Dr. Benjamin Bikman – ‘Insulin vs. Glucagon: The relevance of dietary protein’

Thanks, Eric, thanks for the introduction. Yeah, I’m an insulin-mitochondria guy so what am I if half of this conversation in insulin yes, I can talk about glucagon will be the new character here. Before I get going though, Jeff and Rod, thank you so much for the invitation. I am delighted to be here again. It’s fun to be here now and see friendly faces as opposed to strangers, like it was last year. But last year was my first time and when Jeff and Rod reached out invited me that was my first step into the low-carb community. And it has just been delightful. I have appreciated making new acquaintances and some genuine friendships, and in fact, as a scientist, I’ve really appreciated some actual collaborations that are coming from me getting into this space, so I am genuinely grateful. Thank you. So today, insulin versus glucagon. I have been following
conversations in the community with regards to the role of protein. And it’s been somewhat, sometimes concerning when I hear the fear in people’s voices when they talk about protein and so I’ve made sort of an academic pursuit, and decided to share with you some of my conclusions. Before I get going, here’s my disclosure. I have two, I’m a part of two groups: insulin IQ, where we are trying to make people more mindful of the relevance of insulin in health, and the best my most favorite audiences are the Grand Rounds talks that I get to do to physicians, and then best facts is just our efforts to contribute to this blossoming low carb high fat supplements space. So, last year of my first step into the low carb community, I spoke about the relevance of insulin and ketones, and the effects that they have on the contrasting effects on adipocyte mitocondrial uncoupling. In other words, white fat or brown fat. I’m not going to talk about that today, as you could tell from the title, so collective disappointment, I’m sure. (laughs) Um, but let me give you an update. So, this was the paper we just published a few months ago. My students and I published this paper in a good journal, biochemical journal, where we found that insulin was basically, as I talked about a year ago, and we finished all the evidence here, or put all the evidence in this paper. Insulin was, um, slamming on the brakes of mitochondrial uncoupling, forcing the mitocondria in the fat tissue to be more tightly coupled. In other words, only use energy when you need it. That’s was insulin was doing. I Will give the final update next year. We will have all the rest of the human data with regards to the ketones and I’ll be able to tell the full story. So, if Jeff and Ron haven’t had enough of me, then I’ll see you next year. Same time, same place. Okay, now let’s get into the story then. So, here’s the pancreas. In fact, I had to pick this image for fear of using an image that looked a little dirty. But I hopefully, this is the pancreas, tucked underneath the stomach. And of all the myriad cells the pancreas has, that are cells involved in endocrine functions, cells that are involved in digestive or exocrine functions, we want to zoom-in on the beta and the alpha cells. And these are famous because they produce insulin and glucagon, respectively. And then, insulin and glucagon, in addition, what’s interesting is that they’re produced right beside each other in these little pockets of cells within the pancreas, and they’re enemies, in a way, and they’re each antagonizing the other in almost every posible biochemical event. If insulin is trying to do something, glucagon is trying to stop it. If glucagon is trying to do something, insulin is trying to stop it. So, it’s pretty much like my kids. (Laughs) Nevertheless, we see insulin, to quote Mike and Mary Dan Eades, needs because, they said it, well insulin is the hormone of feeding and storing, and glucagon is the hormone of fasting and burning and what that means then in a bigger biochemical sense, is that insulin is a hormone of anabolism, or building things up, taking simple molecules and making them into something bigger and keeping it, and then glucagon wants to take the complex molecule and break it down. Usually breaking it down into an energy source that the body can then use, so it is catabolic, it is one of those fundamental or prototypical catabolic hormones, whereas insulin is the prototypical anabolic. Now, when we look at these hormones, let’s zoom-in on what they’re doing, because now, mind you, insulin and glucagon are affecting most of the tissues of the body. Then, insulin affects every cell of the body, insofar as every cell has an insulin receptor, and glucagon affects most. But nevertheless, let’s look at these three very metabolically relevant tissues. Now, you can’t necessarily tell what I’m talking about here based on my pictures, so we have muscle on the left, adipose tissue in the middle and then the liver on the far right. When we look through each of these three tissues, these hormones have varying effects. In particular, insulin is completely anabolic at the muscle, promoting muscle synthesis and promoting glycogenesis or the storage of glucose in the muscle to be used later. And glucagon has no effect. This is one of those instances where there are no receptors for glucagon on muscle, so glucagon has no catabolic actions. It can’t tell the muscle to do anything. In contrast, adipocytes have both receptors and so, now, we begin to see this antagonistic yin and yang between these two hormones. Insulin wants to promote the growth of the adipocyte by storing lipids through lipogenesis, glucagon wants to oppose that, and induce the shrinking of the adipocyte through lipolysis or the breakdown of the stored lipid. And then, the antagonistic theme continues in the liver, where insulin is telling the liver to make lipid and make glycogen or storing fat and storing, um, glucose. Glucagon is antagonizing that. We want to break down lipid, we want to break down glucose, we want to make glucose, we also want to make ketones, an alternative fuel, if we can use that word, or just another fuel for the body. Now, they, these hormones don’t have comparable effects across these tissues. So, muscle is then completely driven by insulin, in the case of just insulin and glucagon, and then, adipocytes appear to be more sensitive to insulin than they do to glucagon. So, if you had a one-to-one ratio of insulin to glucagon, theoretically, the insulin is going to win that tug-of-war. Insulin has the chokehold on the adipocyte. In a similar way, glucagon is the primary driver of whatever the liver is doing. So, if the liver’s seen both glucagon and insulin, ususally glucagon is going to be setting the tone. It can beat insulin there, as opposed to the adipocyte, where insulin tends to win that race. So, just like these two hormones, insulin and glucagon dictate the biochemical actions in these three metabolically relevant tissues, and we could have listed more, we need to explore how do then, the macronutrients dictate the levels of insulin