Jay Feldman 0:12
Welcome to Episode 63 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 the first part of a series discussing non alcoholic fatty liver disease. And in this series, we're going to begin by explaining some of the general mechanisms and physiology pertaining to this disease, this condition, and these general mechanisms, this physiology pretty directly applies and correlates to virtually every other chronic health issue and so many of the issues that we talk about. So it's really helpful to understand these concepts. And we are going to try to simplify the physiology with some graphics. So if you would like to see those, then you might want to watch this episode or this series on YouTube, but we will also make sure to explain verbally as well, and then toward the end of the series, we'll go on to discuss what all of this means in terms of diet and lifestyle and supplements that you can use to reverse this condition and various others that are caused by these same mechanisms. So in today's episode in particular, we'll be discussing why fructose does not cause fatty liver. We'll be talking about the three major problems with the research that suggests that fructose does cause fatty liver. We'll be talking about how fat production in the liver can actually be protective. We'll be talking about the role of PUFA and endotoxin in de novo lipogenesis, which is fat production and inflammation. And then we'll be talking about why overeating is not the cause of fatty liver. 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 these studies and articles and anything else that we mentioned throughout today's episode, and this series was inspired by some listener questions. So if you have any questions that you'd like us to answer on a future Q A episode, you can send those in to Jay at Jay Feldman wellness.com and that's j, A, y at Jay Feldman wellness.com or if you're watching on YouTube, feel free to leave those questions in the comments, and if you are dealing with any of these symptoms of fatty liver disease, or if you have fatty liver disease, or if you're dealing with insulin resistance or any other related conditions like diabetes or heart disease, or if you're dealing with any low energy symptoms, maybe That's chronic cravings and hunger or fatigue or joint pain or weight gain or digestive symptoms like bloating or inflammation or troubles with gut motility, or maybe you're dealing with brain fog or poor sleep or hormonal imbalances, whether those are reproductive related or low libido, or if you're dealing with, again, any other chronic health conditions, maybe Those are autoimmune issues. 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 therefore 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 gotten a good couple of questions about non alcoholic fatty liver disease, which alone makes it, you know, worth, worth digging into. But also the mechanisms here are things that we talk about all the time in terms of other disease processes. And we'll talk about why that is, because basically, this process is associated with virtually any other metabolic issue, so it's entirely relevant in that way. And then also, we'll be diving into some of the mechanisms here that help to elucidate things that are also happening, not only in the liver, but elsewhere in the body, when metabolism is off, and when someone's concerned about gaining body fat, or if they're concerned about really, any other issue that results from a lack of energy. I mean, this is much like all the other diseases that we look into. This is basically just looking at that same disease process, but isolated into what's going on at the liver, or somebody who is extremely susceptible to something going on at the liver, and then that leading to this disease pathology in that location. So with that in mind, just those couple of questions that we got, Deb had asked for she had asked about. Podcast on non alcoholic fatty liver disease and whether it can be reversed with diet. And then Kathleen had asked about choline and non alcoholic fatty liver disease in general. So we'll be talking about that, and we'll talk about choline a little bit later on. But again, just as an introduction here, this process of fatty liver is extraordinarily common, as much as, I mean, some of the figures are as high as 1/3 of the US population that has fatty liver disease, which is just an insane an insane figure, and it's one out of every three people, over 30% and it's very strongly associated with, as I mentioned, virtually any other metabolic issue, whether that's just insulin resistance and diabetes directly, or heart disease, or really, any of the other conditions and problems that we talk about all the time. And so, with that in mind, I mean, for one we'll discuss basically what I mean, one place to start is, is, I guess, what exactly does non alcoholic fatty liver disease look like? And on the front, you know, you know, basically on the on the surface, it looks exactly like it sounds, which is that the liver is accumulating fat. It's it's becoming very fatty. It's producing a lot of fat, and there's a lot of fat accumulating there. And along with that, you'll tend to see elevated liver enzymes on blood work. You also potentially see elevated lipids and triglycerides, yeah. Specifically triglycerides, yeah, yeah, and, and, yeah. And, as I mentioned, it's associated with so many other conditions. Is there anything else you want to add there? Mike, I mean, I know you've probably seen this quite a few times clinically, in the hospitals.

Mike 6:34
I think that while it can show with elevated triglycerides and elevated cholesterol and elevated liver enzymes. That's not always the case. I think a lot of people have, like a silent a silent deal where their their panel looks fine, their lipid panel may look fine, their cholesterol and their triglycerides may only be mildly elevated, but they actually have fatty liver so, like, the best way to really determine is through some type of imaging, whether that's an ultrasound or, I mean, I don't recommend a CT scan, but a CT or an MRI is really with an ultrasound, or really the ways that they're you're going to be able to see if you have FA liver or not. And then, like, because the elevated liver enzymes are, like, a higher triglycerides, like those don't necessarily mean fatty liver, like the elevated liver enzymes. Could you have some type of damage to the liver from a supplement or something that you took, or a medication, whatever that is, and then, like the triglycerides, and a lot of high carb diets, triglycerides can go up. And that may not necessarily be because liver is fatty, so it's kind of, you have to the real way to know is going to be that ultrasound. That's, that's probably what the doctor is going to recommend first, because it's, like, the least expensive, least invasive option. So, yeah, that's, that's like the gold standard to be able to tell. And the other thing I want to point out is that fatty liver is a new disease in terms of the scheme of humanity, as far as, like, the medical establishment recognizing it. So, like in the early part of the 19th century, there was no fatty liver. It became more prevalent towards the it like, I think it appeared around the 1950s if I remember correctly. And then it just started, like, increasing drastically, from from like, the 70s and up, and now we're at a point where, like, 1/3 of the population is dealing with fatty liver. And yeah, a lot of people want to, well, I guess we'll get into that later, but yeah, it this is a newer disease, just like cancer is a newer disease, just like all these heart all this heart disease and these autoimmune diseases are all newer diseases, so it's moving in trend with basically everything else that's going on, but it was relatively unheard of in the early part of the 19th century, 20th Century, 20th Yeah, the 1900s Yeah, yeah, yeah.

Jay Feldman 8:57
And it's important, as you mentioned, to point out that those markers that I looked at on the labs, triglycerides and liver enzymes, are symptoms, and so they are symptoms that you tend to see with fatty liver. But as you mentioned, that's not always very tightly correlated. And they can be elevated without fatty liver, and then you can also have fatty liver without those elevations. So yeah, that's worth clarifying. And I also wanted to clarify, normally, when we're talking about fatty liver it's separated between alcoholic fatty liver disease and non alcoholic fatty liver disease, yeah, and in reality, I mean, the reason for that tends to be because, just because they're saying it's caused specifically by alcohol, and there's a different approach as far as the treatment, which is just you have to drink less alcohol, more or less and so. But it's worth noting that the physiology there is not too different. Basically, the exact same thing's happening. It's just, they're pointing out that, in one case, it's caused by alcohol, and the other case, they say, Oh, well, you know, we don't really know, but we'll talk about really how the mechanisms are virtually the same. It's just a question of what's causing it, and there really shouldn't be any separation as far as, like, the actual. Disease process goes it's, it's the same, virtually. Did you want anything alcohol?

Mike 10:06
Alcoholic fatty liver disease has been around. It's a non alcoholic fatty liver disease that became, like a more of a big deal, because it's traditionally known to be caused by alcohol at the fatty liver. And then when they started seeing people pay, I think at first, if I remember correctly, like they started seeing people with fatty liver disease, and they would ask them if they drink alcohol, and they would say no, and the doctor kind of wouldn't believe them. And then eventually they realized that no people are actually getting a fatty liver and it had nothing to do with them drinking like drinking alcohol. They weren't drinking at all. So, but yeah, so the non alcoholic fatty liver disease is the newer disease? Is the newer disease? Alcoholic value liver disease has been known for quite some time.

