Transcription
Hello everyone. Thank you so much for being a member of the Insulin IQ community. And in particular, thank you for joining me for this week's Metabolic Classroom. That is a title that I've always been particularly pleased with. This idea of me learning and teaching. All right, um, thanks again. Um, so today, uh, the focus of the classroom today is to help you better understand, understand the origins of insulin resistance. Um, last time, and, and if you haven't, make sure you go back and watch that episode. We discussed what insulin resistance is. So we really defined it, particularly in the context of metabolic health, uh, and different ways of defining metabolic health, including metabolic syndrome and metabolic flexibility. And then actually revealing, pulling back the curtain and showing you that really at the heart of both of those problems is insulin resistance. So we explained the scope of the problem and why it matters, matters, and why it matters. In particular, that idea is something we'll focus on more next week. Um, so for now, uh, before we get started, I, I kind of like making it a habit of sharing with you guys, uh, a little piece of some newly published research. There was a paper that was published just recently in the journal Cell Reports. And what's interesting about this is that it shows this to invoke a concept of economics, this diminishing returns when it comes to satiety and our consumption of sweet things. So the study utilized rats. I know of no evidence in humans to support or refute this. So for now, we'll assume it's relevant in humans until we learn otherwise. But they fed the, the rats a diet that had high levels of sugar in the water. Now, of course, that's how a lot of people get sugar, right? Any of these sugary sodas or even juice has a lot of sugar in it. And so they had the animals drinking, uh, the sugar water. And then they tested the animals' response to a load of glucose. So then gave them a bunch of glucose to eat. And they found that before they had started, um, this high sugar diet, the high sucrose, uh, they had a very substantial response to the, uh, glucose and it induced a sense of satiety. In other words, they got the glucose load and they felt really full. However, with, with this sugar diet, with the diet that was higher in sugar, it didn't work as well. When they gave the animals this load of, of carbohydrate, they didn't have that same degree of satiety. That signal, that sensitivity to the carbohydrate load had been diminished. Now, they're not using the word insulin resistance there, and I'm not going to either. They didn't really test it. But I will just say they found that there was a diminished ability to sense the, the, the, the calories or the energy coming from, from that carbohydrate. And the animals, um, would have been inclined to just continue to eat more.
All right, so that's a little bit of the science corner of the Metabolic Classroom. Now let's get into the actual meat of the lecture, if you will, the classroom session for today. So where does insulin resistance come from? Just as a reminder, it is insulin resistance is the single most common health problem worldwide. So it is worth talking about. It is worth devoting a career to understanding and, and just appreciating in, in our life and at a global level.
All right, so I have classified, in my understanding, in my exploration and study of insulin resistance, really two categories when it comes to understanding the causes of insulin resistance. And I use the terms primary and secondary. Now, the primary insulin resistance is a term that, um, I use very specifically. In fact, both of these terms are very specific. With primary, I consider the cause to meet that to fall into that category if it has, if it is based on research that has been confirmed in all three commonly used biomedical research models. Now, what do I mean by that? As a biomedical scientist, I will use, and have in fact published papers on all of this, three models or three ways of doing experiments. At the kind of simplest, um, it is just growing cells in a little petri dish in, in a lab. So we have a little incubator that will grow cells. We'll put muscle cells on the petri dish, or liver cells, or neurons, or fat cells. And then we do experiments on those cells. Next, you can do experiments in a whole organism, like in the case of laboratory rodents. So this is mice or rats, where you can knock out genes or overexpress genes. And then you can get all of the tissue to study the fat and the heart and the brain stuff that you just couldn't get from humans, of course, in a perfectly controlled environment in the lab. And then next is experiments done in humans. So these are the three commonly used biomedical models: cells, rodents, humans. So the primary causes of insulin resistance are those noxious stimuli that have been shown to cause insulin resistance in all three of those models. The secondary causes of insulin resistance that I'll share with you are those that maybe have been shown to cause insulin resistance in two of the three, as we will highlight one particular example of that. Or it is actually, there's evidence to support all three, but it does so, it causes insulin resistance by taking advantage of one of the primary causes. So it's not independent of the primary cause. I hope that makes sense. So that would call it, con, that would, um, count it as a secondary cause. Again, if it requires the involvement of one of the primary causes. So it's still coming back to the primary. That if you eliminate the primary, then you've eliminated the insulin resistance. But again, with the three primary causes that I'll talk about in a moment, each of them is capable of causing insulin resistance on their own.
