Jay Feldman 0:12
Welcome to Episode 48 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 working within the healthcare industry. Today's episode will be part two of our series discussing the croissant diet, and in part one, we started digging into the reactive oxygen species theory of obesity, where we discussed the major issues with this theory and dug into the biochemistry and physiology a little bit, and today we'll be continuing that by discussing the SCD one theory of obesity, which builds on the reactive oxygen species theory of obesity and the SCD one theory, basically, is the idea that elevated levels of SCD one cause obesity, and that decreasing SCD one, by excessively increasing oxidative stress is the best way to lose fat. So we'll be discussing the major issues there, as well as why fructose does not drive fat gain or necessarily increase SCD one. We'll be talking about why the polyunsaturated fats are harmful even if they decrease. SCD one and we'll again be discussing why fat burning is not the answer for healthy fat loss. If you are new to this podcast, then after listening through today's episode, I'd highly recommend you go back and listen through episodes one through seven, where we took some time to create a foundation as far as the bioenergetic view of health is concerned. To check out the show notes for today's episode, head over to Jay Feldman wellness.com/podcast where you'll find the articles and studies and anything else that we reference throughout today's episode. And if you are struggling with any low energy symptoms, whether that is weight gain or chronic cravings and hunger, fatigue, joint pain, gut or digestive issues, brain fog, poor sleep or hormonal imbalances, or any other low energy symptoms or chronic health conditions. Then head over to Jay Feldman wellness.com/energy, where you can sign up for free energy balance mini course, where I will walk you through the main things that you want to do as far as diet and lifestyle are concerned, so that you can maximize your cellular energy. And I'll also explain why this is the key to resolving these symptoms and conditions. So to sign up for that free energy balance mini course, head over to Jay Feldman wellness.com/energy, and with that, let's get started.

So the second major component of Brad's diet perspective, or perspective, as far as the best way to achieve weight loss and health, has to do with his SCD one theory of obesity. So I figured we would just start by explaining what SCD one is, and like, where it's involved and when we're going to see elevations and decreases, because that's a huge part of what he's seeing is as a major factor in terms of obesity and health. So SCD one stands for steroidal CoA, desaturate one, which is, you know, it sounds, I guess, a little complicated, but it does something that's relatively simple, which is that it converts a converts saturated fats into monounsaturated fats. And it tends to be very particular saturated fats, which are the ones that we are producing ourselves. And so SCD is found mostly in the liver and in body fat, which is where, which is where you would see fat being produced, typically, and when there is excess amounts of fat being produced, you see an increase in activity of SCD one basically converting that saturated fat, which we only produce saturated fat immediately, and then we convert that saturated fat to a monounsaturated fat. And as we've talked about before, both saturated fats and monounsaturated fats are extremely stable, especially when you compare them to polyunsaturated fats. So while a monounsaturated fat might be slightly less stable than a saturated fat, it's still an extremely stable fat, that is, that does have various purposes in our in our bodies, and we'll get to that and why it's important, but basically so when you'll see an increase in SCD, one is when you are producing an excessive amount of fat. And so that would be a state called lipogenesis, where you're producing fat. What lipogenesis means. And along with that, there tends to be excessive amounts of inflammation too. And so you. The you know, some of the times when you might see this, and we'll dig into this a little bit more, is, for example, in like a rat, when they're fed excessive amounts of fructose and they've got a lot of endotoxin circulating, or they're also eating a lot of polyunsaturated fats, you'll see a lot of lipogenesis. You'll see it in states of obesity and diabetes or non alcoholic, fatty liver disease. You'll see in basically a ton of different excessively stressful states and states where you have basically a blockage of energy production, a blockage of the ability to convert some substrate that's coming from food into energy, which basically leads to that substrate being diverted toward toward the production of fat. So in the liver, this is where we'll be talking about this the most. But basically, an example was for the rent situation, where if you have a lot of polyunsaturated fats, or you have a lot of endotoxin, that's going to block the ability to convert that fructose to energy, and instead, that fructose basically leads to a buildup of Acetyl CoA, because you have blockages along the electron transport chain and blockages along the Krebs cycle that lead to a buildup of Acetyl CoA. And that acetyl CoA, COA gets shunted off and and diverted to a pathway that leads to fat production. So you end up with a lot of fat being produced. And then you have a an adaptive increase in SCD one to convert some of that fat to monounsaturated fat so it can serve various purposes. Yeah.

Mike 6:28
I also think it's important to note here that in obesity, diabetes, non alcoholic, fatty liver disease, excess fructose feeding and most of these metabolic syndrome states, which is like a whole classification of diseases that have like, sort of the same features with hyperlipidemia that they're generally characterized by high by states of high endotoxin, or they call it low grade endotoxemia in the blood and endo and even in other inflammatory states, there's like a generic response in the serum or in the blood. It's called an acute phase response, and it's categorized by the liver producing a series of proteins, but in response to inflammatory mediators like tumor necrosis factor alpha, and then also up regulating lipogenesis. And that can increase cholesterol and increase triglycerides in the bloodstream because they have, they have immune modulating effects or immunoprotective effects, and then they help deal with inflammation and toxins and and every basically it just, it's just a huge general response to stress or inflammation. And so basically, when you have studies where you're going to feed rats a ton of fructose, what they've already shown. And this happens in humans, happens in monkeys, happens in rats, happens in mice, that you find high levels of endotoxin in the portal vein, because fructose isn't absorbed very well by by most, by the the mammal studied, or these types of mammals studied and without glucose. So you so basically what you're seeing is a state of endotoxemia. So when you're trying to draw parallels there, then you can also see that in with the obesity and diabetes, etc, they're all characterized by this high amount of endotoxin and so it's kind of so with the acute phase response when you're when you create hyperlipidemia, where you have that elevation and triglycerides and cholesterol, that is because the livers up regulating fatty acid production. And when you do upregulate fatty acid production in these states, it's going to be saturated. So SCD one also upregulates as well to convert that saturated fat into or some of that saturated fat into monounsaturated fat. So like, it's, it's, it's sort of an association to just say, Oh, do you see SCD one in these and obesity, diabetes and all these rad spread fructose. So therefore sugar, fructose, or whatever, is causing this up regulation, SCD one and an STD one is what's is what's causing fat gain it. There's much more to the picture than that. It's not just a straight pathway. You have to consider the other context, which is that a lot the inflammatory states are up regulating the acute phase response as well.

