Jay Feldman 0:12
Welcome to Episode 64 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 two of our series discussing non alcoholic fatty liver disease, and today we'll be talking in this episode about the true cause of fatty liver and throughout this series, we've been discussing the general mechanisms and the physiology underlying this condition of non alcoholic fatty liver disease, and the part of the reason why we're spending so much time discussing it is because it directly applies to virtually every other chronic health condition or pathological state that we can experience. So it's pretty integral to understand these things, and we've been working to simplify the mechanisms and the physiology using some graphics. So if you would like to see those, then you may want to head over to YouTube to watch the video for this episode. But we'll also make sure to be explaining it verbally as well. And this is a slightly different style of podcast from what we normally do, where we are really digging into the details here that we don't dig into quite as much all the time. So you guys will have to let me know if you do like this style, or if you prefer for us to keep it a little more simple. But either way, we will take some time at the end of the series to discuss what all this means, as far as diet and lifestyle and supplements and anything else that you might want to do to reverse the state of fatty liver in today's episode in particular, we'll be discussing why fructose does not cause leptin resistance. We'll be talking about how our livers produce fat from fructose or from dietary fat. We'll be talking about how a failure of energy production or mitochondrial respiration, is the primary cause of non alcoholic fatty liver disease, and we'll be talking about why increases in uncoupling autophagy, mitophagy and other stress pathways is often a sign of dysfunction and stress. To check out these 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 or articles or anything else that we reference throughout today's episode, and if you are not as interested in the deeper physiology and mechanisms as far as non alcoholic fatty liver disease goes, feel free to head back and listen to any other episode of the podcast. If you haven't listened to episodes one through seven yet, I'd highly recommend you go back and do that where we took some time to build a foundation as far as the bioenergetic view of health is concerned. And I do have a big announcement to make on today's episode, which is that Mike's brand new website is live. You can find it at Mike favenp.com That's Mike Fave np.com and he'll be posting some content there, and he's also offering consultations. So you can contact him there if you're interested in working with him. And as always, you can take a look at my website and my other content, as well as my services at Jay Feldman wellness.com and if you are dealing with any symptoms or related conditions to this series, maybe you're dealing with fatty liver or insulin resistance or any other related conditions like diabetes or heart disease, or maybe you're dealing with other low energy symptoms like chronic cravings or fatigue or joint pain or weight gain, or digestive symptoms like bloating or intestinal inflammation. Or maybe you're dealing with brain fog or poor sleep or insomnia, or any hormonal imbalances that might appear as low libido or reproductive issues of any sort, or if you're dealing with any other low energy 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 a 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 reverse 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 pick up where we left off in the last episode, where we were discussing the carbohydrate overfeeding studies and why overfeeding on carbohydrates might not be such a concern.

We've talked about this in the past, why overfeeding is really not a concern, you know, in this regard, because when we're producing. Seeing energy and using the food that we're taking in while it naturally turns off our hunger signals. That's the whole point of hunger in the first place. So way before this point, and someone who's metabolically healthy and eating a lot of food, they would not be continually hungry to the point where they could even eat that much.

Mike 5:15
They wouldn't become left or left and resistant, right? Is that the thing?

Jay Feldman 5:19
Right. And that? Yeah, well, and that's so I know. I'm glad you mentioned that, because Lustig talked about how fructose causes leptin resistance, and what he was basically showing was that inflammatory pathways that also coincide with fat production in the liver cause leptin resistance. And again, that's not not true, like that is true, but it's not because of the fructose. It's because when you're not producing enough energy, then and literally, ATP is shown in this situation to cause a lack of ATP, shown to cause leptin resistance and a lack of ATP, specifically in the liver and in the hypothalamus in the brain, which is that hunger center. So this idea that it's just caused by fructose is really ridiculous, and instead, you could say it's caused by poor metabolism, high amounts of inflammation and high amounts of fat accumulation, which are happening because of those earlier things. And we'll talk about those, the details of those mechanisms. But, yeah, the fructose does not cause, does not cause that leptin resistance.

Mike 6:15
Well, it's because it's the body. Essentially, is the body doesn't sense Calories. Calories is our construct. The body senses energy. And so it's looking like when you have in the studies that, or I would, I don't know the specific ones offhand, but I would assume in the fructose feeding study that luck, that lusig was talking about with the leptin resistance, it the inflammatory process that occurred with but just pure fructose free feeding was essentially, I mean, well, we know that in general, pure fructose feeding, with the production of endotoxin, is going to cause an energetic failure. So it wasn't leptin resistance. It was literally the body saying, Well, yeah, we ate, but we only, we still have energy, right? So we still need to, you know, we still need to pound it. I remember the leptin resistance. Like, there was an argument in what, when I was in college, in one of my site classes, they were talking about, like, Oh, it's a genetic like, being overweight is genetic thing. Like, there's a leptin resistance response in some part of the hypothalamus. And, like, certain people just genetically will overeat because of that. And it's just, like, overeat, what? Like, because there's some things you can't overeat. Like, yeah, it's kind of hard to overeat steak, it's kind of hard to overeat potatoes. Like, there's very strong satiating signals from some of these foods. So, I mean, it's a little tangential, but yeah, it's the point comes down to that it's measuring and it's measuring energy, not calories,

Jay Feldman 7:41
yeah. And we're not go ahead. Go ahead.

Mike 7:43
No, no, go ahead. Go ahead.

Jay Feldman 7:44
I was just saying, like, as far as the steak and that side of things, we're also not suggesting that you just turn off your hunger signals by filling yourself up and eating very satiating foods, either. Rather, we just want to do it through the energetic mechanisms, like through producing energy.

Mike 7:57
I just thought it was so absurd when I was in school. It was just like, like, they showed a video too. It's like, these people can't stop eating, and then, like, the foods they were eating was like, donuts and and cake and cookies. It's just like, and I just like, I told the professor, I was like, what if you just gave him, you know? And this is a point where doing paleo stuff, it was like, what if we just gave him salads and salmon and and blueberries. Like, how much are they going to overeat on that stuff? Like, if I gave them a plate of steamed broccoli, steak and butter, and then they had blueberries after like, how much are they going to overeat? Like, I would love to see that, instead of we need to, like, target this genetic pathway in the hypothalamus related to leptin. I thought it was so ridiculous, right? Yeah, it like, of course, it had to be a genetic explanation, right?

