that difference that we talked about, in terms of the Randall cycle, and in terms of their effects on the electron transport chain, where you have the competition between complex one and complex two. For this, they use the same electron acceptor, which is ubiquinone. And when that happens and you have both FADH two and NADH, the excess FADH two causes a buildup of NADH that can't drop off enough electrons, and it causes reactive oxygen species from complex one. And so that's the important part there. It sounded like they were more just saying it's the rate, as opposed to the difference in between fat and carboxylation. So I wanted to highlight that. And again, they then say This then leads, in turn, to mitochondrial dysfunction, with consequent progression of liver pathology. But again, what we're talking about is that it's mitochondrial dysfunction first that leads to the excess lipids in the first place, which is what, which is then what causes that vicious cycle. They do mention later on that the development and progression of non alcoholic. Fatty liver disease is characterized by hepatocellular redox imbalance, which may depend on but also contribute to the impaired regulation of lipid metabolism. So they do mention, you know, later on, that the redox imbalance, basically meaning key problems that the electron transport chain, with energy production can contribute to the impaired lipid situation, the impaired lipid metabolism. So they do acknowledge that as a factor, but that's obviously what we've been talking about, is kind of the key factor.

Mike 55:28
Yeah, and this is, I mean, if I if I remember correctly, like, this is like, where they say the higher production reducing equivalence by lipid oxidation causes an overflow of electrons to the mitochondrial respiratory chain, resulting in a high ROS so just for anyone who's like we, I think we've covered it a little bit, but the ROS are like these, these, like free it. It's essentially you have these compounds that are generated that are able to react with other components of the cell and basically destroy them by what is it they they're able to oxidize them, so they'll pull an electron away from them. And when you pull the electron, you basically destroy the structure of whatever that is, and it starts a chain reaction. So one thing pulls an electron, and it pulls and it pulls and it pulls and it pulls, and it's kind of like a big tug of war game. That's the easiest way, I think, to describe it. But what happens is, basically what you described is you have too much fat. It causes more ROS because of that bottleneck that you just described. This is like, I think we talked about this directly when we talked in the SCD one, the fire in a bottle convert podcast series, where you did where they were, the argument was literally to increase this process. And what we're seeing here is that this, and we talked, we actually talked about this too, in that, in that podcast series. But the the higher amount of fat oxidation is creating Ros, and then that Ros is, is it can damage the cell directly. And that's where you see, where they talk about it changes the red ox imbalance. So the red ox is just talking about the oxidative damage to oxidation and reduction balance. So like, the fat oxidation is actually driving the problem, at least in this argument. And like, it could be, it could be that they're, I think they're calling, like arguing for it to be the direct cause, right? And then right? But so even if it's not to direct cause, if it's still, it still adds to the pathology. Yeah, yeah, exactly. And I just think that it's like, it's another argument against the whole SCD one, like fire in a bottle idea, where you want to oxidize high amounts of saturated fatty acids to basically, to cause ROS generation and make the cell insulin resistant. And that's a mechanism that they literally talk about in there, but they just say it happens in fats. So, yeah. So and of note, with the with that type of with those types of arguments, is people who go on that diet basically lose appetite, and it's not surprising why.

Jay Feldman 58:04
Yeah, and the to clarify, again, it's the oxidation of the fat is basically a part of that vicious cycle. It's a part of that situation where, when things are going wrong, that further dries it, that further causes this cycle of dysfunction, that, again, it's the primary cause is not that you just got all these lipid metabolites from eating too much fat. The problem is some sort of mitochondrial respiratory issue. Something's blocking it. Various things are blocking it, and then you have to resort to fat oxidation and and that is just furthering along that whole process, yeah. And that's part of the reason to why there's studies suggesting are showing that increasing NAD plus but in that NAD to NADH ratio reverses this. It protects against non alcoholic fatty liver disease and the fat oxidation, which does the opposite of that, it increases the FADH two to NADH ratio, which increases the NADH to NAD plus ratio does the opposite of that, although, and again, this is, I don't want to, you know, I don't want to make this whole thing about low carb, but it's just so relevant. And again, why it's so important to dig into these mechanisms is, I've had people argue that fat oxidation will increase NAD plus, and it does do that by activating the backup pathway and NAD salvage pathway that only happens when you've decreased NAD so much that you have to activate a stress pathway to bring it back up, whereas, if you're just oxidizing carbs very well, you'll naturally increase the NAD to NADH ratio without activating any stress or, yeah, any of those stress adaptation pathways.