Jay Feldman 10:45
Right.Yeah. And I do want to mention also, I've seen clients with severe fatty livers that have been diagnosed via scans, and I've also seen clients with elevated liver enzymes. And honestly, as far as these disease processes go, it's not all that difficult to to improve. I mean, it's, it's a lot of the same things we talk about, and we'll talk about the details, but these are not genetic problems that you're just stuck with. These are not, I mean it, and it takes a lot to lead to this, you know, really extreme fatty liver situation. And I've seen people who have had severe fatty liver on a prior scan and then the next scan, it's completely gone. Same thing with the liver enzymes, like very highly elevated, you know, several times above the range, and then right in range, you know, not too long after. So it's definitely something that is pathological. And what I mean is that it's not just random, it's not just genetic. There's absolutely metabolic reasons that lead to it, and therefore, a lot of things that we can do. And with that in mind, that's why we're going to spend some time talking through the mechanisms and what's going on there prior to talking about what to actually do. Because that that exact, you know, it illustrates exactly why this is so clearly just a metabolic issue.

Mike 11:55
Yeah, and I've seen quite a few people with fatty liver that weren't gluttonous in terms of how much they're eating. And I mean that even include, included my dad, like he went he was diagnosed with fatty liver, and when I looked at his caloric intake on a regular basis, like it was less than 2000 calories, he's about five foot 10, um, 160 570 pounds, so. And he's not fat at all, like you can't, he's not visibly fat, like, there's not an there's no BCS nothing like that going on. But he, like, when they scanned him, he had a fatty liver, and he has and he didn't have elevated triglycerides, he didn't have elevated cholesterol, he had slightly elevated liver enzymes, and I think it was only as alt, so that's why I was saying it's, you know, depends on the individual and and a lot of people try and break down fatty liver, like, and I've seen this quite a lot, and it kind of annoys me where it's like, oh, it's gluttony. It's like, oh, you're just, you're eating too much. You're eating like, you're not, like, you're eating too much sugar, too much fat, and that's why your liver is fat. And for I have some other relatives who that was the case, right? And that they had severely elevated triglycerides, and they were kind of just binging on food in general, and then they got diagnosed by a scan with fatty liver. So there's, like, there can be multiple causes, as far as, like, a lifestyle effect in fatty liver, but the pathologies tend to converge in the same direction. So you can have somebody who's completely like, binging on tons of food. Like, and, you know, the family members that are doing this, we're like, eating lots of candy and lots of like, just like junk food, tons and tons of junk food. Whereas my dad is somebody who's, you know, severely under eating chronically for an extended period of time, showing with, like, fatty liver for years. And yeah, I mean, he's not checking obviously, he didn't make any changes to his lifestyle, which is why he continues to, or he continued at that point, to show the fatty liver. So I think it's important to realize that it's not just a disease of gluttony, like diabetes isn't just a disease of gluttony, or obesity isn't just a disease of gluttony, it's there's more going on to the situation, and that's what we're going to talk about.

Jay Feldman 14:09
Yeah. I mean, we'll even be talking about the opposite, the potential role of fasting in in lipid fat accumulation and fatty liver. Not that I think that's the common cause, either, necessarily. But yeah, I mean, I totally agree, and we've talked about that quite a bit. I'll link back to those weight loss episodes we discussed where, again, I think it's so terrible how the the assumption is just that if you're overweight, if you've got fatty liver diabetes, you're just overeating, you are just gluttonous, you're just weak, you know, weak willed, and all you have to do is try harder. And if you say you're not eating a lot, you're obviously lying, or just doing a bad job of keeping an eye on what you're eating, because that's the only thing that can cause these situations. And yeah, that's not only far from the truth. In some ways, it's the opposite, where you tend to see the opposite relationship between like low energy and low food intake and obesity, and that's because of this extreme, extremely poor conversion from food to energy. Me, but sometimes you do see overeating. But again, that overeating is not caused by being weak, like weak will. The reason is because, again, when that process is not functioning well, you then become hungrier than you would have been before, because you don't have as much energy, even though you're eating the same amount or even more food, and that leads to that vicious cycle. So you literally have an energy deficit in a lot of states. Is like a cellular energy deficit despite a supposed caloric excess.

Right, right? Exactly. So I will, uh, I'll link back to those episodes we've we've had quite a few of those talking through those, those situations, but a lot of parallels here. So with that in mind, let's discuss some of the basics of what's going on in fatty liver. Basically, what we're seeing is an accumulation of fat at the liver. And to keep that really basic, you basically have more fat production, or just, you know, absorption, or, you know, fat uptake versus the fat that's being removed or cleared from the liver. And that's the basics of it. But there's a lot of things that affect both sides of that equation that are worth considering. So we'll start on the fat production side, because that's normally where people are focusing. And I think there's a lot of misconceptions here. And one of the main ones we'll talk about is fructose being the cause of of this excess fat production. So that that's kind of the main area is basically you've got two you've got two pathways for fat, fat production. You've got what's called de novo lipogenesis, which is the production of fat from carbohydrates and then, and de novo means new so you're creating new fat. Lipogenesis is just the production of fat. And then you've just got regular lipogenesis, which is basically taking fats, or components of fats, like the fatty acids and the glycerols, and putting them together into triglycerides, into fats and and it's not coming from carbohydrate. Instead, it's coming from fat. Basically, those are the two main areas that we're getting that we're producing fat from. Now this is not the main pathway for either of those substrates. It's not like your liver just gets some some glucose or fructose and it just converts it right to fat. And it's not like the liver just gets some fat, you know, some fatty acids, and just converts them right to fat. That tends to be really the last the last ditch option, when the other options that are ideal are not able to be carried out for various reasons that we'll discuss. So generally, when it comes to carbohydrates, we'll start there. The there are a couple places that are preferred for carbohydrates to go. One is just to be oxidized directly as a fuel. So, you know, fuel going into an engine and being burned for energy. That's one of the first places. The other thing is that the liver is one of our major storage organs for glycogen, yeah, for glycogen, and basically for fuel for the brain. In that way, because our brain is our main consumer of glucose, or one of the main depending on how much you use your muscles at a high intensity. And so our brain is one of our main producer of energy or users of glucose, but it can't store any glucose as glycogen, so instead, basically delivers the brain's storage organ for glycogen, as well as the rest of the body too, but for the most part, actually, the liver and brain are the main ones that are using at least a decent amount of that glucose and kidneys as well, besides the muscles, because the muscles have their own sink of glycogen.

Which can be replenished by the liver, you know, in certain ways. But they, yeah, they store their own glycogen there, and again, they're only using that for more intense activity, yep. So, so we've got the carbohydrates being oxidized or in the liver, they're often stored as glycogen. The glucose is converted to the glycogen to be stored. And then one of the other main pathways is that the liver will convert, either convert that glucose to other carbohydrates, or just release it, or, sorry, convert the fructose to other carbohydrates, yeah, including glucose. So, and I guess I should have mentioned this to start, but the reason why people are concerned about fructose in the liver is because when we consume glucose, it goes right into the bloodstream. And you see, you know, a blood sugar spike when we consume fructose, you know, in combination with glucose or not, if it gets absorbed, it goes through the liver first. So the liver is the first, I guess, you know, it's like the first area that determines what, like, what happens to the fructose?

