"Fructose: The Hidden Fat Factory - Uncovering the Link to Obesity and Fatty Liver" #ObesityCrisis

A gram of fructose causes more weight gain and more fat deposition than a gram of anything else, including fat.

Good afternoon everyone, and to our dedicated viewers, my name is Niku. I'm the Director of Operations and Corporate Development at Emory Pharma. It's an Honor to have Dr. Lustig back with us today. He's our legendary speaker and we've managed to bring him back here today. While he doesn't need any introductions, I really wanted to still give him one because he deserves all the hype. Dr. Lustig is a pediatric endocrinologist, a best selling author, a globally renowned speaker. He's committed to educating the public and he's been working with different experts for childhood obesity and metabolic impacts of sugar on processed food foods. He's a professor of Emeritus at UCSF. Dr. Lustig has authored over 180 peer articles and reviewed over 85 of them focused on biochemical impacts of excessive sugar and fructose consumption. In addition, he's authored several influential books such as Fat Chance, the Hacking of American Mind and Metabolical. Through these resources, we've continued to learn a lot in our personal and professional lives. So we are thankful to have you today. This is his sixth visit to Emory Pharma, so we're honored to learn more. And please join me in extending a Warm welcome to Dr. Lustig. Thank you.

So, as Niku said, this is my sixth time here and there's always a consistent theme through all the talks that I've given, and that is that diet matters, and today diet matters also. But you're going to see some other things matter too, and those things are impacting on our children in a big way. And you know, I'm going to ultimately present to you a new idea on why we have this obesity pandemic that we have. And you'll see that it actually encompasses all the data that are out in the literature, answering all the weaknesses of the various models that have been proffered thus far. And it also allows for us to understand what the preventions should be. There are no treatments. There are only preventions. And you will see why as we go. Okay, everybody familiar with the movie? Well, so the out is more than the up, but you'll see why. So here's the obesity curves for adults, and you can see that we've extended it over these past two decades because things continue to get worse, as you can see. And here's for children and adolescents, you'll notice that actually for children there's been a little bit of a stabilization because We've instituted all sorts of preschool and toddler programs, like getting juice out of daycare as an example. And it has actually relatively flattened the curve for toddlers, which is good, but you'll notice everyone else is still going up. So it's still a major problem. But you will see why in a moment. Here's the biggest problem we have. Everybody wants the pillow and there is no pill. And you could argue with me, yes, it's not a pill, it's a shot. Is it? Is it really okay? Is this really the answer? Well, number one, the cost is breaking the bank and will ultimately devour all of Medicare, Medicaid and every aspect of health care delivery in America within the next five years if we continue on this route and turns out doesn't help everybody, it actually only helps about 2/3 of the people who take it and one third of the people who take it have to stop it for side effects. And as soon as you stop it, all the weight comes roaring back. And the reason is because you, you ozempic is not dealing with the cause, it is dealing with the symptom. Okay? It is like basically hypertension. You are treating the high blood pressure, but you're not treating the cause of the high blood pressure. The cause of the high blood pressure is still there and so it is still wreaking havoc because the problem is not being addressed, only the downstream effect. So this is not the answer. We ultimately have to find the preventative. As Desmond Tutu famously said, if you see people falling into the river, you don't just fish them out of the river, you find out why they're being pushed in in the first place. So it is true that obesity is a complex problem with multiple inputs. I don't argue that it's not one thing, it's many. It's energy intake, it's energy expenditure. We will talk about those in great length in just a moment. It's partly genetics, okay? The heritability studies say that about 50% of obesity is genetic. So it's not like that's a nothing. On the other hand, you can't do anything about the genetics, okay? They're fixed and they haven't changed in the last 50 years. But environment sure has. In fact, our environment is completely and totally obesogenic at multiple levels. And we're going to talk about many of these in just a moment. And of course, there are all these lifestyle factors which are ultimately preventable, and we'll talk about that in a minute. Assorted of mating. In other words, fat people Marry fat people. That's a sort of name. Okay? All right. There are two prevailing models of obesity that are out in the zeitgeist currently. There's the oldest one, which is the energy balance or the calorie model, which has basically been with us since 1902, since we discovered the concept of the calorie and the concept that food actually had calories in it. This was done by Dr. Wilbert Atwater, basically developed how to determine the amount of calories within foods by exploding it in a bomb calorimeter. The problem is we are not bomb calorimeters, okay? We do not run off heat. Bomb calorimeter basically measures heat. We unfortunately measure ATP, okay? They're not the same, okay? So the whole concept of calories is, as far as I'm concerned, part of the biggest problem. And my goal and my job is to, quote, kill the calorie. Hashtag, kill the calorie. Okay? That's. That's my job, okay? But nonetheless, this is what most people in this country and this world believe. Obesity is due to overeating because a calorie is a calorie. So if you eat