Ep. 115: LMHR & The Lipid Energy Model: Implications For Metabolism & Hormones

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In this episode we discuss:

  • Whether you should be concerned about high LDL or high cholesterol on a low-carb diet 
  • The validity of the Lean Mass Hyper-Responder (LMHR) Phenotype and Lipid Energy Model proposed by Dave Feldman
  • The metabolic state that drives the Lipid Energy Model 
  • How the “Lean Mass Hyper-Responder” Phenotype and Lipid Energy Model support the Bioenergetic view of cardiovascular disease 

0:00 – intro 

1:14 – what is the Lean Mass Hyper-Responder (LMHR) phenotype

3:33 – how the Lipid Energy Model challenges the mainstream dogmatic view linking high cholesterol levels to heart disease 

6:33 – the protective effects of cholesterol and why it does not cause heart disease, despite being necessary for atherosclerosis 

9:49 – the distinction between Lean Mass Hyper-Responders and those with high cholesterol levels in the context of metabolic dysfunction

15:10 – what is the Lipid Energy Model 

22:10 – how the body adapts to a lack of carbohydrates, leading to elevated cholesterol levels  

27:22 – the hormonal and metabolic state underlying the Lean Mass Hyper-Responder phenotype

32:21 – how adding carbohydrates lowers cholesterol levels in those who don’t have metabolic dysfunction at the cellular level 

37:11 – whether Lean Mass Hyper Responders are at increased risk of cardiovascular disease 

42:00 – why the Lean Mass Hyper Responder phenotype isn’t ideal: stress and low thyroid function

51:10 – the parallels between the lipid energy model and physiological insulin resistance

Links from this episode

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Jay Feldman  0:05  
Should you be concerned about high LDL, cholesterol on a low carb diet? We'll be answering this question today on episode 115 of the energy balance podcast, a Podcast where we explore health and nutrition from the bioenergetic view and teach you how to maximize your cellular energy, to maximize your health. In today's episode, we'll be going over the validity of the lean mass hyper responder phenotype and the lipid energy model, both proposed by Dave Feldman. We'll also be going over the metabolic state that drives the lipid energy model. We'll be going over whether you should be concerned about high LDL or high total cholesterol on a low carb diet. We'll be talking about how Oreos can decrease your cholesterol, and whether we should all be eating Oreos, and also how the lean mass, hyper responder phenotype and the lipid energy model support the bioenergetic view of cardiovascular disease. 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 with that, let's get started.

All right, so we wanted to discuss the lean mass, hyper responder phenotype and the lipid energy model. Both of these ideas have been circulating, permeating throughout the alternative health world. They've been put forth by Dave Feldman and some of the other researchers. He's working with, Nick Norwitz being one of the other main ones who's putting out a lot of content around this, and it's been a large topic of discussion, and something we wanted to dig into for a few reasons. So we both have experience with low carb diets, of course, and also a lot of the people who we work with and talk with and who listen to the podcast have been on low carb diets. Have had these experiences with different different lipid profiles, and so it's worth kind of exploring it from that standpoint, but also understanding the lipid energy model and the lean mass hyper responder phenotype is something that will that can shift the view of cardiovascular disease, the lipid hypothesis as a whole, and generally falls in line with the bioenergetic view of cardiovascular disease. So it's something that's worth exploring for those reasons. It's worth understanding the changes metabolically that are going on. I think it's it really fits right in with a lot of the things that we talk about, between low carb versus higher carb diets, and again, on the on the lipid profile side, it's important to recognize, again, the idea here, I guess I'll just backed up. But the general idea here is that there's this subset of people in particular who has particularly high LDL cholesterol, high HDL cholesterol, and low triglycerides when they're on a low carb diet. And the question basically is, is this pathological, or is this not problematic at all? Is it just a byproduct of kind of a healthy shift metabolically when someone goes on a low carb diet? Or is this going to contribute to cardiovascular disease? And so, yeah, I think understanding what's going on metabolically, understanding what this does mean in terms of cardiovascular risk and health as a whole, is something that directly pertains whether you're on a low carb diet and wondering about this, or whether you're, you know, on more of the bioenergetic side, eating carbs, but still wanting to understand the relationship between your lipid profile and what's going on metabolically and also what might be going on cardiovascularly. So

Mike  3:32  
what I for me, what I want to start out with is I have a lot of respect for both Dave and Nick for actually challenging the entrenched Dogma of the lipid hypothesis. So this idea that cholesterol is directly causing heart disease, and the more LDL cholesterol you have in the bloodstream, the like increased risk you have, or the more atherosclerosis you're going to get. And starting to take this and remove this, like very simplistic understanding, this very simplistic model, and start to put it into different contexts and say, Okay, in this context, LDL is elevated for this particular reason. This is why it's elevated. This is what's going on, and this actually isn't causing the problem or causing cardiovascular disease. And so it's another example, and we've talked about other ones where the what's driving the elevation in the LDL is very important in determining what's actually causative for the heart disease, because the LDL, while it is involved directly in the process, may not necessarily be the direct initiating causative factor. There could be some other element, whether that's hypothyroidism, whether that's endotoxemia or some type of infective process, or whether that's metabolic dysfunction at the cell that backlogs things into the bloodstream, creates reactive oxygen species and vascular dysfunction, etc, and then this drives atherosclerosis, atherosclerosis, and this is extremely important, because in order to actually resolve cardiovascular disease, prevent cardiovascular disease, or anything along these lines, we need to actually. Truly understand what's going on, and we would just say, oh, associations with LDL and and cardiovascular disease. So therefore we just need to lower LDL. And just like, kind of gets relatively simple like that, and then our main strategy is targeting the LDL. We could be targeting the wrong thing, instead of, instead of directly, like targeting the specific causative factor. We're targeting a factor that's a step away or a symptom of this underlying causative issue. And then we're not like, maybe we get some benefit, but we're not actually fully resolving the issue. And so this hypothesis, it's not about whether you're high carb or low carb. It's kind of irrelevant. This hypothesis, the lean mass hyper responders, the lipid energy model helps us to actually have another example, another another tool in our tool toolbox, to understand what's going on with the lipid profile in a specific context and directly challenge this lipid hypothesis. So for me, that's what's so groundbreaking about this. For me, that's what's so exciting about this, and I really have a lot of respect for Dave and Nick to be able to, like to go through, run the studies, to look at the mechanisms and to do the work to actually prove this hypothesis against all the entrenched dogma and people talking about the consensus, instead of being open to try and understand what's going on and coming down to the truth of like different circumstances in different contexts, and understanding that there is there's nuances and there's contextual components here, instead of LDL bad, use a statin or something like this,