and glucagon. And this isn’t as clear as we usually think, and this is, this was, the matter of my pursuing this topic. It was to get to this issue. When we look at carbohydrates, we see this opposing effect. Where carbohydrates will, in any situation, increase insulin and reduce glucagon. The textbook version is this complementary effect of protein, where protein is both increasing insulin and glucagon, making it somewhat of a macronutrient that people in low-carb community fear. And, and I’m not sure that’s justified, and I’m making the case that perhaps we need to revise the way we think about it. And in fact, and each of these are just when it’s consumed in its pure form. If you take a spoon of carb, a spoon of protein, or a spoon of fat, fat will not increase insulin, it will only increase glucagon. And that makes it very friendly to those of us who appreciate, or respect, the relevance of insulin and the pathogenicity of insulin. Aknowledge that it has a hand in virtually every chronic disease. Now, however, one of these depends on context that when we’ve put these arrows the way the textbooks have, and that’s how I’ve done it, it really depends on underlying glycemic status and it’s insulin, the insulin effect, the insulinogenic effect of protein is heavily influenced by the underlying glycemic status. And other, what, well, get into it. In fact, let’s get into one study right here. Now, by way of disclosure, this was a study done in canines, and but before you start thinking oh, well, that’s not relevant to humans, you actually will be hard-pressed to find a mammalian digestive system that is as similar to humans as canines, even to the point of bacteria, where canines have similar mouth and digestive bacteria as humans do. So, it is more relevant than you might think. Nevertheless, challenge it as you will. So, in this study, on the left-hand side, you’ll see the only difference between these two instances is that on the left-hand side they infused glucose and you’ll see right along the very top it mentions a glucose infusion. So, they’re providing these animals an underlying hyperglycemic state. And in the condition on the left it was there no infusion, and the animals were just simply in a fasted state. And then, they had those two repeated boluses of alanine infusions. Now, alanine is relevant, yes, it’s an amino acid, remind you, of course, once we ingest the protein, it all gets broken down to amino acids. So, we always say, well, in protein spike my insulin we technically should say amino acids right, but nevertheless, alanine is the … why is it so relevant? Alanine is is the prototypical gluconeogenic amino acid. When we teach this concept, how certain amino acids are glucogenic, we use alanine as the textbook example. Because it’s so good at bumping up glucose, and you see that there, you see that green line takes a little skip up, whenever they infuse the alanine. That’s all interesting. What happens, then to the insulin and the glucagon? On this left-hand side, what we see in the state where there there’s an underlying elevated glucose level, we see that insulin goes up massively:130 microunits per mil. That’s an incredible bump over where it was already elevated because of the hyperglycemia. It went beyond that, 130 more microunits. So, insulin responded remarkably to this amino acid infusion. In contrast, glucagon plummeted by almost half. Now, when we compare this to the fasted animals, look at that orange line: insulin didn’t change a bit. And glucagon doubled. Isn’t that a remarkable difference? And the only difference is in one state there was elevated glucose, in the other state there was not. And the reason to explain this or how we explain this is we can’t afford to inhibit gluconeogenesis. Because those animals were fasted, if we had had a substantial insulin effect, what would that have done to their fasting glucose levels? And the animals would have lost consciousness. So, we can’t afford to inhibit gluconeogenesis, we need to keep that process going, because that’s the only way the animals are maintaining normal glycaemia. Because of that, insulin was maintained, and glucagon was elevated. And we’ll come back to this in a bit with some human data. So, with this somewhat revised system in place, we will look at, we, I’m now showing what might be happening then with insulin and glucagon in the case of a low-carb environment, where there is not this consistent steady source or stream of carbohydrates spilling into the blood as glucose. And then let’s come back to these same three tissues. So, then, in these instances now, of the low carb individual consuming carbohydrate we still have the same effect, of course. In this case, carbohydrate and protein are both anabolic at muscle and then fat would have no overt effect in this instance of the low-carb individual. Now, mind you, I say that carbon protein is anabolic. That isn’t to say that you can have muscle growth and not actually pay the price. You know, you can’t just take a drink and say I’m getting big. You got it, you got to still earn it. And then, with the adipocyte, carbohydrate once again is anabolic, like it is everywhere. In fact, these two are similar. Because the adipocyte and the liver, both contain insulin receptors and glucagon receptors, we have this contrasting effect, especially in the case of protein. Where there is going to be some degree of anabolic, but also, in the case of a low carb individual, a pronounced, that we can’t ignore, catabolic effect, where, where insulin’s trying to increase the storage and activate anabolic pathways, glucagon is there to counter that, especially in the low-carb state. And then, to make this relevant, or to give it sort of a palatable easy takeaway, I submit that one helpful way of looking at the relevance of all this is to consider the insulin to glucagon ratio and this is particularly relevant in the liver, as we’ll get into that in just a bit. But the insulin-to-glucagon ratio provides this underlying metabolic tone. In other words, it tells the body, or the tissues, the cells of the body, what is the prevailing metabolic pathway I need you to be undergoing or I need activated. Insulin-to-glucagon ratio provides us some understanding of who’s sort of winning. In other words, if it’s a high insulin to glucagon ratio, we know that anabolic pathways are predominating. If, in contrast, it is a low insulin to glucagon ratio, then we know that the catabolic pathways are predominating. And, you know, in this constant tug-of-war and all of this is happening, we have this constant check and balance. But in these instances, high insulin to glucagon ratio represents an anabolic state, low insulin to glucagon ratio represents a catabolic state. Now, one thing that’s noteworthy is almost sort of a pit stop, before I go too much further: having a low insulin to glucagon ratio is relevant because that is what, I submit, actually matters in a fasted state. Fasting has become very popular. And ,perhaps, there’s some justification. I sometimes worry a little