Mike 19:21
Yeah, it's like the regulator,

Jay Feldman 19:24
yeah, exactly. And so one of the things that it does quite often is it'll convert that fructose right to glucose, and then send it back out so that can be distributed to the rest of the body, including to the brain. So those are basically the main things that will happen, and they'll happen to a much greater extent than the fructose will just be converted to fat. As I mentioned, that conversion to fat is really a last ditch option when those other pathways can't be can't be used or carried out. So with that in mind, let's, let's dig in a little bit to the details. As far as what does happen when we're consuming fructose. What are some of the misconceptions here? And we've talked. Some of these, as far as this idea that fructose just directly causes body fat accumulation, or lipid hepatic fat accumulation, liver fat accumulation. So let's breeze through those, and then we'll talk about some of the details of what actually happens with fructose at the liver.

Mike 20:14
Before we get there, I just want to so just to clarify what you're saying, there's three possible routes for fructose to go to a large extent, it's converted into something else, like glucose or lactate. It's stored as liver glycogen, or it goes through de novo lipogenesis, where it creates new fats in the liver. That last pathway, de novo lipogenesis in humans is very low from fructose specifically and and under normal considerations, right? If you're taking the fructose, and we'll get to this if you're taking the fructose in in combination with glucose as and especially if it's in the form of fruit, that de novo lipogenesis pathway is, is, is very small, can compared or relative to the other two pathways, where it's converted to glycogen, or it's basically converted into lactate or or glucose and and sent out to be oxidized by other, by the the tissues of the body. So I think that's just to, like, make that very clear, de novo lipogenesis, especially from fructose in that context, is very, very minimal. Yep, yeah, that's because that's what you're that's essentially where you're getting at that it's just such as it's so because a lot of people the idea, and I think this was promoted by Dr Lustig, with his whole anti fructose crusade, was essentially that fructose goes to the liver and just like alcohol goes to the liver. It's like people like they've conflated these two things. So alcohol goes to the liver and has to be detoxified, and fructose has to be processed by the liver. So then it must be a toxin, which is logical fallacy, complete that doesn't make any sense, especially when you compare the metabolic pathways. But it doesn't just convert straight to fat and make you fat. I mean, if that was the case and these is n equals two, both you and I would be severely overweight, and I think both of us have maintained our weight within relative range for years, consuming ample amounts of fructose, just from just the source is from fruit. So I just want to put that out there that's a very common misconception, and the de novo lipogenesis from fructose from fruit in particular, is very low.

Jay Feldman 22:26
Yeah, and we'll look at those studies in a moment. But yeah, so, so a lot of the people in the Paleo sphere, the Keto sphere, the low carb sphere, the carnivore sphere, will discuss how fructose is just going to be, you know, it's gonna be taken up by the liver, converted right to fats. And as you mentioned, Robert Lustig was one of the main ones who promoted that. And you know, when he looked at the pathways that he describes, and he's like, this is what happens when you take in fructose, it is something that can happen, but it's all the pathways that we're going to talk about that are the last ditch pathways when it's not being used properly. And he looks at these rat studies that show that this is what's happening with the fructose, but there are so many confounding factors there that we'll discuss in a moment that basically prevents us from like it prevents you from extrapolating that to eating fructose actually in your diet. It's really not the same situation because of these other confounding variables that force the fructose into these inflammatory fat producing pathways, which it really should not be doing in a healthy liver when with a healthy fructose source in a human. And, yeah, so let's, let's talk about that now, unless you want to add anything first.

Mike 23:29
Yeah. And the only thing is, Lustig, I think, does have a couple, like, I think there's one human study he did with children, but, like, there was just a blanket recommendation to to eliminate fructose foods, which is like soda, exactly which in the human in modern human diet, particularly in the United States, the most common fructose fruits, especially foods that kids are eating, is like gushers and fruit roll ups and cookies with like cane Sugar, or not even like high fructose corn syrup. And so it's like, it's not like they're telling a bunch of kids, oh, you need to stop drinking so much orange juice. The recommendation was, you need to stop eating so much just straight up garbage, which is, and that's a completely different argument than Oh, you're you're eating too many kiwis, like so. And I think it's very important to make that distinction and and instead of narrowing it down to fructose, we like that needs to be, couldn't put into context of where the fructose is coming from, because there's not a single fruit study. There's not a single study with fruit or fruit juice, 100% fruit juice that shows severe metabolic arrangements or metabolic derangements in general, if any of them, most of them, if any of the studies, if anything, most of the studies show no effect, or they show beneficial effect. So it's like, it has to be put into context. You can't just, oh, fructose bad, especially when they're drawing conclusions from rat studies. And then the extension. Is, oh, we're going to move into children, or we're going to move into humans, and we're going to say, Okay, you need to have a low fructose diet. And they're going to replace, you know, they're going to replace their chocolate chip cookies and their gushers and fruit snacks and their Capri Suns with, you know, with, like, bread or something like that. It's like, it's a very different or potatoes, like, it's a completely that's a very different change than just fructose versus glucose. So, and what I, yeah, we can get into that right now. I just that's just where, like, a lot of it comes from, and I feel like there's a lot of conflation and logical fallacy between things, and without looking at the specifics and the nuance, and that's sort of where we're gonna we're gonna get at today, particularly with fructose. And that's because a lot of people immediately go to fructose as, like, oh, fructose, fatty liver. Like, I've even seen it on other podcasts where, like, I've seen some bodybuilders say, Oh, well, like, I had fatty liver must be because I was eating fruit pre workout. It's like, I highly doubt it was because you're eating fruit pre workout. Highly, highly doubt it.

Jay Feldman 26:01
Yeah, yeah. Probably more stress hormone related. And we'll talk about..

Mike 26:04
why anabolic steroid use with certain different compounds, or running ketogenic diets and things like that.

Jay Feldman 26:10
yeah,yeah, yeah, which and yeah, probably a lot of it is mediated through the the stress hormones.

Mike 26:17
Yeah not the apple that you ate before your 20 sets of squats,

Jay Feldman 26:24
Yeah. So let's So let's dig into the what's found in the research as far as these misconceptions go, and why the research showing that, hey, these rats got fructose and it cause fatty liver like, why is that not relevant to us and what we're actually doing as humans and what we're eating? So basically, say there's three main things we want to consider when looking at the research that people are citing, that fructose will cause fatty liver. And we did discuss this in two previous episodes, so I'll link back to those, and we'll just kind of give the overview now for what's wrong with these. And then what I really want to talk about in more detail is, instead of those things, what happens when humans eat fructose containing foods, and why is it not a problem? So the three main things to consider. The first one is just the capacity of humans versus rats, especially in terms of our livers. And humans have a much larger brain relative to their body size than other mammals, especially rats. And use, I want to say it's like maybe five times like our brains use more than about five times as much energy as rats do. Rats brains like, percentage wise. And then the other thing too is our livers use a huge amount of energy. They're they use the second most amount of energy of any organ to only the brain, and it's only about 10% 10 to 15% less than what the brain uses. So we've got these two very, very energy intensive organs, compared to these rats, which really don't need to have massive livers or or really well functioning livers, because they don't have a brain that they need to fuel that well, they don't have as much need to store glycogen and to use carbohydrates. So with that in mind, there's research comparing humans and and rats and and the livers, including enzyme production, and also just other features and qualities of them. And they've basically come to the conclusion that any research looking at what's going on in a rat liver really shouldn't be extrapolated to humans at all, like, there really can be no comparison, because they're really so different in their capacities. And what we're talking about, in some cases, at least, is a capacity different or a problem, you know, where it's like the liver can only store so much fructose. But when you're using a rat study to to elucidate that, it's really not relevant. So that's, that's the first part, the next two parts, and I'll let you, I'll let you jump in after, after I just mentioned these next two. So next one, which is a huge one, is endotoxin. And so in most of these studies, both in rats and in humans, they'll be giving fructose on its own, as opposed to with glucose. And we don't we and rats do not absorb fructose very well when it's given on its own, it absorbs much better when it's with glucose. And in nature, we only find it with glucose. You never really find fructose alone. And even looking at the ratios, it's rare that you have a major like a majorly high ratio of fructose to glucose. It tends to be very, very close. There are some fruits and like honey and things that might have a higher fructose to glucose ratio, but it's still not all that high. So when you're taking the fructose alone, because it's not able to be absorbed very well, it ends up feeding the bacteria that are in the intestines, and those then end up producing a decent amount of endo amount of endotoxin, which then blocks the liver's capacity to do to use the liver, to use the fructose effectively use the liver. That blocks the ability for the liver to use the liver, so the liver can't use the fructose very well because of the endotoxin and or anything else well, so endotoxin is the first one, right? So, and that's been shown like they have these studies where they found that the mediators here, with the fructose causing fatty liver are things like intestinal overgrowth, intestinal permeability and endotoxin. And then when they give antibiotics, it reverses or prevents any of those effects. So you so you basically see feeding of. Fructose that normally they're saying it caused fatty liver, but when you address these factors, it doesn't end up causing fatty liver at all, meaning that it, in this case, what they're showing is that it really just has to do with an endotoxin issue that's a feature of these studies, as opposed to actually being a fructose issue, where that endotoxin shouldn't be a problem in humans eating fructose from regular foods.

