Physiology of Fasting: Hormonal Model and Weight Loss

Intermittent fasting reduces hunger and increases metabolic rate for weight loss, contrary to standard calorie-based advice.

### Hormones vs. Calories: The Role of Insulin in Weight Gain and Loss
* 🍽 There are two models of weight gain: the calories model and the hormonal model, which focuses on the **quality of calories** and their **hormonal responses**.
* 📉 The energy balance equation states that body fat equals **calories in minus calories out**, but it's a balanced equation, not a **caloric deficit**.
* 🏋 Studies have shown that when you simply reduce calories, the body's metabolic rate decreases, making weight loss **challenging**.
* 🍽 Exercise can increase hunger, leading to **higher calorie intake**, and the body may also reduce its **metabolic rate** to compensate for increased activity.
* 🏃 The constrained model suggests that after a certain point, additional exercise is matched by a **decrease in resting metabolic rate**.
* 🔄 Insulin plays a crucial role in weight gain and loss, as it **inhibits lipolysis**, preventing the body from **burning stored fat**.
* ⏰ Intermittent fasting is an effective way to **lower insulin levels**, and low-carb diets also help, but it's essential to consider both **hormones and calories**.
* 📊 A recent study on calorie restriction with or without time-restricted eating found **no statistically significant difference at one year**, but the study may have been **underpowered to detect a significant effect**.

### Intermittent Fasting: The Most Effective Weight Loss Strategy Backed by Physiology and Clinical Evidence
* 📉 "Small amounts of weight loss can make **huge differences in terms of metabolic health**."
* 🔄 "You have to treat the **root causes** in order to be successful."
* 🍽 "If it's time-restricted eating that allows you to **eat fewer calories**, then that's still a benefit because you can't do that so easily by itself."
* "Fasting is really two things, a way to eat fewer calories by putting in those restrictions and a way of **allowing your body to get the energy that it needs from its body stores**."
* 🍽 "The simplest rule of weight loss is just **don't eat all the time**."
* 🧠 "You have to understand hunger and metabolic rate, because those are your **determinants of your diet**."
* "Fasting is just a tool for you to use. It's like a scalpel, **it can cure you**."
* 📈 "Fasting offers unparalleled options in terms of treatment because you can **change so many different things**."

foreign [Music]. Thanks for having me here. I'm really excited to be here. It's, uh, you know, it's always exciting to be back at live events. So today, I'm going to talk about a little bit about the physiology of sort of weight gain and how intermittent fasting can help play a role for your patients. So, as mentioned, I did, uh, write a few books. I'm also a consultant for Level Two, which is focused on trying to reverse type 2 diabetes. And today, what we're going to discuss is the physiology of fasting, sort of weight gain, obesity, and then review a recent trial that, uh, you know, that may have, uh, questioned it a little bit, and then understand what sort of advantages fasting might offer for your patients. So the real question here is there's always this little tension between sort of these models of weight gain. So this is the calories model, and the idea is that food contains energy, and you measure that food energy as calories. And some people believe that really that's all you need to know about weight gain.

calorie is a calorie. You hear that all the time, and the idea is that all calories are equally fattening, right? Because if you eat 100 calories of broccoli, it's as fattening as a hundred calories of cookies. And that's the idea that's behind most of the way we were trained. If you look at even very recent guidelines, this is from 2021, you can see that their number one sort of advice for weight loss is adjust energy intake and expenditure. So, energy intake, of course, is calories in, calories out. In other words, the standard advice of eating less and moving more, with the second sort of implicit assumption that all of this is under your control. You have direct control of what you eat, you have direct control of your exercise, therefore weight gain is really up to you, and it's all about those calories. And this is found in almost all, I have that in the cadigo guidelines, which is the Nephrology guidelines, but there's another sort of idea that's sort of a hormonal model, which is

similar but a little bit more inclusive. That is, yes, food contains energy, but it also contains information. That is, the response to what we eat is different. We know that, that's just a fact. If you eat cookies, for example, your insulin is going to go way up, your blood glucose is going to go way up. If you eat salmon or an egg with no carbs, for example, it's not going to go up. And those hormones are instructions as to what our body is supposed to do, and both of these are important. So, you really have to look at both the calories and sort of the quality of those calories, or what those calories are composed of, because they elicit different hormonal responses. And this is written again in 2021 by a lot of researchers, including very prominent ones such as David Ludwig from Harvard and Walter Willett from Harvard. So, very prominent nutrition, and they're talking about this carbohydrate-insulin model. So, the main hormone we're talking about is insulin, and we're... you know, we care about insulin for the main

reason is that we know that it breaks down. It stops a breakdown of glycogen and body fat, and increases the synthesis of the glycogen body fat. That is it's a storage hormone. You increase glycogen synthesis, you increase the novo lipogenesis, and you stop glycogenolysis and lipolysis. That's just what it does. We've known that for many years. So what they're saying is that it's the hormones that are really important in addition to the calories. So it all sort of stems back to this model, which is the energy balance equation, which is that body fat equals calories and calories out. And this is the main thing that people talk about when they say, Oh, you have to drive this caloric deficit. But the one thing you have to realize is that a caloric deficit never exists. You cannot ever have a caloric deficit. This is a balanced equation. So if you are looking at this, you have three things. You have body fat, you have calories in, and calories out. So if you uh change one

there are two other variables that have to balance. There's never a deficit, it's always a balanced equation. So when you talk about people who just say, well, just eat less and you're going to lose weight, this is what they're talking about. They say, well, if you eat fewer calories, then you're going to have a lower body fat because of the first law of thermodynamics, and so on. What they're assuming is that the metabolic rate or your calories out stays the same. That's not necessarily true because the first law of thermodynamics doesn't say that you're going to lose body fat. Remember, there's three variables. So if you simply reduce the variables in calories in, you could just as easily balance that equation by keeping body fat the same and lowering your metabolic rate. That is, you reduce calories in and your body burns less calories and your body fat stays the same. So it doesn't break the laws of thermodynamics, which is one of the things that people always say, well, just eat less, you're.