Jay Feldman 9:06
Yeah, and we'll dig into all that in more detail. But as you said, one of the more common things that will drive that state is endotoxin, and that will be a huge confounding factor that we'll that we'll discuss. And so basically, what we're getting at is that SCD one is a part of an adaptive response to a an inflammatory state that involves a lot of fat production. As you said, endotoxin can be involved there, because fat production plays protective effects in our immune system. But also, fat production is something that's going to happen anytime we have excess substrate, and we can't convert it to energy. And again, that fat does have various other uses too, just in our regular health. Of basically all sorts of organs and tissues, you know, like our skin and and eyes in particular, are noteworthy ones where you have various cholesterol or lipid components that are extremely necessary. And so. So SCD one is, again, it's part of this kind of adaptive cascade, and it also has some other effect that are noteworthy. So for one is, is that when you So, one thing that it does is it actually helps to slow down mitochondrial respiration. And as we always talk about, that's generally not a good thing and but it also makes sense as an adaptive situation, because when you are producing excessive amounts of fat, that's, as we said, a state of inflammation, a state of blocked respiration, and so you don't want to be further driving that respiration. We talked about this a lot in the last episode, where, you know, part one of the series, where, when you're producing energy very efficient, inefficiently, and you're producing a lot of oxidative compounds, a lot of reactive oxygen species, and causing a lot of oxidative stress, that's can be extremely damaging to the cellular structure. All the nucleic acids in there, the protein and everything, it can damage the cell considerably and lead to death. So when that's happening, we want there are adaptive responses that are saying, hey, let's let's slow down there, like we don't need to keep pushing this really inefficient energy production. And so SCD one is one factor there that will help to do that, because if there's a lot of fat being produced from excess substrate like glucose or fructose in a stressed out, inflamed liver, then you don't want to keep trying to force that stressed inflamed cell, or those cells and those tissues to keep trying to produce energy. It's going to cause a lot of damage. So it's basically a release valve, exactly, yeah, yeah. And so that's one effective SCD, one that's noteworthy and kind of has this adaptive protective effect beyond just kind of repurposing some of the fats that are produced. And so, as we said, elevated amounts of SCD one are seen in basically degenerative states that involve metabolic syndrome. So insulin resistance and diabetes are are major factors there. Stress is a major factor there. And so it is noteworthy that along with this, along with just, you know, it's not necessarily just lipogenesis, but also oxidative stress, those tend to go hand in hand. That is going to be driving SCD one, and that's going to, of course, play a major role, or it does play a major role, in Brad's perspective here, because he is tends to see that production of reactive oxygen species as a good thing. And so we'll delve into how that relates to SCD one. But along with that, too, there is there are certain scenarios where excessive amounts of exudate, oxidative stress, very high levels of reactive oxygen species will lower SCD one, and that's kind of where he sees fatty acid oxidation as a good thing. And we'll get to that. But just Yeah, questionable, right, right, definitely questionable. So yeah.

Mike 12:54
I guess, before you go forward with getting to that, I just want to point out here that the pair, or the, I guess, the parallel where, if you have a high amount of substrate, so say, if you're eating a high carb diet, like a very amount, like a large amount of carbs, then you can get some fat production in the liver. That is not the same thing as elevating and the acute phase response from, like, something like inflammation induced by endotoxin. While they can both, even at least in the rats, they can both have this upregulation of STD one so it both states don't necessarily mean pathology, whereas one state is a pathology and the other state is is just, you know, that's physiologic. That's what you would want to happen if you you know if you're eating, at least, especially in rats or mice, if you're gonna, if you're gonna feed them a very high sugar diet, you're gonna see their livers produce a lot of fat. And that's, that's just normal. So you it really, you have to look at the whole context here and and the other thing is, you have to with that said, because this applies to things like physiologic insulin resistance versus pathologic insulin resistance, or things like that. It really depends on the context. So it can't just be sweeping generalization of Oh, SCD, one's upregulated. Well, it's like, yeah, when the liver is going to produce a large amount of fat from substrate or in an acute phase response or from an inflammatory response, whatever, then yes, STD one, especially in Rats Mice, will be upregulated. I just want, I think that's important to point out, to make that distinction, so that we don't it's not just across the board. Oh, this is bad, right?

Jay Feldman 14:30
And as we'll get to too. I know, I know you mentioned, like having some sugar fructose, tending to increase libogenesis, and it and it does, but in very varying amounts, depending on the organism, depending on what kind of state they're in, what else is present, like polyunsaturated fats and endotoxin. So, yeah, we'll get to that. But it is worth bringing up that again. It's it very similarly to the situation with reactive oxygen species and hormesis and all of those quote, unquote, stress pathways. Is it depends on the con. Text through which these things are being increased or or we're seeing high levels. And just because they're in this case, just because it's present during pathology or in pathological states, doesn't mean that any increases are inherently problematic, however, you know. And again, they are adaptive. So it's worth mentioning that however, I do think that generally, we don't want to see high SCD one, but we'll get there. So, but there's different.

Mike 15:24
Yeah, all is there's a difference in when it's occurring in in general. I think it's important because so we don't just have, like, oh, anytime you see it, because I think that's sort of what the narrative is or implies. So far for at least from this perspective, I guess you could call Brad's perspective, or the fire and the bottle perspective, whatever.

Jay Feldman 15:45
Yeah, yeah. So let's So, let's explain that. So we kind of mentioned what SCD one is. But the perspective from that, that Brad is putting forth through, you know, the fire in a bottle perspective, is that basically, because you see SCD one increasing in all these situations, and because SCD one increases the unsaturation of saturated fat from fully saturated fat to monounsaturated fat, we don't want to be seeing high levels of SCD one, which, as we said, definitely makes sense to an extent. So we'll get there. But so basically, from his view, decreasing SCD one is is basically paramount. And if you don't, and you have a lot of monounsaturated fat production, that's not going to lead to as much reactive oxygen species production as saturated fats, and that's going to prevent all those effects that he's saying are good from excessive oxidative stress. So we talked about this in in the last one where we from his view, you want to see excessive amounts of reactive oxygen species being produced through the oxidation of mostly saturated fats, and that's going to lead to all of those defensive reactions, the uncoupling and the activation of all those stress pathways, and eventually fat loss. And so he's saying, if you have all these monounsaturated fats from the up regulation of SCD one, then you're going to have a problem. You're not going to be able to produce enough reactive oxygen species, and then you're going to be left without being able to burn fat, and without this this fat Browning state, and without this thermogenic state.

Mike 17:17
And uncoupling and all that, yeah, right, which are all adaptive mechanisms. They're all to deal with the issue of too much ROS.

Jay Feldman 17:26
Right. Yeah. So already, I don't see that, as you know, I see we already acknowledge that we see less oxidative stress as a good thing, but from his perspective, that's not a good thing, and that's why you want to decrease SCD one as much as possible. And so just, he's got a quote talking about this, where he was saying that Native Americans only they got fat if they ate only maple syrup, I think they become fat for the same reason that mice fed high sugar, very low fat diet did massive upregulations of SCD one and lipogenesis in their livers, which then exported huge quantities of monounsaturated fatty acids. These Native Americans would have been pathologically unable to trigger sufficient Ross production, and their mitochondria when burning fat to induce uncoupling protein mediated thermogenesis.

Mike 18:10
I just think it's funny that it's that it's, he's, it's saying it's the pathology is that they're unable to trigger sufficient ROS but it's like your cell is recognizing it as a pathology, because it's it's moving towards uncoupling to deal with the excess ROS ,

Jay Feldman 18:27
Right, right where you're saying so just to clarify, like you're saying that in the state of reactive, like, if you have a lot of oxidase stress, the cell sees that as a problem, and so it leads to uncoupling. And so that that seems pathological to us. Of course, we know that Brad is coming from a perspective where that's not pathological, that's supposedly ideal. We discussed why we don't agree with that last time it is. Yeah, I find it funny, too.

Mike 18:52
I think the fact that the cell has is having an adaptive response to it, what, at least to me, seems to indicate some type of pathology on the cellular level.

Jay Feldman 19:03
Yeah, yeah. I would generally agree, although I would generally agree. I mean, these pathways I definitely see as adapting, adaptations towards stress. And as we've kind of clarified before, it's I do again, I think adaptation can be really beneficial, if it's adaptation to increased energy production, and it can sometimes lead to uncoupling, also it can sometimes lead to autophagy or mitochondrial biogenesis. So those are...

Mike 19:28
it's content, it's always context, right? I know we always say that and it's annoying, but it is always context, right?

Jay Feldman 19:35
So anyway, I think with that quote, I mean, there's some things that we'll dig into there, but again, the main thing is that he's saying upregulation of SCD one due to lipogenesis in the livers, in the liver causes a lot of monounsaturated fat production, which is unable to produce enough oxidative stress, and that leads to a lack of uncoupling and a lack of thermogenesis.