All right, now let's go through the three primary causes. These are the big pillars that really contribute to insulin resistance in cells, rodents, and humans. First one is inflammation. This is one that I feel pretty strongly about and I'm quite familiar with because it was largely the focus of my post-doctoral fellowship research many, many years ago, and work that I had continued and have since then and continue to contribute to. Now, so in this case of the inflammation, it's important for you to appreciate that when I say inflammation, I don't necessarily, I don't mean an immune response. And I don't mean an angry, red, oozing scratch on your arm that's gotten infected. When we, when I say inflammation, I actually just want you to think that of, of a pathway within virtually every cell of the body. And that when this pathway is activated, it, it is part of a, if it were, if we were talking about an immune cell, it would be part of a normal immune response. But for example, muscle cells, muscle cells have an inflammatory pathway or multiple. And those aren't immune cells. Fat cells have an inflammatory pathway, and those aren't immune cells. Those aren't white blood cells that are part of an immune response to defend the body against infection. But all of these cells have these inflammatory pathways. And what's interesting in the muscle, for example, that you activate the inflammatory pathway, and the muscle isn't going to start producing antibodies, but it actually then shows this intersection of the immune system or the inflammatory system and the metabolic system. So anytime you activate inflammatory pathways within a cell, you cause that cell to have a diminished response to insulin. Resistance. So at a cell, at a cell level, you can just incubate cells with an inflammatory protein, like for example, C-reactive protein. Have you heard of that? Does that one sound familiar? CRP or C-reactive protein is a protein that has been increasingly measured in clinical tests because it's such a good marker of inflammation and just overall cardiometabolic health. So if I have muscle cells or fat cells or liver cells or brain cells, and I put C-reactive protein in that little culture bath with the cells, and then I test how the cells respond to insulin, it will be diminished. The insulin response will be turned down. Same thing goes for animals. If you induce an inflammatory response in animals, they become demonstrably insulin resistant. And the same thing happens in humans. In fact, it has been fascinating for me to notice during this period of time over the last few years where everyone's much more mindful of their immune health, that people, and at the same time, people are wearing more continuous glucose monitors, it's been interesting to see how people can almost predict that they have a cold or a flu coming on because they notice that their blood glucose levels start to climb and get more variable, a general sign of insulin resistance. And indeed, that is the case in humans. If you induce an immune response, the body will become more insulin resistant. If you activate those inflammatory pathways, in, in fact, there's some fascinating publications that have touched on this before that have looked at rheumatoid arthritis, like every autoimmune disease, rheumatoid arthritis has an ebb and a flow to it. It will, it will have periods of time where it's really active and aggressive and painful, and other periods of time where it starts to retreat and settles down a little bit. You can actually track the insulin resistance that goes with it. That as the body is activating an immune response, inflammation, or insulin resistance goes with it. So to sum all of that up, inflammation is, we could call that the first primary cause of insulin resistance.
Now, unrelated to insulin resistance is stress. Now, stress is a big term. It's a kind of blanket term that within pop culture has taken on a lot of dimensions that, uh, that are sometimes used inappropriately and other times, uh, precisely. So with stress, this is when I say stress, I really mean the stress hormones. I can't help but think about stress as a hormone response or an endocrine in situation. And specifically, there are two primary stress hormones in the body: cortisol and epinephrine, also known as adrenaline. I'll call it epinephrine, that's the more technical term that's used. So cortisol and epinephrine, these hormones are actually totally unrelated. They are produced in different cell types. They are moved through the, they're produced very differently. They're very different types of hormones. They move through the blood in different ways. They actually act on different cells throughout the body in different ways and have different effects throughout the body. The one thing they have in common is that they both want to increase blood glucose. And so if you have these stress hormones that are trying to push glucose up, there's another hormone that now has to work even harder to bring the glucose down. And of course, that's insulin. And so it's no surprise then that if these stress hormones are continually pushing up the glucose, the body's becoming more insulin resistant. Now, what are some of the causes of stress? Uh, this can be something as benign as sleep deprivation and insomnia. One bad night of sleep will significantly increase cortisol the next day, which causes insulin resistance that next day. Now, thankfully, one good night of sleep wipes that all out. But sleep deprivation is a simple and very common cause of stress on the body, which has a metabolic consequence. Similarly, um, for example, if we drink, there are even more seemingly benign things, but tragic when you couple it with poor sleep, which is excessive caffeine consumption. That if someone's taking in too much caffeine, perhaps to try to make up for their, or to feel better with the lack of sleep, then that increases the other stress hormone, the epinephrine. And when epinephrine goes up, now it's trying to push up glucose, which then makes insulin work harder. And so it's easy to see how a person can fall into this vicious cycle of sleeping poorly, taking caffeine to make up for it, which just continues to drive this insulin resistance. And again, this is something that happens in humans. You give humans a load of, of cortisol or, or cortisol-like molecule, give them epinephrine, and then try to treat them with insulin, they'll need much more insulin to bring their glucose down to what would have been just a nor, a modest amount of insulin prior to the introduction of the stress hormones. Same with animals, and same with cells. Having done those experiments myself, you treat the cells with those molecules, and they become insulin resistant.