Jay Feldman  6:32  
especially when that could come at a potential cost, right? And it's one thing to say that we know that increased levels of LDL increases risk, though, you know we need to lower them, but there's going to be a cost, versus a situation where maybe it's just a symptom, and maybe not even just an innocent bystander, but actually something that's helping to support the vasculature, like the health of the vasculature, in that case, you can be causing harm to the and actually driving the exact problem that you're trying to reverse. So it's a very, very important question to be answering, because it could flip a lot of things on their head. And so I think that's yeah, I'm with you there for sure. And I want to clarify also, when it comes to the lipid hypothesis, the part that's being being challenged is not whether or not LDL or a B is considered to be necessary for atherosclerosis, you can make that argument, but that still doesn't mean that higher amounts increase the risk, right? It still needs to become, you know, it still needs to be deposited in the vasculature. It needs to become oxidized damage. There's all these steps that need to happen, and we'll dig into all that in more detail, not each of the steps, but some other examples that I think really highlight the fact that just because something is necessary doesn't mean that it's the cause. I might as well mention it now. It's, there's, there's one example that that Dave mentions, which is macrophages, right? So macrophages are necessary for the plaque formation because they engulf the oxidized LDL and create foam cells. But just reducing macrophages or increasing macrophages doesn't mean that you're reducing or increasing your risk of atherosclerosis. And also, at the same time, macrophages are very, very important for tons of other reasons, so you don't want to just reduce them, especially just in case like it's a really important question to know whether higher levels of macrophages might increase your risk of atherosclerosis, cardiovascular disease. So yeah, that's essentially the equivalent thing that we're discussing and questioning when it comes to the LDL side of the lipid hypothesis. Yeah. So yeah. And then the last thing I want to echo before we dig into the details of the model, just kind of laying it out and going through it step by step, and then explaining some of its relevance in other ways. Is, yeah, I definitely want to applaud Dave here. I think, you know, listening to his his interviews, his content, over many years, he's despite a lot of resistance, especially early on, like it's one thing now, when there's they have these studies kind of under their belt, to be able to say things, you know, and remain open minded and non dogmatic. But especially when these things weren't the case. And he was putting out some theories and ideas that, of course, I think, held a lot of water or had merit, for sure, there was a lot of resistance, especially then. And he remained, again, open minded, non dogmatic, non confrontational, you know, really just genuinely look, genuinely looking for answers and collecting evidence. And so I think that's definitely something to applaud and, and, yeah, even, yeah, I guess I think I would just leave it at that, unless there's anything else you want to add, Mike, or feel free to dive into just the general lean mass hyper responder phenotype and what that looks like. Yeah,

Mike  9:44  
I just want to jump right in now and like, let's actually talk about the model. So the lean mass hyper responder phenotyper, the profile is somebody who has a high LDL so high LDL cholesterol, and we're not just talking. Like 220 usually we're talking like some people, in some of the studies are up in the five hundreds. These people also have high HDL cholesterol. They have very low triglycerides. And then something that's extremely important is this is they are on a low carb diet, often a Keto, keto diet, ketogenic diet, and they're often very lean. And something important here to understand is that the leaner they are, and also more activity and lower carb intake they have, the higher the LDL is, the higher the HDL is, and the and often lower triglycerides. And so the this profile is, you know, it's very weird, because usually people who are presenting with dyslipidemia are often obese, are often not they're not lean. They have metabolic dysfunction, whereas these people have ridiculously high LDL values, and they are seemingly very metabolically healthy, and they're also very lean. And so the question is, number one, why is that happening? What is the reason? What is the context in which is occurring, like, Why? Why are we seeing these drastic increases in LDL in this particular state relative to another state? And number two, is that even a problem like, is, is this going to cause cardiovascular disease? And I think those are the two major questions that Dave Feldman, Nick norwitz and the other researchers have been looking to understand and to and to delineate and like, actually look at people, look at case studies, look at meta analysis, and then move from there. And so Jay, I think you'll lead us into here with, like, what is actually going on? What is this lipid energy model?

Jay Feldman  11:40  
Yeah, and just to clarify real briefly, there's a very specific definition of lean mass hyper responders, which is an LDL of 200 or higher, an HDL of 80 or higher, and triglycerides of 70 or lower. And that's what they're using in the studies. But the general idea here is just high LDL, high HDL, low triglycerides. And I think there's nothing particularly you it's, it's kind of an arbitrary cutoff, right? You can have generally high LDL, but maybe it's not quite as high, generally high HDL, but not quite as high. So it's, again, the the part that I think is most important here, you have to draw the line somewhere for the studies, but the part that's most important here is what's, what's driving that phenotype? And that's where the lipid energy model comes in. So this is the model that's describing why people, why a certain portion of the population sees this in that context, who generally has low BMI? How does that relate? Why is it seen on a low carb diet? And yeah, so we'll dig into that now, kind of go through an overview. There's really nice graphic that is from one of their studies that we'll use and kind of explain the different steps of the of the process that leads to the phenotype. There's

Mike  12:50  
just one thing I want to add, Jay really quick. The other cut. The other components that they put in with the lean mass hyper responder characteristics is that for men, they have less, less than or equal to 20% body fat. For women, they're usually less than or equal to 23% body fat. And then the other thing they talk about is usually on very low carb diets. So they define that, at least on on Dave's website, is less than 25 net grams, so carbs per day, typically. So we have the lipid profile plus the body fat percentage. Because, as we The reason we're setting it up this way, just so people understand, is that the being very lean and have, like being metabolically healthy, and having this the like, the normal metabolic rate and all that, is actually essential to the hype hypothesis as to why this is occurring and why we're seeing some of the LDL values that we have, and so it's important understand, I think that's the there's a reason those those definitions are in there, and it's because it's a directly involved in the hypothesis, right?

