Instant Genius - Busting the biggest weight loss myths

Episode Date: July 3, 2025

Currently, 60 per cent of people in the UK are overweight or obese. It’s likely that many of us would like to drop a few pounds if possible but with so much information on diet and weight loss available separating facts from myths can be something of a minefield. In this episode, we speak to Prof Giles Yeo, a geneticist and obesity expert based at the University of Cambridge. He tells us exactly how our bodies extract calories from the food we eat, the real effect that exercise has on our weight, and how the reward pathways in our brains are linked to our appetites. To get the exclusive gift box from Shokz, order via this link: ⁠https://bit.ly/4kFt10l⁠ Learn more about your ad choices. Visit podcastchoices.com/adchoices

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Hello and welcome to Instant Genius, a bite-sized master class in podcast form. Every Monday and Friday, you'll hear world-leading scientists and experts talking about the most fascinating ideas in science and technology today. I'm Jason Goodyear, commissioning editor at BBC Science Focus. Currently, 60% of people in the UK are overweight or obese. It's likely that many of us would like to drop a few pounds if possible, but with so much information on diet and weight loss available, separating facts from myths can be something of a mindfield. In this episode, we speak to Professor Charles Yo, a geneticist and obesity expert

based at the University of Cambridge. He tells us exactly how our bodies extract calories from the food we eat, the real effect that exercise has on our weight, and how the reward pathways in our brains are linked to our appetites. So, Professor Charles Yo, welcome to the podcast. Thank you so much for having me, Jason. So today we're going to be talking all about weight loss. So many people watching will likely want to drop a few kilos if possible. So what's the current situation in the UK with our weight overall? So do you know what?

60% of people in this country are either overweight or have obesity. 60%. And if you just look at the obesity numbers, one in four people have obesity. We're just slightly behind the United States, which is roughly one in three people with obesity. A lot is the answer. So we're all different shapes and sizes due to many things like our genes, our lifestyles, etc. But how do we actually classify someone as being overweight?

Overweight or obese? So that's an interesting question. I think there are two ways of looking at it. There is just a pure weight thing. Now, if you're looking at just a weight, then we tend to not just use weight because obviously people come in different heights and what have you, but something. called BMI, body mass index, which is your weight and kilograms divided by your height and meter square. So if you use that particular metric, then being overweight, well, being normal

weight, quote unquote, is having a BMI between 20 and 25. Being overweight is between 25 and 30, and having obesity is above 30. So those are the numbers of just pure weight. The issue, obviously, is that doesn't take into account fat versus lean mass. It doesn't take into any number of different things. And I think more sophisticated, dare I say, nuance definition I think of overweight obesity is carrying too much fat that it begins to influence your health. So that was a very long answer, but I felt that it was probably needed just to get some nomenclature kind of sort of. Yeah. So do you think sort of body fat percentage is a better measure of this? Body fat percentage probably is a better measure. But then on top of the complexity of that,

where you put your fat is also important. So I think you probably want to do body fat percentage plus your waist to hip ratio. So the circumference of your waist over the circumference of your hip. And that then tells you sort of your body shape. And so where you're putting the fat. That I think is the most useful piece of information. So what the boundaries of that ratio then?

Do you know what? The boundaries or the ratio would differ between different people. But put simply, famously apple-shaped people, so people who tend to have larger tummies and more likely are men than women, although not exclusively, will have a higher chance of metabolic disease, of being ill for a given way.

People who are pear-shaped, so those are people who have bigger bums but smaller thums, who tend to be women, but not exclusively, tend to be healthier. So what happens there is if your waist-to-hip ratio is higher, then you are going to be at more metabolic risk. If it's lower, then you're going to be at left. metabolic risk, put simply.

So let's look into something that you've written about, like you wrote a book, why calories don't count. So a lot of people, when they're thinking about food and diet, the first thing they'll go to is calories. So what is a calorie? So a calorie is a unit of energy. It was originally, I mean, it was actually invented to calculate the amount of heat given off when dynamite went off.