going to lose weight. No, not necessarily. It makes no such statement at all. It's a complete misunderstanding of the laws of thermodynamics. So, the question is: What happens in real life if you eat fewer calories? Do you lose body fat, or does your metabolic rate go down? Well, the first studies of this happened in the 1900s. So, this was a study in 1944 by Dr. Ansel Keys, and it was called The Biology of Human Starvation. And it was brought on because they wanted to know what happens to the human body if you don't have enough to eat. This is World War II, so they put people on a 40% reduction in calories, and they were eating 1570 calories per day, which doesn't actually seem so bad. And it was mostly starchy, sort of low-protein, low-fat foods because this is what was available in war-torn Europe at the time. So, again, low-fat foods. This is actually pretty close to what we tell people to eat: 1500 calories, low-fat foods, and

um, what happened? Well, when they measured the metabolic rate, what they found was that their metabolic rate actually dropped by 40 percent. So these people, their heart volume, strength, their heart rate slowed, their body temperatures went down, so what they felt was they felt cold, they felt tired, they, you know, just felt terrible because their bodies weren't getting the energy that they needed to run all the organs, you know, your heart and your liver and your brain and all that sort of stuff and generate body heat. But the bottom line is that if you simply reduce calories, your body has this other option of reducing the calories out. And this is obviously true because if you think about it, there is no possible way that your body cannot adapt its basic homeostasis. If you say, Okay, eat 500 calories less per day, you'll lose a pound a week. Does that mean if you weigh 200 pounds in 200 weeks, you're going to weigh zero? Well, obviously not. So at some point, your body has to adapt. It turns out it adapts almost immediately.

so this is uh again in 1971. So, 50 years ago, they did very much the same thing where they did underfeeding, and what they showed was that if you underfeed somebody, their metabolic rate goes down. So, 10 to 20 percent reduction in your metabolic rate, and this is shown again and again. So, this is The Biggest Loser study where it's an American reality series, and they basically were competing to lose weight, and what they found is that as they lost weight, the metabolic rate just kept going down and down. The diet, of course, was a calorie-restricted diet, and even though they tried to make up for this decreasing metabolic rate with more exercise, at some point, they weren't able to keep up that exercise, and it didn't really affect the metabolic rate because how much you exercise doesn't affect your metabolic rate. Remember, when you're exercising, you're going to exercise your skeletal muscle, but you're not exercising your liver, you're not exercising your lungs, you're not exercising your kidneys. So, the amount of

energy that it's using is is not changed, and it's going down as you eat a calorie-reduced diet. So this is sort of well known even by 1991, so 30 years ago, they did a meta-analysis of 29 studies, basically all showing the same thing. What is the relationship between caloric restriction and change in resting metabolic rate? Remember, that's your calories out. What's your relationship between calories and calories out? And you can see that almost all of them show a decrease in metabolic rate of between 10 and 20 percent. So their conclusion is that the first statement which can be made with some certainty is that a decrease in energy expenditure is a universal response to energy restriction. In other words, if you just eat less, your body is just going to burn less, which is going to keep body fat relatively unchanged. And that's exactly what we see clinically, that's exactly what we see. So then the sort of flip side is, what if you just exercise more? That's going to make you lose weight, right?

again people say, Well, if you increase the calories out, you're going to lose body fat. It's just the first author on Dynamics, but again, it's not. There's three variables so you can change your body fat, which would be great. Or alternatively, your body fat could stay the same, and you could simply eat more. So increase calories out, maybe you increase calories in, and that's going to negate any benefit in terms of body fatness. And again, it doesn't break any laws of thermodynamics. So anybody who says, you know, it's breaking the laws of thermodynamics doesn't actually understand physiology because there are three variables. So the question is, what happens when you exercise? Well, they did a meta-analysis. This was very recent from 2021, and they did all these sort of exercise training interventions on and what effect does it have on energy intake. So they included 48 studies, but a lot of them were very poor quality. So when they threw most of the poor quality out ones, they uh were left with these studies. And when you

sort of put them all together in a meta-analysis. What you find is that when you exercise, you are left with an increase in hunger. And if you're hungrier, you're going to eat more. That's just a natural thing, and that's why they say you work up an appetite. They don't say it for no reason. During acute exercise, your appetite goes down. When you're playing soccer or something, you don't go, Wow, I'm really hungry, because you're busy. But afterwards, that's when you start to feel it. And that increase in hunger is going to naturally lead to an increase in calories in. And that's how you get results like this. And this was done at Harvard. And they looked at the sort of estimated energy gap. So when you do certain activities, are you going to be positive calories or negative calories? So this is watching TV. So you say kids, you have them watch TV, and you calculate how much energy is going in, how much energy is going out. And they're actually positive 100 calories per hour. So that's that makes