Mike 19:56
So on the flip side here, though, the A. You. So just, I guess, to paint the picture on the flip side, if you had a high amount of SCD one, and you had increased amount of monounsaturated fatty acids being produced with the SCD one, then the fat cells would basically not generate as much ROS and they would be insulin sensitive, so that basically, any carbohydrate that you would eat would be shuttled into the fat cell with insulin and then be converted into fats and stored as fats. And so basically, that, that's the that's like, the opposite of what he's saying, that it, or that's what he's saying, essentially, is if you have too much SCD, one too much MUFA, or polyunsaturated fatty acids within the fat cell, and they would be insulin sensitive. And if they are insulin sensitive, then they can take in glucose and convert it and store it as fat. And so the goal here is to create insulin insensitivity, or insulin resistance, so that the fat cells are unable to take in glucose, essentially, or, or that's glucose and basically stored as fat. That's the and then they'd also upregulate their burning of fat, right? And that's through. That's because with the up with the increased ROS and when you get the increased uncoupling protein production, then you on, then basically the electron transport chain and the Krebs cycle aren't linked together anymore, so you're just burning the fats away as heat, right? That's what he's saying. We you want to do that, I guess, that second, that last part that I just discussed, whereas the previous part is what you don't want to do. You don't want the fat cells to be insulin sensitive. And then I think, when the last podcast, I think we talked about, at one point, the spectrum of fatty acids, where you have or glucose and fatty acids from an insulin sensitivity point of view, where when you have a lot of carbohydrate, you increase insulin sensitivity, and then on the opposite end, you have a lot of saturated fatty acids, which would decrease insulin sensitivity. And this is purely from a burning perspective, where polyunsaturated fatty acids are closer to glucose and monounsaturated fatty acids are closer to saturated fatty acids, but not quite as, not quite as strong at promoting insulin resistance as the saturated fatty acids, right?

Jay Feldman 22:14
Yeah. And so with this, this is part of why Brad is not a fan of fructose, and that's because fructose, especially in these studies looking at mice and rats, which we'll dig into, fructose increases SCD one. And he argues that this is at least in part, because it's producing a much lower level of reactive oxygen species than fatty acid oxidation. This is also why he thinks that insulin is a problem, because you see increases in insulin and all these situations where you're seeing increases in SCD one. And then, along with this as well, is that this is he's saying that fatty acid oxidation is able to depress SCD one. He's saying that high, you know, I should specify saturated fatty acid oxidation. So what he's suggesting is that if you're oxidizing only saturated fats, you're going to produce extremely high levels of oxidative stress of reactive oxygen species. And that's going to actually depress SCD one, and that's also going to allow fatty acid oxidation to continue. Since high levels of SCD one, or increases in SCD one, will decrease mitochondrial respiration. They'll decrease fat oxidation, as we talked about, because basically, when you're producing fat, you don't also want to be burning fat. They're kind of opposing pathways. So this is why. So this is kind of, again, support for his view that you want to be continuing to increase fatty acid oxidation from saturated fats, in terms of SCD one, it will help to decrease it. And we'll talk about why we don't necessarily agree with that, but that's just kind of laying out some of his most important views there, I would say, or most central views as far as SCD one goes. Okay. So Brad also talks about the relationship between polyunsaturated fats and SCD one, where the polyunsaturated fats tend to actually decrease SCD one, which kind of kind of has juxtaposing effects, considering the his other opinions on polyunsaturated fats, where they cause less oxidative stress when they're oxidized in the mitochondria. So because of that, they're not as ideal from that standpoint, but they do more directly decrease STD one, and that seems to be more of a regulatory mechanism, potentially because they're already unsaturated fats present. So SCD One doesn't need to produce as many of the unsaturated fats. But may also be kind of more of a regular regulatory situation where the polyunsaturated fats tend to decrease the output of of fat, or exportation of fat.

Mike 24:45
And production of fat by the liver, which is something we've talked about before, right? And that's through I think, I think the mechanism was that we mentioned before, the study was showing that with increased polyunsaturated fatty acids, I think it increased er stress inside. Cell, and then they wasn't able to properly produce fatty acids to export, which I think we talked about being a bad thing in the context of generating an acute phase response, right.

Jay Feldman 25:11
Right. Basically preventing the adaptive response, yep. So while they might decrease SCD one, we don't necessarily see that as as a good thing, but Brad doesn't meant, does mention that part as a good thing, and he says that there are, basically, there are certain polyunsaturated fats that their decrease in SCD one outweighs the lack of oxidative stress that they would cause, but others that might not be the case. So we'll talk about that more too. But I just wanted to mention that as one part of his his kind of position, and then another as well, which is that he's recommending other things to decrease SCD, one that all involve similar stress pathways, as far as the activation of AMP kinase and MAP kinase, M, a, p, k, and so that would involve things like Metformin that he mentions and Berberine, which is kind of looked at as an herbal form of metformin. And we've talked about this before, as far as how those things are basically directly inhibit the production of energy of the electron transport chain, which is what leads to a lack of energy and leads to the increase in activity of AMP kinase and the activity of all these stress cascades and the wasting of sugar through glycolysis and the increased production of lactate because of that. So it basically causes this kind of disastrous state, which, yes, increases AMPK, yes may increasing uncoupling, yes may decrease SCD, one, but definitely wouldn't look at it as as a good thing. But we'll, I guess we'll. We'll get there in a little more detail in a bit.

Mike 26:39
Yeah. And then also, I mean, the other thing with the Metformin was inhibition on the Corey cycle, which can affect everything going on the liver as well. By depleting ATP to basically convert that lactate back to glucose. It, it will inhibit that whole process,

Jay Feldman 26:54
yeah, so you end up being stuck with a huge accumulation of lactate.

Mike 26:57
Yeah haha and the liver can't do anything with it. And the cells are just like, I mean, as known, side effect with decent amount of more of mortality of metformin is metformin and lactic acidosis, where, if Metformin reaches high enough concentrations, essentially, but I mean, and that, I'm not saying that to because you should never take Metformin. I'm not telling anybody that, but what I'm saying is that that's how Metformin, metformin's mechanism in action is basically to push towards glycolysis and essentially waste your substrate. And so yes, it will lower blood sugar levels that way. But I mean, it doesn't push it towards things for the substrate, towards oxidizing through cell respiration, right?

Jay Feldman 27:38
And it does actually, just as a side note, I think we've mentioned this before, but it also has some beneficial effects on beneficial effects on the gut, which has an antibiotic, yeah, right, which is similar to Berberine and similar to a lot of kind of phytochemicals, or flavonoids and things from plant compounds that when they're in the gut, they have beneficial effects when they're absorbed systemically, due to high doses, they have relatively toxic effects that people consider to be antioxidant inducing and beneficial, but they're doing that through stress, and again, that tends to be the certain types of those chemicals or compounds in like in foods, especially from like herbs, you know, but specifically tends to be from like the leaves and Seeds, especially since those are relatively toxic to microbes, but also toxic to us if we're absorbing them systemically. So yeah.

Mike 28:28
And I think you can see this too with like, the effects of either, like high fat high sugar feeding, which is how they produce, like a fatty liver and upregulate SCD one and or even just like a high fructose feeding the effects in like, a germ free mice versus a non germ free mice are pretty like, are pretty different as far as what happens metabolically and they I think you also get SCD one up regulation in those states. But as far as, like, pathology and whatnot, it's not there because you don't, don't have the high amount of endotoxin coming from the gut, especially in like a high fructose feeding model. So there's, like, that is a very big moderator of you have to keep that in mind for any drug or for a lot of these, the feeding trials or metabolic studies.