bit about it. People jumping on a little too quickly, and maybe not fully informed of what’s happening, that there are some metabolic benefits, but also some deleterious consequences, but nevertheless, there are benefits, and I submit that most of the benefits occur due to this favorably low insulin to glucagon ratio. Because these, this ratio induces these sorts of benefits, where we see improvements in insulin sensitivity, we see the activation of autophagy, which is heavily driven by hormones, insulin absolutely clamps down on autophagy, whereas glucagon activates it. And we could say the same thing of this sort of subprocess of autophagy known as mitophagy, where we are recycling old mitochondria, keeping them healthy and viable, and producing fewer reactive oxygen species. Then we have lipolysis predominating and then, of course, what I talked about last year, we have the activation of brown adipose tissue. All of these things are happening in this low insulin to glucagon ratio state that predominates in a fasted state. Yet, the benefit of a low-carb diet in maintaining an, a low insulin to glucagon ratio is that you get the benefits of this fasted state, without actually starving the body. You’re maintaining this fuel intake that allows the body to continue to function well and, of course, it can function well with fasting too. But you’re getting the benefits of fasting insofar as hormones are dictating most of the metabolic pathways we care about. Alright, with that is the pitstop. You can hopefully appreciate the benefits of a low insulin to glucagon ratio. Let’s look at what happens to insulin and glucagon when a person consumes three general dietary states: The one is the standard american diet, next would be just fasting, in a fasting state, and then, the low-carb diet. And let’s look at each of the insulin to glucagon ratio in each of these three states. So, in a fasted state, the insulin to glucagon ratio, not surprinsing, is pretty low, it’s 0.8. That is a true sort of, I say, fasted. I’m not talking 12 hours, this is like a 24 or plus hours sort of fast. Around point eight. This is in humans. We’ve left canines behind. So, all the doubters, skeptics, come back. This is, absolutely, unarguably, a catabolic ratio of insulin to glucagon. We have these catabolic processes activated, and I’m saying that ketogenesis is catabolic. Someone would argue, well, it’s anabolic. It’s catabolic but, even still we’ve made a nutrient from it. So, I could appreciate the counter, but it’s a catabolic. It’s evidence of catabolism. Nevertheless, we can all agree this insulin to glucagon ratio of point eight must be catabolic these are the catabolic processes that are active. Now, in the case of someone consuming the standard american diet, the insulin to glucagon ratio is quite high, relatively at around four. This, we know, is an anabolic state, and we have the activation of anabolic processes, like the storage of lipids, the storage of glycogen, and we have the inhibition of processes that a lot of us care about. We’re inhibiting autophagy and we’re inhibiting ketogenesis. We know that’s happening in this fed state of the standard american diet, with this insulin to glucagon ratio of around four. Now, lastly, our beloved low-carb diet. Here we have an insulin to glucagon ratio of around one point three. A little higher than the fasted state, but substantially lower than the standard american diet fed state. And, once again, we know in a low-carb diet, where carbohydrate consumption is low, or very low, that is catabolic. We have the same biochemical processes occurring in this low-carb fed state, as we do in the fasted state. So, we can say that just what we were seeing with the insulin to glucagon ratio of 0.8 we’re seeing generally the same processes activated at around 1.3. And I’m going to come back to this in the relevance of this number when we talk about the ingestion of protein. But that brings me to that point: what happens, then, when we add protein to the diet, to these ratios. We are a community that appreciates and respects insulin to what degree do we need to worry about the insulinogenic of the amino acids, as a part of the proteins that we ingest. Well, let’s look: In the fasted state, if someone is doing this long-term issue fast, hopefully they’re being smart about it. Hopefully they’re avoiding refeeding syndrome. When they eat protein, we see a change in the insulin to glucagon ratio going from 0.8 down to 0.5. And so, we see this relative increase in glucagon, over whatever relative change is happening with insulin. That’s not surprising. That’s exactly what we saw with the dogs. Do you remember? How the insulin didn’t change? Yet the glucagon changed substantially? It lowered the insulin to glucagon ratio. So, putting this person, at least maintaining them them in this very catabolic state. Now, with the standard american diet, are you ready? When this person eats protein, we see that their ratio goes up to 70. So, about a 20-time increase. And so, this kind of gets to the heart. This gets to the heart of our collective appreciation of the insulinogenic effects of the proteins we eat. Because it’s justified, but we have to put it in the right context. For those of us who are controlling carbohydrates and have a healthy respect for insulin, thus, this is us here. Now, what do you think it’s going to happen? You ready? When a person eats protein on the low-carb diet, it changes from this relatively low level and goes up to … (loughs) There is in fact no change. And, technically speaking there’s a 6% change, which means that it stays at 1.3. … There’s a 6% change, as opposed to this 20- times change that we saw in the standard American diet. So, if we put these two head-to-head, and we feed them the diets, the standard American diet and the low-carb diet, as was done years ago, and we give them one gram per kilogram of protein, and this is sort of recapping what we just talked about, and we look at the insulin to glucagon effects, we see that there is this dramatic increase in the insulin to glucagon ratio on the standard American diet fed side. And yet no such phenomenon occurring. We have the maint…, the maintenance of the relatively low insulin to glucagon ratio that we see with the standard american diet. Ando so, the numbers changed accordingly, like we saw earlier. The substantial effect, and the standard American diet fed people, who have glucose coming in quite readily, the …, an insulin climbing and the protein simply adds to that. It compounds the insulin effect of the carbohydrate. Where oral carbohydrate consumption is quite limited, we see no such effect. Why might this be? As a repeat, in fact, let me quote one of my heroes, Dr. Roger Unger, he mentions, without exception, that the insulin to glucagon ratio is dictated by the need for gluconeogenesis. And because, in those low-carb fed bodies, gluconeogenesis is important, it is important, we can’t afford to have insulin spiking too high. Because, if it did, it would clamp down on gluconeogenesis, and