Mike 30:20
And I'll let you go with Go ahead. Well, it's and we have the graph too if you want to pull it up. But essentially, in, yeah, pull that up now, yeah, in the the fructose, since the R intestine can only absorb a certain amount of fructose, and it's dependent upon the individual, but I think it's shown anywhere from individuals from anywhere from five to 50 grams by itself. Now it when you and the reason why this is because fructose, I think it uses a glute five receptor in the intestine. I think, if I remember correctly, it's glute five, but it uses glute five receptor in the intestine to be absorbed. Now that's by itself, if, if glucose is also present, then there's like, a co transport where glucose will pull in fructose together. So you can actually have, like, if you have glucose with your fructose, you'll have basically unlimited amounts of of fructose that can be absorbed. So when that, when that fructose isn't absorbed, when there's no glucose with it, and you've reached your intestinal saturation or capacity, then the bacteria have access to it, and then they can essentially, essentially produce endotoxin. And the study that I, that I was referring to, they literally, yeah, so the fructose will come in. This is the intestinal mucosa. The microbiome will gain access to it, and then, then you it'll produce LPs, which is endotoxin. The LPS will up regulate or trigger toll like receptor four, which is basically an immune receptor that senses certain components of bacteria. Toll like receptor four specifically senses endotoxin, which is a component of the bacterial cell wall. And just to put this in context for people, the immune cells of the body sense different components of viruses, bacteria, parasites, and they recognize those components, and then it basically triggers off an alarm system, kind of like, oh there's a bacteria here. So when the body gets accessed, or when the immune system is exposed to toll like receptor four, it automatically triggers the inflammatory process. And then also tll four is TLR four is upregulated in conditions of fibrosis, and has been shown to lead to fibrosis, but so when this tll four is activated at the liver. It causes the liver it basically or endotoxin in general, but TLR, for signaling with endotoxin, up regulates cytokine. And it's not on here, but it's called tumor necrosis factor alpha, and this, this cytokine basically causes the liver to directly up regulate fatty acid production. That's cholesterol as triglycerides. So why does it do this? Well, when you have and so that's through triglycerides and de novo lipogenesis, which is right next to it there. So when, when you have these fatty acids, they are able to bind endotoxin, and and they inhibit that endotoxin from reaching the I think it's the comfort cells, or kuffer cells, which are the macrophages in the liver, because the macrophages in the liver sick produce or signal with tumor more tumor necrosis factor alpha with the more endotoxin that they're exposed to. So the fatty acids will bind that endotoxin, and it once it's bound to the fatty acid, the triglycerides or the even chylomicrons from the intestine, or the lipoproteins and the blood, the your HDL, your LDL, VLDL, etc. When it binds to all of those, it basically inactivates the endotoxin. So then the endotoxin reaches other cells within the liver that basically break down the fats and the endotoxin, excrete that into the bile, and it gets carried out to digestive tract. No problem, right? But if and then basically, that endotoxin isn't able to reach the cup for cells or the liver macrophages, the liver immune cells, so it's a negative feedback loop. It turns off the inflammatory process. But when you're chronically exposed to this endotoxin, and you're chronically up regulate your production of tumor necrosis factor alpha, and then your de novo lipogenesis and triglyceride production and and cholesterol production in the liver, you were also the TR necrosis factor alpha also inhibits some of the oxidation of the fat in the liver. It basically causes, like, a metabolic derangement. So you have, like, a lack of you have all this production of fats and an export into the bloodstream, and then the liver. It also inhibits the liver from taking it back in, and it basically clogs up the whole system. It's a defensive mechanism, but it's supposed to it's called the acute. Phase response, and it's literally supposed to be acute. It's supposed to happen for a short period, period of time when you have this chronic up regulation of it, when you have pure fructose by itself. Or another example is alcohol, which basically does the same process. The alcohol itself causes damage to the intestinal mucosa, allowing endotoxin to reach the liver, and when that endotoxin reaches the liver, it basically upregulates the same process. And what you find is in germ free mice, mice that have no intestinal microbiome, they basically when they're exposed to fructose or to alcohol, they don't develop the fatty liver to the same extent, they definitely don't develop the hepatic fibrosis or hepatitis, the inflammation of liver, or the cancer that eventually happens after those processes basically go on for an extended period of time. Now, if you take bacteria from mice in general and other mouse, and you put it into the intestinal environment of these germ free mice, and then you expose them to either fruit, high concentrations of fructose or high concentrations of alcohol. You basically get fatty liver, um, depending on how much PUFA you have in your liver, hepatic, uh, hepatitis. Then Fibro, fibrosis, or cirrhosis, and then liver cancer. That's kind of like the progression of how it goes. So it a lot of this is mediated through endotoxin, because the endotoxin, the endotoxins metabolic effect on the liver, basically it like deranges the whole process, because the livers, the liver is flowing energy through, right? So you, you're taking in energy in your diet, and then the liver is basically, it's like an accountant, to some extent, or a regulator, where it's seeing, Oh, what do we have here? And then how are we going to partition it? Oh, we're going to put some, like, glycogen. Oh, we're going to send some out to your muscles and your organs. Oh, we're going to, you know, we're going to, we're going to take these amino acids and use them this way. So it's like, it's kind of like that turning point, that fulcrum, where it's making the decisions on where things go and how they're going to be used, and processing them in different directions. When you take endotoxin and you throw it it, imagine the livers like an office. It's like throwing a bomb into the office. You just the whole office is like panics, and then they're unable to maintain the processes that they need to maintain. It's, everybody's frantic in the office like, Oh, what are we going to do? What are we going to do? Um, and yeah, so It arranges that whole process, and we'll actually, we're going to actually break that down. But yeah, that's, that's what I think is the most important piece to look at here. Is you this metabolic derangement is the central piece, and then you have these mediating factors, like endotoxin that causes the issue. And the other thing I want to point out that's kind of interesting is the rats, the germ free mice, that were exposed to alcohol, like the alcohol actually didn't cause such a derangement in the in the metabolism in them, because their livers weren't exposed to the endotoxin they wrap, they were like, able to process the alcohol and then the acetyl aldehyde that's produced from the alcohol, like, relatively easily, compared to mice that had the bacteria and were exposed to endotoxin. So it's it like removes it was very interesting study, because it removes the sense of like, alcohol is this primary toxin. It was more like the primary toxin with alcohol was endotoxin, and alcohol was kind of secondary, like it obviously is not a good thing, but its effects were mediated largely through endotoxin, as far as the pathology of cirrhosis and steel, hepatitis and whatnot.