Jay Feldman 8:44
And and circling back to the to the leptin situation, another thing that really like to say that is fructose is so insane. When you see that, one of the most and you see this, but also just gaining weight and causing pretty much any issue, is when you take a rat and you put them on a quote, unquote, high fat diet. That's another like, that's a a reliable way to cause all sorts of issues, including leptin resistance. So if you want to just go on what happens in the rats in these ridiculous studies, then you probably shouldn't be eating any fat either, which most of the people who are, who are talking about the fructose causing leptin resistance are in favor of high fat. So it's basically like a parallel, yeah, just a parallel, you know, research driven conclusion.

Mike 9:27
Well, basically, everyone's trying to find something that's the point supports their particular ideology, right? Yeah, so, but like it needs to be supported, like it needs to actually make sense physiologically. I think that's going to be the final representation, not whether it's fructose or fat or whatever, whatever some somebody wants to like, scapegoat the problem as so I think looking at left into the through the lens of energy, as opposed to calories, I think, is probably the most important. Uh, shift ideologically or or mental, mental framework shift for things, because, like, it's easy to get, it's easy to get caught up in that reductionism when you, like, when you're conflating calories and energy, right? It's like, right? Like, alcohol gives you X number of calories, but it doesn't give you it like our body doesn't effectively raise temperature to raise water one degree Celsius with alcohol, like it does with fruit juice, right? And I'm saying that jokingly, yeah, but it's just..

Jay Feldman 10:35
That's, that's how people measure a calorie. It's dependent on, on like they use, you know, it's the amount of energy required to to raise a gram of water, one degree Celsius.

Mike 10:45
It's just weird, because it's like, calories, having the associative, um, it has so strong association with energy, because there's a gage of amount of food, but it's not actually telling us, like, what's happening at the cellular level. And I think this is where, when we start to get into the mechanics, where it becomes, like, more important, you start seeing the derangement happens at the cell and then bleeds outwards from there. And it's basically like a whole host of backup systems to make sure that the cell, like, is somehow dealing with the situation.

Jay Feldman 11:18
Yeah, so let's so let's get to, let's get to that right now. Like, what's, what's going on there? The one thing I wanted, one thing I wanted to mention, too, you had mentioned alcohol a couple times, and I didn't want to mention that fructose has been shown to double the detoxification rate of alcohol increases by it increases it by 100% which is just worth mentioning. It just like, kind of shows such a, such a contrast with this idea that fructose is also a metabolic toxin, because if it was, it would definitely decrease it would probably cut it in half instead of decrease the amount of detoxification of of alcohol, not increase it. So I just figured that was worth mentioning. But, yeah, so, so basically, what we're getting at is that the and where we started here is that the oxidation of carbohydrates, or when carbohydrates are not being used, well, they're not being oxidized, they're not being stored. They're not being released. As you know, convert to glucose and released, then that backup option is to be converted toward fat. And the same thing can be said for fat as well, where, if the fat is not being used, then it'll be stored. If it's not being converted to something else, it'll be stored. It's not being stored. It's not being converted to energy, it'll be stored.

Mike 12:28
If you have any type of nutrient deficiency, like a rank nutrient deficiency, or like even deficiencies and things like choline, which is what the what a lot of people will talk about with fatty liver, and what one of the questions was specifically related to, you cannot process fats effectively without that so, like, it could, they're all and it can go hand in hand with deficiencies and, like, even with alcohol, like, even with alcoholic liver disease, like the processing of the alcohol and the effects of alcohol and liver cause deficiencies over time, because It speeds up the utilization of those nutrients and also impairs absorption, and basically causes wasting of those nutrients as well. So there's a lot that goes into it. It's not just, oh, fructose is the poison and that's it, or saturated fat is the poison and that's it. It's like, there, like you need to be able to process those saturated fats. Need to be able to process the fructose effectively. And this is why, when you start looking at like, particularly fructose, like, Oh, you're taking it in, in with fruit juice, that changes it drastically from just like drinking straight up agave nectar or something which is almost pure fructose, like one of the only things. So those are like, drastic differences, and in it involves, and I guess we'll get into some of the nutrients as well. But, yeah, you go ahead.

Jay Feldman 13:47
Yeah. So let's, let's, I just want to map out that basic because we've said, like, Okay, if all these things aren't working, then fructose gets converted to fat, or the fat gets converted to other fats. You know, fatty acids get converted to fats, and that's what leads to this production of fat in the liver. So I want to just use this diagram to show how that's happening. I think it matched it out nicely. Obviously, if you're looking at this, it looks a little complex at first, but we'll break it down. So basically, at the top here, we've got these inputs coming in. We've got the carbohydrates, which they're noting, particularly fructose. You've got the free fatty acids that are coming in, and the protein as well, which the protein as well, which the protein isn't particularly relevant for, for this right now? Yep. So when we're looking at both the carbohydrates and the free fatty acids, both of them end up getting into the mitochondria, and you know which is right here and going through the citric acid cycle, and or beta oxidation. Beta oxidation is just for the fatty acids, and what's basically, if there is some blockage going on here, something's not happening, or something's not working well, you end up with a large amount of citrate, and we'll talk about this a little bit later on. Yeah, yeah, but basically, you get this excess citrate, and that citrate is the thing that's right here. Is the thing that gets converted to the fat. So we see that right here. This is that pathway where you get the citrate, gets it basically leaves the mitochondria, then it gets converted to acetyl CoA, the malonyl CoA, and then palmitate, which is one of our saturated fats. And then the palmitate can also be converted to stearate, which is another one of the saturated fats that our bodies produce.

Mike 15:23
Those are the two main ones that that are produced from any type of substrate coming in. And I think it's important to point out for people, because everybody, like, wants to hate on palmitate. And it's like, that is the primary fatty acid that our bodies.

Jay Feldman 15:38
Yeah, yeah, yeah. And so this is that basic process of fatty acid synthesis, and it comes from any like anything that's blocking the citric acid cycle, the Krebs cycle, mitochondrial respiration, anything that's blocking that is going to lead to an accumulation of citrate, that citrate then leaves the mitochondria and ends up getting converted to fat. And this can happen both from using carbohydrate as an entry point into mitochondria respiration, or the free fatty acids. And just for clarification, here you see that the free fatty acids are carried into the mitochondria from that CPT one.