the person would become hypoglycemic. Now, let’s look at the liver, and look at this particular process, in just a little more detail. In the standard american diet and the low-carb diet, I’m … I’m submitting to you, that the reason we have these differences in the insulin to glucagon ratio is because of the need for gluconeogenesis. In the standard american diet state there is no need for gluconeogenesis. In the low-carb fed state, we need gluconeogenesis. And I’m saying that and yet even as I’m we need the glucose, as a scientist, I only know of one cell that actually needs glucose. And we know there’s no exception. Do you wanna, do you wanna do you know what it is? Some people are saying brain, and yet, I’ve never seen a study that proves … Has anyone? I’m putting this out there … (public – “the beta cell”) The beta cell, can’t use, can’t use any other fuel? Neither ketone o lipid or anything else? It can, it can. I think so. But it’s erythrocytes. (Public – “Oh, Yeah, yeah”) We know erythrocytes. We know for a fact, that’s my little erythrocyte there. We know for a fact, erythrocytes, that lack any sort of mitochondrial presence, absolutely must use glucose for fuel. There’s no alternative. We always say that brain needs glucose and yet, well, the brain readily uses ketones. In fact, I would submit the brain prefers ketones because, as ketones become available, the brain begins using it more, and displaces the glucose. But, I appreciate this is purely academic, because you couldn’t test this in a living mammal, because they would die from the lack of glucose. But there’s no study that I have ever seen that proves the brain needs glucose. Can you see where I’m going? I’ve never seen that being proved. But that’s way off topic. … But maybe someone will talk about that later. Anyway, if you know, if anyone knows of a study that proves that, I genuinely would love to know. Okay. So, we have gluconeogenesis, we have these respective insulin to glucagon ratios, high insulin to glucagon ratio and the sad, low insulin to glucagon ratio in the low carb, and in each instance, we have this very expected regulation of gluconeogenesis, where we have the inhibition of gluconeogenesis in the high ratio state, and the activation of gluconeogenesis in the low insulin to glucagon ratio state. Now, in addition to main regulating gluconeogenesis, what else do insulin and glucagon regulate at the liver? What do you think? Ketogenesis. Yeah, this beloved process, or feared, or much maligned, whoever we’re talking with. But nevertheless, they both regulate ketogenesis, just like they regulate gluconeogenesis. And here, the standard American diet, and its roughly insulin to glucagon ratio of 4, very potently inhibits the insulin to … inhibits ketogenesis, sorry. And then, the low insulin to glucagon ratio of the low-carb diet activates ketogenesis. Now, then, what is the relevance of protein in this process, and this why many people fear protein, because they’re chasing their ketones so doggedly that they worry: wolf it’s gonna kick me out of ketosis. I can’t eat it. And I, I submit, and the reason I wanted to talk about this is that I think that leads to somewhat bizarre eating, in a way. Where we, we end up issuing real food because it has protein in it. and we end up just adding oil to everything. And I, I’m not, I don’t think that’s the best way to do it. Even if there is some alteration in ketosis. Nevertheless, let’s briefly just look at l the biochemical process of how ketogenesis occurs. Yes, indeed, low insulin is in fact, a part, in fact a necessary part of ketogenesis. But the other part of this is that we must have elevated glucagon. And this was highlighted in the study published just last year by some very good friends of mine. And you’ll see along the y-axis they’re measuring this relative change in beta-hydroxy butyrate in these animals. And along the bottom it’s a somewhat confusing axis, in a way. So, I’m going to clarify it. They had animals with functioning beta cells producing insulin, and animals that were not producing insulin. Then they had, within that, those groups, subgroups with animals with functioning glucagon receptors at the liver, and animals without functioning glucagon receptors. In other words, no glucagon signaling. And then, let’s look first then, at the no glucagon states between insulin and no insulin. Within that group we see that in the absolute absence of insulin, we see ketones go up from the left side to the right side, by about four or so times. A small little bump, right, and if you think about insulin being the absolute driver of ketogenesis, you’d think if there is no insulin, which there’s none in those animals that we’re talking about, an untreated one diabetic here, you would say they’re dying from ketoacidosis. There should be massive amounts of, of ket, ket, of ketones here. They should be well into ketoacidosis. And yet, there’s just a very subtle increase. That we would say that there may be in ketosis in this state. That’s because there’s no, there are no functioning glucagon receptors. When we, then, look at the differences between insulin deficiency or surplus, and functioning glucagon signaling, we signaling, we see that once we add glucagon signaling into the mix, we have this almost 50 times increase in ketone production. And this is just simply indicative of the need for functioning glucagon, in the process of ketogenesis. And the fact that ke … protein increases glucagon, then is another reason to appreciate the protein. And indeed, even the proteins ketogenic effect. And this was highlighted by one of my other academic heroes, Denis McGarry, where he mentions that glucagon is the primary driver of ketogenesis in the liver. But, despite me emphasizing insulin and glucagon, before I finished this little bit, let me mention that there is one other player that needs to be discussed. And that is carnitine. And this fact this was mentioned earlier. I think Rob Wolfe mentioned this yesterday. Carnitine is this escort, basically. No in the bad way. It is escorting, it is escorting the lipid into the mitochondria, allowing the lipid to be oxidized. And, just as a reminder, we must have a lipid be oxidized for it to then be ketogenic. We have to get down cleaving off those pieces, those two little pieces of carbons at a time, and then that turns into acetyl-CoA, and then gets turned into the ketone that we know and love. So, we have to have sufficient carnitine to escort the lipid into the mitochondria, and induce the oxidation, and then we have the magic of ketogenesis. So, all of these are relevant. This was a study by Denis McGarry in animals, in rodents, where he took the livers out of animals that were fed, and fasted. And you see that when the animals were fasted, the level of ketones was about three times higher. That’s that upper level. And in the fed animals, he simply took and fed their normal standard chow, and then supplemented carnitine. Now, mind you, we all make carnitine. But there are, in fact, known instances of