Mike 59:39
It defeats the purpose. Like, you want those equivalents to then move through the electron transport chain to produce ATP. You don't want to just take them and create more. And it's it's not about having NAD. It's not about directly having as much NAD as possible. Like, yes, the ratio is important, but to NAD to NADH, but the ratio is looking at what's actually going. On in terms of energy production. It's a it's a symptom or a signal or a symbol of you literally taking the NADH and oxidizing it through the electron transport gene and producing adequate amounts of ATP. And then you get NAD plus back after that. Not just have like, because this is another thing I see currently, is like, everybody's like, NAD, NAD. It increases life. I need to take a nicotinamide riboside. I need to take nicotinamide mononucleotide, like all these different stuff, it's like, or you could just make sure that your elect, your mitochondria are functioning well, and you're oxidizing your oxidizing at your carbs and and you're always going to oxidize fat to some extent, but you're going to oxidize both of them appropriately, without having dysfunction at the cell, like then your NAD to NADH ratio will be just fine. You don't have to actually add the NAD directly in. You do need a certain amount, right? Like, that's why we take that's why we have vitamin b3 which is nicotinamide or niacin. But the like, once after you have the optimal amount for the cell. Like, just trying to increase it for the purpose of increasing. It isn't like, it defeats the purpose. It doesn't make any sense.

Jay Feldman 1:01:05
Yeah. And we talked through this earlier, we use that analogy of the assembly line, and it's like, you know, we were talking about the people carrying the pieces of wood that then go to the end to become the chair, and that those pieces of wood, or, you know, or the people carrying them, or like the NADH, when they have the wood and when they don't have the wood, it's like the NAD. So, as you're saying, it's what you're not doing. By activating those stress pathways is helping to drop the wood off at the end and create more chairs. The these, in this case, like these adaptive stress pathways are just a way to, like, throw the wood somewhere else where it's not going to harm anything. You know, throw it out of the out of the factory or something. And then you've got these people who are then able to go and grab the earlier parts of the assembly line so that part can keep moving. But yeah, you don't want to have to do that. You just want to fix the the last part that wasn't working in the in the first place.

Mike 1:01:54
Yeah, you want to fix the part where the wood gets turned into the chair. You want the chairs. That's the whole point of the factory. So if you're creating a situation where the people are dumping the woods, they can go get more, but no chairs are being created. Is kind of a useless process now, in cellular dysfunction, as far as a backup pathway to kind of get you through whatever's going on. It makes a lot of sense. It's great. And we can get to, I guess we'll get into this now. But like in studies where they knock out the enzyme sterol co ad saturase, one which basically takes saturated fats and turns them into monounsaturated fats and creates triglycerides, which are the storage form when you get rid of that and you just have the buildup of the wood, and you're not able to store the wood, you actually make the situation worse. So the fatty acids being stored in the liver are actually a protective mechanism against the energetic defect. The production of or the export of the fats back to fat tissue is a protective mechanism against the energetic defect in the cell. It's, it's, it's extremely necessary to have those going on when you have that energetic defect, the uncoupling is protective. So it the question is like, Oh, we don't want to like the we don't just want to, like, go to all these protective mechanisms fix the problem. We want to actually fix the direct problem so we don't have to worry about uncoupling and increased intra hepatic fat and whatnot. And what, and essentially what you see with non alcoholic fatty liver disease, the progression I described earlier with non alcoholic fatty liver disease for quite, for quite a bit of people that have it, they never progress to actual, like inflammation, where you have non alcoholic steal hepatitis. So most and the researchers found this out, and they basically had to figure out, like, what is the primary shift in the cell that moves to to non alcoholic steel hepatitis? Like, why do some people go and some people don't, some people just got fat in their liver and, like, call it a day, and that's kind of it, you know, like, and a lot of people can have fat in their liver and not have any, like, objective laboratory signs of it, where they don't have high blood lipids, and they don't have high high insulin or diabetes and all these different pathologies, they just got fat in their liver, and there's still, there's still a defect going on energetically, but it's not bad enough to create, like, a whole systemic it's systemic, but it's not like to the extent where you're diabetic or you're going into like, severe inflammation. The switch with that is where you start having, like, excessive amounts of reactive oxygen species being produced and high amounts of oxidative stress, where you're just destroying the cell in the mitochondria and the energetic defect in the Mito, or deficit, not defect, but deficit gets so high that the mitochondria is just like, look, we're done. Guys like, we gave it our shot. It's kind of it. And then the cell is just like, Well, if he's done, I'm done too. So they all they just kind of like, the factory's just like, All right, we're closing up shop. That's it. And then, right.

Jay Feldman 1:04:55
All right, that's going to wrap up this episode in the next. Episode of this series, we'll be discussing the role of the stress hormones, including cortisol, specifically, and adrenaline in fatty liver, and then we'll begin discussing the most common causes of energy failure in this condition. So make sure to tune in to that episode. 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 really do a lot to help support the podcast and are very much appreciated. To check out the show notes for today's episode, you can head over to Jay Feldman wellness.com/podcast where you can take a look at the studies and articles and anything else that we referenced throughout today's episode. And if you're dealing with any of the low energy symptoms that we've been discussing, or low energy conditions that we've been discussing, whether that is fatty liver or insulin resistance or any of those related chronic health conditions or any other low energy symptoms, maybe that's weight gain or fatigue or joint pain or brain fog, poor sleep, hormonal imbalances, or any gut or digestive symptoms. 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 lack of energy, and also 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 for 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.