Now, the third and final of the primary causes, I leave in the final pole position, if you will, um, in order to, uh, just really emphasize it because it's the one that I believe is, over time, chronically the most relevant of all of them. And that is chronically elevated insulin. Now, let me just introduce a brief tangent where some people will say or they'll want to think that I'm saying any insulin spike is bad and should be avoided at all costs. That's not what I'm saying. But I want someone to appreciate the impact of multiple insulin spikes that are stacked together. Now, to, to elaborate on that, if someone eats a load of carbohydrate, because protein and fat are generally going to have no, uh, elicit no insulin response, if someone eats pure carbohydrate, insulin will come up. And the insulin will take, usually about two hours, hours to come back down in an insulin-sensitive person, maybe, you know, between two and three hours until the insulin comes back down to normal. Now, remember, the reason I'm talking about this is because too much insulin causes insulin resistance. You can do this in humans. You can do this in rodents and in cells. And I've done it in, not in humans, but others have. Give humans an infusion of insulin and then give them a few hours, and the insulin starts working worse and worse and worse. So it's increasingly resistant the body is to, to it. So you have the person who gets an insulin response to a carbohydrate load. Unfortunately, the average person not only eats a very starchy, sugary breakfast, but they do the same thing with a mid-morning snack. And so right around the time insulin's about to come back down to its fasted levels, we have a culture of incessant snacking and eating. They spike it right back up. Then they spike it right back up, and they do it again. They do it for lunch. They do it for an afternoon snack. They do it for, uh, dinner. They do it for evening snack. So every waking moment is spent in a state of elevated insulin. Elevated insulin causes insulin resistance. The nice thing about all three of those primary causes, and this is an upcoming topic before the end of the month of about how to resolve insulin resistance, but I'm sort of getting a little bit ahead of myself. It is that of all three of these primary causes, again, inflammation, stress, and elevated insulin, it's the elevated insulin that can be corrected so quickly. For example, if you had someone who you were a clinician, or you're talking to a loved one, and you found out that they had all of those things: high stress, high inflammation, high insulin, you would say, "Hey, your stress is high. You need to lower your stress hormones." Well, you don't know exactly how they're doing it. Or maybe you know that they're sleeping poorly, and you say, "I know you're insomniac. You have insomnia. Um, you're not sleeping well. You need to sleep better." And they're going to say, "Oh, thanks. Now I'm going to be stressed even more than I was before about my lack of sleep." And so it's difficult to really get a firm grasp on stress to turn it down. Same, same with inflammation. That if someone has an elevated C-reactive protein, for example, uh, knowing how to reduce that can be a little tricky. They might not know. It might not be something that they're even doing in their lifestyle. It could be a result of their fat cells, which I'll get to in just a moment. But insulin, we know what spikes insulin. And so it becomes a lever that we can grab. Whereas the other two are slippery, and it's difficult to grab them. This one we can grab it and immediately start pulling it down within a day, improving insulin resistance as a result. So those are the three primary causes.
Now let's go on where, again, just to reiterate, we have evidence, multiple publications across all three commonly used biomedical models, that these are all on their own capable of causing insulin resistance. Now, some of you may be thinking that there are some conspicuously absent causes here. For example, why haven't I mentioned seed oils? Well, now I will. Let's transition from the primary causes to the secondary causes. And I speak about seed oils with enormous respect, in all sincerity. Um, the, the amount of papers I've now been introduced to, despite not being an expert on seed oils, is, is remarkable. And these are definitely contributing to diseases across the board. I just, of course, focus on my area of expertise, namely insulin resistance. There is evidence in cell cultures that linoleic acid, the primary omega-6 polyunsaturated fatty acid that constitutes linoleic acid, that constitutes soybean oil and the other refined seed oils, that in cells, it can cause insulin resistance. Kind of, there's mixed evidence there. Um, next, in animals, if you have an animal eat a high, animals will eat a high soybean oil diet as opposed to say, coconut oil, the soybean oil diet consumers will get, um, more insulin resistant than the coconut oil. So there's something more uniquely pathogenic. But in humans, I've just never seen a study in humans where you have the person eat soybean oil specifically, independent of any other types of fats, and then they become insulin resistant. That's why I haven't quite been able to graduate seed oils into the primary cause. I, I believe it's contributing. In fact, I'll mention a reason that it might be a bit indirect, in, in a moment, with regards to fat cells. But, um, the direct effect of just eating the linoleic acid, do you get it? Um, do you get the insulin resistance? Uh, no, no, I've not seen the studies on that. But again, I'll revisit that in just a moment.
All right, now, the other secondary cause of just two that I'm going to mention, and then I'll mention the last one, which is very unique, is uric acid. Um, thanks in large part to my good friend Rick Johnson at the University of Colorado, the world has really woken up to the dangers of uric acid. And just as a reminder, as much as the world has focused on meat as a sole cause of uric acid, because of some of the unique, um, molecules within it, fructose will increase uric acid far more than any amount of meat will. And that's primarily what Rick has focused on. This fructose, um, every time you metabolize a molecule of fructose, you're producing some uric acid. So it's a heavy, heavy contributor. Now, interestingly, uric acid has been shown to cause insulin resistance in all three biomedical models. You treat cells with uric acid, they become insulin resistant. You increase the uric acid in the animals, they become insulin resistant. If you block uric acid production, they don't become insulin resistant. And the exact same thing is seen with humans. More uric acid, as you spike it up, more insulin resistance. You block uric acid production, insulin resistance gets better. It's pretty robust evidence. Now, why don't I put it in the category of primary? Because if you block the influx effect of the uric acid, there's no insulin resistance, or you wipe it out. And so this is the case that I alluded to earlier, where you have a trigger, a stimulus, but it is acting through another mediator. And that if you take away this mediator, so it's dependent on specifically inflammation. And in the absence of inflammation, there's no insulin resistance. So it's dependent. So uric acid causes insulin resistance dependent on its ability to increase, increase inflammation or activate these immune path, these inflammatory pathways. That's why I put it in the secondary realm. Because remember, with the primary, all of those are capable of causing insulin resistance on their own, in the absence of any other signal. They're not dependent on anything but themselves.