carnitine deficiencies, where the human is unable to create sufficient carnitine for functional mitochondrial processes. So, in this state they added carnitine to these animals diets, and look at what happened to ketogenesis. So, I’m simply wanting us to appreciate there’s this extra player here, where we need sufficient carnitine for ketogenesis. Well, indeed we need it for just lipid oxidation in any general sense. So, these are the three characters then, or part, the parts or components of the formula, where we look, we need a low insulin level, and elevated glucagon level, and at least sufficient carnitine, and then we’ve created, we have the formula for ketones. Now, this is a pretty academic way of looking at it, me saying low insulin, increased glucagon, and perhaps the more practical side is to simply add in the relevant macronutrients. And I submit, when w’ere eating a real diet, and nevertheless, appreciating the relevance of carbohydrates and keeping them controlled, it ends up being a mix that would look something like this. Where we have protein combined with fat, combined with carnitine, providing the recipe for ketogenesis. And you might look at this and say, where could we get such a magical food, that contains it’s this wonderful mix of stuff? Well, it’s not very hard to find it: red meat is the perfect source of these three components of ketogenesis. Now, I appreciate, as I, as I have been offering this version of a low-carb diet that is not assuring protein to the degree that some people do, I appreciate that I may be inadvertently upsetting people. And so, here’s my diplomatic conclusion here. There are multiple ways, of course, to do what, to adhere to a low-carb diet, I kind of have two versions of that presented here. On the left it’s a version that is somewhat more appreciative of protein, on the right it’s a version that is wary of protein. But, what do they have in common? They both are controlling carbohydrates. And that really is the common strength between these two. And that’s, that’s the foundation that they share. And then, what might be relevant in determining which of these two versions of the low-carb diet is best? I submit, perhaps it’s helpful to consider the underlying glycemic status of the individual. In other words, if someone is starting from this metabolically unhealthy state of hyperglycemia and hyperinsulinemia, in other words, prediabetes up to type-2 diabetes, most of, most of the adults in the civilized world, or industrial and not even industrialized, we have this very common, it may be justification to be a little wary of protein at first. Perhaps, depending on what the person would prefer to eat. Nevertheless, I submit the unifying sort version of these two or hypothesis, or union of these two versions of the low-carb diet, could be that the person is starting in this version on the right, where it is relatively low in protein, and then they’re progressing as the insulin and glycemia is improving, towards this state that is still controlling carbohydrates, yet acknowledging the relevance of protein. Now, then, what might this look like? Because I’m not your physician I’m gonna give you some advice. (Public laughs) And I have no fear of litigation. Because this is purely academic. Here’s mine, here’s here’s one way you might do this. And this is my sort of cheeky attempt at making it memorable and, and, of course I’m using alliteration quite heavily. So, firstly I submit to maintain a low insulin to glucagon ratio, a person, one must control carbohydrates. To a person then, I submit, would be well-served by then prioritizing protein. Ensuring sufficient protein intake to maintain lean body mass and healthy function. And then, third, all the remaining calories are filled with fat. And so, let’s talk about each of these. But, just a moment, in more detail, very briefly. By controlling carbohydrates, I do mean this very widely accepted range of around 50 grams or so per day. And this depends, of course, on the person. And that would have to be optimized. A little lower or a little higher, whether the person can fudge it up a little bit. But, nevertheless, whatever range they come to, to have a healthy range for that person, they do need to scrutinize the quality of the carbohydrate, and this is no surprise, of course. I exclusively define a carbohydrate as good or bad, based on the degree to which it’s going to spike insulin. And so, this would be just some very simplistic version of that. Next one, prioritize protein. By this I mean that when a person is ensuring, um, sufficiently controlled carbohydrate consumption, there is then, I submit, a benefit to ensuring the person’s getting that range of protein, one to two grams per kilogram body weight. And, please, throughout this talk I’ve had references in corners. If I ever feared there was something deeply controversial, please, look into this, and make your own conclusions. Just like I’ve done by just pursuing data and coming to a conclusion. But I submit to you to maintain healthy lean body mass. We need to make sure we’re getting in that range. And I think our love of fat sometimes prevents us from getting that. And that’s why I wanted to mention this. Now, mind you, as I just turned 40 very recently a mindful of my getting older and my kids are getting older, they’re, our need for dietary protein goes up as we age. So, as we’re getting older, we need to make sure we’re on the higher end. Dr. Stuart Phillips has found that and he’s really one of the legends in this area, that the older we get, the less capable our body is at converting ingested protein into muscle protein. So, we do indeed need a little more, and I worry that we’re sometimes not getting it. And then, third, as I mentioned, we fill all the remaining calories, whether that’s 1500 or 2000 calories, that is fat. All of our remaining caloric needs come from fat. And, once again, as our, we know this very well, and Nina spoke about this very well yesterday, we need to scrutinize the quality. And, in essence, I basically say, we just stick with the fats we’ve been eating as a species since time immemorial. It was either from the animal, or make a lever big enough to compress the fruit and get the oil from the fruit. It was simple we’ve been doing it. So, animal and fruit fats, I submit, are better than any industrial seed oils, as we all now. And so, in sum, I submit that this overtly simplistic paradigm of three steps of a healthy diet, it is, I consider healthy because it maintains what I consider a smart, metabolically prudent insulin to glucagon ratio, keeping it low, keeping it in control, allowing the the benefits of the fasted state, yet without the need for caloric restriction. And then, it also ensures that we are properly nourishing the body. We’re giving the body what it needs, by making sure that there’s some focus on protein or, to maintain the alliteration, a priority on protein. With that, I thank you for listening, and I look forward to any questions during the Q&A. Thank you. (applause) Thank you