Jay Feldman  13:52  
And I don't, I do think when they're doing the studies, they're not actually isolating people based on their body fat percentage or BMI, but they all typically happen to have low BMI, low body fat, because that is normally a characteristic here. But I think the strict definition in the actual studies, they aren't using like, again, those are kind of typical or usual characteristics, but they aren't actually controlling that when they're isolating the population in the studies,

Mike  14:18  
unless they're looking at some of the studies looking at the like meta analysis and relationships between BMI and and LDL values and things like this. They're actually using the specific cutoffs, but you're talking about like in some of the specific studies, where they're actually testing out some of the hypothesis. They're not choosing all people like you by using some type of scan to look at body fat percentage,

Jay Feldman  14:39  
right like they're stratifying by BMI and body fat to identify what this population normally looks like in those studies, where they're kind of evaluating prior data, but in the ones, there's new ones that they've been doing where they're specifically using a lean mass hyper responder population and comparing them to a non lean mass hyper responder population. And in those they're not iso, they're not preventing, like it's it's not the lean mass hyper responder is not defined by the BMI or body fat. It's just the lipid profile. Yeah, yeah. All right, so let's dig into the the lipid energy model a bit and over. You know, as an overview, the essential idea here with the lipid energy model, as it kind of suggest by the name, is that this is a model that is a representation of what's going on when we shift to lipids as the main fuel source, instead of carbohydrates. So instead of relying on glucose coming in, instead of relying on stored glycogen, primarily, again, when we're eating carbohydrates, it's not just carbs. We're using carbs and fats, but in the shift from a more balanced macronutrient utilization, or at least one that includes carbs, to one that doesn't really include any carbs, where the body begins to rely on fat and switches to needing to transport that fat between all the different tissues and different kind of packaging, that is what leads to this lipid energy Model, and what leads to the lean mass hyper response. Responder profile, where, essentially this is a way to distribute fuel, in this case, fat, through free fatty acids and through lipoproteins. We'll take into what that looks like, and that is what they're essentially getting at, is that the lipid profile we see is just a an indication of that. It's not very similar to someone who is not on a low carb diet, not using fat as a fuel, not very lean or glycogen depleted, who has high LDL. Those are very different scenarios, and the LDLs increase for an entirely different reason. So that is part of the importance here of recognizing the lipid energy model and why having this distinction and having this understanding can really change the outcome. So we'll dig into each of the steps here and the outcome in terms of cardiovascular risk or health in general. So we'll dig into each of those steps here when it comes to lipid energy model. But before we do, I did just want to mention, of course, for many people on low carb diets who are looking to a low carb diet or are looking to improve their lipid profile, they might be dealing with various symptoms and issues. This could be low energy, joint pain, high blood pressure, high cholesterol, chronic cravings and hunger, brain fog, poor sleep, various low energy, chronic health issues, again, cardiovascular related, autoimmune conditions, things like that. And so if you are dealing with any of those issues, I'd recommend you hand over to Jay Feldman wellness.com/energy where you can sign up for a free energy balance mini course, where I'll walk you through how you can adjust your diet and lifestyle to resolve these low energy symptoms and conditions, and also show you how to do that without actually needing to decrease or remove the carbohydrates. So again, you can head over to Jay Feldman wellness.com/energy, to sign up for that free energy balance, mini course. So with that in mind, looking at this, the lipid energy model graphic, it's kind of isolated out here with each particular step. And so the first kind of requirement, or I guess, if we're thinking of this in chronological order, the first thing that goes on is there's glycogen depletion and also relatively low body fat. And that leads to a system where there's not only a shift to fat as a fuel, but there's a relatively higher demand for using fat as a fuel. And as a result of that, we're going to see increased lipolysis from the adipose tissue that'll be released as free fatty acids. And we're also going to see increased lipoprotein production, specifically VLDL from the liver as a way to transport triglycerides. And there are certain regulation here that's going on, which we'll get into in a second, that has to do with hormone sensitive lipase and lipoprotein lipase. And these are each regulated by hormones and then fuel demand. So in general, if we kind of go through this sequentially, there's, again, we have someone who's relatively lean, relatively high fuel demands. And initially they have carbohydrates. Now we're shifting to a lower carb diet. The glycogen is going to be depleted. There's going to be a decrease in insulin, and there's going to be a shift hormonally toward increased glucagon, and especially in the beginning, increased epinephrine and increased cortisol, and those things are going to increase the activity of HSL, or hormone sensitive lipase, which causes the release of free fatty acids from the adipose tissue. And those free fatty acids are then going to typically be going to other peripheral tissues, muscle and organs and things like that. And they'll also be sent to the liver as well. The liver will take up those free fatty acids. And not to get on too much of a tangent, but we talked about this in terms of fatty liver, and that this is actually the metric. Actually the mechanism, and that's responsible for most of the fat that accumulates in fatty liver is actually fat coming from the fat stores. I'll link back to that episode where we talked about that. So we have that as as kind of the first set of of responses to the low carb. Diet, and then along with that, we basically have increased delivery of fat through the lipoprotein system. And so the next thing that will happen here is the liver will increase its production of VLDL and excretion of VLDL. And VLDL is a lipoprotein that has a large amount of triglycerides, which is basically just fat that's going to be used as a fuel. Those are sent out from the liver, and then those can be picked up by both the adipose tissue and then also by the muscle or other peripheral tissues to be used as energy or repackaged. In this case, the idea is mostly this is going to be used as as energy, although in the fat stores and in the liver, we kind of have this, uh, this like you have this revolving door where you have in the liver, you have free fatty acids coming in and VLDL coming out, and in adipose tissue, you have triglycerides from VLDL coming in and then free fatty acids coming out. And so you're kind of repackaging and delivering these different fats to different tissues in order to support the needs of the body using fat for fuel. And there, there's one other part that's important to mention here, which is as a result of producing more VLDL, and those VLDLs dropping off their triglycerides at peripheral tissues, again, adipose tissue or muscle organs, other tissues that use fuel. There, what that does is it causes the VLDL to become LDL. And there are also other aspects, or what are called remnants, of the or not remnants, but other other components of the VLDL that get kind of taken up by HDL. And so the idea is that that is where the increase in HDL and increase in LDL is coming from, is basically it's coming from VLDL as they drop off their triglycerides. And so that's the, the kind of main lipid energy model. It's like, the the kind of step by step, what's going on in people as they shift to a low carb diet.