Like seriously, that was the gunpowder went off. So it was used to measure by the French. in Napoleonic times, okay, to try, maybe slightly later, to try and measure, well, when it, when something went boom, okay, how much boom was it? And so the calorie was actually used for that initially. Then people began to actually begin to use the whole concept of the calorie within agriculture. They were beginning to use it in food and they wanted to know, oh, okay, well, if we fed, you know, cows or chickens or whatever, you know, X calories of food and then what came out the other side. They were trying to get sort of like using it as a, how efficient were animals at converting

food into a product. Okay. And then latterly, it has now been moved from animals sort of food to then human food. So that's the sort of history of the calorie and how it ended up being sort of labeled on the side of a packet food. Yeah, so we have them on packets food. But not all calories are equal, there's something called caloric availability. So can you explain that for us? The caloric availability is the amount of calories you can extract from a food versus the total amount of calories stuck in the food. I'll give you an example.

So if you had sugar, okay, like table sugar, sucrose. So one molecule of fructose, one molecule of glucose, one molecule of glucose. And if you had 100 calories of that, you get pretty close to 100 calories, probably 98 calories or so because it just needs one cut and we absorb it. Okay. And so that means that sugar is probably 98% calorically available. So that's probably one extreme. Now if we deal with the other extreme, sweet corn, corn on the cob. Now, if you had 100 calories of sweet corn and you were and then you looked in the loo the next day, it would be pretty clear you have absorbed nowhere close to 100 calories of sweet corn. But yet, if you actually take corn and then you desiccated, you

you turned it into a massa and then make a contortia, you make cornbread, whatever. Suddenly a far greater percentage of those calories are made available because of the processing of that corn. But yet, it's corn. And so that is why where the calories come from really matters because we eat, I guess the bottom line is we eat food and then our body has to work to extract the calories. And depending on what you're eating, your body has to work more. or less hard to extract the calories.

So let's stick with calories for a while then. But let's sort of change gears a little bit to nutrients. Okay. So you often hear people talking about something called empty calories, you know, nutritionally useless foods or drinks or substances. What do they mean by that? I don't like the term empty calories. I don't think it's a real thing because I think most food that we eat

will have some nutrients in them or some nutritional value, some more than others, I guess. I think what people, however, and what the public consider empty calories are foods that are calorically high, but nutritionally low. In shorthand, for nutritionally high, you were talking about nutritional density. This tends to be either protein, fiber, micronutrients, vitamins, you know, and iron, that kind of stuff. And if you can, you can have a food that is high, colorically, like you're eating just purely sugar, for example, but low in everything else. There's no protein and obviously in sugar. There's no fiber. There's nothing else in it. So that is an example of an empty calorie, quote unquote, it clearly isn't empty. But I think that is

what the term means. It means high calorie food, low nutrition density. So you mentioned their protein. So we eat protein, carbohydrates, fats. But we process them differently, don't we? So can you explain that? You know, what happens in our bodies? So these are called macronutrients and we'll take the two easiest macronutrients for our body to process and those are going to be fat and carbs. Now fat and carbs are made exclusively

from three atoms, carbon, hydrogen and oxygen, but sort of in different configurations. So therefore our body has an easier time to sort of deal with it because when you eat food, there's only two things you can do with food. You either store the food or you burn the food. That's it. You can't magic it out. You can't sweat it out.

You can't detox yourself, right? Those are two options. And so if you only have those three atoms, they're easier to deal with. The problem with protein is protein is primarily formed of carbon hydrogen and oxygen, but also a lot of nitrogen. So about 16% on average, depending on what we're talking about, of protein that's going to be nitrogen. Because you either use it or store it,

if you actually have to store a protein, there is no inert store of protein in our body. There is for sugar, which is glycogen. There is for fat, it's fat. There isn't for protein. All the protein in our body is active. It's either there for this. It's there for repair.

And if you eat too much, it has to be stored as fat. But if it's going to be stored as fat, the nitrogen needs to be taken out. This is a lot of words. But it's also a lot of energy. And so for every hundred, and you wee out the nitrogen as urea, uric acid. This is what come up.