more than you burn, you will gain weight. If you eat less than you burn, you will lose weight. Therefore, it is about calories in, calories out. It is about two behaviors, gluttony and sloth. Therefore, if you're fat, it's your fault. Therefore, diet and exercise. Therefore, any calorie can be part of a balanced diet. Therefore, the food industry says, don't pick on our calories, go pick on somebody else's calories. All of those come from the notion that calories are fungible based on the energy balance model. That's where this comes from. Remember, it is a model, and as George Box famously said in 1976, famous British statistician, all models are wrong. Some are useful. The question is, how useful is this model? And we're going to get there. Now, the energy balance model, also, since the advent of leptin, dictated that the brain is responsible for the control of weight gain, you know, through this phenomenon called leptin resistance. Now, I'm a great believer in leptin resistance. I'm one of the people who first identified insulin as an antagonist of leptin action. So I have a lot invested in this concept of leptin resistant and that the brain controls weight gain. After all, I am a neuroendocrinologist. That's what I do. Having recognized its failings and its shortcomings, I have moved on from that. And you will see how and why as we go. Then there is this second model, and you've probably heard of this model. It is called the carbohydrate insulin model. And what it says is that insulin is the primary driver of adiposity. There is no fat gain, there is no weight gain without insulin. Insulin is essential. And we know this because all you have to do is look at type 1 diabetics and how much weight they lose and how much fat they lose because there's no insulin to push on the adipose tissue in order to get it to increase its size. And that is also true. So the goal is keep your insulin down. Well, what makes insulin go up? High glycemic index, carbohydrates, and in particular, sugar. So this says that it's not how much you eat, but rather what you eat. That it's not the quantity of food, it's the quality of the food that matters. And that insulin is the primary driver of fat cell storage and also cell division. And those things are true. The question is, is the model true? Okay, again, all models are wrong. Some are useful. How useful is the carbohydrate insulin model? Okay, so this is the energy balance model in a simple schema. Here's overeating, here's physical activity, here's energy intake, here's energy expenditure. They increase circulating metabolic fuels, which then lead to fat storage. But the problems are here, old news. All right, are these. Is this model supported? And the answer is, well, yeah, but it's also refuted the support. It is possible to lose weight on a variety of diets. That has been shown by numerous investigators. Okay. Suggesting that if it doesn't matter what kind of food you eat, just eat less of it, that calories do count. Also, we know that consumption of ultra processed food does cause weight gain because it causes overeating. Because, in fact, sugar is addictive. And so if sugar is in everything, well, that's why you eat more. Therefore, it's still about calories. So the support says. But there are a whole bunch of challenges. There are a whole bunch of refutations to this model as well. Here's one. For any given caloric intake, BMI was higher in 2006 compared to 1988 at any given BMI. It doesn't address this concept of developmental programming which we have learned in pediatrics is extremely important. This concept that something is going on in utero, weight loss does not last because the body defends a set point. If it were only about calories, that shouldn't be true. Exercise does not induce weight loss. It induces fat loss, but induces muscle gain. But if you're burning more than you're taking in, you should lose weight, right? Well, it turns out that's not true. Right. And there's plenty of people who gain weight without overeating. This has been documented. Know 50 ways from Sunday, particularly those people who are stressed. So here we're looking at energy intake. Notice essentially no change since 2000. It's not like we're eating more, but the obesity rate's still going up. Okay, here's the. What do you call it, the energy, the total energy available. It hasn't changed either per, you know, per capita. Okay. But obesity sure has. So this energy balance model does not fit the data, except everyone believes it. So the question is, when is the data enough to make people stop believing it? Well, when you have something better, that's when. Okay? When you can change your belief system based on something that's more worse, rational. That's how. All right, we. And we're getting there. We're getting there. So now let's look at the carbohydrate insulin model. So let's start with insulin. What does insulin do? Well, it regulates storage of metabolic fuel. That's its job. It is the energy storage hormone. Insulin makes fat, more insulin, more fat. This is an axiom. You can take this one to the bank. Okay, the question is, is it the cause of obesity? That is a different question. Okay. It does stimulate fat synthesis and deposition, and it does inhibit fat oxidation. It pushes on the fat cell to keep the cell from releasing its fat. Therefore, more insulin, less chance of being able to lose weight. All those things are true. The question is, does insulin cause obesity? That's a different question. So does insulin cause weight gain? Well, increased insulin definitely makes you hungry. That has been shown again 50 ways from Sunday. You infuse insulin, you get hungry, it activates receptors in the brain. We know from people who are over insulinized with diabetes that they all gain weight. And it's one of the reasons why teenagers with diabetes don't take their insulin because they're afraid of weight gain. And they all end up in diabetic ketoacidosis, which is of the banes of my existence as an endocrinologist. We know that insulin secreting