Mike  22:00  
Yeah. So the model, there's a couple of things I want to add to the model, not like to add to what you said with the model. So essentially, the what, I think, the big thing to understand here is that when you don't have carbs, the backup fuel in all circumstances is fats. Once you deplete your carb stores, you're out of you're out of glycogen storage muscles. You when the muscle glycogen is not going to come back out of the muscle, it stays in the muscle. You have to rely on fats. And so in the fasted state, when you're not eating, the question is, where, where's this? Where's the fuel sources coming from the fuel sources for lean mass hyper responders is coming from their fat tissue. And so their fat is releasing what's called non esterified fatty acids. So they're not in the triglyceride form. They're free fatty acids. And then those free fatty acids are being delivered to the tissues, the muscles, other organs, and then also to the liver. And the liver is repackaging these fatty acids into triglyceride form, putting them in the lipoproteins, and then sending them out to the tissues that need it, like the muscle tissue. And then what happens is the muscle tissue picks up the triglycerides. And what, what I think people need to understand is that VLDL is very low density lipoprotein, or and then you have intermediate Density Lipoprotein, which is IDL, and then you have LDL, which is low density lipoprotein. They are the same thing, essentially, just like each one has less triglycerides on it, and some of the fatty acid composition gets shifted. So when you take the triglycerides off of the VLDL, like the muscles you think of, I think Dave Feldman puts this as like a boat. So it's the you can think of the VLDL as a boat. It has a bunch of fat stores on it, like one of those big container ships that's not making it through the Suez Canal right now. And then what winds up happening is the boat gets, brings the fat to the muscle, the muscle pulls off that fat, the triglycerides. And then you're just let then it gets turned into an LDL. So it gets turned into a smaller boat, because it doesn't have the triglycerides anymore. And then some of the other components of the boat, of this VLDL, the lipoprotein, some of the cholesterol components, etc, go to become HDL, or go and get added to other HDL molecules. So you're having this, this increased LDL and HDL as a function of transporting all these fats to the tissues. And it's, again, this is, I think, specifically under, though you're under the carbohydrate restricted state, and then you're not, you're not necessarily under a feeding state. Under a feeding state is relatively the same, except now that a lot of the fat source that's coming in is coming in through Kylo microns, which is being taken up by the intestine, and then that also goes to replenish the fat in the fat tissue, and also goes to the liver, and then also creates more HDL in these different components. So under this state, you're basically just seeing, okay, we don't have carbs available, so we're going to up regulate all these processes. Is to transport fats to all the tissues that need them and and liberate fats in different areas, and have this like new distribution network set up for fats for the energy needs. And the thing with this model that is interesting is that the more lean you are, the less fat tissue you have, the more you have to upregulate transport of the fats from the liver to the tissues through VLDL, because you don't have all this energy reserve in the fatty tissues Your body is like, really trying to make sure you have enough, like, fuel substrate available. Because also the people who are very lean probably have, like, a higher metabolic rate. They have this higher they would have this higher lean mass, or, if like, relative to their body size, with the higher metabolic rate relative to body size, and they're gonna have this increased energy demand, and they don't have carbs. So then there needs to be a system for them to use fats. And what, what this model is describing is that specific system. How is all this stuff being transported and whatnot, and when, when somebody is heavier, has more body fat. The idea is that they would have lower LDL values because they would get the fatty acids from the local fat tissue, releasing the non esterified fatty acids into circulation in those areas. And you won't need as much VLDL production from the liver to actually transport this stuff. And so it's the to put this all into context as like, the importance with the cardiovascular disease stuff, what we're seeing here is LDL is elevated as a function of transporting fats to the tissues. It's not the it's not elevated because you have this, like, lack of ability to take up fat at the tissues. The tissues are sucking up all the triglycerides out of the VLDL, and then you're getting the LDL and HDL as a as a backup after that, whereas, in another profile, like a metabolic dysfunction, the tissues are not taking up the fatty acids super well, or glucose, because they have metabolic dysfunction, and you're getting a backlog in the lipid profile because you have all the fats kind of transporting around, and The ships are like, you know, where are we going to drop this stuff off? Nobody's taking up our product. And then you start building up the different metabolites in the serum. And, like, this model is extreme this, that's the difference between them. And this is very helpful for understanding, like, how the fuel is being used in these different contexts.