Mike 16:14
Carnitil palmitoyl transferase, one Alpha, right?

Jay Feldman 16:18
Yeah. Carnitine palmitoyl transferase, one which, it's important to note that just because people will, you know, when you're talking to a physiology, people will talk about that as a an important step to consider, yep, so you have, so this is just a basic fatty acid synthesis. And then, along with this, when you have this process shifting toward all this fatty acid synthesis, you then further block respiration. And so the one of the things they talk about here is that the melonyl CoA, the presence of malonyl CoA, blocks the CPT one, a the carnitil, the carnitine palmitoyl transferase, so it blocks the carrier, yeah, the thing that that transports or allows for the fatty acid basically, to get into the mitochondria, or the acetyl CoA to get to mitochondria, the Melano COA blocks that so everything, and there's a bunch of other enzymes that go on and blockages that happen along this whole process that prevent things from being oxidized more. Because what they're basically saying is we've got this overload. Things are not working well. We're not able to produce energy or do other things with it. So it has. We're just gonna have to shift towards storing everything extra that we have right now as fat. And when this happens, there's another, you know, another two things I want to point out. Well, one thing here is, is the SCD one. So when we end up with a lot of production of palmitate and steerate those fatty acids in the liver, we then end up with an activity, an increased activity, of SCD one, which converts these fatty acids to monounsaturated fats. We've got the pulmonolate and the oleate, and those then can get used to produce, to produce triglycer triglycerides. There's a couple different pathways you can see here that basically go from the production of fatty acids to the production of triglycerides. And the triglycerides and the triglycerides is just a few fatty acids put together with with a glycerol backbone. And that triglyceride is the fat that we're talking about when you're talking about fatty liver is high amounts of triglycerides, and that gets just a downstream conversion effect from these fats, these fatty acids that get produced, and then that's where you end up with all these triglycerides over here. And so the reason I wanted to highlight that CD one is because we talked about that in more detail in a previous episode about why it is definitely a something you don't want to see elevated. It's a sign that that this is happening, that you know you're not using the substrate well and you're producing a lot of fat. But it's not necessarily the target or the main focus that is determining something. It's more just on the surface level as a response so, or as a symptom. It's like a

Mike 18:45
It's like a marker.

Jay Feldman 18:46
Exactly, exactly.

Mike 18:47
Yeah.

Jay Feldman 18:49
So is there anything else you want to add here to this graphic? We'll dig in in a little bit in some more detail about what actually is going on in the mitochondria here that is causing this to happen in the first place. And there's a really great graphic that we'll use to dig into that in a second.

Mike 19:04
The one thing I just wanted to highlight here, and something that you you did talk about, and you did mention, is that it's this build up of citrate in this system, is where you start to see this, like the citrate, and then you move to malayal CoA, and then you have the shutdown of CPT, one, a so it's like, this is the derangement happens in the mitochondria. And then eventually what you see is the build of the citrate. And then that's when you start to see, okay, once you start to see, like, high it's all about concentrations, right? So once you reach the certain concentration here, you start to see things move downstream into producing the palmitate and steri. And then we did talk about this in the SCD one. What was that? About the fire in a bottle? Stuff? That was a podcast. So we talked about this and that the SCD one, I think we we came to the conclusion that it was upregulated, because when you convert the the saturated fatty acids into the mono and saturated. Fatty acids, they're easier to process and move around and and things like that. And then eventually, what we showed is that when you have this high buildup of the saturated fatty acids inside the cell, that's when you start getting the lipo toxicity. So the SCD one here is actually there for a reason. It Like It's a release valve on what's going on inside the cell. And it just wanted to highlight the those, those key areas. So it's this concentration of citrate based on what's deranged in the mitochondria, and then also, um, the SED one is like a release valve for the production of the saturated fatty acids so that they can be processed. Because you have the liver, which, which you have, basically have, like a storage in the fatty acids. And you can have it intramuscularly. You don't necessarily want so much that, but you have like this deliver, you have the depots for the fatty acids, which can take these triglycerides, and you can deliver, can hold some as well, and it can move for storage. But once you start like, maxing out that system, or you impair, like this process of exporting and whatnot, you can start to run into some serious issues and and that's where you start to, like, part of this lack of ability to basically export the fats out of the liver is one of the problems. You can't export the fat, and then you also have, like, the derangement of the mitochondria. So you're basically creating bottlenecks inside the cell, and that's, that's where you start seeing the derangement happens inside the cell with these bottlenecks. I think that that's, that's the key that we're going to get to in the next couple slides, or whatever graphics, whatever you want to call them, because it's not really a PowerPoint.. but.

Jay Feldman 21:29
Yeah, the other thing I want to point out here is that when everyone's so focused on fructose causing these problems, but if you have this issue with mitochondrial respiration, then you still can have the free fatty acids coming in, getting converted to acetyl CoA outside of the mitochondria. And then they go to be converted directly into triglycerides themselves, like basically through the well, they're showing it in a dotted line here, but really it's going through this whole pathway over here, through the melonial CoA and whatever else. But this can be caused just as much by fatty acids as it is by fructose. So just wanted to highlight that as well, that an issue with any sort of mitochondrial respiration here, that's really where this is all centrally happening, is going to encourage these things to move toward fat. And what a lot of people focus on is this idea that it's not a problem with respiration. Instead, it's when you've got so much you've been doing it so much, you've got so much substrate, whether it's fructose or fats, that you're going to produce a lot of ATP, and then that's going to slow this down, because you've got enough energy, so then that's going to cause all these other issues. But in reality, that is very, very rarely the case. Normally, the problem is things are getting stopped way before you have too much energy. But instead, there are other things blocking this process that prevent, actually prevent the production of energy. So yeah, and again, to clarify, and we'll show this another diagram this. This is not the only thing that happens. When things are blocked in the mitochondria. You also have the conversion. You can increase the conversion to glucose, increase the conversion to lactate and things like that. I mean, you convert to glycogen as well. But this is just what's happening on the fatty acid production side, or, sorry, I should say the triglyceride synthesis side.