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100 thoughts on “Dr. Benjamin Bikman – ‘Insulin vs. Glucagon: The relevance of dietary protein’

  1. Simple question: is animal protein the only viable source in this scenario? It seems to be the assumption here, yet in these compromised times, consuming good quality red meat is not as easy or as safe as it used to be. Antibiotics, hormones, added sugars…

    Feeding a family with wholefoods grass-finished bison would cost $150 a day in protein alone.

    I would love to know whether protein supplements etc have a place in this paradigm (purely to satisfy the suggested protein intake, not as a source of the fat aspect etc)

    Many thanks

  2. Outstanding video. Very helpful… I better understand the role of insulin and Ketosis. Glucagon was the missing element for me Being T2D. My focus is reducing insulin levels and becoming insulin sensitive.

  3. This was an AMAZING talk! Thank you Dr. Bikman, for clarifying this very confusing subject for many! well done!

  4. The importance of this talk cannot be understated. It really puts the carnivore diet's success into perspective. low carb, high carnitine, continued insulin sensitivity despite high protein intake. Awesome

  5. I've watched this three times and learn more every time. I am so thankful to know that Dr. Bikman teaches Med. Students. There's still a glimmer of hope for the medical field in the future !!!😊

  6. any phd or doctor posting videos and giving amounts of protein people need to eat each day better have some good insurance ……what you guys are doing is the equivalent of a psychiatrist giving an analysis of someone they have never met…..

  7. "you'd be hard pressed to find a mammalian digestive system that as similar to human's as a k-9's"

    Bro, did you skip biology 101 and 102 in undergrad? Feed corn and potatoes to a dog for 10 days and see what happens.

  8. Why doesn't he like fasting? What are these 'potentially deleterious consequences' he's referring to?
    Aside from refeeding syndrome, that is.

  9. I found this one article on the necessity of glucose for brain functioning. I'm unsure about whether or not it "proves" anything though. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900881/

  10. Can you just have a couple of tablespoons of fat on a water fast. If it rise our insulin. Does the body really digest the fat. When it’s mtc oil

  11. Okay, this is awesome news, but I noticed it was implied that glucugon has no effect on muscle at all, does this means no gains can be made on strict no refeed low carb/keto?

  12. Yeah but what about poison ( secondary plant metabolites) in those low insulinogenic veggies? I preffer to eat white sugar!!

  13. I might also add there was a lecture that noted that the ketogenic diet assisted those in cachexia because of cancer, which is an inflammatory condition that inhibited muscle renewal.