Jay Feldman 38:37
Yeah, yeah. And another important feature I want to highlight here is that the endotoxin, both the endotoxin itself and all of the effects of it, the like inflammatory responses, also inhibit energy production, leading to that low ATP that we're seeing. And that is what causes and we'll, we'll get into this in a moment, in a few in a bit. That is what causes the fructose to, instead of being converted to energy, become converted to the fats. And as you mentioned, which is huge, this is protective. This is a protective it's meant to be in a protective, acute response to the endotoxin to help deal with that problem. The the then problem comes about when this is not only when this is chronic, but it's not something we want to have even ideal in the short term, or to even be happening in the short term. Of course, like it's never something we we really want to be happening much, but we are. We do have ways to deal with it, but over time, those ways come at a cost, and so this is essentially the cost. Well, petty liver is a cost, and endotoxin is a cause that can lead to this as a cost. There are a lot of other costs to dealing with a lot of endotoxin, but this is one of them. So yeah, I think that that's the main thing I wanted to mention as far as this goes. But there's another thing that you alluded to as far as PUFA goes. But is there anything else you want to add as far as this graphic?

Mike 39:58
Well, yeah, we can get to the PUFA. I. Want to add here that the acute phase response wasn't necessarily like adapted to high amounts of endotoxin. It's when you have an infection in general, you help regulate the acute phase response. When somebody is septic, they'll have increases in blood lipids as a protective effect as well. So it's like, it's while endotoxin is triggering it from the gut. And lots of these cases, there's also, it's like, main effects, I think initially, was for infection. It's like, if you have a like, an infection, you're going to drastically up regulate your lipoproteins to protect yourself and triglycerides. And basically, in animal models, when they inhibit that process, the animals have, like, much higher and worse mortality without that response. So it is very protective. But again, it was supposed to help you get over the infection while your immune system clears it, so your body isn't destroyed by all this leaking of endotoxin from wherever the bacteria or whatever, what have you is infecting you is releasing. So it's like, again, it was initially developed just for an acute response during infection, and that's why it's called the acute phase response. And then that was it. The other thing I want to point out here is that when you have the acute phase response, when you when you have this response, a whole host of other inflammatory mediators and systems are elevated, including like sympathetic nervous system and Ras cascade. And the RAS cascade, which we talked about in other situations, has direct negative effects on the vasculature. So when you have an acute phase response, it's kind of hard to parse out if the actual triglycerides and lipoproteins are causing the damage to the vascular bed, or is it the inflammatory system in which those lipoproteins and triglycerides are present in inducing oxidation in them and then cause and also damaging the vasculature and then having them deposited? It's not just, oh, high cholesterol. The cholesterol itself is the problem. It's like, what is the environment that that cholesterol is in? And looking at the acute phase response, like it's kind of hard to tell if it's actually the inflammatory state that's inducing the problem, which, I mean, we know the inflammatory state's inducing the problem, but is that what's causing the damage from the high cholesterol itself, because it's oxidizing the cholesterol, or is the high cholesterol itself problem? And I just bring that up because in a lot of these metabolic deranged states, like diabetes or obesity or fatty liver insulin resistance, like people want to be jumped so quick and say, Oh, it's your cholesterol is high, so you're going to get heart disease from your high cholesterol. And it's like, I don't think it's the cholesterol per se. I think it's the actual state, the actual inflammatory state, and the cholesterol being the protective mechanism directly trying to lower it. Doesn't like you want to lower it by solving the problem. You don't want to just lower cholesterol. Lower Cholesterol for the sake of lowering cholesterol, especially with its known protective effect. So I just want to point that one out here, because there's a reason why these things are going awry, and it's not it's it's not just random.

Jay Feldman 42:56
Yeah, and we talked about that, we talked about what it's all linked to those episodes, talking about heart disease and cholesterol, and why the lipids themselves are not the problems they're they're just symptoms that are actually a part of the defensive response. And so, as you're saying, I don't think that there's anything wrong with this defensive response. I don't think it's like one of those situations where it was meant to deal with this, but it's instead, it's dealing with this. I mean, the situation that we're the problem is just that we're putting our bodies in these environments that are continuing the need for that response, not that there's anything wrong with the response. Like, as you said, it's really helpful for something like an infection, and most of the things that we're doing now put us in a state of basically chronic infection. So it's the right response. It's just chronic infection does not, does not really assist with a optimal health, you know, like, in the same way, like feeding these microbial older growth overgrowths and infections in the intestines is not going to be supportive of of optimal health. So of course, those things are going to cause excessive acute phase responses to the point where they become chronic, and that's not going to be a good thing in the same way that they're not great in the acute situation either. But yeah, it's just again, it's a it's just the mechanism that we're seeing this happen. It's not the problem, it's not the cause. And that's what you were getting at with the the essentially the same situation in heart disease, right? Yeah, yeah. So the last piece here is that is the polyunsaturated fats, and you mentioned those real quickly, but when it comes to these problems with fructose and seeing the pathways that it activates the inflammatory pathways, one of them that Robert Lustig points out is, is the JNK pathway, which is just an inflammation response, and the fat production that comes with it when there's a really great study where they blocked one of the downstream metabolites of omega six, is a pine saturated fat. And when they did that, the fructose that was originally causing this fatty liver and fat production didn't do it at all. They couldn't they couldn't like they no matter how much fructose they were giving, the fructose was not being converted to fat. And so again, this is just another huge factor where, of course, every single rat is fed a lot of PUFA. So you're going to see the situation in any study with fructose, whether it is mediated by endotoxin or not, or it's just a feature of rat liver versus human livers. You're always going to have this confounding variable of PUFA in there, and that's going to encourage the conversion from fructose to fat instead of all the other places that it can be used for. And part of the way that it does that is through amplifying these inflammation signals, for example, maybe in response to endotoxin. That's one of the main things that the prostaglandins do, which are downstream metabolites of omega sixes, and yeah, and that's like part of their main effect is amplifying that inflammation response, so and not in a necessary way. This isn't one of those things like you're discussing with the acute phase response, where you need that amplification in order to respond to this. That's more of a more of a just feature of of the input in the environment of having a lot of PUFA, that's telling us that we need to essentially, that we need to encourage that inflamed state even further, because we are being bogged down by the the polyunsaturated fats.

Mike 46:01
Yeah. And the other thing with the with PUFA too, is that in order to move from non alcoholic, fatty liver disease to non alcoholic, steal hepatitis, which is an actual inflammation, it requires oxidative stress in the liver. And that oxidative stress, am I going too far?

Jay Feldman 46:19
That's fine. I mean, we'll, we'll dig into it more. I mean, you can, yeah, it's a little sneak peek, but we'll talk about that more when we're actually talking about, like, what is causing fatty liver? Yeah, because it is, yeah, PUFA is a big factor.

Mike 46:31
The PUFA there is essentially converts it because it in, it allows for increased oxidative stress. And we can go into the mechanated mechanisms a little bit later on. But, yeah, it's like, that is a huge, a huge factor in in this situation. And it's not like, people say it's protective, and I guess we can get, we're, we'll get into that too, where they, Oh, it's protective because it's an unsaturated fat, and it's going to lower, it's going to, like, lower lipid fats and yada yada yada. But like, not necessarily, and it really like.

We'll get into it.