Mike 23:04
Well, I even think the most important thing, or the most negative thing that happens is when you start seeing all that ROS generation in the mitochondria. And we're going to get to that. So I know what you're saying, Every there can be converted to other things besides triglycerides, like you can also have gluconeogenesis and whatnot going on, or glycogen. Once those get maxed out, though, then you're starting to move in towards basically, that's where you start getting more derangement. But the ROS, I think, is where we're going to see the biggest, the biggest problem, and then that's where PUFA will come in.

Jay Feldman 23:36
Yeah, one. And that is something so you do end up seeing, when you're seeing increased lipogenesis, you also see increased hepatic glucose output, which is normally something that's seen in insulin resistance and diabetes, and that's what causes high fasting blood sugar. Is this propensity to shunt out or send out a lot of glucose from the liver, because typically, either the liver is under stress or some other aspect, you know, some other areas under stress, and that's causing high stress hormones, so, and that tends to be caused by the lack of energy. So you've got this, this perfect system going on that all contributes to this problem. And so unless you have anything else to add there, Mike, I'm going to go on to the next diagram talking about what actually could be causing this, and then all the different places that it could, you know, all the different effects that could be happening.

Mike 24:19
I just this is like, kind of, I didn't look at this directly, but it's kind of like amusing when we were looking at the diagram. I wonder if the protective effect of the so called unsaturated fatty acids, whether mono or poly, is because they already have the double bonds in them, so they're easier to export, whereas the saturated fats, when they go to the towards, into the liver, have those extra steps, and so you can maybe saturate the pathways and cause that. That's what's leading to the to the metabolic issue with excess because they do show in studies, when you overfeed on saturated fatty acids, or at least there was two studies that showed this in humans, that when you like overfed by 1000 calories, which is a lot. They showed that you did get a increase in in fatty, fatty liver. Yeah, yeah. More so than with PUFA. More so than Exactly. And I think what may have been occurring there is perhaps there's like a little bottleneck at where the enzymes become saturated, and then processing the saturated fat can cause, like, can slow down that process where, with PUFA or mono unsaturated fats, because they're already converted into those forms that are more easily movable, it's like it there's less, there's less, less likelihood for bottleneck. But then that does, that isn't that changes the dynamic of like, what's underlying the problem, right? Because even though there's less bottleneck with like, something like PUFA, we you still have the oxidative issue. So I that's just amusing. That's something that we'll have, we'll have to look at separately, but I think that it may have something to do with the enzymes like that, where it's like the saturated fat causes the bottleneck because of a processing issue, not because the saturated fats are inherently metabolically harmful. And then, obviously, if you have too much substrate inside the cell, then that's where it's metabolically harmful. But that's not a feature of the saturated fatty acids. That would be a feature of just having too much substrate inside the cell, too much fat in general.

Jay Feldman 26:18
Which is also a feature of how well are you using it right? It's not just you have too much, but is there something preventing you from using it effectively that's going to cause relatively too much? The other thing too is, is that, like you mentioned, is this also perhaps a protective mechanism? Whereas, when you're having a lot of PUFA, maybe you don't cause fatty liver, but you have these other pathologies going on elsewhere that are potentially worse, you know, maybe you'd prefer fatty liver in that point, at that point, considering the the extremely toxic and harmful metabolic effects of and other effects of PUFA.

Mike 26:49
So yeah, and the reason I bring that up for the audience and everyone is that a lot of people like the causative factors for fatty liver, everyone is like, oh, it's fructose and saturated fat. So yeah, that's, that's kind of why I bring that, that up there. It's like, how are they actually causing it? Because we have explanations for why fructose is causing it in that particular way, but we haven't really, um, we'll have to dig in a little more unsaturated fat. Yeah.

Jay Feldman 27:14
I mean, it's basically the same thing. Yeah, I would say. But anyway, I did want to mention one thing you, you mentioned there just real quick on that last diagram that I didn't highlight as much was the exportation of the fat. So you do have the accumulation, but you also, so we have this, this accumulation here, of triglycerides, but you also have an increase in exportation of the triglycerides as VLDL or LDL. So that's also a feature that you see in this situation. But again, it's just a downstream effect of these other things. But moving on to the next thing that I wanted to it digs in, basically into these mechanisms a little further, which I'll just we'll kind of go through this, and then we'll talk through some of the studies reflecting it. Yep.

Mike 27:56
Is this going to be the big one?

Jay Feldman 27:59
Yeah?

Mike 27:59
Crazy one. Okay.

Jay Feldman 28:00
Yeah, yeah.