Now, in all of these, what all of these have in common is that they will manifest with classic signs of insulin resistance. And remember, there are two real aspects. It's the analogy where you will have cells that aren't responding well to insulin, and in the whole body, insulin levels will be elevated. Which makes the elevated insulin cause of insulin resistance particularly vicious, because if elevated insulin is a cause of insulin resistance, which is then causing more elevated insulin, which then contributes to further insulin resistance, you can see how this becomes a positive feedback and a vicious cycle.
So the last one that is totally unique is starvation. Now, I need to define that term, because too often people will think of starvation as just fasting. No, there's a big divide between fasting and starvation. In fact, that divide is something we can pinch and jiggle, namely our body fat. That if you have body fat to burn, this is a topic for another time, so I'll be a little sparse on it. Then you're fasting. The moment you are restricting calories and you've run out of fat, now you're burning your lean mass, you're burning muscle for energy, in particular, and even bone and everything else. You'll start eating away at your body to just continue to make enough energy for the brain to survive. And in that state, the body becomes very insulin resistant, which is primarily, interestingly, a stress response. But it's unlike the earlier stress response that I spoke about, because in this instance, where the body is wasting away, you are insulin resistant, but insulin levels are low. The body can't afford to keep insulin high, because if insulin's high, then the body is attempting to store energy, which would deprive the brain, because the brain can't handle a state if energy is just being stored, stored, stored, because it doesn't store energy. It needs to be pulling it from the blood. We'll talk, we'll revisit this idea when we talk about the metabolic origins of Alzheimer's disease in, in, up, in an upcoming lesson. But nevertheless, just to reiterate, this unique metabolic state, starvation, is insulin resistance through stress hormones, but it's unique because insulin levels are low. And any other instance of insulin resistance that I'm aware of, and I think I'm aware of all of them, insulin will be elevated. If the body has insulin resistance, including physiological insulin resistance, and we'll, we can talk about, we'll talk about that at a future time.
All right, now let's move on, um, to a next sort of segment as I wind up the lecture, classroom part of this, before we do some Q&A. All of these stimuli that I've talked about are direct effects. If you directly increase inflammation due to illness, for example, or a food sensitivity, the body becomes insulin resistant. But if you remove that stimulus, they're insulin sensitive. Same with stress, same with elevated insulin. So these are direct effects, direct noxious stimuli causing insulin resistance. But there's a more creeping version of insulin resistance, which now brings us back to the fat cell. There are multiple theories of which tissue of the body becomes insulin resistant first. Some will say that it is the muscle that becomes insulin resistant first. Some will say that it's the liver. Others will say that it's the fat cells. Um, anyone who says it's other than the fat cells is totally wrong. Now, I expect, say the same thing about me, but I'm right. Fat cells are the beginning. That is the first domino to fall. You know, probably by now, of my affection for alliteration, fat falls first when it comes to insulin resistance. And the, now, so what makes the fat cell get big? This is actually a topic that I just spoke at, um, at a recent meeting, a low-carb meeting, in the upcoming Metabolic Health Summit, at the time I'm recording this, and I will post this lecture, um, at a future point on the Insulin IQ site. But it's basically the name of that is Shrinking Fat Cells: Energy Versus Insulin. And when a fat cell is, uh, when a fat cell starts to grow, that's that's a process called hypertrophy. And as the fat cell continues to grow, it, it starts to experience two problems. First, it can't grow anymore. It's actually reaching the limit that the cell membrane can hold together. It's like a water balloon that's getting so full that it's about to burst. It's going to pop, and then everyone gets messy, and we get water all over the house. Now, one solution, let's just stick with the, the analogy comparing the fat cell to the, to a water balloon. If we can't disconnect the balloon to the tap that is filling the balloon, what if we could just poke a small little hole in the balloon without popping the whole balloon? Now it's starting to leak out some of the water to match the fat that's coming in. That's really analogous to what's happening with the fat cell. As it gets too big, insulin is continually telling it to grow, mostly by inhibiting its ability to release the fat, but, but also by force-feeding it. And so the fat cell basically says, "Insulin, you're not letting me break down this fat. I'm not listening to you anymore." And so it's going to become insulin resistant. And so it becomes insulin resistant to stop growing. This, this is why people on average can't limitlessly get fat. There is this point beyond which they can't get any fatter. Now, there are some exceptions where some people genetically have the ability to make new fat cells. They can multiply their fat cells. Those are people who continue, who can continue to get fat, but that's uncommon. So the big fat fat cell, the hypertrophic fat cell, becomes insulin resistant to stop future growth. Second, as it gets so big, it starts to get pushed further and further away from capillaries, which is the essential blood vessel where a cell gets all of its oxygen and all of its nutrients, and then dumps all of its waste products into the blood to be eliminated from the body through the kidneys or the liver or the breath, in some instances, like CO2. So it's the capillary. And so the fat cell that's getting so big is getting pushed too far from the capillary, and that becomes what's called hypoxic, in other words, it's running out of oxygen. In one response to that, the fat cell is saying, "Hey, I'm suffocating here." It will start releasing pro-inflammatory proteins, what are called cytokines. Now, through the body, this begins to turn on all of those inflammatory pathways that will then cause insulin resistance. But at the level of the fat cell, one effect of one of these pro-inflammatory proteins will be to tell the capillaries to start making new capillaries. So it will increase the vascular, the vascularization of the fat cell, helping it start to breathe better. It can get oxygen again. But again, a consequence is that it's spilling the inflammatory proteins throughout the body.