Okay, this is what makes your wee smells like wee. And what happens is for every 100 calories of protein, imagine if you ate 100 pure calories of protein, only 70 calories are usable to us. 30 calories is given off as heat, as energy, just to kind of sort the protein out. You might wonder what the other macronutrients then do. Well, fat, which everyone is always the most interested in,

sadly is pretty close to 100%, because fat is nutritionally dense, very, very calorically dense. and so 100 calories of fat is 100 calories of fat. Sugar, 98. Now, carbohydrates, complex carbohydrates, now it depends whether we're talking about something with fibers, the whole meal, or without. So if you actually take a look at just white bread or white pasta, you know, like refined pasta, okay, then we're probably looking at 95% available. So 5% of the calories from white starches are going to be used to sort of sort it out. 95% available. Whereas if you eat something home meal, if you have whole meal bread, if you have quinoa, if you have anything with the husk on, then suddenly you decrease the availability to 90%. So it takes about 10% of the calories in order to sort it out. Incidentally, so calories on a whole are about 5 to 10% wrong, quote unquote, because everything I just told you, none of it is reflected on

the side of the package of food. So the calories that are there are just the calories in the food. And they do not reflect the amount of energy, the cost of business. It does not reflect the amount of energy it takes to actually process and metabolize and actually sorts out the macronutres. So kind of like the overarching message of that is not all calories are equal. They are once they are in you as a little proof of energy. But in the presence of food, as you are kind of sorting out your food, your meal and digestion and metabolism, it's not equal. So the moment it's metabolized in your mitochondrial, and ready to go, they're equal. But there's so many steps to there.

Yeah. And that's why they're not equal. So lots of people go on calorie-controlled diets. You know, is that a good idea? It is if you're doing it, well, okay, it is if you're doing it in a balanced fashion. So say, for example, you have actually quite a balanced diet. You just eat too much of a balanced diet.

And hence, and hence you have obesity or overweight. And if you are then doing a calorie, counting that by saying that, well, normally I have whatever, 2,000 or 2,500 calories a day, I'm now going to eat exactly what I eat, but I'm now going to cut it by 20%. Yes, then it will work. But that's not how we work, right? Because if suddenly someone says in some diet, oh, you have to limit your lunch today to 400 calories, say, okay? You go and you might look at the back back of the pack and suddenly says, oh, look at it, look, this chocolate bar is only 400 calories. I know this is a slightly ridiculous example. But,

Clearly there's a difference between having 400 calories of a salad or yogurt or a chocolate bar. So that is, I think, where the calorie counting falls down. So if you can do it in a balanced way, and that is why a big reason why these energy replacement shakes are popular. Because they are nutritionally balanced. They typically come in 400 calorie sort of serving sizes. And so you may have two. If you're trying to do a low calorie, it typically is 800 calories a day. for whatever reason. And so you have two or these shakes, one for lunch, one for dinner. And that's fine.

Of course you're going to lose weight and you're going to lose it relatively okay, right, in terms of that. But a lot of people just blindly count the calories without considering the nutritional content of the food they're eating. And that is the issue. So what can the consequences of that be? You know, if I'm thinking, well, I want to eat for 800 calories a day and I'm just having a fizzy drink and a chocolate bar, what's going to happen to me? you need enough of everything. This is the problem, right? And so how much is enough?

How much is enough? It depends on what you're doing. But ultimately, we do need balance because we need fat and we need carbohydrates. But most importantly, and those two are very easy to come by in most foods, okay? But most importantly, we need protein. And the reason why we need to eat enough protein, back to a point I made earlier, is we do not store protein. Our protein is there for repair, for growth, for use. And so we need to eat enough protein to make sure we can continue to do that.

Because fat within ourselves anyway, obviously everything ends up as fat at some point as storage. So the problem with having a poor quality diet, and this is why it's useful to use protein as a shorthand. You can't have too much protein, but it's useful as a shorthand because that is the one nutrients we need to eat and we need to eat enough of. So the problem with having a fizzy drink, it has got no protein in it at all. That is where the problem will come down to protein. So what happens if I have too much protein? The gym bros hate me when I say this because you can't have too much. You can have too much protein.