Jay Feldman 47:06
So yeah, yeah, I would definitely. I don't want to jump here, yeah, because I want to, I want to continue this, this whole fructose situation, and just kind of put that to rest, as far as this idea that fructose is going to be causing fatty liver. So we talked through some of those main misconceptions, and what's some of the problems with the research. And now I want to, I want to dig into what's actually happening, instead of that, especially in humans, especially maybe relatively healthy or even some just average humans, what is happening with fructose, and what is evidence that we're seeing that it's not really going to cause fatty liver? And so, as we mentioned before, there's a few different pathways that the fructose can can go through, and this is in the liver. For one, it'll be converted to energy. It'll be oxidized through the mitochondria used to produce ATP and CO two, so that the liver can function. And as I mentioned, that's a huge pathway, because the liver requires a huge amount of energy, almost as much as our brains, and that's because it has so many functions as far as detoxification goes. And you know, detoxifies, endotoxin is one of those things, and that's one of the main insults we have to deal with. So that's a huge, a huge piece. Another thing, or one of the other places it can be converted to, is glycogen, where it'll be converted to glycogen and stored in the liver. And our livers can store a pretty decent amount of glycogen, about 100 grams or so, depending on the situation. It can vary, but around that amount, and then it can also be converted to gluco glucose or lactate, and then exported, and converted or exported to the rest of the body, to the rest of the tissues, and used for fuel. And we talked about some of the problems with lactate production in the CO two series. But that's not the same as this conversion to lactate, and then that lactate being used as a fuel elsewhere, as far as like a if we take a muscle cell that's getting either glucose or lactate, if it's getting lactate, that's only one step away from from being converted to pyruvate and then to acetyl CoA. So it's very close to just jumping right into the Krebs cycle. It doesn't actually require all the enzymatic processes that glycolysis, that are involved in glycolysis from glucose. So as a fuel, it's actually totally fine and a pretty efficient one. The problem is rather when you end up producing a lot of lactate in, for example, a muscle cell, that's a sign of derangement, to sign that things are not or in any cell, really, it's a sign that things are not being able to be converted farther down. So just to clarify that this conversion to lactate and distribution is not really a problem. It's it's not the same excessive amounts. Yeah, well, I still don't see it as a problem to the conversion.

Mike 49:31
I'm saying, I'm agreeing with you. I'm just saying it's okay if the muscle cells producing lactate is because it's not doing oxidative phosphorylation. It's not oxidizing to CO two, ATP and water, which for creating that in the process, it's just going to the process, it's moving the substrate through lactate, whereas the liver is putting out, like, it's a little different.

Jay Feldman 49:50
Yeah, yeah. And there's studies showing where they like inject lactator are given lactate as a substrate, and that doesn't really cause much, much in the way of issues. So. It tends to be used pretty well. So that's some of the main effects of of, or main pathways for, for fructose. But in particular, the you know people well. And then the last one too, of course, is it can be used to convert, to be converted into fat. And people will always say that that's the main route that it goes. And we talked about endotoxin and PUFA being major, uh, confounding factors there. But I wanted to go through a couple studies just showing how well fructose is used and how well it's stored. So there's one study where they were giving either a 30 gram dose or a 60 gram dose of fructose, and this was in people who are on the lower side as far as weight goes, the average was about 130 pounds. And between those two situations, the 30 grams and the 60 grams, there's no change in triglyceride production, you know, fat production and the same percentage was oxidized. So between 55 and 60% of that fructose was oxidized, which is a pretty it's pretty noteworthy for two reasons. One, if we're concerned about capacity for fructose, you would expect to see that there's a limit, right? That, in this case, going from 30 to 60 grams, which is a very large dose you would expect in one sitting, yeah, yeah. And you would expect there to be a major difference in fat production. You would expect that, you know, in the 30 gram dose, maybe 60% is oxidized. But in the 60 gram dose, maybe only you know, 30% or 40% is oxidized because you can't oxidize all the extra fructose. You can't handle it. And that's kind of the idea, but that's not, not at all what they were seeing here, where instead, they were able to handle that fructose perfectly well, and it didn't increase any increased triglycerides significantly between those two doses, whether it was 30 grams or 60 grams. So that's that's a pretty noteworthy one to do anything that in there. No, go ahead. Okay, and another one, this one they were doing, and also, for reference to, like, 30 grams of fructose. Normally, we're getting that in the form of sugar, that is glucose as well. So that would be like the equivalent of a soda and a half of if the sodas with cane sugar, like, that's the amount of fructose, that there would be 30 grams of fructose in, like a soda and a half. And then for the 60 grams, would be, like three sodas worth of fructose and in one sitting at one time. Yeah. So it's a pretty big dose, not talking small doses. Here in this next study, they doubled to carbohydrates. So these people went from having 324, grams of carbs today a day, to 648 and they also increased their fat. So they went from having 117 grams of fat today to 148 grams of fat a day. And they did this for five days. And during this time, their calories skyrocketed as well, of course. So they went from 12 went from 2700 it was 2723 calories a day, to 4550 calories a day. So we're just seeing basically huge overfeeding, most of it coming from carbs and some amount coming from fat. And these were not athletes. These were average people. Their their average weight was 165 pounds. And when they were consuming that, the when they were overfeeding, they were eating the almost 700 grams of carbs per day, and the 100, almost 150 grams of fat per day, they were only producing five grams of fat from the fructose, the amount of de novo lipogenesis in the liver was only five grams per day. And that's not nothing. I mean, it's not like you don't want to have that much, but I mean, five grams is like nothing compared to the amount that was taken in, and you're only looking at it at that time. Obviously it seems like in these people, first off, they almost double. I mean, they their calories went up by 1800 so this is not something that would have been sustainable for them, but that they would have continued doing. And as soon as you go back down, you'd probably just oxidize, you know, those few extra grams of fat that you had produced in the liver. So, I mean, that's huge. I mean, if the whole idea here is that all of this extra fructose that would be in the carbohydrates that you're consuming is going to increase fatty liver, then, I mean, it's just not at all what you're seeing in these studies. And then there's another one that was just looking at a review, and they had reported that about one to 5% of the fructose that's consumed gets converted to triglycerides through de novo lipogenesis. Yeah, yeah, and so. And they also pointed out that this amount of fat, like the five grams in the last one, tends to be only around 1% of the total amount that a fat that you would typically consume in your diet. So yes, you're producing the small amount of fat from fructose, but the liver also picks up fatty acids. Like, when you're eating fat, they can also be picked up by the liver, and they are picked up by the liver. And so if you're eating 100 grams of fat and producing two grams from fructose, like, what is really the like? Is that really a concern? Is that really a problem? And how? I mean, how different is that from just picking up some fat that you were taking up, and what we're trying to get at here, or at least one of the things, is that a, we use fructose really well. It's not as simple as just eating fructose causes fatty liver. And B, it's the processes that are leading to the fat production that we'll talk about that are really where we want to be focused on. Because when those. Is when our metabolism is deranged, it increases those things, and then we end up storing a lot more of the food that we're taking in, whether it's fats or carbs, and whether it's glucose or fructose, we'll end up storing a lot more of that as fat when like when these things are deranged.

Mike 55:14
So I just want to put something into perspective here. So there's 453 grams in a pound, correct? Or four?