Jay Feldman 29:12
Yeah. And I mean, that's kind of a nice transition. Why don't we start talking about some of the problems, which we've kind of touched on along the way. But let's really dig into some of the problems with these perspectives that all we want to do is just decrease SCD one. Anything that decreases SCD one is a is a good thing. We want to be producing a ton of reactive oxygen species to help decrease SCD one. Things that, you know, and the way to do that is through fatty acid oxidation, and the way not to do that is with fructose and insulin. So, yeah, why don't we dig into all that?

Mike 29:45
I guess you might want to start because this was your favorite, your favorite point here where you basically, uh, fatty acid oxidation couldn't produce. I mean, at least based in the study that I think this is the study that Brad was actually. Be using is, I don't think fatty acid oxidation could produce as much ROS as that was needed to actually shut down SCD one, and now it's just looking at comparing it. In the study, they compared it with different levels of hydrogen peroxide at the cellular level to see, like, how much was needed to actually shut down SCD one. And essentially it was more than was needed for what for like obesity and diabetes, which are states characterized by high ROS at the cellular level. So it's essentially calling for getting such, getting maintaining high levels of ROS at the cellular or maintaining high levels of ROS in general, more than states of obesity and diabetes to shut down SCD one production so that, so that you don't produce monounsaturated fatty acids, you can keep your fat cells insulin resistance and continue to uncouple and burn through your fatty acid stores.

Jay Feldman 30:56
Yeah, it's basically like an insane emergency situation. But yeah, so to to add some context there, basically the this idea that glucose oxidation is going to produce some amount of reactive oxygen species, and that's increasing SCD one, and then fat oxidation is going to produce way more, and that's going to decrease SCD one, and that kind of excessively high oxidative stress, I think, is, yeah, it's very unlikely as especially when you're looking at the study and they're they're used. So what they basically did is they introduced all sorts of different damaging things to the liver that lead to a defensive reaction of lipogenesis, and that leads to all this inflammation. They used endotoxin in a couple of different doses, which we talked about quite a bit. They also used other factors, like angio, angiotensin, norepinephrine. They exposed them to hypoxia and and then also sugar, and we'll get anti amounts. Yeah, right, right. And so what they found was that basically, in response to like, things like endotoxin and hypoxia and norepinephrine and angiotensin, all these stress factors, they all increased. SCD one. And again, that makes sense, as we talked about earlier. SCD one is there as kind of one of those adaptive stress pathways to, you know, when there's a lot of lipogenesis going on, which is a part of that defensive reaction in the liver and the so. So basically, if you're arguing the first argument here is that fatty acid oxidation is going to produce more reactive oxygen species than these other things. So you're saying that basically a pretty decent dose of endotoxin. And when we were looking at this dose, it was insanely high compared to, like, endotoxin.

Mike 32:40
It was on an intracellular level too, right? Yeah, yeah. But what was it like? It was Nana. It was, what, 50 nanograms or something. And when you're looking at, I think what we looked at was, if you looked at like a gram negative infection, you had blood plasma levels of what was it?

Jay Feldman 32:59
was in the peak, it was like up to 500 picograms.

Mike 33:01
Yeah, it was like 450 picograms. So, like, we're on a completely different scale, like we're at completely different units by what, like a factor of 1000.

Jay Feldman 33:11
Right. Yeah. I mean, 500 picograms would be half of a nanogram, so which is 1/100 of what they were using, the the dose that they were using for endotoxin. So they used 100 times that dose in the cell directly, and found that that produced some that produced a lot of oxidative stress, and that oxidative stress increased SCD one. And so what Brett is basically arguing is that, forget endotoxin, forget all those other things. If you're just burning saturated fats, you're going to produce even more oxidative stress than that, which I think is, I mean, there's, there's there's definitely nothing in that study to suggest that that's the case.

Mike 33:46
Well, the other thing too is that that's not accounting for the cell upregulating, uncoupling or anything like that, to decrease ROS production as well. And it's obvious that the cell doesn't want that much ROS that's why it is undergoing these adaptive mechanisms, like increasing brown fat, or anything like that. But to say that that is the best way to lose body weight, I think is, or, I don't know if he said it was the best way. I don't want to, like, make a straw man argument for him, but like, essentially trying to lose body fat through that way, I think is probably is questionable. Like, at what do you what are you exchanging like, if you're trying to, first of all, we're not reaching that much Ros, but what's the trade off of trying to get that much ROS to induce uncoupling and upregulation of brown fat and cause physiologic insulin resistance At these ridiculous levels, or whatever is being proposed.

Jay Feldman 34:42
Yeah, yeah. And so along with this, too is all of these stress inducing factors tend to increase fatty acid oxidation. Generally, anything that increases stress does that. So when you're saying that something like endotoxin or hypoxia increases reactive oxygen species. Considerably and increases SCD one, and increases fatty acid oxidation. If that fatty acid oxidation was able to produce enough reactive oxygen species to decrease SCD one, then those other things wouldn't be able to increase SCD one. Then after endotoxin, you would see a decrease in SCD one, you wouldn't see an increase. So it's, I mean, those things are pretty hard to circular reconcile, yeah, yeah. I don't see how you can have both of those things. And another was norepinephrine, which, again, notoriously increases.

Mike 35:28
Yeah, fat oxidation and lipolysis, yeah.

Jay Feldman 35:33
So if you have a lot of norepinephrine, increasing fatty acid oxidation and increasing SCD1, it's hard to argue that increasing fatty acid, oxidation decreases at CD1.

Mike 35:42
That's as long as your tissues are saturated with, from this perspective, saturated with saturated fats, right? If you have high amount of PUFA or monounsaturated fats in your fat stores, then when you increase norepinephr or even on the cellular level, when you increase norepinephrine, then technically, you would still be insulin sensitive if you're going to oxidize them.

Jay Feldman 36:00
Sure, right, right, yeah. And along with that, too, as you mentioned, like, as we're talking about this study, they were looking at obese, like obesity states and diabetic states, which are states of insulin resistance. So in talking about this, they are in an insulin resistant state.

Mike 36:17
And they already have elevated free fatty acids. Yeah, they are. They are oxidizing. Those states are especially diabetes. Type Two is characterized by the oxidation of fatty acid in high states of insulin and and blood sugar levels. It is literally an inability to oxidize glucose, yeah, at least appropriately.

Jay Feldman 36:37
Yeah and yeah and with and in that state that they're looking at, there is increases in SCD one, not decreases. So just looking at all these things, I don't see a way that you could argue that fatty acid oxidation is going to produce so much oxidative stress that it's going to decrease SCD one. And as you know, as we get to as well. Like, the next kind of point there is that if you're getting to that point where you're producing so much oxidative stress that you're decreasing SCD, one things are pretty bad, like, it's a really degenerative state. So I'm going to perfect time to pull it up. Yeah, I'm going to pull this figure from that study, where they're looking at, on one hand, we have the adaptive stage, which is where you're producing, you're in an obesity, diabetes type state, and you're producing a decent amount of oxidative stress. Here the glucose is not being used efficiently. You are going to be driving towards fatty acid oxidation and whatever else. But in this case, because you're in the liver, and you're not converting that, that sugar to energy, you're actually going to be producing a lot of fat, which is what leads to, you know, that's the lipogenic state, and that leads to the increases in SCD one is a, you know, backup mechanism, or an adaptive mechanism, converting those saturated fats to monounsaturated fats. So we see that on the left, where you have, you know, in this non ideal state, you have an increase in SCD one. It's blocking fatty acid oxidation. It's which also happens, you know, it's also blocking pathways that lead to apoptosis. And, you know, you have this kind of first stage. And then on the right.