since you watch TV you gain weight well that's almost the exact same as when you do mild exercise. When you do mild exercise, the overall net effect is positive 99 calories per hour. It's not going down, you're not losing weight because you're in a positive energy balance, and it's because you're hungry. That's the only way you can do it because the actual exercise, of course, doesn't lead to weight gain. And even playing video games is positive if that makes sense, but you have to get this sort of moderate exercise before you're neutral. And then if you get to very intense exercise, then you can start to get negative. But this sort of oh, just do a little bit of exercise, it's not really very effective advice, and it doesn't break any laws of thermodynamics. And there's one other thing in terms of calories out, which is that it's not just the exercise but your metabolic rate. So your calories out is two things. If you increase your exercise, you might get more hungry, but the other thing that

might happen is your metabolic rate may go down to compensate. So this is a model which we all think happens, which is the standard model here, which is the additive model on the left. And what that says is that you have a baseline sort of metabolic rate, and you simply add the exercise, and the more exercise you do, the more energy you expend. There's another theoretical model, which is the constrained model, which is that at some certain point, any additional exercise is simply going to be matched by a decrease in your resting metabolic rate. And what they did here, and this was again fairly recent, 2016, they measured exactly that what happens with exercise, and they use doubly labeled water. They use five populations of 332 adults, which is it the additive model, which we think it is, or is it this constrained model, and it turns out it's constrained. So if you look at total energy expenditure on this x-axis compared to the amount of physical activity, what you find is that after a certain point, you don't get any more

total energy expenditure, that is, any additional expenditure that you're getting with exercise, is going to be matched so that the line goes flat. You can't expend more energy after a certain point; that just doesn't happen. So the body always adapts. It's, you know, the basic principles of life, its homeostasis, and this is what happens. There's a certain point where the slope becomes zero. And again, looking back at this bigger biggest loser study, this is from 2021 when they went back and they said, Okay, we know that these people using this calorie-restricted diet and increased exercise, we know that their metabolic rates went down. Let's compare that to how much exercise they got. Well, the people who did less exercise dropped their metabolic rate, but the people who did more exercise dropped their metabolic rate more. So again, that's your heart, your lungs, your kidney, your brain, all using less energy. So even though you're doing more exercise, more skeletal muscle activity, you're, it's being matched by a decrease in body generation. So there's a point

where you actually don't get any net benefit even in terms of energy. And this is uh the idea if you simply eat fewer calories, which is our basic sort of you know advice. It doesn't necessarily lead to lower body fat because there's an alternative. Your body can either you know lower the body fat, or it can lower its expenditures, and which one it does has a critical role in how much body fat you carry. And of course, that is ultimately determined by the hormones. Same thing with exercise. If you exercise more, it doesn't necessarily lower body fat. It could in an ideal world, but you could just eat more, or your metabolic rate could go down. And again, which one happens again depends on hormones. So ultimately, it all depends on hormones because our whole body runs on hormones. You know, our body has no calorie receptors, right? There's no cell receptor that says, Oh, here's a calorie, this is what I'm going to do. Our body runs on hormones. Those are instructions as to what to do, how much to pump blood.

how do you know how much body heat to generate everything in our body is run on hormones not calories so ignoring the hormonal side of things is not a great idea. So if we think about feeding and fasting this is sort of what happens. It's not just about calories. So this is the calories going in. So it's like energy, it's food energy, that's all it is. So I've depicted it here like coal and a coal burning power plant. For example, when you eat, you're eating calories, your body senses this because insulin goes up and insulin is a nutrient sensor. It tells your body, hey, food is coming in, this is what you need to do. So you store some of it, right? So you generate sugar like glycogen, right? Sugar glucose molecules, they string them all together, stick them in the liver, that's glycogen, that's glycogen synthesis. If you have more glycogen, then you generate body fat, which is the novo lipogenesis, and that's one option. The other option is you burn it. So for metabolic rate for exercise.

what you can't do is you can't take stored fat or sugar and burn it. Because we know that insulin inhibits lipolysis. Remember, insulin is a nutrient sensor. It's telling your body, store this energy that is coming in. You don't want to burn your stores. You want to put more in, right? You can't put stores in and take stores out at the same time. That's just working against yourself. So if insulin is going to tell your body, go in. So what you cannot do when insulin is high is burn body fat. That's just basic. And this is, again, just you know, we've known it for a long time. This is just one of the most basic functions of insulin is to inhibit lipolysis. It's only when insulin starts to fall that you disinhibit the lipolysis. Then you can break down your glycogen, which is glycogenolysis, right? You take the glycogen, which is chains of glucose, you break it all up, throw that glucose back into the blood, and you have a source of

energy. That's the reason you don't die in your sleep every single night. But it depends on this insulin falling to get that back out. Or if there's not enough glycogen, then you break down triglycerides and use it as a source of energy. So you take your stores and you burn it. But that depends on the insulin falling. One of the ways you can do that, of course, is fasting. That's how you're normally supposed to do that. So as insulin falls, remember other hormones go up. And these are the counter-regulatory hormones. These are going to take energy from its stores and push it back into the blood. And this includes the sympathetic nervous system, so mediated by the vagus nerve, noradrenaline, growth hormone, and cortisol. All of these are basic counter-regulatory hormones, and they all go up as insulin starts to fall. And that's going to have an effect because if you are going to stimulate the sympathetic nervous system by noradrenaline, well, your metabolic rate is going to stay more stable because you're