Jay Feldman 55:24
Yeah? Something right? 454,

Mike 55:26
Yeah. So it would take, it would take 90 days producing five grams of fat from your liver per day to increase fat by one pound. And that's just like anybody who wants to go into like basic calories in, calories out, or like a macros in, macros out, type of deal. It's like, I don't find any of the explanations that people like to talk about for calories in, calories out and and, like some of these bioenergetic explanations, like very feasible, unless you start talking about modifiers like endotoxin on the liver, or some type of metabolic derangement, or like a hormonal situation, which we can actually, we'll actually get into as well in this podcast and and the one thing I want to point out is, like for somebody, for someone like you or I, right? Like for both around 190 200 pounds and, like six foot two. So just to maintain our body mass at rest on a basic caloric calculation, it comes out to be around 2020 100 calories a day. That's to do absolutely nothing, that's to just lay down right all day long. So if I work out X number of times a week and I walk around and I do whatever I do, right? Like I go for a walk every day. That number, based on those things, can jump to about 3000 to 3500 calories in a day, depending on how many days a week I work out and what my other activity levels are like. One of the things that kind of annoys me with all this stuff is like to meet 3500 calories in a day, like the amount of fat, because after, and this is in consideration of of protein, right? There's only so much protein you can eat. There's only so much protein you want to eat. And going into, like, 300 400 grams of protein a day to meet your caloric intake just isn't feasible. And financially and like physically, it just does. It doesn't make any sense to do anything like that. And that's especially if you're going to be doing with whole foods, if you're going to be mainlining protein powder into the vein, that's a different story. But I mean, none of us are recommending that, so it's like, you have to make up that difference with carbs and fat. Those are going to be the bulk caloric content of of the diet. And the thing that frustrates me is, in a lot of these studies, or a lot of people talking about fatty liver, this and that. Like, they discuss things from the perspective of, oh, like, you can't have fat and you can't have carbs together, or you can't have like, you can only have what, like polyunsaturated and monounsaturated fat, and then you also, like, you can only have starch. It's like, you know how difficult it is to eat 300 or 400 grams of carbs from starch a day to meet your caloric intake, especially if that's from, like, if you're like, Oh, I'm gonna use sweet potatoes or potatoes, it's like, it's impossible. You're so full from that. And then the other thing to put in context there is, like, it to there's no way that you can safely consume all of your fat from, and I'll get to this in a second. Why I'm talking about this. But you could safely consume your fat from polyunsaturated and monounsaturated fat. You couldn't do it because you would just like, the the only fat source that you could do it with would probably be macadamia nuts or macadamia nut oil. If you tried to do it with another type of oil, your omega six content would be so high, it would it would like, it would just be a terrible strategy from from a dietary perspective, from an inflammatory perspective. The reason I'm getting at this is because, like, people's concept of things like, Oh, you have to eat less than x number of grams of fructose a day, and you have to eat let you can have saturated fat, which is something that people say causes fatty liver. And so it's like, you severely limit what people can eat in a lot of these states. And then basically it's just like the solution, oh, you have to starve yourself. You have to eat like, you have to severely undereat, and then you have to, you have to exercise more and stuff like that. And then, like, it automatically goes to this gluttony thing. But it doesn't make sense in any of the context. When you can look at somebody's body mass, size, and then how much they like, how much they should be eating based on their activity level, according to, like, a generic calculator, which just gives you a baseline, it just doesn't like, it doesn't pan out. It's just not like, the recommendations aren't possible to manage in like, a sustainable and and healthy way, right? I don't, I don't. I remember when we tried to eat 400 grams of starch, I remember trying to do it with plantains and being like, I don't think I even absorbed it. I think most of it went out the other end, just because it's so much bulk, the digestive system just couldn't handle it. So and then, as far as, like, meeting it with polyunsaturated, monounsaturated fat. The only safe, mostly monounsaturated fat source is macadamia oil or macadamia nuts. And so like that doesn't that doesn't seem feasible to me as like this is going to be the solution to solve these problems. You gotta you can only have 25 grams of fructose a day, which basically cuts out almost all fruits juice. And then you just Okay, so you can only have starches. And it's like, how much bread and and potatoes and sweet potatoes can you eat in a day? And then it's like, so then you're left with, to fill the bulk of the calories is going to be fats. And it's like, so has to be monounsaturated, polyunsaturated. It's like, how much Omega six you can eat in a day? There's, there's only so much fish oil that makes sense to eat, or even alpha linoleic linolenic acid. From from like this, alter from these, their alternative were mainstream from their alternative health perspective, before you start drastically increasing oxidative stress and damage. So, like, you couldn't you, you couldn't possibly make up the bulkier calories from that. It just doesn't make any sense. Like, I don't, I don't get what the strategy is, from there, are you gonna have, like, like, like, 2030, grams of omega omega three in a day from alpha linolenic acid, like, that doesn't sound like a good idea. Like, I don't see any studies supporting that as a as a beneficial strategy for lower it for health, like your dress, you're gonna up regulate oxidative stress drastically with that. Just like, that's so it's the point I'm trying to get at is, like, the opposite recommendations of the things that we're talking about, like, just based on looking like, oh, fructose causes fatty liver. So just limit fructose to X number of grams a day. Like, even in a dietary context, it like, doesn't make any sense. And then, like, them talking about de novo lipogenesis, oh, it increases at five grams over the course of a week, it's like, okay, so how is this causing obesity? The fructose, by itself causing obesity. If it would take 90 days to gain one pound of fat, like when you have an obese child, you think that he put on or she put on all those pounds of fat in their five years of life, based on that equation, right there, by itself, like that doesn't make any sense, right? That's kind of what Go ahead.

Jay Feldman 1:02:02
Yeah. So a couple things just real quick on that last point, that the de novo lipogenesis we're just talking about in the liver. So when the so in some of this, I mean, the next study we'll talk about, especially, they did find that de novo lipogenesis could occur in the liver if you're eating, like, huge amounts of carbohydrates, and that could contribute to fat, body fat. But the other thing is, you can have fat production in the fat cells even when you're not producing fat in the liver. Yeah, so, but, but that aside, what you're it sounds like what you're getting at. So like, the mainstream view is fructose is bad and causes fatty liver, and saturated fat is bad as and causes fatty liver. And so what you're kind of getting at is like even, and from the mainstream they suggest having a decent amount of carbs, right? So it's like, what even does that diet look like? And as you said, it basically just requires a ton of grains and vegetable oils. That's like, you know, if you're getting some amount of fat, it has to be all unsaturated, so you're getting a bunch of vegetable oils. And from the carb side, you're getting a bunch of grains, because that won't have much fructose. And that is typically what those recommendations are. But you know, the other thing too, so obviously, I don't think there's most people, I think, who are listening to this, or most people who are talking about fatty liver outside of the mainstream, are either saying it's fructose or carbohydrates in general, or it's saturated fat, you know, and you've got, like, the anti saturated fat people, maybe more on the vegetarian, vegan side, and then the other side, you've got, maybe the lower carbers, right, who are suggesting that fructose is this metabolic poison. And obviously, like a low carb diet, you can get a lot of calories from from a low carb, high fat diet, and vice versa, you can get a decent amount of calories from a low fat, high carb diet. So I don't like it's worth pointing out that, like this mainstream view just leads to, basically, you have to have, like a grain and vegetable oil diet, which, I don't know who that. I mean, it doesn't sound like reasonable at all to us. It sounds pretty insane. But to people you know from who are following the food pyramid or or my plate or whatever, maybe that's not so absurd. But yeah, I mean, and so I want to continue discussing, like, why this, this idea that fructose is the problem is not the case. But as you mentioned, it's also worth discussing a little bit of why consuming fat is not the problem either. And so we'll get to that right after.

Mike 1:04:18
I just wanted to put it in context, because, like, people want to break it down into calories and calories. And calories out. And like, talk about bioenergetics from that sense, and then not consider the other areas and then make recommendations off of that. And like, even with the five year old, even with fat production occurring in fat cells, like, Can bioenergetics alone explain that based on the amount of calories they're going to eat in a day? Like, could they severely eat that much calories to make themselves obese at like, five years old? Like, my point is that there, there has to be some modifying factor going on, besides, just oh, they ate too much fructose, or oh they, they ate too much. They, they too many burgers, too much saturated fat. Like, there's something else more going on. In a lot of these situations, I think.