So here, and this is a pretty there's a lot going on in this diagram, so we'll, we'll kind of go through it. The other thing that I don't like about this diagram, so I like that it has a lot of these features, but I don't like the organization of it, the numbering, because I think it's kind of out of order in my view. So I'm actually going to go through it in the order that I would say it happens, and then we'll go from there. So we talked about how really the bottleneck seems to, you know, the bottleneck tends to be at mitochondrial respiration, at the product production of energy. We talked about this in virtually every condition, because it tends to be in virtually every condition. So what we're seeing, we're seeing that really over here at number seven and number six, but basically this whole area right here, this is the electron transport chain, and so this is the last piece of mitochondrial respiration where we're producing that ATP. And what they're saying here is that, and they're not exploit, they're not giving a reason for it. But there are a lot of reasons why this can be deranged, why this cannot be working properly. Part of it could be because you're burning a lot of fat and stuff, a lot of carbs. Part of it could be because you've got a lot of nitric oxide. Part of it could be because of endotoxin, which directly comes in here and blocks some of these components, or its downstream effects with TLR four and TNF alpha, like all of the all the stress and inflammatory processes, have blockages, basically, along this electron transport chain, and then a protective way that we've discussed before. Basically, you want to conserve energy when things are not great. So that's what we're seeing here, where they're noting for one day note which I love this they know the low NAD and fad relative to a high NADH and FADH two. So this is basically showing a low NAD to NADH ratio, and they're saying that that's happening because the electron train is not able to function well, and so you're not able to offload the electrons. You aren't able to convert NADH to NAD so you end up with a large amount of NADH, and you also end up with a large amount of FADH, two in the same process, it can't offload its electrons, so you end up with a high amount of those relative. To NAD plus and fad plus. And so that's one thing you get. Another thing that you get when this there's blockages here, is a high amount of reactive oxygen species, which you see right here, and that ends up causing some downstream effects that we'll come back to. You also end up with low ATP, which they don't describe directly here, but that would be another piece that you see. So that's what I would say, is really what's starting this. And then they also mentioned some of these react, the reactions to this, which these are a little farther downstream. So they mentioned uncoupling up here at number six. But what they're really talking about is just what's going on at the electron transport chain. When things get really bad there, you do see increases in uncoupling. And this is a feature that you see in non alcoholic fatty liver disease, you see increases in uncoupling. You see this effect on the NAD NADH ratio. You see increases in fat oxidation, which is counterintuitive, because people think if you're producing a lot of fat in the liver, you're probably not oxidizing much, but you actually end up favoring that fat oxidation. You also, of course, do see increased lipogenesis. You also see increased hepatic glucose output, or gluconeogenesis, which we'll talk about more detail. You see increased SCD one, which we mentioned in the last one, and is not shown here, because this isn't focusing as much on the fat production. And you see increased free fatty acids and the release and increased stress and lipid peroxidation, which the peroxidation you see here. So so we've got this the situation of the electron transport chain, and then what that does is that's going to block the function of the or the, I guess I should say the complete function of the citric acid cycle or Krebs cycle. So they're talking about an increase here, which does happen as an adaptive effect that we'll talk about later, where, basically, because there's a lack of energy as a backup response, you try to run respiration harder, but it's not able to run all the way through because you've got this block at the electron transport chain. So instead, what you end up with is a buildup of citrate. You can also end up with a buildup, buildup of oxaloacetate. And so then, just as we talked about before, that buildup of citrate ends up leaving the cell or the and the oxaloac state gets converted to malate. So those both end up leaving the mitochondria, excuse me not, the cell down here, and they get end up, they end up getting converted to one of two things, either fat. Yeah, either glucose or fat. So here, number five, we've got the increase in de novo lipogenesis, the conversion to fat. You also end up with an increase in ketogenesis, which, again, we haven't talked too much. We've talked about this before, where ketogenesis tends to be regulated by excessive stress and excessive stress hormones. And you see that here, where you increase the production of ketones as a as a response to stress. And then over here on the left, as you mentioned, you see the increase in gluconeogenesis that's here on the left, number four, which is also happening from those same byproducts. So this is what you see happening when there's a lack of mitochondrial oxidation or respiration. Things are not the materials, substrates are not being used properly. And then if you follow that up a little bit. So we mentioned the increase in citrate, increase in oxaloacetate, it also leads to a buildup of Acetyl CoA within the mitochondria, and that then blocks a lot of the upstream effects. So you end up blocking pyruvate dehydrogenase. This is all features of the ranzyl cycle two. I'll explain that a second, but you basically see this situation where you block the usage of glucose in respiration, and you actually shift toward increased beta oxidation to an extent which they're noting here as well. And as I mentioned, you see increased fat oxidation relative to glucose oxidation in this state, and that's because of the Randall cycle. So basically, all the Randall cycle is it's not really a cycle. It's just a situation that happens when you are burning fat or you're not burning glucose. Effectively, you end up with a lot of reactive oxygen species. You end up with a low NAD to NADH ratio that controls the citric acid cycle and the Krebs cycle. It leads to a buildup of citrate. It leads to a buildup of CoA. And then you also have the low NAD NADH ratio, and that blocks several steps that lead that allow for glucose to be converted to Well, eventually through the citric acid cycle, and then eventually to to energy, to ATP. So basically, we're just seeing that here is a function of insulin resistance where we know insulin resistance is just in an inability to burn glucose as a fuel. And that's happening in this case because of all these backup pathways, and it blocks all the enzymes that help along that pathway, and it also slows down mitochondrial respiration as a whole. And I'm gonna, I know, I just dug into the weeds, and it was kind of going, I guess, a little quickly, so I don't know, Mike, do you want to maybe help me summarize some of those things before we talk about the lipid peroxidation and oxidative stress and the other inflammation components here.