Now, what is it that makes the fat cell get big? There are two essential elements to this. You cannot have one without the other in the whole body. It is impossible. And again, you'll have to watch the talk in the future, um, in order to, in order to understand it. So you must have an elevated insulin level to signal to the fat cell that it needs to grow. That's the stimulus telling the fat cell, "Grow." And then you must have sufficient energy or enough calories available to fuel that growth. I hope that you can appreciate the difference. A fat cell that is swimming in a sea of calories in the absence of insulin will not store any of those calories. It is totally, completely physically impossible for a fat cell to not only grow, but even stay big if insulin is low. It cannot hold on to its energy. So you need an insulin stimulus and you need sufficient energy to fuel that stimulus to grow. Now, you have a hypertrophy or fat, fat cell. And then you have this kind of more creeping, insidious version of insulin resistance that you know, that's sort of settling in over time as the person's gaining this weight in a unique way by making the fat cells get big. So that is the sort of final sentiment here.
Now, one other point where I mentioned I would bring back the soybean oil or the linoleic acid. Linoleic acid contributes to insulin resistance in part through this fat cell effect, because linoleic acid will inhibit the fat cell's ability to multiply. And so as a fat, as the fat tissue, elevated insulin, sufficient energy is being told and fueled to grow, if there's linoleic acid coming in, it accumulates in the fat cell, converts, becomes this other molecule called 4-HNE, for-hydroxy-nonenal. 4-HNE. And 4-HNE will basically dictate to the fat tissue and say, "Fat tissue, you've been told to grow. I'm going to tell you how to grow." And that's specifically through hypertrophy. Now, insulin does that too. Um, insulin will also selectively promote hypertrophy. But linoleic acid contributes to that. So this is another unique mechanism whereby it contributes to insulin resistance by selectively influencing the way the body gains fat.
All right, that is it. Let's now, thanks for listening. Hopefully, you took some notes. And again, that talk that I referred to, Shrinking the Fat Cells: Insulin Versus Energy, um, that's one that will get posted here soon, and you will really enjoy it. You'll like it. It's really me diving into these last points that I was just talking about, namely taking the big fat cell and shrinking it. All right, let's move over to the Q&A. And thank you for those who have joined live and those who watch later. I hope you come to another session with some of your questions. Um, but those who are here live, um, Rich, thanks for tuning in. Ben, so glad you're talking about insulin resistance. An old but new theory out in the plant-based world is that fat actually is a cause of insulin resistance. They're trying to show that plant-based diets are more effective. Yeah, yeah. So a common, um, refrain in the plant-based community is that fat causes, well, specifically saturated fat. In fact, they will use these really scientific terms like "gum up" or "clogs up" the insulin receptor, which is just silly. Um, but there's an, there's an ounce, there's a speck of truth in what they've found. And, and in fact, I've contributed to this. So whether they know it or not, in some instances, they're actually invoking my own work, um, from my earlier research during my post-doctoral time. So if you take cells or you infuse, treat them with saturated fats, or you infuse them with, or you infuse an animal, rather, with saturated fat, they will become insulin resistant. That's not the case if you say, um, treat the cells or infuse the animals with oleic acid, the monounsaturated fat. And then it's kind of varying responses in the case of the omega-6 polyunsaturated fat, linoleic acid from soy oil, for example, or any refined seed oils. Um, so in this case, there is some evidence. Um, but remember, infusing saturated fat, you know, me having Rich, you come into my lab, and we stick an IV in you and infuse some palmitate, that is not the same as you eating palmitate. And so now we go to the human studies, like some of the work from Jeff Volek at the University, at the Ohio State University. And he has found that in his work, you can have a, a low-carb group that is eating multiples more saturated fat than a low-fat group, and they not only have a greater reduction in inflammation, but they have this significant improvement in insulin resistance. So at the level of what goes into your mouth, which is where we should care, um, where this happens, um, especially if carbohydrates are restricted, the saturated fat is not causing insulin resistance. Now, to complicate it a little bit, if you have someone eating a high-carb diet, and then you add to that high-carb diet saturated fat or monounsaturated fat, the, the saturated fat does have cause greater insulin resistance. Um, but of course, that's in the context of a high-carb diet, which does not apply, of course, to a ketogenic diet. That's the opposite of a ketogenic diet. So these plant-based, plant-based advocates that are vilifying saturated fat, they're just selectively taking some lines of evidence and applying it to fit their ideas. Now, what happens when you take a plant-based diet and compare it to a ketogenic diet, um, which generally is to be on the opposite end of saturated fat consumption? There is not a single study to show that a plant-based diet outperforms, um, the ketogenic diet. Now, that is not the same as, like, the Stanford twin study that was just published. That was not ketogenic. They had a plant-based group and then they had an omnivore group, which was eating lasagna and hamburgers, you know, all kinds of stuff, not, not ketogenic whatsoever. So it was heavily, heavily skewed to find the result that they wanted to, that they wanted to get. And of course, immediately Netflix made a documentary about it. I can highlight that study in the future Metabolic Classroom, just specific to that report, um, which, which I will do from time to