I just want to, I want to point that out with the fructose and the fructose, that makes me think of that because, like, they put these harsh recommendation on fructose, but like, even their own explanations don't make sense around it, right? Like, it doesn't. It's not, like, adding up in that model. And that's why we're talking that's why that's the whole point is that it doesn't add up within the model that they want to, like, they and out of one side of their mouth, they're explaining things as calories and calories out. And then on the other side of their mouth they want to, like, harp Oh, it's fructose and and then, like, the their equations don't necessarily follow with the calories and calories out model. Like, the there's, it's the modifier that they're talking about there that from the mainstream or their mainstream point of view, I would say.

Jay Feldman 1:05:47
So you're kind of saying, what you're saying is that the idea that fructose is a problem directly, uh, conflicts with the idea that it's just about calories. Is that what you're getting at?

Mike 1:05:56
Yeah, like, it there's there, maybe not directly, but to some extent, like, there's, there's conflict there, if you were to break it down, is like, yeah, that's that's like, you can't hold both at the same time, like you have to start saying, start. It makes you start to think that there's something else going on.

Jay Feldman 1:06:11
Yeah, and I don't know how many, I mean, a lot of times when you hear the calories and calories out, which, by the way, I do not consider that to be bioenergetics, at least not the way that we describe it. I mean, that is sometimes referred to as energy balance, or bioenergetics, and that's not what we refer to when we talk about those things, because calories and energy are not equivalent. We've talked about that previous episode, so I'll link to those. But you would just mention bioenergetics.

Mike 1:06:33
I wanted to clarify that that's the only thing I could think of to because that's what they call it. Like every textbook you first get, it goes through the cell, and then there's a chapter on bioenergetics, talking about anabolism and catabolism, and breaking it down in the concept of calories and so, and that's where I'm getting it from.

Jay Feldman 1:06:49
I call it calorie balance or something, because it's, I consider that to be more accurate. I mean, either way, though it's like a nonsensical concept, and we discussed that before, but I don't know. I mean, a lot of times the calories and calories I was used as a reference for body fat gain. I don't normally see that as like, I don't normally see people saying that non alcoholic fatty liver disease in the mainstream is caused by too many calories. So I don't want to be like, you know, conflating things there, like creating a straw man, the

Mike 1:07:20
The solution that people tend to to like the solutions that I've seen offered in the mainstream, for the cat, for the fatty liver, is like, you need to go on a caloric deficit. Like, that's the automatic response. And it's like, okay, sure, but it's like that, like, while it roundabout may solve the issue, like, it doesn't get to the core of the problem. And that's kind of, that's why, I guess, like, this is why I'm getting at that is because, like, the solution is automatically, oh, intermittent fasting and or, like, you need to only protein and, no, you have to have a low carb diet, and then you also have to have, like, a lower, like, a non saturated fat diet to solve the fatty liver situation, like I've seen that recommend. I guess I, like, went 10 steps ahead again. But to see the recommendation there with people, I see that very, very often. It's like, no fructose, you have to have a higher protein diet, and then you also, like, you can't have saturated fats, and you can't eat too many carbs. And it just like, So, what do you eat? Like, it's a low fat, low carb, high protein diet. And it's like, it basically like, Okay, we need to go into starvation. Like, those are the recommendations that I kind of see. It needs to be caloric restricted. And then maybe you can do like, like, give yourself an eating window so it's not as hard. Like, I've seen that recommendation, like, in quite a few places for for solving the fatty liver situation. And I know with your clients, that's not what you're doing. And I know that no, of course, yeah, that's not the recommendation I've made for other people. And have seen, like, seen changes without having to starve them. Yeah, yeah, yeah.

Jay Feldman 1:08:55
I guess I'm more I'm more familiar with people saying, like, fructose is causing fatty liver or saturated fat, not as much just going calorie deficit and high protein, low carb, low fat diet. But that is, we talked about that before. That is, like the very mainstream idea, like, everything is bad except protein and vegetables. So that's what your diet should be, yeah, although animal protein is bad, so it's like, just vegetables and vegetable proteins that are, you know, some highly processed vegetable protein too, so you can get that.

Mike 1:09:22
Well, those that's like, the plant based stuff is, like, your diet beans and grains and like, that's considered, that's going to be your health food for you. And it's just, like, if you've ever just eaten beans and cream, like, I don't know how sustainable that is, that that's what I'm getting at. Like, it's just it doesn't make sense in a large overall picture that's being described. Maybe I jumped too many steps ahead, but yeah, I don't mean to derail us entirely, so that's okay, yeah, let's go back to fructose and continue from there.

Jay Feldman 1:09:52
Yeah. So the next thing I did want to talk about, so we talked about how well fructose gets used. It gets oxidized really. Well. We really don't produce much fat in our live. Even when we're having a lot of fructose. And then the other thing too is just how well we store it, which is just really, it's a lot more than people would expect. So they there's this carbohydrate overfeeding study. I've referenced it once before, whereas with athletes, they glycogen depleted them by putting them on a lower carb diet and doing some workouts, and then they gave them between 750 and 1000 grams of carbs per day. And what they found was that during this time, the athletes, initially, they were, they were oxidizing about 400 grams of carbs. And it then, I mean, right, like at the beginning of this carbohydrate overfeeding, and then it increased to as much as 1000 grams of carbs per day that were being oxidized. So it means that you are burning over two pounds, because 1000 grams is a kilogram, which is like 2.2 pounds. So that means that these athletes were burning as fuel over two pounds of carbohydrates, which is insane. That's like a huge amount and just and at some points too. It's worth mentioning that they were adapting the way that they were burning more carbs at some points than the amount they were taking in. So they might have only been taking in 800 grams at the time. Yet, at some points, they were burning more than that, which just shows our immense capacity for handling carbohydrates. So that's worth mentioning. Another thing too is that they found that de novo lipid synthesis, de novo lipogenesis as a contributor, as a contributor to body fat production didn't happen until the glycogen stores had at least 500 grams of carbohydrates. And they found that even after that point, there was more glycogen, though stored up to around 800 to 1000 grams of carbs stored as glycogen throughout the body, in the liver and the muscles, which is also just, it's just pretty profound to see how much carbohydrate we can store, and that means that that's like carbohydrate above what you're using. So whatever's left over, we have an incredible capacity to store carbohydrate, and we really don't start converting much of it to fat, if we're healthy, until those stores are pretty well saturated, and we're really forcing a lot of overfeeding. Not to say that these people's diets were perfect anyway, either. But, and again, 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 energy and using the food that we're taking in, well, 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. All right, before we wrap up this episode, I did just want to add in as far as that carbohydrate overfeeding study that I just mentioned, where the participants were burning as much as 1000 grams of carbohydrates per day, that that's equal to 4000 calories per day, and that's just carbohydrates. It's not considering any fat or protein that's being oxidized or used anywhere else. So just to add some scale to what that really means to be burning 1000 grams of carbohydrates per day. And in part two of this series, we'll be discussing how fatty liver is really caused by a failure of energy production, and we'll be digging into the research and mechanisms underlying this concept. And 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 a five star rating. 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, 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 as I mentioned earlier in the introduction, this series was inspired by listener questions. So if you have any questions that you'd like us to answer on a future episode, please send those in to Jay at Jay Feldman wellness.com that's j, A, y at Jay Feldman wellness.com and if you are dealing with any of these symptoms that we described today, maybe you're dealing with fatty liver disease or insulin resistance or any related conditions like diabetes or heart disease, or if you're doing with any other symptoms or chronic health issues like chronic cravings and hunger, low energy or fatigue, chronic pain, weight gain, digestive symptoms like bloating or slow motility or brain fog or insomnia or any hormonal imbalances. Or if you're dealing with any other chronic health issues, maybe something like an autoimmune issue, or one of those chronic health conditions I mentioned earlier, 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 by adjusting your diet and lifestyle to maximize your cellular energy and therefore 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.