Mike 34:38
I think the biggest thing that people need to understand is that it's, it's just a it's like a bottleneck and then a backlog. So when you have that backlog there, it basically this cycle. It's literally a cycle. It may show you show it moves in a singular direction. When this backlogs here, it shuts down this process. On the Krebs cycle, or the citric acid cycle on the left, and then that backlogs everything coming into here, your acetyl CoA from all of these, these substrates. And then it basically shunts everything in, sort of like, like backup pathways per se, and that's where you start to see that shift in towards beta oxidation. So literally, you don't need to understand all the different enzymes. You don't need to understand all the different cofactors, the different mediators that are produced here, succinate, fumarium, malate, et cetera. What you need to understand is that when you have this ratio shift over here at the electron transport chain, it shifts everything back, and then when everything gets shifts back it it basically you have all of these processes that that are that are still trying to run. Because basically you're having a flow of energy. You're taking the food, you're taking the electrons off the food, you're putting it on carriers, and you're running it through this process. That's literally what this is. It's trying to flow energy from food to produce energy for the cell. When the cell can't flow the energy in order to, like, not basically implode on itself, it moves that energy into different ways, because you can't have all these electrons or the electron carriers just, I mean, essentially what you get is you have too much saturated electron carriers with your NADH and your FADH two. So then this, when that happens, the cell doesn't have anything to carry the electrons anymore. And so it's kind of like, Oh, what do I do? So it starts shunting to de novo lipogenesis. So it turns it takes whatever the substrates that it, that um, that it, the food that it converted into the substrates. It takes those substrates and it shunts them into storage as a noble lipogenesis, and then it shunts them into producing them as as glucose with gluconeogenesis, and then it backlogs the process. And then at a certain point, it's like, I can't keep producing fats or producing glucose or backing the process up, because you still have the substrate coming in, so then it starts to uncouple. So basically, what you're showing here is that the Krebs cycle, the citric acid cycle, which is number three, gets uncoupled, which means it's not linked anymore to the electron transport chain, which is number seven. When that occurs, it basically the energy that's produced, or the carriers that are produced from the citric acid cycle just get pushed through the uncoupling protein and generate heat to as a way to waste the excess energy. So what the cell is saying is like, I can't process the energy effectively, so I need to find ways to get rid of it. And that's that's what's going on, and that's why you start seeing the backlog of fats and the and that shunting of these shunting of these mediators to producing glucose with these mediators, and then burning the excess through de no light, through uncoupling. And the whole process is just based on that energy failure at the cell. So you need to figure out what's causing that energy failure at the cell. And it could be like a series of different things, but you you need to figure that out, and that solves the problem, not anything outside of that, right? You need to fix that energy, the energy failure at the cell. That's really what it is. The cell is just pushing everything in all these different directions. Because when this flows, it flows nicely. You have your glucose, your fatty acids. They come in. The fatty acids will run through beta oxidation. The glucose will come through the citric acid cycle. Then the whatever, then the acetyl CoA for beta oxidation will go through the citric acid cycle. It'll produce FA NADH plus and FADH two, that will run through the electron transport chain. You'll get ATP, you'll get CO two and and throughout that whole process, you'll produce water. You're good to go. It's very simple, but when you have that bottleneck, when you when you start losing electron carriers and there's nowhere to store these electrons, you basically get screwed. Your cell is just like has all of this stuff coming in and nowhere to put it. So it just starts storing it in all these different directions, trying to solve, basically, trying to solve its problem. So you need to solve that, that that issue there. First, you need to get the cell to start oxidizing correctly through the citric acid cycle and through the electron transport chain. So you need to find out what the block is. What the block is, and that's, and I think that's the simplest way to put it. It's, I guess, an analogy. It's like if you add a supply chain in a factory. A very, very relevant one is if you have a meat factory, right? And you produce steaks, if you have x, you have 100 100 cows, or 100 cattle come in per day, and you put out 10,000 stakes, right? If you have a, if you're ruin the machinery that puts in the stakes and but you still have 100 cattle coming in per day, you're loading up. The fact. With cattle without that bottleneck for the steaks to be without, or you have a bottleneck so the stakes can't be produced. So it's just like, you start storing the cattle, the carcasses of the cattle, in the freezer, and just like, until you can fix the machinery, but you need to get the machinery going again. That's really what that's really the problem. You don't want to stop the cattle from coming in the factory. Maybe you want to stop it for a little period of time so that you can fix the bottleneck. But the ultimate goal isn't to stop the cattle from coming in. The ultimate goal is to start making the stakes again, and that means getting the machinery to function appropriately. And that's the easiest way, I think, to break it down, so that people, people understand what's going on. Now, the next step that you're going to get into, and you explain it, and you can explain it, but the idea here is that in the next step, you're still trying to run the machinery, but the machinery is messed up to produce the stakes. So it's creating a lot of smoke inside the factory. That's essentially what you see going on. Your conveyor belt is broken, but you're still running it to produce as many stakes as you can. And in some cases, you're, you're, you're, you're running in the conveyor belt for the cattle, the carcasses to come in, and you're just moving all of them into, like, I don't know, like to a garbage pile. That would be your uncoupling. To some extent, you're just but and in this process, you produce a lot of smoke because the machinery is broken, and that's what you're that's what you're about to explain with peroxidation.

Jay Feldman 41:27
Yeah, yeah. And so the just, I know might have gotten lost in the analogy, but the uncoupling is a response to a lot of reactive oxygen species and oxidative stress, and relieves those things. It doesn't tend to cause those but...

Mike 41:39
I'm trying to put it in the Yeah.

Jay Feldman 41:44
I know. I know that it's yeah analogy.

Mike 41:46
The analogy is not perfect, yeah, right, right,

Jay Feldman 41:48
So, but what so is what is happening? So we talked through kind of the initial parts here, and then one other byproduct that you see in non alcoholic fatty liver disease is the increase in oxidative stress, which you're seeing over here, and the increase in peroxidation and inflammation and eventually apoptosis. If things are getting so bad, you're producing so much of the oxidative stress, basically, you're there's a lot of reactive oxygen species getting produced that ends up leading to all of these backup pathways. And you also happen to see a couple of stress pathways that they noted here, you've got the nrfs and PGC one alpha, and these are things. I'm just highlighting them because some people will note them as good things that happen in response to stress. And I mean, they're good in that they help us adapt to stress, but they aren't things that we want to be, you know, encouraging or forcing as as increased, or forcing them to be increased. So, yeah, I think, I think that explained most of what I you know, most of the mechanisms that I wanted to touch on, as far as this goes, Okay, anything you want to add?

Mike 42:53
I just wanted to when you talk about so when you the Ros is basically, they're free radicals, per se, right? They're, they're components that are going to pull electrons, is correct? They're going to, you're going to pull electrons from other components inside the cell, and that's what's being generated here at number seven, at the electron transport chain in this derangement. And you have some one of you have some components inside the cell that can solve that problem. That's where you see your glutathione peroxidase in your manganese superoxide dismutase. Those are there to basically soap up those free radicals. So those are protective systems as well. But what happens is the reactive oxygen species that are produced can basically go grab electrons from other components, whether that that, whether it be inside the cell, the DNA of the cell, or it can go to the cell membrane, or any of the fats in the cell, and that's where you're seeing the peroxidation. That's where you're seeing the they're they're basically destroying the fatty acids in the cell, and the ones most likely to be destroyed are going to be your polyunsaturated fatty acids. And then what you see below MALDI aldehyde, hydroxy Neo Nano. It's h, n, e, I can't pronounce the other one. And then the oxysterols are all the peroxidative, damaging aspects, and then these aspects are the shift into the actual highly inflammatory state when you start seeing a lot of these. And that's where you see the difference between hepatitis and just like a fatty liver disease or fatty liver.

Jay Feldman 44:37
So you're saying, like fat production versus fat production with inflammation. And again, the inflammation being here, the JNK, which I mentioned that pathway earlier, that Robert Lustig liked to point out, and NF, kappa B, which is another just inflammatory marker. So yeah, you've got the peroxidation, meaning the damage of of fat, specifically polyunsaturated fats. And you mentioned those byproducts there that we're seeing here. And then also inflammatory markers. Yeah.