And they're saying, well, I have, you know, whatever, some, so and so, whatever, however they count it. But they're lifting. Or an Olympic athlete or a professional athlete. They are damaging their muscles through using it so much. They need a buttload of protein. Now, mere mortals like us, you don't need no protein shake. Like, seriously. So the problem with having too much protein when you're not using it is you have to store it, right?

Which means that there's all the process of having to deal with nitrogen. So you put stress actually on your kidneys and probably also your liver, not because these are toxic, but because you have to process it. It's got to get from your blood into your wee, you know. And if you suddenly have a lot, a lot, a lot of nitrogen coming through the system, more than you might naturally have if you're having a balanced diet. You put stress on your organs that sort out extracting the nitrogen from your body. That's the primary reason. Wishing you could be there live for the big game, soaking up the atmosphere in the crowd. But too often, life gets busy or the price holds you back.

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intermittent in the famous 5-2 so where for five days in a given week you eat normally and two days you fast or eat very, very low calories. But it also now includes what we call time-restricted feeding. And so some people instead, 16-8, for example, where I only eat

between noon and 8pm every day or something. Okay, so that there is a period of the 24-hour period of the day where you don't actually eat. The principle, so first of all, they tend to be quite effective as a weight loss tool. They are effective because there are a useful strategy to get you to eat less. So you do end up with an energy, a caloric deficit. Hence, you end up losing weight.

The question to ask is whether or not there is any additional metabolic benefits beyond simply the fact that you've eaten less. It's surprisingly difficult to answer. I mean, from animal studies, because obviously that's controlled, you can do this, you can that. I think there is a subtle metabolic benefit to it. Humans, it's very difficult to do dietary studies in humans because the goal standard for any kind of study is a randomized control trial. And blind it, if possible. The problem with a diet is you can't randomize it. You certainly can't blind it, okay, because you're either fasting or you're not.

And so it tends to be observational. But I wouldn't be surprised if there was a subtle metabolic benefit. The underlying principles are this. If you fast either for a longer period of time over a couple of days or if you make sure that between, that you only eat during a certain period today, the store of energy that goes the quickest is glycogen. So glycogen, this is where you store your carbohydrates. We don't store a great deal of carbohydrates in our body.

We store 100 to 150,000 calories with a fat in our body because that's our primary energy stores. We only keep about two to two and a half thousand calories of carbohydrates in our body, largely within our liver and muscles and a little bit floating around our blood as glucose. We burn through that pretty quickly because carbohydrates are the easiest to get ATP from.

They're not very dense, but they're very, very responsive. So we tend to go through that first. And so what happens is when you do fasting, you sort of get through a lot of your glycogen, stores, getting your body to try and go into burning fat. So therefore, producing ketones. Okay, so ultimately that's what happens. If you burn carbohydrates, you don't produce ketones. If you burn fat, you produce ketones. This is the principle of the keto diet? Yes. It's the principle of the fasting diet. Same things, because you go through your glycogen,

you produce ketones. Ketones naturally make you feel fuller. Sorry, that was another very long answer. But that ultimately it is. There is an overlap between the fasting approaches, and something like keto because you force your body, or at least you encourage your body to burn more fat, producing ketones. That's the underlying principle. So just going back to something that you said there, ATP, so what role does that play in our energy systems? It's very important, isn't it?

It is very important. It is, I mean, it's how we actually, let's go back to a calorie, if we can briefly. So what's the calorie? So if we actually define a calorie, a unit of heat, a calorie, a food calorie, A food calorie is the amount of energy it takes to raise one liter of water, one degree Celsius at sea level. And so how many calories does it take to boil a liter of water? 100 calories because you need to go from zero to 100. That's assuming from freezing.