stimulating the system. So, that's its basic function. Is to take the energy out. So, if we think about weight loss. We think about these three variables. Let's think about how we're trying to lose weight. If you simply restrict the calories. But you're keeping your insulin levels very high. You're eating low-fat foods. So, high carbohydrates. You're eating constantly from the minute you get up. So, the mini go to bed. Insulin is going to stay up. So, in a steady state. You're going to have 2,000 calories going in. 2,000 calories coming out. Now you want to lose weight. So, you reduce it by dropping it to 1,500 calories per day. Well, insulin stays high. You still have 2,000 calories here. So, you're not in balance. You cannot have an imbalance. So, where are you going to get the extra 500 calories from? Well, you can't get it from your fat stores. Because your insulin levels are pumped up really high. So, the only possible way you can balance this equation is to drop your metabolic.

rate which is, in fact, exactly what we've shown in our research for the last 50 years. Compare that to the same calories, but you're going to use, say, an intermittent fasting strategy where you're going to allow the insulin levels to fall. So, again, you're going to start with 2,000 calories in, 2,000 calories out. You're going to reduce your calories to 1,500 because that's what you're trying to do. But in this case, you're going to allow your insulin levels to fall. So, what happens is that you simply take those 500 calories out of storage and use them. Now, you're perfectly in balance. Your metabolic rate never had to drop because you've opened up the storage facilities. That's what insulin does. That's its whole job. It's not necessarily good or bad. That's its job, is to keep it in storage. If you haven't kept it, if you are opening up that sort of storage door, you can take it out. So, the question is, which one is sort of

more powerful. And this is a very interesting study done a few years ago. Where you said, Well, let's think about these hormones versus the calories. So let's keep the insulin levels high but reduce our calories. What's going to happen? Well, if you believe all in the calories and calories out model, you'll say, Well, you're going to lose weight because you reduce calories, as opposed to the hormonal model which is going to say, Well, you're going to gain weight because insulin levels are high and that's the main driver of weight gain because our body runs on hormones. So this is the study they did in type 2 diabetics. And basically at Time Zero, they ran zero insulin. Over six months, they bumped up the insulin to a hundred units a day. So quite a lot. And at the same time, they reduced the calorie intake from about 2,000 calories to 1,700 calories. So 300 calories per day less. So you're going to expect over six months a significant weight loss if it's all about calories.

so what actually happened, which shouldn't be a surprise to anybody who's prescribed this, is that they gain 20 pounds even as they reduce their calories. So it was never about calories and calories, though the insulin is telling your body, hey, store this calories as fat, so therefore the rest of the body simply has less energy to burn. That's the only way that you can actually gain weight while eating fewer calories. So in the whole scheme of things, both calories and hormones are very important. You shouldn't focus on calories and ignore the hormones, and you shouldn't focus on hormones and ignore the calories. And the main hormone we have to think about is insulin. So intermittent fasting is probably the most efficient way to get your insulin levels down because you're eating zero, and you can't get lower than zero. Low carbohydrate diets are going to come very close, but it's not going to come as close as fasting. But what you shouldn't do is sort of say, oh, I'm going to fast, but then I'm going to eat whatever I want.

because if you simply fast and then over feed, you're getting the hormone part right, but you're not getting the calorie part right because energy is still a part of the mix. There, you have to get both right in order to do it. So this is the most recent study, which was in the New England Journal of Medicine probably two months ago. And what they did was a calorie restriction with or without time-restricted eating. So, you know, so here, here's a good study, right? Calories or calories plus intermittent fasting, which is time-restricted eating. And so both of them, both groups are calorie restricted. And at one year, they said, well, there's no statistically significant difference. So therefore, it's not really the fasting that's important, it's all about calories. But you have to look a little deeper into what they actually did here. You can see that at six months, the between-group difference was 0.5 kilos. At a year, it's 1.8 kilos. So the difference is increasing, but it's not

statistically significant. So when it's not statistically significant, the first question you have to ask is, well, is it just underpowered because there's an effect there but you don't. It's not statistically significant. So is it just underpowered? And of course, the media went crazy. The New York Times and everybody else said, well, there's no benefits to time-restricted eating. And the problem is that it really was kind of underpowered because when they did the power study, they calculated that they had to be able to show an extra 2.5 kilogram difference between the two groups in order for this study to be positive. But if you look at the fasting time, they only went from 13.8 hours to 16 hours. We had a 16% increase in your fasting time. Given that the control group lost 6.3 kilos, which is pretty good actually. To get an additional 2.5 kilos means you have to have an additional 40% benefit. So you know if you're thinking that you're going to just increase the fasting Time

by 16 and get a 40 difference in weight loss, it ain't going to happen. So it was really underpowered and, and that's the real problem with jumping to the conclusion. The study is the study. I think I'm all for studies, but you simply can't conclude that there's no benefits because the increased weight loss was only 28, and therefore they said negative. But clinically, that could still make a big difference. We know that small amounts of weight loss can make huge differences in terms of metabolic health. Um, the other problem is that the way they did the study was that when you're comparing two things A and B, if they're independent of each other, then you can do a study like that A Plus B versus B alone. However, you can't do that when the study is a causes B, which causes C. So if you're keeping B fixed and then measuring C, they're going to be the same. But it doesn't mean that this is irrelevant because this is the ultimate cause. So you have to treat the root causes in