Mike 45:00
Yep. And then, I guess you could just say the NRF one and two and then the PGC one alpha are basically just like they sort of upregulate cellular defense in response to the oxidative stress. So they help the cell deal with that oxidative stress and ROS better. But their their backup pathways to what's going on. Ideally, what you want running is you want the cell to be able to just oxidize the glucose or or the fatty acids to your ATP and your CO two. That's that's the ideal state. You want to just basically run through nice and clean and not have to worry about upregulating the NRF one and two, PGC, one, alpha. And this is where, when, this is where. When we talk about hormesis, we have to issue because a lot of people focus on these hormetic pathways, rather than just like, that's step two. That's like step two, step three down the road, instead of just making sure the system works right the first place. And this is Pete's whole idea, and why Pete initially turned us on to the issues with with hormesis and whatnot. Yeah, yeah, yeah.

Jay Feldman 46:06
So this, this is a nice transition into pointing out, like, I know we talked about all this as this, this is what happens. But there's a lot of research supporting all these points. And I want to start with just this idea that the central problem here is a problem with mitochondrial respiration, a problem with ATP production that's leading to this issue, and so and so, and we already mentioned, like poor fat oxidation, poor carbo oxidation being the problem. So I'm going to read a quote from a study, and this study has a graphic as well that we can gloss over a little bit, but basically what we're going to be seeing here, well, okay, so I'll read the quote so the the article states markers of my top 50 were increased, but proteosomal degradation activity was reduced in non alcoholic fatty liver disease mice livers suggesting a ATP deficiency because of the reduced stability of oxidative phosphorylation. Complex units contributed to inhibition of ubiquitin proteasome and activation of mitophagy. In conclusion, the heavy water metabolic labeling approach shows that increased degradation of hepatic oxidative phosphorylation subunits contributed to mitochondrial impairment in non alcoholic fatty liver disease mice. That was a jumble of words, but it did have meaning to it. So what we're basically seeing there, so for one they were saying markers of mitophagy were increased, and you mentioned hormesis. And so this is something that you see is that in disease processes, you see increases in autophagy and mitophagy, which are basically recycling of components of the cells. And people say that's a good thing, but you see that in this dysregulation, in these states, and this point they're seeing markers of it increasing. But they actually mentioned that the degradation of the of the like the proteolytic activity, like the degradation, the recycling of the pro protein components, was actually reduced. It wasn't happening well. So it's almost the equivalent of trying to stimulate autophagy, but it not functioning for some reason. And this is again, one of those major main problems with hormesis, where, if you're just trying to do the things that are going to increase autophagy, if these other problems, like, if there are other problems going on, then it's just going to make it worse, because you're causing those stress signals, which is already going to make it worse, causing stress, but you're not even able to to perform autophagy, or in this case, my autophagy, because of these problems, you See derangement of those processes. And here they mentioned that it's because of ATP deficiency and a reduced stability of the oxidative subunits, the the components that allow for the production of energy through mitochondrial respiration or oxidation. And so they have a essentially energy failure, exactly energy failure with stress. So they're trying to activate these stress processes, but they can't, because there's an energy failure, and they're saying that this happens in non alcoholic fatty liver disease. So here's the they've got a little graphic here. What you see here is basically what they were looking at in the study where what they found in the case of fatty liver disease was that the there's a couple things that were going on. So one was that mitochondrial respiration was not functioning too well, and they saw an increase in NADH, and remember, we talked about this before, with a low NAD NADH ratio. That's the equivalent of an increase in NADH, but it's accumulating because it's not being converted down here at the electron transport chain. And what that then leads to is a slowing down of the Krebs cycle and increasing acetyl CoA. And that ends up causing increases in all the fat production pathways, which they mentioned. And then you also end up seeing because, and I guess this kind of starts earlier, is the decrease in ATP, so they mentioned that right over here, and along the way, they also mentioned that there's an increase in reactive oxygen species production coming from the electron transport chain. So it starts here, and then they show that happening over here on the left. So I don't want to dig into this too much. We kind of already talked about it, but this is just basically what they were seeing in the study. Was might. 100 respiration not functioning all that well, and leading to the situation of non alcoholic fatty liver disease.

Mike 50:07
Is what we just said, all broken down into one slide. And I just the one thing that's nice about this one is that you have the NADH elevated here as and showing it as Central. So you're seeing that you basically have so your electron carriers through the citric acid cycle is going to be your fad and then your NAD plus. And when you when those are, when those are fully saturated with electrons, which is what you see with your NADH and your FADH two, then you don't have anything else to pull any more electrons. You basically run out of carriers. You run out of the ability to hold that energy, and then that's, that's the central piece of clogging up the chain. I think that's the most important piece that I think people need to understand, is that it, it's and I wish I don't have an analogy off the top of my head right now, because that, like, perfectly relates. Because, like, even with the last one, like, it's kind of hard to have it hit, all the hit, all the explanations, but you're essentially when this happens down, when you basically don't have any carriers, then you start you impair energy production at the cell. And then we talked about this previously, but you have that, the bottleneck that develops, then you have the ROS production. And so basically you have an energetic failure, and with that energetic failure, and this is so important because it flies in the face of this idea that the longer if you want to live a long time, you need to have a low metabolic rate, right? Because this is showing that if you have a lower metabolic rate, you increase your ROS production. And this, like we're showing it through fatty liver, which I think is important. But like in all of these disease states, it states it wounds up being the same thing. All the metabolic syndrome winds up going in the same place. You have an energetic you have energy failure at the cell, and then you have increased oxidative stress. And then with the increased oxidative stress, you basically, can you start peroxidizing lipids and causing DNA, DNA damage inside the cell? Well, then enough of that, you start getting basically, what is it? What's the word that I was is it? No, it's not autophagy. My autophagy. No autophagy, yeah. Or apoptosis? There you go. Okay, yeah, yeah. So it's like the metabolic and energy production is central to everything that's going on, and slowing the metabolic rate or functioning on backup pathways is just not the answer.