time. We'll just do, uh, Metabolic Classroom that's based on just analyzing a popularly published manuscript, and that would fit the bill. So anyway, um, the plant-based diets only improve insulin resistance because they restrict energy, um, because you just start to have a calorie restriction as you only eat plants. Um, and so that's how it works. If you try to put them on a higher calorie version of it, they won't have any improvement. Um, in fact, some of the studies that have compared plant-based diets to just normal standard American diet show modest improvements or no improvements whatsoever if you're not making them go into a low-calorie state. But remember, the fat cell, if it's really, really big, or one thing I didn't talk about, but I do in this talk that I will direct everyone to once it gets, once I share it on Insulin IQ, if you start restricting energy in the diet, as you do so, every single study that's ever looked at a plant-based diet has taken people from their standard American diet that they were eating, which is high carb, high calorie, and then lowered the calories and put them on a plant-based diet, even lowering the total amount of carbs they're eating, which sounds crazy. And so any of these studies that look at low-fat plant-based diets, if you actually look at the insulin, it goes down because you're taking them from this high-calorie standard American into the plant-based. You do anything to those people, and they're going to get better, including a plant-based diet. The problem, the more your plant-based diet, the more nutrient deficient you become. So this, this Stanford twin study, for example, even after just a couple of weeks, the people were getting low and nearly deficient in vitamin B12. Uh, so, uh, that's that's a problem, of course, um, where B12 is essential throughout the body. All right, Rich, hopefully that helps. Um, Carly, thanks for joining. Lindsay, this may be a dumb question, but will you see hyperinsulinemia when the underlying cause is inflammation or stress? Yep, yep. So I, I mentioned that, uh, with those primary causes. Well, of course, with insulin, that's one, that one's obvious. But yes, if you induce insulin resistance through stress response or an inflammatory response, as the body becomes insulin resistant, elevated insulin is soon to follow. In that case, in that instance, it's a consequence of the insulin resistance, but it is an inseparable consequence. There's no splitting that apart. Carol, thanks for tuning in. Yes, to ask more about Rich's comment. From the Mastering Diabetes perspective, they promote a no animal product and no fat diet. The claim is that this is the method to lower IR. Yeah, again, Carol, you note this further down. Anytime you start depriving the body of energy, insulin comes down, and thus it's no surprise that the body will become insulin resistant. My counter to that is, how long can you continue to restrict the energy? And how long can you afford to deprive yourself of essential nutrition like heme iron or vitamin B12, for example, or omega-3 fatty acids, the essential ones that you cannot get from plants? So the more, I have very strong feelings about the plant-based diet because I just generally view it as an anti-human view. That the more you try to force humans to only eat plants, the more you are weakening them and even killing them, for example, and ruining the species. If you put men on a low-fat diet, guess what happens to their testosterone? Guess what happens to their sperm production and motility? Down. And the more a woman is deprived of vitamin B12, the more incapable she is of carrying a fetus, carrying a baby full-term. So you literally start to kill the human species. And that, to me, is pretty telling. All right, Jerry, allulose touted as not causing a glucose response, but does it raise insulin? Wonderful question. It does not. In fact, we are six weeks into an animal study on allulose, and we're just about to start a human study. So anyone living in Utah Valley, if you're wanting to participate, I'll be making an announcement soon about that. But no, there is no insulin response to allulose at all. One of the other reasons I'm a little enthusiastic about allulose is that it's more than just a replacement for sugar. Like every other sweetener is, whether it's stevia or erythritol, and those are fine, um, monk fruit extract, they're all fine in my book, um, but they just act by replacing sugar. The thing about allulose is it also replaces table sugar as a rare sugar itself, but it increases GLP-1. Um, and GLP-1 helps not only keep glucagon in check, which is why it's likely so helpful with people with type 1 diabetes, but it also delays gastric emptying, making you feel fuller for longer, which is, of course, very beneficial. All right, Jack, um, share a question from a follower, um, Ben, from one of our followers. I heard Dr. Vickman talking about diet soda. He sounded like he was saying people overeat from drinking diet soda because it makes one hungry. Jack, let me see if I can expand that. Okay, I think that's the end of the question. Oh, I believe some weight gainers are not overeating due to the soda, it's the insulin effect alone. So no, there is, uh, diet soda alone, the aspartame in the diet soda will not cause an insulin spike. I have, I've really looked into that to, because I know it's such a commonly enjoyed sweetener because of its presence in, in diet sodas. There is no insulin effect. However, there is something that's referred to as the caloric effect, where you taste something sweet, and then the body is expecting the calories from that sweetness. Um, and that's understandable, especially from carbohydrate. It wants a glucose load because in nature, there is nothing that is sweet unless it is a carbohydrate. There's no sweet fats, there's no sweet proteins, it's only carbohydrate. And so the body's expecting a glucose load because of that. And so, but not everyone appears to feel this. So my general sentiment on diet soda is, if you are, in your most honest moment, capable of enjoying a diet soda and you don't start snacking, you don't have this kind of perceived effect on the