Now we eat on average, what, say, let's say 2,000. 2,000 calories a day, 2,500, 500 calories a day. So that is enough energy in us to boil 20 liters of water. order from freezing. If all the food is poof, just just burnt burnt off like that. There's only six liters of blood in us. Okay, so why are we not boiling? And the reason behind that is because we metabolize our food. And what we do is we take that 2,000 calories and divide it up amongst these little units of energy called ATP. So ATP adenosine triphosphate, three phosphates. And the key thing is the three phosphates, because it takes a lot of energy to sort of put those

phosphates together chemically. And first law of thermodynamics means that you don't throw away energy. It's stored. And so those phosphates have a lot of energy. And so if you actually break off one of the phosphate groups so that you end up from adenosine triphosphate to adenosine diphosphate to, okay, so one poof of energy, one phosphate group goes off. There's a little poof of energy that gives off. And that, we then use that in order to do it. And what you do is you then cycle. So metabolism is burning is going from ATP to ADP. Metabolism then puts the phosphate group back onto the ADP to make it ATP again. And so we have here probably someone average size between me and you three to four grams of ATP in our body at any one time.

But we cycle through our body weight of ATP every day in order to move. So those three four grams are recycled ATP, ADP, ADP, ATP, ADP, B, B, B, B, B. And those 2,000 calories are divided up amongst the 75 kilos, okay, of ATP-ADP cycling. That's what the ATP is. It's sort of like a very rapidly charging and discharging battery. So coming off the back of that, let's talk about exercise. Yep. So a lot of people that want to drop a few kilos, I think, well, you know, the best way to do that is, yeah, I'll exercise.

You know, how does that work? Well, exercise. Just be crystal clear here. We don't want to give the wrong message. There is nothing better for you in the whole damn world than exercise. If you could bottle it, we should bottle it. It's good for your mental health. It's good for your physical.

It's good for everything except weight loss. And that's the irony. And it's one of these things where, and whenever I say this, people think I'm anti-physics. I am not antiphysics. Clearly, if you take it to, if you look at elite athletes, particularly endurance long-distance athlete, Moe Farrah, you know, the tour de front cyclist. So clearly, they can exercise enough to lose weight and eat like a horse.

Okay, they eat whatever, five, 10,000 calories a day in order to do it. Most of us are not doing that. And so what we tend to do is two problems is when we, first of all, when we exercise, we do obviously burn through calories, but we get hungry. Anyone who's done any level of exercise will know, maybe not immediately after, depending on what you're doing. But at the end of the day, you're going, oh, I'm famished, I could actually eat. and we tend to sort of overestimate how many calories we burnt during exercise.

These garmany things tell you, or what have you, and you think, whoa, I exercise today, I can eat this, I can guilt-free have this muffin or what have you, and you end up eating more than you need. So exercise is actually not particularly good at all. For everything else it is, not good for weight loss. It is, however, good for weight maintenance. So once you've lost the weight, which you need to tackle the food intake for, and you've reached some plateau or some target weight you want to do,

then actually exercise is quite a useful way to help maintain it. Because as you lose weight, the smaller you become, the lower your metabolic rate is. This is the weird thing, right? And it's not weird. A mini will always have a lower fuel use that a rate drover. That's always the case. So as you lose weight, your metabolism drops, trying to bring yourself back up to the weight you were before.

So exercise, when you have. exercise, your energy expenditure, your metabolism, goes up temporary. So when you're exercising, you're obviously using ATP, you're giving off heat, you're doing all the things. And then when you stop, it then comes back down again. So once you actually reached your target weight, then you can increase your physical activity. It doesn't have to be going to the gym, gardening, walking your dog, whatever. Again, during that stage, you are temporarily raising your metabolic rate and sort of mitigating against your brain, dragging your body weight back up to what it was before. So sticking with metabolic rates, is it true that the sort of fitter that you get,

the less you burn at resting? I think the difference is between a super fit, a professional athlete, is they're able to sort of at rest, they're very efficient, but the moment they go, the moment they're doing whatever, they actually go up. So I think it's that, and then their heart rate drops again very, very, very quickly the moment they stop exercising. It's one of the big measures of fitness, actually. How quickly does your heart rate go from whatever it is you were doing back down to your base heart rate after you stop actually doing something? And the less fit you are, the longer that takes.