Jay Feldman 52:33
Yeah, yeah, yeah, definitely. So moving on from from there, I did want to just note a couple other studies that were just talking about how integral the mitochondrial respiration is to to the situation, and how it's shown to be impaired in fatty liver. And one of them, I think, is particularly important this first one, I won't spend too much time on, but I just wanted to share the quote where they mentioned that increased levels of cardiolipin and ubiquinone, which are the major factors in the electron transport chain, help to may help to preserve mitochondrial function in early non alcoholic fatty liver disease. And then later on, they mentioned that these data suggest a close link between accumulation of specific hepatic lipid species, mitochondrial dysfunction and a progression of non alcoholic fatty liver disease. Just pointing out that connection. And that did remind me, you mentioned an analogy, like wanting, you know, some sort of analogy, and we had a decent one in the past, which was an assembly line. And I think it's a helpful one, where, basically you have these carriers that are carrying electrons, or something with energy, something with value, to somewhere else to produce something. So you have some, you know, some people are carrying some I think you had, what was the example you gave? Maybe like making a computer. Let's say like making like a let's say like making a chair, right? And so one person has to create the legs, one person has to create the scene, one person has to create the back part, and then somebody else puts it all together. So everyone just has their own job. And so you have the people who are they're carrying all the legs over to the person at the end. And these, you've got these other people who are carrying the seats in the back of the chair over to the person at the end who has to assemble them. And that's those people carrying the things over are like the NADH and FADH two. They're carrying these, these things that are potentially going to become something of value, but on their own don't really do anything. And if that is, if that person at the end, if there's not enough people at the end, or for whatever reason, they ran on a glue, or whatever, puts the chairs together, and so they can't put them together, you just end up with a bunch of people walking around with those components, and there's nothing to do with them. And so that's like the high value, like the high NADH compared to the NAD plus. The NAD plus would be people without anything, who are going to get more and bring it back. So you've got all these people holding onto these components of the chairs, and they don't really have anything to do with them. And then you meant, you know, to add on an extra little piece here is we've got the reactive oxygen species, which is that, basically, when you have this happening, and this isn't, I guess this isn't perfect, because reactive oxygen species. This is really happening at the end there. I guess what's happening with reactive oxygen species, you could say, like, the people with these components keep trying to dump them off to the people at the end. People at the end don't have enough glue to put them together, so they're just, like, chucking those components out somewhere. And they like, you know, they're breaking stuff. They're just throwing them out maybe that, maybe it's causing some sort of a fire or something. So it's all wood. And that's like the reactive oxygen species, where it's like you've got this bottleneck, you can't use the components, and they just start causing havoc elsewhere, because there's nothing else that can be done with them. And along the way, I guess another piece here is that, instead of then using this wood to make chairs, because the whole chair making process isn't going well, you start using the wood to, I don't know, do something harmful, and like, the wood just accumulate. I guess the wood just accumulates.

Mike 55:48
You're just piling up pieces of the chair all over the place, inside, inside this factory.

Jay Feldman 55:54
But it's not even pieces of the chair. It's like, pre those pieces. It's like, you've got the wood that it was carved from. You've got this huge amount of that wood. And that's the fat accumulation, right? Instead of starting to take those pieces and put them through the chair making process, you know, it's not working well, so you just start stacking up those huge stacks of wood, and that's like the equivalent of the accumulation of fat that's happening because of this other process that's deranged. And so these studies are where, where these ideas are coming from, showing that the process, the this process, is what's limiting, what's the limiting factor in non alcoholic, fatty liver disease, and is causing the fat accumulation.

Mike 56:29
So essentially, the chairs, there's something blocking the assembly line so the chairs can't be produced. When the chairs can't be produced, then all the people who are carrying parts are stuck with their parts because it's not flowing anymore, and then that backlogs all the way up so that the wood that's coming in to make these parts, there's nowhere for it to go, so they just start storing it in places inside the factory. Once you have excess amount of wood inside the factory, you're not the factory is not able to function appropriately, and then eventually the factory explodes, and that's apoptosis.

Jay Feldman 57:00
Thank you for that was a good way to piece it all together. At the end, that was good though.

Mike 57:04
While they while the while they're trying to make the chairs, the ROS is essentially like, they can't make the chair, so they just start breaking the pieces of chairs that are there to get rid of them. They're like, just like all these shards of broken chair all over the place, and, like, it damages, it damages the factory workers, and then there's damage to the factory itself. And so that's what happens when there's no flow anymore. And that's basically what's happening. That's what happens at the cellular level. You don't have that flow of energy. That's the most important piece. And that's what, that's why Pete always like when people ask him, like, how, like, what do you do to stress? Like, how do your friend aging? Like, it's always just like, the flow of energy, the flow of energy, the flow of energy. It's because that's what it essentially comes down to, everything, sort of like, is breaking at that level. And it is, like it's at every single, every single disease. The other thing I wanted to point out on one of the previous slides that we didn't discuss was at the top, it just said an increase in insulin resistance at the fat, the white adipose tissue and the muscle cell. So what it's showing there is that this process has already occurred to some extent, at your your fat tissue and at your muscles, and then it started, and then it can start to back up to a degree to the liver. So it's like the same thing that's occurring at the liver cell has happened to some degree at these other cells, and then the last, the last frontier of this problem to occur is at the liver. And then when it starts happening at the liver, it just like, it becomes like a severe derangement. So it's kind of, and I mean, they you see that because, like, diabetics is fatty liver can have like, the worst outcomes compared to the diabetics that don't want most diabetics tend to have fatty liver. So it's like, that's diabetes. It's like, this state on a systemic level, happening with like, many, many cells inside the body. So, yeah, that's, that's, um, there's the analogy. And I just want to touch that, because I was going to say it before and I forgot.

Jay Feldman 59:04
Yeah, perfect. All right. I hope you enjoyed that episode. If you did, make sure to tune into Part Three, where we'll continue discussing the role of energy failure in non alcoholic fatty liver disease, as well as why fat burning is actually one of the main causes of fatty liver, one of the main pieces of this pathological state. If you did enjoy today's episode, please leave a like or comment. If you're watching on YouTube and if you're listening elsewhere, please leave a review or 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 on anything else that we referenced throughout today's episode, and if you are struggling with any of the symptoms or chronic health conditions that we've been discussing throughout this series, whether that is fatty liver and. Resistance or other related conditions like diabetes or heart disease. Or if you're doing with any other low energy symptoms, whether that's chronic cravings and hunger, fatigue, joint pain, weight gain, poor sleep or insomnia, digestive symptoms like bloating or inflammation or issues with slow motility. Or if you're doing with brain fog or any hormonal imbalances that might be presenting as low libido or various hormonal issues or reproductive issues, or if you're doing with any other chronic health conditions, maybe it's an autoimmune issue, or really any other chronic health issue, 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 also walk you through the main things that you can do from a diet and lifestyle perspective to maximize your cellular energy and therefore reverse 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.