Jay Feldman  27:20  
Yeah, yeah, absolutely. And so a couple of things to tack on there. So as you were saying, the way that the leanness, or the reason why the leanness matters is because, generally, there's less baseline lipolysis going on, and there's also greater energy demand. And those two things go hand in hand. And so because of that, you have, again, the two kind of regulators here being the lipases. So you have the hormone sensitive lipase and the lipoprotein lipase. So the lipoprotein lipase is produced by the tissues basically when they need more fat, or when they want more triglycerides, they want to basically take up the triglycerides. And that typically happens if the tissue is stressed, if it's low on fuel, if there's a lot of lipid oxidation going on, there's certain other hormonal regulation, but so that the idea is that that's going to be going on to a greater extent in someone who's lean, and then on the H the HSL side, the hormone sensitive lipase, that's also going to be regulated by a similar situation, and is largely hormone regulated in terms of low insulin and high glucagon being one of the kind of, like central ratios. And of course, that's something we see on a low carb diet. We've talked about that before, and again, we're not we're just kind of describing the model here. We're not necessarily, not necessarily saying it is beneficial or benign or harmful. We're just kind of describing the idea. And then we'll dig into that question next of whether these things are potentially beneficial, harmful or just, you know, neutral. But an increased glucagon to insulin ratio is a big part of that also increased epinephrine, increased cortisol will drive increased hormone sensitive lipase, and as they mentioned here, low leptin will also drive it. So those are going to be the things that increase the release of free fatty acids from that opposed tissue, again, something we talked about a lot. Of course, under stress. This is a clear time when this would be happening, but also on a low carb diet, partially because of the stress that's involved. So we'll be digging, digging into that in a bit more detail, in terms of its ramifications. There's two other things I want to mention. One is in this model, we explained the high HDL and high LDL. It's important to mention that there's low triglycerides, and what that means is that there's not a the triglyceride value when you're looking at a blood test is talking about the triglycerides that are located within the lipoproteins in the blood. And so what it's saying in this case, if we have low triglycerides, it means that there's low VLDL in the blood. The VLDL is a lipoprotein that has a lot of the triglyceride, but in this situation, there's not a lot of VLDL hanging out in the blood, and we see that because there's low triglycerides. And instead, what's happening is there's a lot of turnover, so there's a lot of VLDL being produced, but there's also a lot being converted to IDL. LDL, and mostly LDL, because if there was a lot of IDL, you would still have higher triglycerides. So a lot of that LDL is VLDL is is going to turn over into LDL, and that's because of the increased lipoprotein lipase, the increased uptake of the triglyceride, yeah, of the triglycerides into the peripheral tissues. So that's where you're getting the low triglycerides from. And so the idea, as you're getting at Mike, is that the high LDL is not, you know, in a case of of like an atherogenic lipid profile, normally you're going to see high triglycerides and generally low HDL alongside the high LDL, suggesting that there's excess lipid circulating because the cells are not working well metabolically, like the tissues are not working well metabolically, so they're not using the fat. And there's excess fat hanging out in the bloodstream, and we're not seeing that. Here. We are seeing excess cholesterol hanging out in the bloodstream, especially in something like LDL, not excess triglyceride, but excess cholesterol. And we will be talking about that a little bit as well, and whether that may or may not be indicating an independent state, an independent sub optimal issue, or an aspect of the state that is also not, that isn't ideal, but it's kind of separate from the direct explanation here in the lipid energy Model.

Mike  31:19  
Yeah. So I think the there's some major pieces that I want to add here that I think are really important to understand in the model. I think the central piece is understanding what's going on specifically at the cells. So the cells saying, Hey, we don't have enough carbs. And so the body is then creating these mechanism to actually provide fats instead to the tissues that actually run on fats. And so the way you can think about is the fat tissues, like an Amazon warehouse for a bunch of storage products, and the VLDL or the trucks, the Amazon trucks, where the packages are being sent to the liver, the liver is kind of or it's being sent directly from the warehouse, and then the liver is distributing these to these trucks, VLDL to the tissues, and then the LDL and HDL are kind of like the empty trucks. To some extent. It's like what's left over once the packages are released and they're going back to the liver, and everything's being circulated around. And so the delivery site, the home, is the cell, and the cell is using these packages. It's using the energy. And so it's just a distribution model. Now, something I want to point out with with the and this is maybe slightly tangential, so I don't want to go too far with it, but when we talk about this model, when people adding carbohydrates to this to this low carb diet, and I see this with clients all the time. You see this with clients all the time. We see the cholesterol levels precipitously drop. And this will lead us into talking about the Oreo study. But essentially what's happening is you don't need to run on the fats as much anymore. You shift all that hormonal profile, the insulin, the leptin, the glucagon, the adrenaline, the rate the release of fats with hormone sensitive lipase versus the lipoprotein lipase uptake. And what winds up happening is LDL, HDL, drop significantly. And then there's a transition period where triglycerides actually initially bump up with this, because you don't, people aren't uptaking the fats as much anymore, because now they have the carbohydrates present. And then eventually triglycerides also come down as well with the profile, because they're running primarily on carbohydrate now. So there's like, once you add in carbs, the body then switch back to try to use carbs as a as an energy substrate. And so this is these circumstances aren't pathology, because at the cell, there's no problem. Metabolically, the cell can oxidize the fats. The cell can oxidize the carbs. It depends on what you're going to give it. Well, I'm not saying that this is ideal to then run a low, low low carb, high fat diet, but this is very different than somebody else who has metabolic dysfunction at the cell and they can't take up the Amazon packages anymore, and now you have a bunch of loaded trucks floating around the bloodstream, and there's, there's a bunch of other problems going on with that, also because of the metabolic dysfunction. And Dave and Nick inside one of their mechanistic papers discuss the like inability, the impaired release or or uptake of substrate utilization and obesity with both with fats. But then Jay and I have also talked to other papers with those problems with also carbs. So that points to the central problem in the DIS the dysfunctional state, versus this kind of would be considered a physiologic state being related to energy metabolism at the cell, and that's why I think it's with all of these models, whether you're using carbs or using fats, or whether you have this, the dismetabolic state, the biggest thing to kind of understand in this in the context, is what's going on at the cell with its utilization of energy, and why are all these things switching with these different contexts? Or why are we seeing a backup in some of these other other contexts, like obesity and diabetes, where you're seeing this elevated LDL, elevated triglycerides and. And you're seeing the higher blood glucose levels and all those problems it's like that is metabolic dysfunction of the cell. Here you're seeing it just because you don't have carbs and the person doesn't have a lot of fat tissue. And then when somebody has carbs and they don't have metabolic dysfunction, you're seeing a lowering because they don't actually need the run on all the fats anymore. So there's these different situations where you're seeing different effects for different reasons. It's important to understand why in each circumstance, and the central piece is metabolism at the cell, yeah,