order to be successful. So, for example, if you have a drug such as semaglutide which causes you to not eat, eat fewer calories, and that causes weight loss, well, we know it's a very good weight loss drug that's been published and so on. But it's the drug that allows you to have fewer calories. If you simply fix the fewer calories and show the same weight loss, you can't conclude that the semaglitide had no benefits. The benefit was that it allowed you to eat fewer calories on a more successful basis. And it doesn't mean semaglotide has no benefits. And that's exactly the same problem with time-restricted eating. If it's time-restricted eating that allows you to eat fewer calories, then that's still a benefit because you can't do that so easily by itself. And we have many studies that show that if you simply restrict the time that you're eating, you're going to eat less overall. This study, for example, which is in Cell

metabolism. They did find something very similar. They took four hours versus six-hour time-restricted eating versus control. And what they found, of course, was that without telling people to eat fewer calories, they ate fewer calories. So, the time-restricted eating resulted in about a 500 calorie per day less without people sort of knowingly counting calories or doing it. So, it's that time-restricted eating. Because obviously, if you have less opportunity to eat, it's going to be easier to eat less. If your rule is don't eat after six, then you're not going to be as tempted to go out and have, you know, some chips or something at the late night because that's your eating rule. So, it's the time-restricted eating that is allowing you to do that. The thing is that you always have to think about these ultimate causes. Because if you say something like, Oh well, the problem is you have an emotional eating problem which is causing you to eat too many calories, you're just calling weight gain. You can't say, Well, that's irrelevant because that's

your root cause or you're eating too much sugar. You're eating too much you know to to out too much or bad habits. You always have to treat the root cause, and that's the most important thing if you're going to be successful. The second thing is that this is a more comprehensive, that is, this is why they're gaining weight, but this is why they're doing that to gain weight, right? So you're going that sort of one level up. Yes, you're eating too many calories, but why are you eating too many calories? Maybe you have too much opportunity to eat calories, and that's your problem. And by restricting that time, you're going to be more successful. It doesn't mean that there's no benefits here. I mean just saying, you know, treating this is like saying to somebody who's depressed, Oh, just cheer up. Like it doesn't work like that. You always have to understand your root causes, and if your root cause is that you're having too much time, too much opportunity, then fix that. And that's what time-restricted eating does.

so when you're talking about clinical weight loss you know if we take this example where you have you know 2,000 calories in 2,000 calories out you're eating breakfast lunch and dinner. The idea is not to take more calories. The idea is simply to take this meal and make sure that you're getting those calories out from body fat. And the way you do that of course is you allow your insulin levels to fall, and that's what's really important. So fasting is really two things, which is a way to eat fewer calories by putting in those restrictions and a way of allowing your body to get the energy that it needs from its body stores, because body fat is nothing more or less than a store of calories that you ate in the past. But if you close those doors off, if you keep insulin high, those doors are locked, you cannot get that energy back out. So the only way you can get it is to eat more to satisfy your energy requirements. Think about it this way, if your insulin

levels are always high. Like you see with type 2 diabetes, when we pump them full of insulin, what happens is that if you eat a thousand calories, all that's going to go straight into stores, which is body fat. Then your body's like, hey, I have no energy here, I still need to generate body heat, go and eat something. And this is why if people who are eating, you know, in the past, these low-fat diets, they eat two slices of white bread with jam, by the time they get to, you know, 10:30, they're ravenous. So they're looking for a low-fat muffin. Why? Because your blood glucose spiked up, your insulin spiked up, all of those calories that you ate with breakfast went straight into your stores, and you have nothing left to concentrate, to do all your stuff. If you ate the bacon and eggs that your grandmother did, well, that wouldn't happen because the insulin levels not going so high. So this is exactly, of course, the hormonal model, which is that both energy

and the hormones are very important. You can't ignore one versus the other. But really, is it that because, again, trying to think that one step more, this is the way we think about energy balance. Body fat equals calories in minus calories out. Well, we say, well, this is your diet, this is your exercise. It's all under conscious control. So if you're overweight, it's your own fault, you made that decision. But is it really? Because let's think one step deeper. Why are you eating too much? Well, maybe you're just really hungry. Maybe you're just hungry all the time because all of that energy went into your body fat, right? And it's not just exercise, it's your metabolic rate. And these are not under your control. You can't decide to be less hungry, you can decide not to eat, but you can't decide to be less hungry. You can't decide to burn more energy in your metabolic rate. So in the end, what is controlling your hunger and your metabolic rate, because those are your

determinants of your diet. Your calories in, your calories out, which is going to drive body fat, but this is understanding it at a very superficial level, and this is understanding it at a much deeper level of why. So it's hormones, of course, what drives hunger, while ghrelin is the hunger hormone. GLP-1 is a satiety hormone. So if you're full, you're not going to eat. That's as basic as that. Your metabolic rate, while your sympathetic tone, your adrenaline, if you're pumping up your metabolic rate, you are going to burn more energy. So let's think about the things that we know cause weight gain and weight loss. Well, the insulin, we know insulin causes weight gain. This is from the DCCT trial, and they gave type 1 diabetics a lot of insulin versus sort of less insulin. And yes, the people who got tight glucose control with a lot of insulin did better. But how many gained weight? Well, like at the end of the trial, almost 30 percent.