  14. So what's the conclusion? Does this mean I don't have to worry about insulin spikes if I eat a lot of protein with zero carbs and a little fat? I was on the Keto diet and now the Carnivore diet, but recently instead of losing more weight I'm starting to gain weight again. Someone adviced me to go higher protein and lower fat by eating leaner cuts of meat. Any thoughts?

  15. Doesn't this suggest that, theoretically, a low-carb diet could actually RAISE blood sugar levels, due to the effect of glucagon in the liver?? Especially for someone who's diabetic?

  16. Are there long-term studies that prove eating this way reverses heart disease? If not, then I may stick with the whole-food, plant-based diet that did reverse MY heart disease (and TYPE 2 diabetes, and high blood pressure and arthritis, and…I could go on). Seriously, I am waiting for the peer-reviewed studies to come out that prove the consumption of all that saturated animal fat will help you live longer, reverse chronic disease, etc.

  17. does it mean that when doing keto we do not need to keep our proteins at 25% or our macro?? is it actually raising the glucagon level, plus promoting catabolic effects on adiposytes and liver?

  18. Woa, watching this a second time I caught an error in his presentation. @21:00 he shows the Insulin arrow getting bigger and the corresponding I/G ratio goes from 4 to 70. Ok, that's consistent.

    On the other side, he shows the Glucagon arrow getting much bigger, but says the I/G ratio stays at 1.3. Why no change when the Glucagon arrow gets so much bigger? Hmmm?

  19. I'm a bit confused with the concept of a SAD spiking the ratio by x70 when SAD presumably would include protein? Also curious about the impact of nutrient timing. And thirdly, what is the optimal way to build muscle to tone your body while adopting a keto diet?

  20. Your comment at 31:46 re low carb, low protein, HIGH Fat got laughed at, can I just say THANK YOU, the reasons you gave why some people have to do this WOW light bulb moment. I'd just been having hypo's hmm researched Hyperinsulinemia WOW I can lay claim to all it's symptoms -Dr Joseph Kraft informative. A confirmed Carnivore [I developed T2 d n 14.5 yrs of Atkins] I'm virtually vegetarian, now lost 65lbs normal blood glucose all down to eating lower protein [WHO guidelines] & Dr Fung's blogs. 20lbs to my celebratory steak dinner! Hopefully when at ideal weight I will break the insulin resistance/weight issue once and for all and protein will be the first macro I increase to maintain!

  21. He keeps saying things like 'it's because the body needs gluconeogenesis on the low-carb diet because otherwise …'
    Wish he'd be more careful about language: that's NOT WHY the insulin stays low: it's just (presumed to be) why people in whom it stays low were evolutionarily selected. The REASON for the phenomenon is going to be biochemical and probably really really REALLY useful to find out but it's not because otherwise you would die: the biochemistry doesn't know that!

  22. Amazing lecture, I’ve never heard this approach before, even in my medical school years.- thank you 🙏

  23. This is great information!! As a Type 2 diabetic I have witnessed how too much protein can be the cause of rise in glucose. This will definitely encourage me to not short myself on the protein I should be eating! One thing that is not addressed in this subject matter is there is a difference in how different types of protein can cause elevated insulin response. For instance lean meats vs eating fatty meats. Ground beef causes higher insulin response than a fatty steak. Look up "Insulin Index chart", this will give you an idea of how foods raise insulin, and it goes into covering how different proteins affect the increase of insulin. Also remember that every time you eat you cause insulin to be released, so if you are a diabetic, then eating less meals should be considered!

  24. Very interesting science. Have I understood it correctly? When you are on a ketogenic diet you shouldn't fear protein shakes after your workout because they won't spike your I/G ration? Is that correct?

  25. Glad I've been following common sense about protein!
    I always reasoned that if ancient man kills a wildebeest he eats it, muscle, fat and all. That's a lot of protein. That's what our body and brain are built around, eating all the fat and muscle protein together. Thank you Dr. BB for confirming what seems logical.

  26. does anyone know to answer my question? if i eat 70 gr carbs throughout the day but the 50 gr are after work out(dumbells, free weights) is this a reason not to be in ketosis or after working out you need carbs for glycogen therefore is kind of ok? 50 gr of carbs are in my protein-creatine formula.

  27. I'd always been told that as you get older you need LESS Protein overall, and fewer calories from protein and fat to stay healthy. Become fruititarian and live forever. Be vegan and run marathons as a centurian,..centarian,? centenarians? Centuryboy? If my body is worse at healing seems like it should need more , not less protein. But nobody listens to you if you don't have letters after your name. Thankfully for me and my own reputation, Bikman does.

  28. Hmm, so would supplementing with L-Carnitine, in conjunction with One Meal A Day (O.M.A.D) Keto Style and a caloric deficit, accelerate fat loss?

  29. At 10:45, Dr Bikman (and the slide) indicate that glucagon plummeted in response to the alanine infusion. But from the graph, it looks to me that it spiked in a similar way to insulin, at least initially. Although it seems to be a bit lower following the spike than before, that only applies to the first infusion, and not the second. Either way, I certainly can't see any decreases as radical as 45 pg, as written on the slide. Can anybody help to show me what I'm missing here?

  30. Outstanding presentation! Truly scientific and humble job of trying to untangle the complexity of our biology.

    The protein effect on SAD probably sums up all the bad press proteins and meat have been having since institutionalised nutrition science.