Jay Feldman  35:26  
yeah, yeah, absolutely. I think that's a great explanation of it. And I did just want to mention or clarify one thing, which is in the Oreo study that Nick did, there was actually an initial or a decrease when he added the Oreos in in terms of triglyceride levels. And that's not unexpected in the short term, just because insulin actually increases the triglyceride uptake off of the VLDL. So it would be normal initially from the increase in insulin to have reduction in triglycerides, reduction in VLDL. That's not Yeah, like that would be expected short term, Yep,

Mike  36:05  
yeah. I my what? There's been times where I have people add in carbs, even, like, metabolically LD people, the reason I bring this up and when they're trying to switch from carbs to fats, the the lipid profile just downward pretty precipitously, like LDL drops, total drops, yeah, once you add in carbs and then triglycerides, then again, this is not just within a couple days. This is like, this is, you know, they're switching over a couple weeks, triglycerides bump up initially, and then things start to come back down. And I think that is partially related to what's going on with carb versus fat metabolism, whereas I think the insulin action is will lower the release of free fatty acids than the triglycerides and things like this. But I think over the long term, there is this whole shifting back and forth between the substrate utilization,

Jay Feldman  36:55  
yeah, yeah, totally. And I think the amount of carbs would probably make a big difference here and and also someone's like gaining weight, you'll often see the triglycerides coming up like that. But yeah, so I think what that brings us to is the next, the kind of underlying point here, behind this model, behind the lean mass hyper responder phenotype, the underlying suggestion and kind of question that is being asked is that, with this in mind, if this is the situation that's driving the lipid profile, why would it actually increase cardiovascular risk if it is representing a very different metabolic state from typically high LDL? That's really the question that's being asked here, and that's because, in general, as we mentioned, normally, when you see high LDL, you also see high VLDL, high triglycerides and lower HDL. And this is normally the lipid profile profile that's associated with the higher risk of cardiovascular disease. Of course, in this case, you see the high LDL alongside low triglycerides, low VLDL and high HDL. And so the kind of essential question that's being asked is, well, does that other lipid profile represent a poor metabolic state that is associated with cardiovascular disease, or is it the high LDL itself that is directly causing the increase in in cardiovascular disease? And that's, that's basically the question, but, but the the assumption that is starting to be supported by the evidence, supporting not only the model, but also just the the what's Well, yeah, supporting the model, and then also looking at this question, trying to explore whether this is associated with cardiovascular disease, and suggesting that it doesn't seem to be right? It doesn't actually seem to be. And instead, what it points to is that that other profile was just a symptom, just a marker of a poor metabolic state, a marker of insulin resistance, a marker of metabolic syndrome, marker of Yeah, like a poor conversion of fuel to energy, caused by all sorts of multitude of factors, and that that is actually what is contributing to the increased cardiovascular risk. And so I think that is what like that's one of the next things we'll be focusing on, is the evidence, or the model, and then the evidence that whether this is something that would increase cardiovascular disease risk, Yep,

Mike  39:21  
yeah, and that's this is why we're describing the model this wire. But understanding what's going on metabolically at the cell is is so essential, because inside that is like the metabolic syndrome profile, obesity, diabetes, there's a problem with the utilization of fuel, whether that's carbs and fats, there's problems in both circumstances. And so the lipid profile in that circumstance where you have somebody who doesn't who has this metabolic issue, versus somebody who's a lean mass hyper responder, who doesn't necessarily have this metabolic issue, right there it looks like mitochondrial functions working. Well, they have a decent amount of lean mass, they don't not carrying a bunch of body fat mass, and then you're seeing this elevation lipid profile. And it's like, you know why that's the big point is, like, what is this even pathologic in these circumstances? Because the overall picture of these people would indicate that they don't have metabolic dysfunction, but their lipid profile is semi similar to people who would have metabolic dysfunction. And then, you know, when we'll talk about some of the other studies, what you see is that the you're not seeing the cardiovascular issues that that you would see in the other profile. And again, I think the difference is not like the the difference isn't necessarily around or or the problem is not necessarily around LDL. The problem is around metabolic function, and then how that metabolic function is driving LDL. Why is the LDL elevated? And the question, when you start to ask the question, why, and start to look at the answer, why, then you can start to solve the problem. And then, if it's just because you don't have enough carbs on board, and your body is relying on backup substrate in the fuel, fat, in the form of fat, the fat is a fuel. And it's like, okay, this may not be problematic. This is just transport. This is just transport of fuel, whereas in the other circumstances, like, we don't have a utilization of the fuel that we've transported. And it's like, now we have a big issue, because we're not flowing the fuel into energy. We're just backing it up in the transport lanes, and that's causing a bunch of issue, plus the energetic failure could be creating a context or a circumstance that maybe oxidizes the cholesterol and drives increased reactive species oxygen species production, damaging the vasculature, etc. And I think my hypothesis, at least, would be that that is more likely the problem in the driving factor in somebody who has atherosclerosis and dyslipidemic profile than somebody who's a lean mass hyper responder. Lean mass hyper responder. They just need fuel. The other person, they can't use the fuel. And that's the core problem, not that their LDL values are both high.