had major weight gain so we know insulin causes weight gain. Anybody who's taken it or has prescribed it has got patients come back and say, Man, I just gained like 30 pounds. We've all had that experience. And is it a calorie agent or is it a hormonal agent? Obviously, it's a hormonal agent. It's the hormones which drive the behavior. We know GLP-1 again is very successful at weight loss. This is that trial from the New England Journal of Medicine about a 17% body weight loss. That's a huge percentage. Well, is it a caloric agent? Are you counting calories? Not at all. Counting calories just doesn't work. We've tried it. It doesn't work. What it does, of course, is it makes you not want to eat because you're nauseous, so you don't eat, and guess what? You lose weight. But it's a hormonal agent, and what you're doing is affecting the hormones, not the calories. Nicotine, so nicotine causes weight loss. This is the people who smoke, so you see that they're much lower than the

people who don't smoke. And this is the people who quit. So when you quit, you gain weight. And is nicotine a caloric agent? Not at all. This has nothing to do with calories. In fact, it's a hormonal agent. It affects you on multiple levels, but noradrenaline and norepinephrine is one of the major things. So it's a sympathomimetic. It increases your metabolic rate. At the same time, it has effects on agouti-related protein receptors to decrease appetite and increase satiety. So people who smoke just aren't as hungry. At the same time, they're bumping up their metabolic rate. So therefore, they're going to lose weight. And they sustain it. You see that they sustain it. When you quit, you gain that weight right back. But it's a hormonal agent. So the two things that are going to drive your weight gain is hunger and metabolic rate. Forget calories in, calories out because that's a very superficial understanding. You have to

understand hunger. Are you more hungry if you're more hungry? You're going to eat more. Well, how does fasting affect hunger? Well, this is ghrelin. So, ghrelin is a hunger hormone, and you can measure it if you fast. So, this is a study. They fasted people over 24 hours, and they measured ghrelin. So, they have three spikes. Most people have three spikes: lunch, dinner, and breakfast. The interesting part is what happens if you don't eat lunch, for example. So, you're busy, you're in, you know, the or you're busy, you miss your lunch, you're hungry. But what happens is that ghrelin actually falls right back down to baseline. So, by four o'clock, you're actually equally as hungry as if you had eaten. What happened? Well, your body just took the calories it needed from its stores. That's all. Same thing at dinner. You skip dinner, you're hungry, yes. But then when you don't eat, your hunger actually just falls right back down to baseline. You're no more hungry than if

you are more hungry immediately. But if you give it time, that passes because you're gonna get it's going to get your energy from somewhere else. This is over multiple days of fasting. What you see is that you get this up and down, but over two, three days, four days, durellan actually starts to go down. The pad, the effect on gorillin. In terms of, uh, clinically, this is a study in which they compared caloric restriction versus alternate daily fasting. And when you measured relin, what you see is that this is a p-value of 0.048, so significantly different. Those people who just did caloric restriction increased their ghrelin, which means that they are more hungry. So if you're just restricting calories, you're more hungry. It's not some psychological Voodoo thing. They are physiologically more hungry, an effect that you do not get with the alternate daily fasting. If you look at metabolic rate again, what's going to determine that? Well, people say, well, if you're going to fast

you're going to, you know, go into starvation mode. Your metabolic rate's going to go down. Well, this is what actually happens. You take people and you measure them, and you fast them for four days. At day zero, this is their med, their weight. It's steadily going down. This is their resting energy expenditure, so how much they're burning. And this is their VO2, so the amount of work that they're actually doing. So after four days of not eating, what you see is that they're burning about 10 percent more calories than they did at day zero. Your body's not shutting down, it's ramping itself back up. And again, why? It's basic physiology. Your sympathetic tone has gone up, your adrenaline has gone up. And that's why, interestingly enough, growth hormone has also gone up, which is very interesting because you think, why is growth hormone going up? Well, again, when you start to eat, you want that growth hormone up so that you are able to maintain your lean mass. This is again another study looking at

human adipose tissue after 72 hours of fasting. So this is noradrenaline. So noradrenaline's just pumping itself up, that's the effect. And so when you look at resting energy expenditure, what happens, how much energy are you burning? You've gone from 1684 to 1729 after three days of no food. You're burning more energy than on Day Zero. So this whole idea that oh you're going to kill your metabolic rate is actually completely false because if you understood the hormonal effect of fasting, you would say No, it should be the exact opposite, you should be going up and that's what all our physiologic testing is showing. And once again, that's this study comparing 32 weeks of alternate daily fasting versus calorie restriction and again you see calorie restriction with a p-value of 0.045, means that they have dropped their metabolic rate, they're burning about 76 calories less per day with calorie restriction, versus the alternate daily fasting which is the p-value of 0.4.