I haven't considered it before as a low energy expenditure before being fit. So I need to think about that. But for sure, if you're fit, you are able to switch between states and get to a higher metabolic rate, exercise metabolic rate, far quicker. So let's have a look at appetite then. So this is really, you know, something that seems like thrown around everywhere. It's actually more complicated than you'd think. Like, do people sometimes really have bigger appetites than others?

Yes, they do. So appetite is an interesting term. It's quite a complex term because it's an integrative term. It integrates at least, I'll go, at least sort of three concepts, feelings within us. So it includes hunger. We understand what hunger is. It includes how full you feel. Completely different circuit, completely different part of the brain,

hungry and fullness. And it includes how nice you feel when you eat, the reward pathways of the brain. They're like a triangle with, you know, of all three bits. with appetite in the middle. And you can change how nice you feel about the food, how full are you, and how hungry you are, because they all speak to each other. And so appetite sits in the middle. And so ultimately, if we look at the genetics of this, why some people feel more hungry or have a higher appetite than others, it can be because of any three reasons, and they're not mutually exclusive. Some people feel more hungry. Some people take more food to get filled up. Some people need to eat more

to get that same high from food, quote unquote, okay? But all of us have a mix of that. And so ultimately, if you have a higher appetite for any one of those three reasons, you end up finding it more difficult to say no to food than others. And so why some people are larger than others? So how about sort of, you know, mental conditions such as stress? Because you hear people saying that they're stress eaters. And I think like some people are stress, not starves, but, you know, their appetite plummets when they're stressed.

So do we know anything about that? So, I mean, you can probably divide the world into two broadly for people who stress eat. Or you can even use the term emotional eat. So in other words, their stress. And so therefore they eat in order to try and mitigate against the unpleasantness of being stressed. And people who lose their appetite when they're stress. I mean, my wife is that latter. You got to distinguish, incidentally, between tightness.

stress and everyone reacts to tiger stress in exactly the same way. Run like hell, you're not interested in food. Okay? So that's that is an acute stress, the fight or flight. Now, we're talking chronic stress, work stress, exam stress. That's kind of stress. And then you have this interesting. It's the same hormone.

Cortisol goes up. My wife says, ah, no appetite. Okay, I won't eat. You know, whereas I do eat when I get stressed. My response tends to be, you know, putting my face into a bowl of noodles, for example. Why? Mechanistically, we don't actually know. Okay. However, I think the reason it happens, mechanistically, we don't know, is being stressed is unpleasant. And as all living creatures do, if we are feeling unpleasant, we want to remove that unpleasant feeling. And so we use different strategies to sort of feel pleasant. I mean, for some people, that's eating. Eating to a lot of people is pleasant. And so you eat in order to try and feel pleasant to counteract that unpleasantness of being stressed. Other people use drugs of abuse.

Other people drink. Other people go run marathons. Other people bungee jump, right? And so I think there are different ways of making yourself feel more pleasant in a stressful situation. And some people do it with food. The mechanisms, neurons, the circuits, still not known. let's move on to something else thing, which is age. I don't think you'll mind me saying we're both middle-aged.

We are. And, you know, this term middle-aged spread, is that a real thing, or is it just an excuse? So, you know, this is a more complex question to answer than you might actually imagine. Because I think I would probably have given you a different answer if you'd asked me five years ago, actually. Oh, right. So let me give you the wrong, not the wrong answer. the less right answer first. And I think the less right answer

is that we are born and then we have very, very high metabolic rates. Then we hit 18. You know, that's probably our peak. Okay. And then it sort of stays and then around the, what we call middle age, 40 to 50, suddenly it begins to dip and drop.

And that used to be the explanation for one of the explanations for middle age bread. Now some guy, a colleague of mine actually, John Speakman, so he's based up Aberdeen, and also he has a lab in Beijing, where he's shown that actually, for any given

amount of muscle you have, lean mass, okay, because that primarily drives your metabolic rate. Actually, you don't drop metabolic rate till you reach your mid-60s and older. Okay, so he's done, he's done the sum. So this is new. This is actually new, new, relatively new science.