Jay Feldman  41:57  
Yeah. So I totally agree with that, and it there's another aspect that I want to discuss here. So the question behind the model, as we were saying, is, does this confer risk in terms of cardiovascular disease? But I think there's, and I think that's a good question. As you're saying, what we're saying, what it seems to point to. And there's other lines of evidence for this too, but just focusing on it through this lens is that it doesn't seem like it's as simple as LDL equals increased atherosclerosis, but there are other aspects going on in this lipid energy model that I think are worth touching on. I kind of alluded to them when I was going through it, that I don't think are necessarily benign or ideal for health in general, or for cardiovascular disease, either, and the two that I would focus on. So for one, we talked about the hormones that govern hormone sensitive lipase, and those are typically the blood sugar regulating hormones and the stress regulating hormones typically are the same ones. That's insulin, glucagon, epinephrine and cortisol. And so in order to have this increased hormone, hormone sensitive lipase, this increased HSL that you see when you're shifting into the kind of lipid energy model, form of fuel utilization, it requires a decrease on one side, a decrease on the insulin side, and an increase on the other side from glucagon, epinephrine and cortisol. We've talked about this in number of different contexts, and I'll link back to these episodes talking about how blood sugar gets regulated on a low carb diet, but it requires at least high glucagon, and often also increased levels of epinephrine and cortisol. You'll see those especially in the first month or so, four to six weeks, and then over time, you'll more just see them in bursts, but still to a greater extent than when you're on a high carb diet. And this is something that is integral to the transportation of fat, the utilization of fat in the state, and that's really important to recognize. You need to have that in order to increase the release of free fatty acids from data post tissue. You also need to have that in order to stimulate gluconeogenesis, which you do need to have in this state as well. Of course, that's not a major focus, but that is something that I think is, as we've mentioned in the past, something that acts as a signal overall, to down regulate our metabolic state. One of the ways that it does that is by reducing the conversion of t4 to t3 and that is the other thing that you see here that isn't depicted in the lipid energy model, but I do think there's an aspect of it that can be caused by the low t3 and this is also something that's shown in some of the research where they're looking at lean mass hyper responders. It's also something that Dave and Nick both mentioned, is that they both have low levels of t3 and in some of the studies that we'll be going through in these next episodes there, they show that basically low t3 correlates very well with the increase in LDL. They have a direct inverse correlation, where, when you're on the low carb diet, as a lean mass hyper responder, LDL goes up. T3 goes down. If you add the carbs in, immediately you'll see a switch. The t3 goes up, the LDL goes back down. And then if you go back off the carbs, you see the switch again. T3 goes down, LTL goes up. And so we've, of course, t3 and thyroid hormone in general, is the overall regulator of our metabolism, as far as how much fuel we're going to be converting to energy, and this has a lot of implications for cardiovascular health, for brain health, for all sorts of things. We did a whole five part series on thyroid that I think is worth checking out. So I'll link back to that. But in this case, I think that the I don't think that that is just happening. I don't think that those two things happen alongside each other, the increase in LDL and the decrease in T3 Of course, there is going to be increased VLDL to LDL turnover, and that's going to increase the LDL. But one of the other main things that T3 does is it increases the cellular uptake of cholesterol and its conversion into the steroid hormones, starting with pregnenolone, then all the reproductive hormones and some others. And so when you have low T3 you're going to have less of the cholesterol uptake and utilization, and that's going to mean less deposition of cholesterol or or less essential essentially, like usage of the LDL. And so that's also going to be something that I think is a contributing factor here to the increased LDL levels, and again, just in description of the model, I think that that's something that that it should be considered, but then also big picture wise, and we'll talk about this a bit later on, I think that this Alongside the increased stress hormones, glucagon, adrenaline, cortisol, is a is a good demonstration of why this, even though the LDL itself might not be an issue when it comes to cardiovascular risk, this might not be ideal when it comes to an overall health standpoint,

Mike  46:54  
yeah, I think those are all really great points, Jay and I think the question here is, there's first question Is, is is this path? Does this create pathology for cardiovascular disease? But then the next step after that is, is this ideal? Is this optimizing health in the long run? And I think, based on arguments that we've done, you know, quite significantly in the past, probably not, not an ideal state to be in the long run, because even the stress hormones, even lowering insulin signaling, even raising glucagon, even raising adrenaline, even raising cortisol, even raising fatty acid oxidation, has other negative effects. So even though you're even though you're raising your lipid profile to transport fats and that may not cause cardiovascular disease, are there other aberrations that could be caused by running a keto diet or a high fat diet over the long term that are separate from this, and you're seeing one of them play out in the you're actually seeing them discuss this directly in this research and in this model, where you're seeing the raising of these stress hormones and lowering of some of these other hormones that signal energy repleteness. And you're also and you're seeing this lowering of thyroid hormone, which would be another indicator of energy repleteness. And then this causes issues, can cause other issues downstream that aren't being discussed in this model. And so I think it's really important to put those things in perspective. There's also talking about things in terms of what's going on with mitochondrial dynamics, and the changes in ROS production in the mitochondria, and changes between NADH NAD plus ratios, FADH two NADH ratios, and then the shift inside the electron transport chain. And what is the long term effect of these things? What is the long term effect of having lower thyroid hormone function? What is the long term effect of having increased glucagon levels, or increased glucagon signaling metabolism? What's the long term effect of up regulating adrenaline and cortisol, or at least cortisol and adrenaline signaling over the long term. What's the long term effect of creating the ROS inside the mitochondria from this type of diet? And so, like, that's the next step after this is okay, this doesn't cause cardiovascular disease, but what is there? How do we optimize health? Is keto the way to go? Are there problems that go hand in hand with prioritizing this fatty acid oxidation over glucose oxidation? And I think, you know, I think that those are pretty significant problems, and it, you know, this isn't the optimal way to set things up long term. So this model does, it does help us to show a lot of value in understanding context with cardiovascular disease and the relationship with LDL, but it doesn't necessarily then make keto, or a low carb, high fat diet, the ideal setup for long term health, through these other mechanisms that still have to be, you know, would still have to be rectified. And then the other thing is the lowering of t3 and the increasing of these other stress hormones and the lower of insulin, lowering of insulin signaling, are basically showing us what this state is representing to the body. This state is representing an energy depleted state where the thyroid hormone is the mass regulator of energy metabolism. And you're seeing the active thyroid hormone t3 the most important thyroid hormone to have its effect, being down regulated in the state. And you're also seeing down. Population of hormones like insulin, which are not the bad guy, is the hormone basically of anabolism and surplus, and letting us know that we have enough energy on board, that we can create more muscle tissue, that we can store more glycogen, things like this, and that's getting drastically decreased. And then what you'll see over time, you know, people running low carb diets, they see changes in their steroid hormone profiles, hormone binding, globulin, concentrations, all this type of stuff. And again, all of this is the body saying, all right, we don't have fuel the we don't have optimal fuel availability. So you're going to run in this backup system, and we're going to undergo all these transport mechanisms and hormonal shifts to support the system so we can continue to survive. But the question is, does this allow us to actually thrive in the long term. And I think based on the mechanisms, when you look at the effects of glucagon, cortisol, adrenaline, fatty acid oxidation versus carboxydation, the benefits of thyroid, we start to say, okay, maybe there's other problems with this overall. And so I think that's really important to highlight, even though this model is great and it's not, we're not refuting the model, but I don't think this is necessarily reason to specifically go keto just because the elevated LDL isn't causing heart disease, or may or is less likely to be causing heart disease than if you had an atherogenic dyslipidemia.