significant. So if you're just trying to do calorie restriction, you're going to be more hungry. So you're going to increase your calories in. At the same time, you're going to be burning fewer calories because your resting metabolic rate went down. What's that going to do to body fat? Well, you know, you just have to look at the energy balance equation. Increase calories in, lower calories out, you're going to gain body fat through calorie restriction. And of course, this is the standard advice we've been giving for 50 years, the one that's been so unsuccessful. If you want to be successful, you have to be able to decrease hunger and increase metabolic rate. So this was a very interesting study of how do doctors lose weight. So they took a poll of 900 female doctors and asked, What do you use to lose weight and what do you tell your patients? And these people were pretty successful, actually. So they weren't that overweight, but body mass index of 24.9, and they were able to lose 13.2 pounds on average. What

did they do well 75 percent of them use intermittent fasting. They didn't tell their patients to do it like 25-30 percent, but they did it for themselves. Why? Because if you want to lose weight, you're not going to go for that strategy that just doesn't work. You're going to go for the stuff that works, which is intermittent fasting. There is another question about eating disorders. So, this is very important. Of course, there's always this question that, hey, if you're going to diet or if you're going to fast, are you going to increase hunger and therefore leave people susceptible to eating disorders? The other issue is that you may decrease tryptophan, which is a precursor for serotonin, and leave people sort of just thymic, a little bit depressed, and therefore prone to eating disorders. There have been several studies to look at this, and this was one of the most important ones, which is, uh, the short-term fasting promote eating disorders. And this was 218 participants, and they did a 24-hour fast, and they

monitored them for disordered eating, and basically their conclusion was no, it does not significantly predict an increase in Eating Disorders. This was another trial in 2000, and they took people with actual diagnosed eating disorders and said, Well, if you fast them, do they get more? And again, the answer was no. They said a period of acute food deprivation did not trigger eating pathology. And this one, the same thing, what happens when you give an acute fast, do they eat a lot more afterwards? And the answer is no. Even a 36-hour fast did not induce a powerful unconditioned stimulus to compensate, that is, if you don't eat for 36 hours, you eat a little bit more, but you're not completely uncontrolled, which is the problem with eating disorders. So essentially, the food contains energy, which is calories, and also information, which is the hormonal response. The fasting is just a very efficient way to eat fewer calories, at the same time, allow the hormones that allow body fat loss. And the reason it does is because it tends to reduce the hunger and increase

the metabolic rate, which is exactly the opposite of the standard advice we give people. So, whereas the New York Times is telling people that time-restricted eating has no benefits, it's actually completely untrue. Because the whole point of time-restricted eating is that you're going to create a structure to your eating day. That is, you eat between this hour and this hour. Outside of that, don't eat. That's a very simple rule that everybody can follow. As opposed to, hey, eat all the time whenever you want, but count the calories. Well, you have no idea how many calories are in your food. If you're eating whole unprocessed foods like we tell everybody to do, they don't come with calorie counts. You need a piece of steak. Well, you have no idea how much it is. It's a completely nebulous rule. It's completely amorphous. You have no idea. Nobody has any idea. When they do studies of calorie counting, every single person is off by a lot. As opposed to simply saying, don't eat between this hour and this hour. Now.

you have a structure that you can be successful at because it's very simple to follow. This builds dietary consistency because if you're going to do this breakfast, lunch, dinner, nothing after dinner, well, you're going to build consistency, and consistency is going to build habits. Why is that important? Because habits don't require willpower. If you are in the habit of not eating after dinner, it's not difficult in the afternoon because that's what you always do. That's the point. You want to build consistent dietary habits so that you can be successful without doing anything because that's just your baseline. It's a very easy way to reduce calories because you're counting hours of the day, which is very simple and hard versus calories, which is very hard to do. And it's simply a traditional way of eating. You're supposed to have a period of time that you eat and a period of time that you don't eat where you are going to digest those calories. That's it. So the simplest rule of weight loss is just don't eat all the time.

it's not going to work. And if you look at the advantages of fasting to your patients, there's a huge number of them. You don't have to use it, but fasting is just a tool for you to use. It's like anything else. It's like, you know, a tool. Like a knife, it can kill you. But if you use it like a scalpel, it can cure you. It's just the way you use it. The tool is the same, but it's very simple. People understand it. You can explain it in 30 seconds. If you want to try and explain rules for, you know, whole food plant-based keto, this is going to take you forever. And if somebody's 75 years old and has eaten a certain way their whole life, they're not going to understand. But this is a very simple rule. Don't eat between this hour and this hour, whatever you want to choose. It's free. You don't have to have a lot of money because if you have disadvantaged populations, they're not going to be able to buy like

you know free-range organic eggs, which is great, but it's expensive. This is completely free. It's convenient that you're not taking more time. You're not saying cook all your meals from scratch and raise your own chickens. It's convenient. It's not. You're going to save time because you don't have to go buy the food. You don't have to eat the food, and you don't have to clean up. So it's just a lot more convenient for people. It's going to make your life simpler. It's flexible. You don't have to always do it. You can do it sometimes and not do it other times. If it's holidays, you might say, I'm not fasting at all, but then after the holidays, I'm going to do a lot of fasting because I gained a lot of weight on my cruise. And it applies to any diet. So this is important because this is not a diet. Diets are the foods that you eat or choose to eat. Fasting doesn't tell you anything about.