Mike 38:10
Before you get there, I think it's important to, just to show here that the you're up regulating saturated fatty acid production and obesity and diabetes, and then SCD one is up, is up regulating concurrently with the saturated fatty acid production and converting those saturated fatty acids into monounsaturated fatty acids. So I think it's what's you you produce palmetic and stearic acid, and then it converts it to Palmetto Lake and oleic acid, and then then basically pushes them into triglycerides, where the liver can push them out into the bloodstream and move them towards the cells and tissues and and what have you. So that's the first pathway on the left. And then in that state, you also have an increase in glucose and insulin as well.

Jay Feldman 38:53
Yeah, pathologically, if you want to call it that, because they aren't, you know, glucose isn't being used well. And you have excess...

Mike 39:00
High amounts of fatty acids in the bloodstream, and then your body's trying to increase. And so the glucose can be upregulated from gluconeogenesis at this point as well, but also from intake. And then insulin is up regulating as well, trying to get that glucose into the cell. So you sort of have this like mishmash of substrate in the bloodstream at this point with high amounts of fatty acids and then also glucose and insulin. And basically the first diagram is just showing that the STD one here is actually adaptive, because it's converting all the saturated fatty acid being not all of them, but converting some of the saturated fatty acid being produced into monounsaturated fatty acids to be exported. And this is important because like, and there's a study that I guess you can put in the show notes. But without SCD one, without high levels of SCD one, you'll upregulate saturated fatty acid production. And then you can essentially just get it'll just stay in a liver, and you just have really high amounts of like you get fatty liver, essentially. But then you can go to the maladaptive one next, which is you got it, yeah, yeah.

Jay Feldman 39:58
Well, and just to clarify too, when. You're the problem in that state where you're mentioning the fatty liver, and you're not able to convert those saturated fats to monounsaturated fats like that is an adapt you know, it's worth noting that that's an adaptive process. Also, we don't even want to be in a position where we're producing a ton of fat in the liver in the first place. That is already a sign of things like obesity, diabetes. Of course, it can happen outside of those stages and low amounts, but in large amounts, it shouldn't really be happening ideally. Yeah. So, yeah. So we have this not great situation on the left, obesity, diabetes, all these problems and high SCD one on the right, you have what they say is the maladaptive stage, where you have so much oxidative stress, things have gotten so wrong that you have an inhibition of SCD one, and at that point you no longer have you no longer have an inhibition of fatty acid oxidation. You also no longer have an inhibition of apoptosis, and this is a state that they see in lipotoxic cardiomyopathy. So basically the heart damage.

Mike 41:04
So it's, this was done at this was done with cardiomyocytes. So this was looking at cells, the cells specifically, and what happens when excess nutrient stimuli, hormonal stimuli, and so that that's basically with, I think, the norepinephrine, lipopolysaturide, angiotensin, endothelial in one hypoxia, or if you have, like, high amounts of exposed to high amounts of glucose, you had the increased saturated fatty acids that that's basically the context of the picture. And then when you're going on the maladaptive side, the only differenti differentiator between them is on the maladaptive side, you had such high amounts of strong oxidative stress that it actually turned off STD one, and then you just basically had a high amount of saturated fatty acids at the cellular level that led to increased fatty acid oxidation and also increased apoptosis with lipotoxic cardiomyopathy. But I think the increased fatty acid oxidation May I, I'm guessing at this point based on the diagram, but you the when you had the massive increases in fatty acid oxidation from the saturated fatty acids there, you probably generated even more ROS that signaled apoptosis at the cellular level.

Jay Feldman 42:19
Right? Yeah, it's probably at that point of feed forward reaction. So yeah, I mean, the important part here is, when you have such excessive amounts of oxidative stress that you're decreasing SCD one, you're in a like in this case, if that's happening in heart cell, you're in a lipotoxic, cardiomyopathic state, definitely not something that I would say you would want to be increasing. And so they have a quote that's discussing this. This is from that study where it says that increased expression of SCD one might protect from palmitic acid induced fatty excessive fatty acid oxidation and apoptosis through mechanisms involving the down regulation of AMPK, inhibit inhibition of ceramide and Dhg synthesis and inhibition of mitochondrial ROS generation. So again, it's basically saying that that SCD one is a protective mechanism. This is on that left adaptive side. It's a protective mechanism to protect against excessive reactive oxygen species production, excessive fatty acid oxidation and eventually excessive apoptosis. So and then to continue on with that quote, it says, we suggest that this period is an adaptive stage. On the other hand, SCD, one expression is reduced when oxidative stress is increased. In this condition, saturated fatty acids are no longer converted to monounsaturated fatty acids, and ceramide synthesis increases. And as a consequence, strong oxidative stress contributes to the onset of lipo toxic cardiomyopathy. Thus we propose this as a maladaptive stage. So to clarify and relate this to Brad's point of view, he's suggesting that that's essentially what we want. We want to be in that state where you're producing so much reactive oxygen species from fatty acid oxidation that that's happening which a, I don't think is possible, just from fatty acid oxidation, and B, I don't think is desirable.

Mike 44:02
Yeah, the other thing I want to point out here is they're using obesity and diabetes as the starting points here, and those states may be characterized by increased saturated fatty acid production by the liver, but they're also characterized by high amounts of endotoxin. So you don't only have saturated fatty acid causing the problem. You also have mitochondrial issues from the elevated endotoxin levels from and usually I think it's gut derived endotoxin, so you have like a chronic low grade endotoxemia. And then you also have the that generates the acute phase response, which increases saturated fatty acid production by the liver, but also increases a whole host of inflammatory mediators, like tumor necrosis factor alpha, interferon gamma and a whole like and and norepinephrine and angiotensin, etc, etc, etc, that has, like a systemic effect beyond just Oh, saturated fatty acids are being produced by the liver and so. A, you know, in push towards triglycerides or whatnot, whatever, what have you, whatever it is. So there's, like, it's a systemic issue. It's not just a question. They're not just states of excess nutrient or, I guess, over nutrition is what people like to say, like, there's actually, like impaired oxidation of the nutrition in combination with nutrient deficiencies and and possibly low grade infections and, etc, etc, or over exposure to polyunsaturated fatty acids. Like, there's a whole lot of issues going on. It's not just, Oh, your liver is producing too much saturated fatty acid and you don't have enough SCD one, or what, whatever the the argument could be based on this, like, one pathway.

Jay Feldman 45:45
yeah, no, exactly. I mean, that's, that's a huge point, which is, again, another thing that Brad is arguing against IS, IS fructose and insulin, because supposedly those increased SCD one and as that study was showing they do, or they do in in that particular I think, I think that was mice. But that's what you're what you're getting at is the problem in these states is not just you have fructose, and the fructose goes to the liver and just becomes fat. That's not what's happening. It's not what's going to happen in a healthy human, especially

Mike 46:15
when you change the fructose source from just granulated sugar or purified fructose added at a percentage of the diet to say, like orange juice, if you, and if you look at any of the studies where you where you have, like orange juice or or grape juice, or whatever it is, like 100% juice, and then you put them in high fat, high sugar feeding, controlled studies with rats, they actually are protective, which doesn't, which shouldn't be explained based on their sugar content, which they're high in, obviously, including fructose, including fructose, yeah. I mean, they're 50% fructose, right? Yeah.