Jay Feldman  51:11  
Exactly. Yeah, and it goes the model, I think, runs parallel with the idea of physiological insulin resistance, right? There's a difference between physiological insulin resistance and pathological in the same way, there's a difference between LDL increase in this case and LDL increase in the state of insulin resistance and metabolic syndrome, right? It's very parallel in that way. And the physiological insulin resistance does not actually mean that you can't oxidize carbs. It just means that you're not and you're shifting to a fat burning system. And there's the differences in mitochondrial respiration, differences at the electron transport chain, differences in glucose uptake, that are all really important. That the fact that that's not the same as pathological insulin resistance is important. It's a really important distinction. But it doesn't also mean that it's benign. And so I think that's exactly what we're what we're getting at here. It doesn't mean that it's ideal, I guess is another way to put it. And along with that, we always talk about this, the lipid energy model, like we talk about aspects of it, right? We talk about how in your shift to a low carb diet, you're going to see increased lipolysis. You're going to see increased fat oxidation. But much like any taking any sort of symptom, any sort of marker, and correlating that with some outcome. That doesn't mean you're automatically going to have increased fat loss, or it doesn't mean that you're automatically going to improve your health, because you've now lowered this pathological insulin, right? All it means is that you've just shifted to the fat burning system. You have more fat coming in, more fat coming out, and you're not relying on a glucose as much. So you're not again, in the same way that this is not like just because it is not contributing to a pathological situation in terms of cardiovascular state, it doesn't mean it's contributing to the opposite. It doesn't mean it's supporting insulin sensitivity or supporting broader physiological health. And yeah, I think that's something that, again, we'll dig into a little bit as we also talk through the evidence for, for the theory, some critiques against it, the counter arguments, and kind of dig through all that. And then we'll, we'll talk through some of those details as far as how it applies to what we actually want to be doing. And of course, that's a really

Mike  53:13  
important question, yeah, yeah. I mean, I don't, I don't have too much to add. I think we're on the same page. Not, it's not, it's not. May not be causing cardiovascular disease, but is there longer pathological considerations from running the stress state and changing towards fat oxidation, et cetera in the long term? And I would argue that, you know, yes, there is based on some of the mechanisms that we've discussed before.

Jay Feldman  53:35  
All right, yeah, I think that that really wraps it up. So, Mike, can you share where people can find you.

Mike  53:42  
Yeah. So if people want to find me or my work, they can check out my website, mikefabe.com and if they're wondering about how to transition from a low carb diet to a higher carbohydrate diet, or trying to come off keto, carnivore, paleo, et cetera, I have a guide on my website called the nutrition blueprint. It's a PDF, and now there's a video course with it, so you can pick that up@mikefave.com

Jay Feldman  54:03  
Awesome, awesome. All right, if you did enjoy today's episode, please leave a like or comment. If you're watching on YouTube, if you're listening elsewhere, please leave a review or five star rating on iTunes. All of those things really do a lot to help support the podcast and are very much appreciated. To check out the show notes for today's episode, as always, you can head over to Jay Feldman wellness.com/podcast where I'll link to the studies articles and anything else that we referenced throughout today's episode. And as we were discussing, while LDL itself might not be a concern if you're on a low carb diet, there are other reasons why it might not be ideal and might not actually lead to the improved health that we're looking for. So if you are looking to switch to a bioenergetic type diet that includes both animal protein sources saturated fat along with carbohydrates, then you're going to want to download the energy balance Food Guide. The energy balance food guide will help you determine exactly what to eat to optimally support your metabolism and help you lose weight, improve your digestion, get amazing sleep, boost your energy and so much more. Four the energy balance. Food Guide is a one page infographic that organizes food on a spectrum based on how effectively they support your metabolism, and it also has a separate spectrum that adjusts the scale for you in the case that you're dealing with various digestive symptoms. The Food Guide makes it extremely easy to get started with a bioenergetic approach to optimizing your health. So head over to Jay Feldman wellness.com/guide to download your free energy balance Food Guide, and with that, I'll see you in the next episode. You.



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