that whether you want to be keto, or you want to be plant-based, or vegan, or paleo, or whatever you want, it works with all of those diets. It tells you nothing about what the foods you should eat are. It only tells you that you should set aside a little bit of time to use the calories you've taken out, whether that's 12 hours, or 16 hours, or you know, 20 days. That's up to you, that's completely up to you. It's always under your choice. And then the final advantage is that it really offers unlimited power. Because if you have a situation where people have to lose weight for their health reasons, type 2 diabetes or whatever, and you're not doing well with a paleo diet, well, you can't get more paleo than paleo. If you're vegan, you can't get more vegan than vegan. Like there's no nothing further you can do. Whereas with the fasting, you always have a choice. You can increase the duration of the fasting, you can increase the frequency of the

fasting. You can do whatever to get the results that you want because, again, remember, you're just allowing your body to use the calories, to use the energy that it has already stored. It is literally the reason we carry body fat. It's not there for looks. It's there for you as a source of calories. So, if you don't eat, let your body use it. If you're getting sick because you have too much of this body fat, let your body use it. That's what it was there for, and that gives you sort of unparalleled options in terms of treatment of patients because now you can change so many different things. Not only can you change the diet, but you can change the fasting time, you can change the duration of the fasting, the frequency of the fasting, whatever you need to tailor it to your patients. And that's the power of intermittent fasting, a tool that we've ignored for so long yet is literally the oldest tool in the book, is the oldest dietary intervention known to humanity, and is probably the most effective in terms of weight loss.

because you cannot get lower than zero, so most diets restrict some foods. Fasting restricts every single food, so as long as you're doing it, you're understanding it. This gives you a very powerful tool to treat your patients and make them better. Thank you.

How to Lose Weight the Scientific Way | Intermittent Fasting | Jason Fung

Scientific videos on how to lose weight and reverse type 2 diabetes with diets and intermittent fasting.. Official channel of Dr. Jason Fung - specialist physician, nephrologist and New York Times best selling author of The Obesity Code, The Complete Guide to Fasting, The Diabetes Code and The Cancer Code. Dr. Fung has experience from treating thousands of patients over many decades and shares his insights on weight loss, diets, nutrition, type 2 diabetes reversal, and intermittent fasting. 

The success rate of basic weight loss advice of calorie counting has been shown to be abysmally low. To lose weight, don't follow strategies that have been proven to fail. Instead, Dr. Fung focuses on understanding the science of calories, diets and fasting as well as practical tips and regimens. He shares patient stories, photos and actual regimens (with permission). To start losing weight and getting healthier, subscribe and hit the bell for notification.


Jason Fung

The Role of Intermittent Fasting in Weight Management

Intermittent fasting is discussed in relation to the physiology of weight gain and obesity.

There is a tension between the calories model and the hormonal model of weight gain, with a focus on the role of insulin.

The study of human starvation in the 1940s provides insight into the effects of calorie reduction on the human body.

The Impact of Caloric Restriction on Metabolic Rate

Caloric restriction can lead to a significant drop in metabolic rate, making the body feel cold, tired, and low in energy.

Despite efforts to counteract this with exercise, the decrease in metabolic rate persists, making it difficult to lose weight.

Additionally, exercise can increase hunger, leading to a higher calorie intake, which can offset the calorie expenditure from the activity.

Studies show that even moderate exercise may not effectively create a negative energy balance, as hunger increases with physical activity.

The standard additive model suggests that more exercise leads to higher energy expenditure, but the constrained model shows that additional exercise is met with a decrease in resting metabolic rate.

Research has found that after a certain point, the total energy expenditure from exercise plateaus, as the body adapts to the increased activity.

The body's response to exercise and energy expenditure is heavily influenced by hormones, particularly insulin, which inhibits the burning of stored fat and is essential for the release of energy stores during fasting.

The Role of Insulin and Fasting in Weight Loss

Insulin levels play a crucial role in weight loss, as they affect the body's energy storage and expenditure.

High insulin levels can prevent the body from using fat stores for energy, leading to a reduction in metabolic rate.

On the other hand, intermittent fasting can help lower insulin levels, allowing the body to access and use stored calories, thus aiding in weight loss.

A study on time-restricted eating and calorie restriction showed that while the difference in weight loss was not statistically significant, the study may have been underpowered to fully capture the benefits of fasting.

The Significance of Time-Restricted Eating for Weight Loss

A study's conclusion that time-restricted eating has no benefits due to limited weight loss is flawed, as even small weight loss can significantly impact metabolic health.

The study's approach of comparing fixed factors fails to consider the root causes and benefits of time-restricted eating in reducing calorie intake.

Time-restricted eating has been shown to effectively reduce overall calorie consumption without conscious effort, making it a valuable tool for weight loss.

The Role of Hormones in Weight Management

Hunger and metabolic rate are the key determinants of weight gain and loss, controlled by hormones such as ghrelin, insulin, GLP-1, and nicotine.

Ghrelin, the hunger hormone, can be regulated through fasting, while insulin is shown to cause weight gain.

Hormonal agents, not just calorie control, play a significant role in weight management, as seen in the success of treatments affecting these hormones.

The Truth About Fasting and Metabolic Rate

Fasting for a few days actually increases the number of calories burned, contradicting the belief that it slows down the metabolic rate.

Studies show that fasting can help maintain lean mass and does not significantly predict an increase in eating disorders.

Time-restricted eating can be a simple and effective way to reduce calorie intake and allow for the hormones that promote body fat loss, in contrast to the standard advice of calorie counting.

Intermittent fasting promotes dietary consistency and habit-building by eliminating the need for willpower and simplifying calorie reduction.

It is a flexible, cost-free, and convenient approach that can be easily incorporated into any diet and allows for personalized adjustments.

The practice offers unparalleled options for weight loss and patient treatment, making it a powerful tool for improving health.