tumors, insulinomas, cause weight gain, okay? And there are a whole bunch of genetic variants that affect insulin secretion. And in fact, if you have a defect that increases insulin secretion, you will gain more weight. And if you Have a defect that reduces insulin secretion, you will gain less weight. So all of those things are true. And decreased insulin action leads to weight loss, like, for instance, under treatment of type 1 diabetes, diabetic ketoacidosis. And we have the adipocyte insulin receptor knockout models of Ron Kahn at Joslin to demonstrate the mechanism by which insulin exerts its effects on adipose tissue. Okay. Known as the furco mouse, the fat insulin receptor knockout. These are animals that can't gain weight. They are very lean, and they stay metabolically healthy because they don't respond to insulin because the insulin receptor in their fat cell is broken. Okay, so all very interesting. All right, so this is the schema for the carbohydrate insulin model. High glycemic load, carbohydrate, lots of sugar leads to insulin secretion. That causes changes in circulating metabolic fuels, just like we did before. That also leads to fat storage on its own, and that ultimately, because of the increase in deposition, that leads to the increase in hunger. Everybody see how that's different from the energy balance model? Yes or no? You see that? You see the logic and the difference in logic. So these two models have been duking it out, I would say, for the past 15 years. Which one's right? Here's the support and the reputation for the carbohydrate insulin model. We know that ketogenic and low carbohydrate diets promote weight loss more effectively than low fat diets. We know that because they keep insulin down, inhibition of insulin secretion increases weight loss in those patients who are obese, who are dieting. We know that the current western diet is highly insulinogenic. We know all those things. All those things are supportive of this. But there are some challenges. There are some refutations, too. This concept of developmental programming, how does that work in utero? Why is it that we have an epidemic of obese newborns when they don't diet and exercise and they're not eating excess carbohydrate, high glycemic index. Processed foods have many new ingredients, and those new ingredients may have their own effects. So it may not just be the glycemic index of the carbs. It may be some of the other things, like, for instance, artificial sweeteners and adipose tissue. Fat storage can occur without carbohydrate and can occur without increase in insulin, because there are other things that drive adipose tissue, too. So these are the things that get in the way, and these are the things that the different investigators will bring up as being issues for either one. Whenever these things are, you know, fought about. There was a big meeting in 2022 in London over this whole thing, and everyone went home with a headache because they didn't solve a damn thing for all these reasons. Okay, so if we compare the two models side by side, okay, the drivers are slightly different. Here it's caloric content. Here is specifically insulinogenic content. Okay? Ultimately, positive energy balance comes before adipose tissue storage. Here, positive energy balance comes after adipose tissue storage. And you might say, like, who cares? Why do we care? Well, ultimately it does matter, because if this is the correct model, it gives us something we can do, like get rid of the sugar. If this is the correct model, it relies on everybody to do their own thing, which is what we've been doing, and it hasn't worked. So policy change is contingent on which model is correct and which model is correct any given society adopts, which is why we are in this conundrum that's not getting any better. Most recently, David Ludwig, who is a proponent of the carbohydrate insulin model, by the way, I, you know, full disclosure, I was a proponent of the carbohydrate insulin model for 15 years and only recently have changed. Okay? He and Thorkild Sorensen in Denmark have basically tried to conglomerate the two to try to placate all the critics. And this is their integrated model that they published that basically says you can come in on either side. Okay, so maybe that's true, too. Maybe it doesn't matter. Or maybe for any individual person, one might matter more than the other. But here's the conglomerated, because here's this and here's this, and they both end up in the same place. Maybe that's it. But there are problems with that, too. So here's one of the problem. Two of the problems. Okay, they're on this slide. This is a paper that was published in 2020, looking at records of people all the way back to the Civil War to determine body temperature. It turns out that body temperature, white or black, male or female, no matter what the age, has been declining for the past 150 years. We produce less energy at rest, we give off less body heat at rest than we did 150 years ago. This cannot be explained by either model. Neither model can explain how come you're generating less body heat, because body heat is coming from the mitochondria. And all of these other models have nothing to do with the mitochondria. But very clearly, the mitochondria are very important, because otherwise, why would our body temperature be going down? Duh. Problem number two, these are not humans. These are lab animals. These are animals in captivity eating the same chow they always did, and they're gaining weight as well. If it's about the ultra processed food, why are the animals eating the lab chow gaining weight also? Unless they're exposed to another stimulus that we're also exposed to that has nothing to do with the food. Everybody with me here having fun? Am I stretching your brain? I will tell you, my very first job in science as a freshman in college was taking rats temperatures. And it's a good thing I'm not doing that anymore. Yeah. 1974, Richard Wertman's lab at MIT. All right, so that's one set of problems right there.