back end of it, then it's fine. What do I mean by that? If you're sipping on a diet soda, and then you feel, "I'm gonna get the fries too, and I'm gonna get this big hamburger, and I'm gonna eat the bun," you know, whatever, um, because I have the diet soda, or you, you feel like you need to eat just because it makes you hungry, then it's a problem. And I think you should wean yourself off of diet soda. If you're able to enjoy a diet soda and it stops with the diet soda, and mind you, that's not something that necessarily happens hour an hour after. It could be that you have the diet soda at noon, and maybe you're getting really snacky and hungry in the evening. Um, then you need to monitor your consumption more. But again, just to confirm, there, or reiterate, there is no direct effect to the aspartame increasing insulin, which is increasing fat gain. It's a, it's a consequential effect because, uh, in some people, if they start to eat more or indulge more after. All right. Carly, on a hangout yesterday, we talked about allulose and the source matters, since some sources come from corn. Anything you can add to this conversation? Yeah, yeah. As far as I know, there's no difference, um, whether it comes from figs or corn. It is allulose. And not in any other way adulterated. Um, I'm pretty confident on that. As I've become more familiar with allulose, I'm unaware of any evidence. Fact, this I can state conclusively. I'm unaware of any evidence, but you may say, well, that's just because you're ignorant. I'm pretty, pretty sure there's nothing out there, um, that suggests the source is going to matter. Um, Joseph, one of my clients mentioned how every time their blood sugar goes up, she gets knee pains. Could this be the inflammation you talked about? It could be, Joseph. It could be inflammation, but it's difficult. I always try to be careful in the order of events when I talk about these things. And the way I spoke about inflammation in the context of metabolic health was from the position of inflammation then creating the metabolic problem, not the metabolic problem creating the inflammation, if that makes sense. So in this case of the knee pain, I actually would be more inclined to think of the a possible, this I might be really kind of getting a little kooky here, but it was the first thought that came to mind, so I'll go with it. It might be a systemic vasoconstriction and a relative blood flow restriction. So one of the interesting things about the knee and these joints is that, um, they generally have very little blood flow. And so if you compromise the blood flow even a little more, they go from little to almost nothing. And if you eat a big spike, you get a big spike of glucose, that that activates your sympathetic nervous system. This is one of the reasons why many people sleep so poorly, is because they indulge on glucose-spiking starches and sugars in the evening, and they go to bed hyperglycemic, wondering why they're anxious. Well, you're not anxious, you've just activated your sympathetic nervous system. So you're hot, you're sweaty, your heart is beating hard. But another effect related to the heart beating is that you get what's referred to as a systemic vasoconstriction. So in the sympathetic nervous system is turned on, it starts to restrict the blood vessels. Um, and that might be what is contributing. If I had to guess, that's actually where I think it would fall. Joseph, I think it would be more on this acute response to the hyperglycemia and the restricted blood flow. Rich, Ben, the plant-based diets also tout that it lowers cholesterol. Is there a benefit in lowering cholesterol? No, I do not believe there is. In fact, many, many lines of, admittedly correlational evidence, which is the only kind there is when it comes to longevity, show that the longest-lived people typically have high cholesterol levels. Now, a lot of these plant-based people will, of course, invoke the idea of Blue Zones, and we'll address that in a future classroom. But I firmly believe the whole Blue Zone phenomenon is based on fraudulent, it's all a fraud, actually. There's some pretty convincing evidence. The only, the only evidence that exists that in every one of these so-called Blue Zone areas, whether it's Okinawa, or whether it's Sardinia, they actually paradoxically, on average, have among the lowest life expectancies and among the lowest literacy rates within their respective countries. And what this person has concluded, this was an Australian scientist, it is that, um, these are people who are fraudulent in reporting their birth dates, and they can, because of poor recordkeeping, the areas are very generally a little more impoverished, but they're doing this to, um, get, um, retirement benefits earlier. And so I, I actually think that's all pretty validated because the evidence is so hard to reconcile. These are areas with poor literacy overall, lower mortality rates in the rest of the country. So on average, people are dying more, and then we're expected to believe that there are these paradoxical anomalies in their midst where they're suddenly living to well over a hundred. I think it's all based on fraud. Indeed, they're poor, which is why they aren't eating a lot of meat. Um, and then, in fact, in some of the longest-lived countries on, on the planet, like Hong Kong, they have the highest per capita consumption of meat. So that doesn't quite work with that idea. Um, and again, high cholesterol might be part of the benefit. Um, interestingly, a paper was just published, and I'm going to do a little Instagram post on this in a bit, where just today, where they found that, um, people who adopt a ketogenic diet, there's this big concern, you eat all that saturated fat, and your cholesterol is going to go through the roof. What this group found was that this is a phenomenon that only happens in people who are already fairly lean. This is part of the lean mass hyperresponder phenomenon that Dave Feldman has really posited and now continues to grow in attention and evidence that if someone is
overweight they don't appear to have have this LDL increased effect in response to the ketogenic diet.