Jay Feldman 46:52
Yeah. And, and we have talked about that quite a bit. I'll link back to those, some of those episodes where we talked about why fructose is not a problem, and why sugar is not a problem and why it doesn't inherently lead to fat accumulation in the liver. I'll link to a couple articles on that. You know, where I've talked about that too, but to kind of summarize it, here, it's and we've you've touched on a few times. We've kind of alluded to it, but basically, in a healthy human, we should be able to handle quite a bit of fructose in the liver. It gets converted to glycogen. Some of it is going to be used directly to produce energy, and some of it will be converted to other you know, converted to glucose, converted to other things, and then released out of the liver and kind of spread out throughout the body. So we're able to handle quite a bit of a fructose when we're healthy. But there are a lot of things that can prevent that from happening, and instead will cause that fructose to become fat, one of those endotoxin another one is polyunsaturated fat. Another one is if you become a rat, and that's because rats livers are generally shown to be able to handle very small amounts of fructose compared to ours, before they start converting it into into fat. And that makes sense, just because we need to have a much higher, much more capable liver, considering that our liver is basically a storage organ of of fuel for our brains, of of glucose for our brains. And so the fact that fructose goes directly to the liver, it's kind of that fructose ends up basically being that main fuel for our brains. It gets converted to glycogen, yeah, to glucose, and then glycogen liver, and then that ends up getting released for a brain to use. So considering that we have much greater brain capacity and needs demands compared to a rat, we need to have much better functioning livers that can handle a lot of fructose, and ours happen to do that. And so that's why you see rad in mice studies where, when they have fructose, they tend to convert a lot of it to fat. There's also studies showing that that even that doesn't even happen if you take away Polly and saturated fats, or if you block metabolites, or the polyunsaturated fats and or, as you said, germ free mice is another situation like that. So there are even in rats, they can, they may be able to handle fructose more than it seems to even show in the in the research, if they're not exposed to endotoxin and polyunsaturated fat. And the problem is that in most of the fructose research, they're exposed to both of those things, especially endotoxin, because normally they're feeding pure fructose, which is not well absorbed and leads to endotoxin production in the gut. But even without the pure fructose, even if it's pure sucrose that can sucrose, that can still cause similar issues, you know, on from there.

Mike 49:28
Yeah, and I mean, the other thing is, it's kind of rare to find isolated fructose in in nature. I mean, I think the only real sources are if you had apple juice or, like, honey or agave nectar, which, I mean, it's, it's kind of, usually it will come with glucose. And eating a lot of those, the other thing too, I mean, eating a lot of those, you'll probably get digestive symptoms as well as whatever liver issue you're going to get, because it can, it'll induce, for some people, probably. Coding and DIAR. But then the other thing too is, for rats, digestive physiology and anatomy, it is pretty different as well. So it's kind of like you can't really draw a parallel from, oh, I'm going to read feed rats x grams of or X percentage of diet of free fructose. It just doesn't. It just isn't. It just is across well. And then the other thing too is in a lot of like in in some of the studies, even with humans, where they they don't really show necessarily the same thing. But in overfeeding studies, like you'll you're probably going to see increases STD one, and that if you're going to overfeed somebody by 1000 calories a day, they're probably going their liver will probably increase um will increase fat production, and then we'll probably increase SCD one to export the fat is in a monounsaturated form. So, I mean, and that's, that's expected, that's understood, like, that's what's supposed to happen if you're going to overfeed, and a lot of them, it's like an overfeeding study, it'll be high amounts of, you know, something in the form of like glucose or fructose or sugar and white flour and some type of specific type of fat to form a muffin or something like that. So again, it's it's still using purified nutrients as the sole source for the experiment.

Jay Feldman 51:15
Right. Well, even in those over feeding situations, normally, they're limited by other factors, like nutrient availability, polyunsaturated fats that are going to lead to more lipid accumulation, like just eating extra, you know, an extra 500 calories or 1000 calories doesn't even necessarily mean that that's going to happen. It depends on the context. But for example, when they looked at athletes, who you're, they're kind of assuming or metabolically healthy. It takes 1000s of grams of carbs before you're seeing you know, considerable amounts of lipid production in the liver, 1000s. Yeah, and that carbohydrate overfeeding study, they weren't really producing significant amounts of fat from carbohydrates until they had around 1500 grams of until they're taking about 1500 grams of carbs over a couple of days. What's of days. Wasn't until that second day of eating basically 800 grams of carbs that they were starting to produce some amount of lipids. So part of that was because they had to refill a lot of glycogen. But they're also oxidizing a huge, you know, pounds of pounds of carbohydrates, like half a kilogram, which, because it's like a pound of carbs that there was that was just being oxidized. So, so yeah, I mean, at that point, SCD one would be regulated, as you were saying, but it does require quite a bit of of overfeeding.

Mike 52:32
Yep. And I'm just saying it makes sense that SCD one would would upregulate with de novo lipogenesis at that point.

Jay Feldman 52:38
Yeah. And I also don't think that that's really a concern. Physiologically, we've talked about how our hunger signals at that point would be telling us not to continue eating, assuming that things are functioning well, you're oxidizing the carbs, well, you have enough energy that's going to turn off those hunger signals. I'll link to some of those studies and when we've talked about that before, where basically ATP levels in the liver and brain are some of the main regulators of hunger, and also allow for leptin to have it to actually function properly, where, if you have a lack of ATP, the leptin signal won't actually turn off hunger. So, and that's something go ahead.

Mike 53:13
Well, I was just going to say, I mean, as long as assuming you're not eating Oreos, it's your main carb source, then you would probably be generating ATP from that carbohydrate, because it'd be coming, if you know, it's coming from sweet potatoes or or fruit juice or fruits or whatever. Then within those categories, then it would be coming with nutrients as well to allow the carbs to be oxidized, which is also an important point, because you know, and that this one of the issues you see with with some people with diabetes or obesity whatnot, is you're eating a high amount of refined carb sources. What do you see in the rat studies? And depending on you can basically deplete B vitamins, which are necessary for for the utilization of those carbs. So there's more to there's there's a lot more to the picture than just carb intake by itself. It's like, what type of carbs you're eating. A lot of these rat studies, it's fructose, sucrose, glucose in free form, and that's what they're in. Like, it's just added as a percentage of the diet. Like the rat diet can literally be soybean oil, casein, protein, some type of whatever your carb source is, whether it's starch, sucrose, fructose or free glucose in isolated form of vitamin mineral mixture, and then some methionine, because casein is slightly deficient in it, just like the most purified. So unless you're moving that direction, which would be, I guess, akin to eating Oreos, which also has other stuff in there, yeah, like, if we're talking about, like a whole foods diet changes, the picture specific, like pretty specifically. And you know, your fruit juice, your whole fruit, your dried fruit, sweet potatoes, white potatoes, etc.

Jay Feldman 54:49
Yeah, assuming low endotoxin, low PUFA, all, all of those factors too. And one thing you were talking about earlier too, is fructose absorption, and you mentioned like apple juice and agave and things like that. Did want to clarify, also, that some people don't have an issue. So I wanted to clarify, first off, what you're saying is those are all sources of carbohydrates that tend to contain more fructose than glucose. The the ratio of fructose to glucose is a lot more fructose than glucose. Yeah, but that isn't always an issue. Some, some people you know, are able to, you know, even something as small as five grams more fructose is able to cause an issue, which could actually, you know, depending on how different that ratio is, could require a decent amount of carbohydrates. It depends before you get to five grams more fructose than glucose, but for some people, they can absorb even a lot more free fructose than that. So there is individuality there.

Mike 55:39
The study, I think I read on, it was between five and 50 grams for participants with an average, I think around 20, yeah, if I remember correctly, yeah.

Jay Feldman 55:47
So with that being said, some of those higher fructose foods might not be an issue for a lot of people, but it's yeah, that's kind of individual, yep. I agree. Yeah. And also you were, again in talking, quote unquote negatively about those things you do also have, in those cases, some of those beneficial plant compounds and nutrients that will help in other aspects of especially apple juice, exactly, yeah, yeah.

Mike 56:11
Agave is and honey are relatively they have other components in them, but it's mostly just sugars in a solution form, right? A combination of free and free sugars and sucrose?