Why do we get this middle-aged spread? I think for a number of different reasons. So first of all, On average, the older you get, the richer you get, not so you're rich, but you've been to accumulate either wealth, staff, you do different jobs, you tend to be set on your backside more in your job. So you do get a tapering of physical activity as you get older. That is just on average. That's the situation. As a result, you begin to lose muscle mass.

And as a result of that, your metabolic rate drops, but not if you divide it by the muscle that you actually have already. Do you see what I'm saying? So you're losing muscle mass, and hence your absolute metabolic rate is dropping, but not per gram of muscle that you actually have. Problem number one, and I think that's probably the key driver. The second key driver is less biological, but what happens is you get richer. As you get older, you buy better food, you buy richer food, you eat in different places, and what happens is you probably end up eating a bit more.

and you mix that with the fact that you are more sedentary because of your job, because you're older, your muscle mass dropping, and I think that is the explanation for middle-aged bread. Now, clearly, that trajectory is going to differ between you and me and someone else. It's going to differ between a male and a female, and it's going to differ between ethnicities. But as a concept, I think that's the reason why. So let's have a look at a new phenomenon then, which is these weight loss, So, you know, what are they, do they work? Are they safe? Excellent question. So, I mean, I think the most famous one is Ozmpic, but others are available now Monjaro.

And what all of these new class of drugs are are modified versions of naturally produced gut hormones. So your brain needs to know, broadly speaking, two pieces of information to influence your food and say. You need to know how much fat you have. and it needs to know that because those are your long-term energy stores, okay, how long you'd last without food. So it needs to know that, hormonal. But it also needs to know what you're currently eating and what you have just eaten, okay, short-term energy stores.

And these are going to come from your gut, your stomach and your gut. And all of these signals are hormonal. And so two of these hormones are something called GLP-1 and JIP, GIP. And both of these go up after you eat, okay, the natural hormones. These are now not the drugs, the natural hormones. These natural hormones, GLP 1 and GIP, are called incritons, and they call incritons because they enhance the secretion of insulin for every given gram of food that you might actually eat.

So that's why they're called incritons, and that's why these drugs, which are based on them, were originally diabetes drugs. The second thing which they do is they signal to the brain to make you feel full, and that's why they're used as obesity drugs. the magic power of what the pharmaceutical companies have done is they have sort of decorated, molecularly decorated these natural hormones to keep them in the blood for longer.

Because the half-life of GLP-1, as it goes up, is two minutes. So typically, it's designed to do this. Okay, as you eat, it does this, whatever. And then there is an enzyme in your body called DPP4. It doesn't matter, but it sort of chops it up. So as, if you inject yourself with native hormones, it's not a good drug at all. because what happens is it just gets destroyed. So these drugs are modified versions of these hormones

that now, obviously, I mean, originally they were once daily injections, but now with those EZempec and Mungaro, they have now become once weekly injections. And actually, there are the ones coming down the line from other companies, which are going to be ones monthly injections. And so because of the way they have molecularly changed the molecule, it's still the hormone, GLP 1 or JIP, but because of the molecular modifications, they stick around the blood for longer, therefore helping with diabetes and helping with obesity.

So is there any danger to using these? Do we know? Danger probably yes and no. So let's go with that. So the class of drugs actually, Incretin class of drugs, as we call them, happened in use for two decades. First, that's the once, well, actually first that's twice daily, then once daily, then once weekly. And so they've been around for a while and we would have thought

and millions of people have therefore been on them that if the class in of itself is dangerous we would have seen them. Dangerous in terms of as a toxic or addictive or something like that. None of this is true. There are, however, side effects when you're actually on these drugs

and they tend to involve the gastrointestinal tract, right, your gut, because that's where the hormones are come from. these hormones, broadly speaking, the gut hormones, help to regulate the flow of food through the tube, the food to poop tube, right? Speed and anything else. So, for example, if you had a bad prawn, okay,

and had food poisoning, and then you ran to the loo explosively, what happens there is because gut hormones, and particularly GLP 1 has spiked. It really goes pung and you go, blah, okay, it comes out the other side. Hence, the most common side effects of these drugs is, because you can imagine, I know people who are slightly more puky than others, you know, I feel puky. So if you are more sensitive to the drugs, then you may very well feel nausea when you actually take it.