  31. I have been on keto for six months I lost 7 kg from 87 to 80 kg, I am 181 cm tall, but my triglycerides tripled from 90 to 270. How can it be possible?

  32. Been a carnivore one month and a day! been Keto 2 additional weeks! Down 26.5 lbs…but the reason I am doing it is my auto-immune issues…I have Fibro-myalgia very seriously and have had it since I was born. I have thyroid issues, I have chronic anemia, and extreme allergies, plus asthma. My acid reflux has improved.

  33. Surely all of this research collates back to our hunter gatherer primarily carnivore ancestors..
    They had to worry about saber tooth tigers..we've got forthcoming 5G smart cities to deal with

  34. So the S.A.D. Insulin:Glucagon ratio of 4 represents someone who is in a fasted state, but has chronically elevated glucose due to diet? If so, what fasting glucose/insulin levels would predict how your I:G ratio will respond upon eating? Alternatively, is there any way to infer one's Insulin:Glucagon ratio (i.e. energy needs) after a meal since measuring directly doesn't seem probable?
    And is the issue with 'refeeding syndrome' that the metabolic costs required after eating, will pull more key nutrients from the already-depleted blood? If so, what should be the approach, plenty of salts/minerals with the meal?

    Also enjoyed the points about points about how erythrocyte (Red-Blood-Cells) don't have a mitochondria, and therefore can only use glucose for energy.. and Glucagon needs carnitine to transport fatty acids into the liver for the production of ketones!

  35. A truly exceptional presentation!

    That was the clearest, and by far the best, explanation of protein's actual role in LCHF/ketogenic diets (and thus in the low-CHO/keto-adapted body) I've seen to date.

    I am in awe!

  36. Now a high fat diet is the 'healthy' diet? With respect, the idea that we haven't had an evolutionary adaptation to grains is asinine, furthermore you can clearly see it in physiology.

  37. this is awesome lecture. I have one doubt. we are focusing on producing more ketones but that can lead to ketoacidosis. Any idea how to avoid it.

  38. It appears to me that if you go on a ketogenic diet purely for weight loss, then you don’t need that much extra protein. But if you’re on the ketogenic diet and you are exercising heavily, your muscles are going to demand more. Your muscles include your heart. And as you get older it’s even more necessary.

  39. AFAIK the red blood cells, renal medulla and retina need glucose due to their mitochondrial deficiency, but their needs can be easily met by gluconeogenesis

  40. Interesting segment on ketogenesis. Carnitine I think is only needed to transport long chain fatty acids. Also if supplemented, it needs to be taken with simple carbs to increase its bioavailability to muscles.

  41. Fruits and vegetables either are high oxalate (paradoxically low lectin) or if low oxalate then high in lectins. People have died from high oxalates and people become autoimmune with high lectin. Answer for these people, from an academic perspective is a carnivore diet.

  42. 8:44 You'll be hard pressed to find a digestive system as similar to humans as canines. Nevertheless challenge it as you will.

    Me: *takes him up on his offer, types in "digestive system most similar to humans," finds pigs as the top result.

  43. 1-2g protein / kg…Really? So I don't have to worry about eating 100gs of protein since I usually just have lower than 20gs of carbs?

  44. I love this guy. A real scientist on the right track. So generous with his time and efforts to help and so able to explain it clearly. This is the second stage of the revolution where professionals are taking over from the talented amatuers. A significant development.

  45. Still not comfortable about the build up of Uric acid on a all meat diet so I tend to lean towards fat as the main benefactor of the success story of a no carb diet

  46. I like the doctor but he is talking googly Guk to me speak in layman's term not doctor terminology it is hard to stay on track with this guy

  47. I eat one meal a day my blood sugar keeps going up it takes two days of fasting to get my numbers down and low one hundreds I take a test it is 110 115 I eat it will go up 50 points from where I don't know what to do

  48. Dogs have digestive systems like ours because dogs are wolves that we started feeding 10,000 years ago, and in the time since then the ones that were healthiest on our food had the most puppies.

  49. I know Its common to label substances as antagonistic( insulin:glucagon, copper:zinc, etc) But I think of them.as.working as a team.

  50. I am a bit late with this video.. But about 8 years ago, I had this very same information in my textbook.. "amino acids dramatically increase glucagon levels if there is no carbohydrate intake" .. And we don't update our textbooks so often here (Serbia) ..

  51. This is truly a great lecture. Well written, well spoken, great slides and science that makes sense to ever low carber consuming more than 15% protein. Love the low carb down under channel and definitely want to see Ben’s lecture this year. Bring it on!

  52. Dr. Benjamin Bikman – What about the APO-E-Gene? People with APO-E-4 will die if they eat "any" fat. Most of the population have the APO-E-3/4 Gene, which medical results state that we should eat a "low fat" diet. Then there is the APO-E-2 Gene. It's recommended that they eat completely different too.
    There are studies now, on "cancer" patients using a DNA test to see which APO-E-Gene they have. Do you know anything about this Gene? Should we all be getting a DNA test to see which # we have before we embark on a KETO diet or LCHF diet? This is very confusing & scary.

  53. Benjamin Bikman is at the cutting edge of the latest research into the way our bodies work. His lecture about uncoupled mitochondria via brown fat adipose tissue was equally enlightening. A must watch for anyone into low carb diets and anyone just interested in the physiology of nutrition mixed with endocrinology.

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