Jay Feldman 56:26
Exactly. Yeah. So circling back to SCD one, and Brad's views, one of his other points that we talked about was the polyunsaturated fat side, where the polyunsaturated fats do decrease SCD one, which he sees as a as a bad thing, but he also sees that they or he sees as a good thing. Excuse me, but he sees that they decrease, supposedly decrease oxidative stress when they're burned in the mitochondria, which we would say is not necessarily accurate. We talked about that in the last episode, that they end up increasing oxidative stress, because most of the time, the concern is not what's happening when they're being oxidized in the mitochondria, but what's happening outside of that.

Mike 57:05
If they're incorporated into the actual mitochondrial membrane, yeah, among and then also reaching the process of getting from your mouth to your mitochondria, are they peroxidized In that process? Right?

Jay Feldman 57:18
Right. But but. So I do, you know, I did want to point out some discrepancies here too, or just some issues that with the idea of PUFA being either harmful or beneficial, depending on whether their ability to decrease SCD one is able to outweigh their, uh, their, you know, negative effects when they're being oxidized in the mitochondria. And, you know, I did think it was so. So I'm going to include a couple of quotes of his, and then we'll, I guess, kind of discuss that, because I don't want to be putting words in his mouth. So he says, All unsaturated fats lower. SCD, one production polyunsaturated fats, more than monounsaturated fat, bear fat can be relatively, can be relatively high in the polyunsaturated fat, linoleic acid, similar to corn fed lard. So if a native person is eating bare grease, SCD one will be lowered to create an overall relatively saturated blend of body fat. The same thing is true of monounsaturated fats to a lesser degree. But there are a number of unsaturated fats that inhibit SCD one much more specifically into a far greater degree.

Mike 58:17
So there's a lot going on here, right? Right? That statement.

Jay Feldman 58:22
Yeah. But the main point is that he's saying that the, at least the lowering of that CD one is, is a is a good thing. But he also then states that he still has, he's still not recommending PUFA consumption. In fact, you know, that's one of his main things that he's against. And he explains a little bit of this later on, where he says, paradoxically, the soybean oil and starch eating American has lowered overall pressure to upregulate SCD one compared to the dairy eating person, due to the SCD one suppressing effect of polyunsaturated fat and soybean oil. However, the specific fatty down regulators of SCD one, which are CLA palmettoleic acid, arachidonic acid, and others, are much more powerful down regulators of SCD one, and soybean oil doesn't have them. That's problem number one. Problem number two is that stored linoleic acid will start to cause a pathological inability to drive Ross production. When cells switch from burning glucose to burning fat, a small amount of Ross tells the cell it's burning glucose and SCD one should be upregulated. So he's basically saying that there are two problems with PUFA. And specifically he's talking about soybean oil in this case, just like kind of what maybe a typical American diet would involve. He's saying for one, yes, it increases SCD one, but not very strongly, basically, not as strongly as CLA Palme pulmitoleic acid and arachidonic acid, although arachidonic acid would be a downstream metabolite of the linoleic linoleic acid, he mentions, but...

Mike 59:54
But it'll be a full Yeah, but it'll be in preformed version in the dairy Right, right? Because it'll just be, there's not a linoleic acid, but there will be arachidonic even small, small amounts.

Jay Feldman 1:00:05
Right, right. And so then problem number two that he's saying is that when you're storing the linoleic acid, that's going to lead to an inability to produce enough reactive oxygen species when it's being burned by the fatty tissue.

Mike 1:00:18
So then you'll basically have insulin sensitive fat tissue is the argument, right?

Jay Feldman 1:00:25
So, yeah, it's, I mean, I guess I don't have too much to add there. I just don't see it as.

Mike 1:00:35
I don't see this as, like, the foundational principle to focus on, especially it just doesn't you're saying SCD one or SCD one, yeah, like it just don't see it as, like, the primary metabolic switch that we're looking for to determine what makes you obese or not, because, especially because it's just the mediator and in, in, like, the chain where, basically anytime you have increased de novo lipogenesis or our influx of saturated fats into the liver. The liver is going to upregulate SCD one to convert them to monounsaturated some of them to monounsaturated fats, to export them to other tissues throughout the body, because the body needs a certain amount of monounsaturated fats as well as saturated fats. I don't like. I don't see it being the make or break on the entire situation, especially since we already broke apart the idea that you need to generate X amounts of ROS to shut down insulin sensitivity at the fat cells level. It just like that. That part of the theory just doesn't seem like it's going to hold water so and the other thing is, is the body seems to be up regulating SCD one on purpose, like it's, it's need, it's, it needs, apparently, my guess would be that the body needs a certain amount of monounsaturated fatty acids. So when you have so like trying, basically trying to modulate around SCD one is just sort of like beating around the bush of STD one. Well, if we have enough PUFA, then we can lower, then we can lower STD one, and it's like, well, yeah, because you don't need to produce the monounsaturated fat now, because you have a more unsaturated fat, but in even, from our argument, that would that's not necessary, because the polyunsaturated if you're going to intake a lot more polyunsaturated fatty acids, and he already recognized it's not a good thing, but now you're going to have a lot more peroxidative damage, or you're more likely to have peroxidative damage with an increase in polyunsaturated fatty acids so and then, for him, it was, oh, they'll then they'll be stored in the fat tissue, and then they'll be insulin they'll be more insulin sensitive. It just, I just don't see where, like this being the, the fulcrum, or the, the main point to focus on in the system, especially when you start looking at confounders for endotoxin in a lot of these states as well, I think it's, I think it's more likely that in those states, the endotoxemia is causing the issue and driving the fatty driving the increased deposition of fat by changing hormonal function and also mitochondrial function in general, and then upregulating liver fat production. I don't think that the SU one is causing a problem.

Jay Feldman 1:03:11
Yeah, yeah, no, I agree. And just kind of focusing in on the PUFA situation as well. You know, we talked in the last last episode about the problem being that, like our you know, from our view, he's viewing these as, uh, agents of decreasing oxidative stress, and we view those, them as increasing oxidative stress. And I think that this is kind of similar here in terms of the SCD one situation where he's saying that the Omega like that the polyunsaturated fats, are going to end up leading to more saturated fat, basically being stored. And that may or may not be true in storage. It's relatively beside the point, I would say. But I mean, like by that knowledge, you're also just going to have a huge accumulation of saturated fat in the liver. And anyway, the the other side is that we know that the amount of polyunsaturated fats that are consumed is going to be reflected in the membrane composition of the mitochondria and of the cell as a whole, which whether or not it's a membrane, again, doesn't really matter here. It's going to affect the structural components here, and that's going to directly lead to some of those issues that we talked about the last episode, as far as increased lipid peroxidation, a much decrease, like in a very decreased ability to produce energy, basically a direct uncoupling effect, which he's saying is a good thing in the first place. Yeah.

Mike 1:04:42
I just don't, it just doesn't the, you know, it's like making SCD one the centerpiece and then trying to modulate around that just doesn't make sense to me. Because your body is using SCD one just when you have higher states of saturated fat in the liver to convert it to unsaturated like, I don't see that as a pathology. So I don't see that as a problem. I don't see that as driving lipogenesis, especially. And I said this before, just we, we don't like we don't have evidence that we're generating enough ROS with saturated fatty acids oxidizing in the fat cells to induce this insulin resistance at the fat cell level. Um, or that's not to induce insulin resistance, but to turn off SCD one, excuse me, because we do know that those bad cells become more insulin resistant with or cell with saturated fat oxidation, right? Um, so I just don't, I don't know. I not. I'm not seeing it, seeing that as the as a primary driver, right? Especially when you're the states you're comparing it in where, like we have, we have an unknown and understood mechanism of why SD one is upregulated in states of obesity and diabetes and impaired glucose tolerance, fatty liver, whatever it is, yeah.