The other problem is the other end. Okay, it also regulates the right speed or it can be sometimes too fast or sometimes too slow, the other end. Okay. And so hence, those are the other two common side effects, either diarrhea or constipation, depending on where you sit on the distribution of speed of flow. those that are a relatively common side effects. But the vast majority of people who started the trials of these drugs completed the trials. So it can't have been that bad.

And I guess more and more people are now taking them. So are they dangerous? They're not amphetamines. You're not taking cocaine. All right. So then they're a natural hormone. Where I think I would cost them as dangerous is here. I think these drugs are very useful because they're powerful and they work.

They're dangerous because they're powerful and they'll work for pretty much anybody. They'll work for a 350-pound man looking to lose 100 pounds and that's great. They'll also work for a 16-year-old girl who's 75 pounds. And that's not good. Okay. And so these are drugs. I think they should be used as a drug, which means that it should be used to treat obesity and the associate conditions because you are ill.

I do not think they should be used as a cosmetic tool. And I think ultimately, why do we want to lose weight? There are cosmetic reasons, I'm sure. But I think these drugs should be used to treat the illness. And so that's why they're dangerous. Because there is no, if you're this weight, they suddenly won't work. So by way of summary then, say somebody does want to lose a couple of kilos, what's the best way to go about it, you know, the healthiest way?

In moderation is the real answer. Let me get, because I think that if I had a really good, good answer, I wouldn't be here talking to you. No, it's not true. I think, I think, I think ultimately, I think this is the real. The answer is you have to find a way that suits you. So, so I think everyone is, okay, different strokes, different folks type of thing, but it's true. Okay. So I think most people say that 95% of diets don't work. And that's not true. 95% of diets you can't stick to. That's the problem. All right. Now, the drugs have come in and have, they have very, useful because they remove the hunger aspect of it, which means that you can stick to whatever

is you're doing a lot easier. But leaving aside the drugs just for two seconds, if you're doing it in a behavioral perspective, you want to get on a diet, you want to do something, then you can't just do the diet and stop because what happens is the weight would just come flooding back in again. So you need to, if you want to do it using by changing your diet, then you need to change your diet and find something moderate. Because by definition, if you pick something extreme, you won't stick to it. So moderately. Now, they're clear, like me.

My wife thinks I should lose a stone, stone and a half. She's right. Don't judge me. And no one is going to give me a drug. But there are going to be situations, actually, where you are either very, very ill for a given weight or really have quite severe obesity for any number of different reasons. And there, that is when the drugs, and at the most severe end,

probably surgery comes in, but that's very, very extreme. But that's where the drugs come in. So I think if you want to lose a couple of kilos, the likelihood is behavior will probably sort of help, but then you need to come up with a strategy to try and stick to it. If you need to lose 10 kilos, okay, which is obviously a lot of weight, there may be something like a drug in conjunction with a diet. Because remember, these drugs just make you feel full.

They'll make you eat less of whatever it was you were eating. So in other words, if you were eating chips and Oreos, then all it will do is make you eat less chips and Oreos. And so hence, that's not a healthy diet. So you do need to also have a healthy diet. So there is a spectrum. The more severe your obesity and or illness, then I think you need to go away from simply trying behavior,

because otherwise behavior would have worked previously, to maybe having some pharmaceutical help. Thank you for listening to this episode. episode of Instant Genius brought to you from the team behind BBC Science Focus. That was Professor Giles Yo. If you liked what you just heard, then please do consider subscribing to Incent Genius on your preferred podcast platform. If you'd like to see our guests and hosts in person,

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