All right Mindy, um, do you know anything about a sugar called trehalose that you can share with us? That's a great question. Um, I am familiar with trehalose. Um, that it's a it's a very uncommon sugar and I just am going to kind of look up how what it gets digested into. And I think it's just two, I think it's a it's a basically a starch or a glucose molecule bound together with a, what's called the glycos, two glucoses bound together with a glycosidic bond that the body has a hard time digesting. Um, that we don't split that bond very well. We have an amylase enzyme that can split lots of other glucose bonds, um, taking that bread, that polymer of starches and turning it into a lot of glucose. But with trehalose, we don't split that very well. Now, I'm speculating a little. Um, I can't totally remember it, even though I've become, I've been familiar with it in the past, but I believe that's how it acts. We basically don't digest it very well and thus we taste the sweetness as it hits our mouth, and yet we don't have any, um, glucose impact. But I'm kind of speculating there. Mindy, I'm sorry that I'm not more familiar with it. I'll, I'll bone up on that.
Um, all right, another one. Tanya, how does Hong Kong stack up on the rates of heart disease? Yeah, yeah, super low. Um, you can look up the incidence and mortality, especially mortality of heart disease and longevity, and it's one of the longest-lived countries on the planet. So that's pretty impactful. But also, you guys, just as a, just as a counter to that whole narrative that meat is causing these diseases of civilization, or what I call the plagues of prosperity, look at what has happened to red meat consumption in the last 120 years in the United States. It went down a lot from the early 1900s through the 1960s, 1970s. Um, what was up, up, up, up, and then it plummeted in the 1970s and it's come back a little bit and then flatlined, and it's been flatlined for about 20, 30 years. So we're not eating more and more meat every year. But what is happening during the same time span with heart disease, with cancers, with diabetes? They're all skyrocketing. They continue to go higher and higher. So just at this global, superficial, 10,000-foot view, the whole thing falls apart. I hope that anyone who listens to this, so those tuned in now, can be honest in looking at this that way. That if you, again, if you look at meat consumption, red meat consumption, it has gone down since 120 years ago per person. And during the same span, heart disease and diabetes in particular have just skyrocketed and continued to climb. Red meat does not continue to climb. So again, even at just the simplest glance, this whole story starts to fall apart.
Jackie, we'll say this is the last question for today, and please join me next week. So I'm overweight and my LDL is sky-high, but low triglycerides and high LDL and insulin below three. So Jackie, interestingly, you are probably among those few people who have what's called hyperplastic fat growth. So this is the process whereby fat cells multiply. So when there's elevated insulin and sufficient energy to fuel the growth, that insulin stimulating rather than each individual fat cell getting bigger and bigger and bigger, there are people who have this ability to make a new fat cell. So before this fat cell gets too big, we have a new one that can start to carry some of that metabolic burden. And so none of the fat cells ever end up getting too big, and thus they prevent the insulin resistance and thus they prevent the inflammation. So the fact that you are overweight now, and just as a reminder, women naturally have more fat than men as a consequence of sex hormones. It's natural, it's by design, and it's healthier for women because of how women store fat, including a little more hyperplasia, a little more multiplication of fat cells at the butt and hips areas. Those are areas that can get bigger by making new fat cells, which helps the woman stay more insulin-sensitive despite the fat mass. Jackie, in your instance, it could be what's that's what's happening. You have this ability to make fat cells, so you have more fat cells, but they're smaller, and so you're insulin-sensitive. The fact that your triglyceride to HDL ratio is so low, to me, matters way more than your LDL. And this is supported in published research that LDL doesn't predict the heart disease, um, risk, but triglyceride to HDL ratio does much, much better than LDL. Um, there's in fact one particular study that highlights this looking at triglyceride to HDL ratio and LDL and plotting them on this kind of three-dimensional curve or or plot, finding that across all of the LDL levels, if triglyceride to HDL ratio is low, there's no increase in heart disease risk. But the moment you look at the triglyceride to HDL ratio going up, now all of a sudden heart disease risk goes up, regardless of whether LDL is high or low. And the fact that your insulin is below three suggests, in combination with the triglyceride to HDL ratio, that your body is very insulin-sensitive. And of course, as a reminder, never giving medical advice, just your friendly neighborhood scientist. You guys, thanks for tuning in. I hope that you feel that you are much more familiar with the causes, the origins of insulin resistance, primary, secondary, and the unique ones, and the contributing role of the fat cell. And I look forward to you tuning in next week where we'll discuss more about the consequences of insulin resistance. I will see you then.