Jay Feldman 1:05:57
,I mean, I basically see it as another offshoot of the the exact, you know, the reactive oxygen species theory of obesity, which, of course, it is. I mean, that's why he's putting them both forth. They go hand in hand. It's the same for, my view, the same reductionist idea coming from hormesis. It's the same hormetic argument. And you know, when you all end up arguing for that, you also end up arguing for basically anything that causes stress, which I don't think is always really recognized, but.

Mike 1:06:27
It's like, let's cause a pathology so that we can so the body will have an adaptive response, right? Like, so what happens if the pathology is not there?

Jay Feldman 1:06:36
Or what happens if it is there? Are you supposed to create further pathology?

Mike 1:06:40
Well, I mean, when we went through the graph, that's essentially what the point of view was, right? It's like we want to get to this point where we have this ridiculous amount of like, basically toxicity is what the argument seems like it's for, at least from my perspective, I don't want to put words in his mouth or create a straw man or anything. But it was like we want to generate enough ROS to shut down SCD one, but it's already recognized in the in the article, I think that that he actually posted that shutting off SCD one with extensive amount of ros, number one didn't seem like it was possible to be just from fatty acid oxidation. But also number two, it would, it would actually cause apoptosis and fatty acid toxicity within the cell, lipo toxicity within the cell. So, like, the argument, like, I just, I just don't see that that night. I don't see this mechanism as being very relevant, as being like something to focus on for, for, like, excessive amounts of weight loss. Now, whether or not his dietary strategy works for not as far as, like, focusing on saturated fatty acids and whatnot is like, I don't disagree with him there, as as trying to avoid PUFA in general and keeping more towards the saturated fatty acid. But again, I don't see eating monounsaturated fatty acids as a problem either. I just don't think that this is the main mechanism of the issues, especially in states of obesity or diabetes or impaired glucose tolerance or non alcoholic fatty liver disease. I see those astaxanthinized by high amounts of endotoxin, and then endotoxin inhibiting mitochondrial function and then also driving an acute phase response, and then at the same time, changing the hormonal profile to one that induces deposition by outregulating adrenal function and cortisol and whatnot. So it's that seems more like more of an important mediator than anything to do with this one enzyme in the liver and pushing high amounts of reactive oxygen species, which I don't even think is a good idea, especially through this mechanism, right?

Jay Feldman 1:08:39
And I like that you mentioned apoptosis and that maladaptive side, because that's another one where you don't know. You hear that all the time and again, this is kind of coming back to hermesis, not necessarily something apparatus said, but, you know, apoptosis is a good thing. It's just, you know, it's clearing out dead cells, and it's anything that stimulates it is going to be good, just like autophagy. And it's like, that's the problem with looking at these things in a reduced form, not in the in the greater context, not as a systemic hole, is that then you consider something like apoptosis is generally good, yet that's what you see in that study where they were showing a LiPo toxic cardiomyopathy. Yeah, so, and I think, yeah, I think that CD one is an equivalent situation, focusing on that as as as the main determinant of what is of whether something's healthy or not is its effects on SCD one. And along with that too, I just wanted to circle back to one thing that I mentioned, as far as hormesis goes, or you kind of mentioned too, which is just that when when you're in a dysfunctional state, that's when you're seeing excessive amounts of oxidative stress. You're seeing dysfunction and adaptive stress pathways. You're seeing excessive fatty acid oxidation. We know that that's the backup, the backup form of respiration. And yet, if you're arguing in favor of of hormesis, then what you're saying is that those dysfunctions are the product of a lack of. State of stress, and you just need more. And, yeah, I just think that, you know, that study that we were talking about and with SCD one, happened to be a really good example of showing that that's not the case. When you add it oxidative stress on top of pathology, you end up with, you know, like that, what they call maladaptive cell structure, yeah, death, destruction, yeah, which...

Mike 1:10:20
Is not what you want, right? So, I mean, just it comes back to what we talked about in the beginning, like, well, some of our views on, like, strategies or implementation on in the real world, you know, not on this more theoretical world. As far as you know, saturated fats are good in a diet, are, you know, probably better than the unsaturated fast, where the focus on, like, either butter, beef tallow, chocolate, uh, coconut oil, and even monounsaturated fats, which is, I guess, a discrepancy with him, like, where I would say that, you know, quality olive oil or or a mono macadamia oil wouldn't be a bad thing. I mean, yeah, I don't think like I have number one. I haven't seen them to cause massive amounts of weight gain, to be honest, especially considering a decent amount of monounsaturated fat. I mean, n equals one, but and people that I've worked with using those oils hasn't caused the issue, but I just it's, I feel like the pathway itself, or the idea, or like the lens that we're looking at, at this hormetic lens, is, like, besides being, like, very focused and I guess, a little bit reductionistic, it also, like, we already went through it just doesn't pan out, like, we're not Gen like, How could just oxidizing fats create that much ROS you know, we're not seeing it, and then, like, we're seeing protective effects of SCD one in certain states, and it's like in other states, yeah, when they didn't when, when they didn't have SCD one, they didn't have, um, they didn't get diabetes or obesity or whatnot. But that was dependent on, like, the research model. Because I think before we talked about, before we did the last, the last video, when we were, when we were going through some of the SCD one stuff, when they fed the rats and increased amount of saturated fatty acids on top of not being SCD. One knockout mice, they actually developed issues where, in the other models, they had feeded that they had fed them high amounts of polyunsaturated fatty acids. And so, like, when you when you then exacerbate where the pathology is, in terms of, like, feeding them high amounts of saturated fatty acids without SCD one, then they develop serious issues. And so that CD one is there for a reason. I mean, it's there to modulate the high, any high like, and again, this is, you know, in just because saturated fats decrease or don't oxidize as much as polyunsaturated fats, doesn't mean that then eat unlimited amounts of saturated fats, and it won't cause an issue. There's still, you know, the body has a preference for a certain amount, and it's right. It's regulating that by SCD one. So trying to dance around the SCD one does it doesn't seem to make, you know, especially when we already, especially when we have the context of the SCD one issue being related to all these possibly being related to all these other factors, or, like, the obesity and diabetes and fatty liver being related to other contextual factors around seeing the upregulation SCD one, like, it's an association, and it's because in those states you have upregulated fatty acid synthesis in the liver. I don't know if I'm making if I'm being very clear, but it's like, I see it as the SCD one is an associated factor, because in all these states you have upregulated fatty acid synthesis and liver, which we already know, is saturated. I see it more as that, and the context of why these states are developing being the actual issues, and not that the liver is producing fats and then SCD, and then SCD ones converting them to monounsaturated fats. I don't see that being an issue.

Jay Feldman 1:13:55
Yeah. And of course, if it's happening in excessive amounts, it's a sign of dysfunction, exactly. Yeah. All right, that's going to wrap up this series discussing the croissant diet. If you did enjoy it, please leave a like or comment. If you're watching on YouTube and if you're listening elsewhere, please leave a five star rating on iTunes or a review. 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 articles and anything else that we reference throughout today's episode, and if you are dealing with any low energy symptoms, whether that is weight gain, chronic cravings and hunger, fatigue, chronic pain, brain fog, poor sleep, digestive symptoms or hormonal imbalances or any other sorts of low energy symptoms or chronic health conditions. Then head over to Jay Feldman wellness.com/energy where you can sign up for free energy balance mini course. Where I will walk you through the main things that you want to do to maximize your cellular energy, and also explain how these symptoms and conditions really come down to a lack of cellular energy, and again, how you can adjust your diet and lifestyle to resolve them. So to sign up for that free energy balance mini course, head over to Jay Feldman wellness.com/energy, and with that, I will see you in the next episode.