ZOE Science & Nutrition - Lose weight by controlling these hormones | Bariatric surgeon Dr. Andrew Jenkinson

Episode Date: October 9, 2025

🥑 Make smarter food choices. Become a member at http://zoe.com  Have you ever wondered why you can lose weight on a diet, only for it to come back with a vengeance? If you’ve blamed yourself for a lack of willpower, our guest today argues you’ve been misled. The old mantra of “eat less, move more” is failing us, and the key to understanding why lies deep within our biology. In this episode, Jonathan is joined by Dr. Andrew Jenkinson, a bariatric surgeon and author with decades of experience in the science of metabolism. Dr. Jenkinson dismantles the calorie-counting myth and explains the powerful biological system that controls our weight: the "set point." He reveals how our modern diet and lifestyle have broken this system, but also provides a clear, science-backed path to fixing it. Dr. Andrew Jenkinson is a consultant bariatric surgeon and the author of Why We Eat (Too Much): The New Science of Appetite. In this episode, you’ll learn: Why the idea that weight loss is simply about willpower is a damaging myth. The science of the "weight set point" and how your brain fights to keep you at a certain weight. How your metabolism acts like a "dimmer switch," slowing down to prevent weight loss when you diet. The crucial role of hormones like leptin and insulin, and why our modern diet causes "leptin resistance" — the reason your brain can’t tell it’s full. How yo-yo dieting can actually raise your set point, making you heavier in the long run. A practical, step-by-step plan to lower your set point by changing what you eat, not just how much. The truth about new weight-loss drugs like Ozempic and their long-term effects. How managing stress and improving sleep can be as important as your diet for sustainable weight management 🌱 Try our new plant based wholefood supplement - Daily30: https://zoe.com/daily30?utm_medium=zoe_podcast&utm_source=podcast_platform&utm_campaign=d30 *Naturally high in copper which contributes to normal energy yielding metabolism and the normal function of the immune system Follow ZOE on Instagram |  https://www.instagram.com/zoe/ Timecodes 00:00 Introduction 00:20 Is gaining weight as we age inevitable? 01:38 Why ‘eat less, move more’ is a myth 03:53 Is your weight predetermined by your genes? 06:36 How your mother's experience in the womb can alter your dna 10:35 Why most diets are doomed to fail in the long term 12:16 Your brain has a weight 'set point' it tries to defend 15:27 The 'weight anchor': your body's powerful defence against weight loss 17:22 The reason you often end up heavier after a diet 19:00 A shocking study: yo-yo dieting made mice fatter than a junk food diet 21:35 The 'joker in the pack' controlling 70% of your energy burn 23:12 Your body has a hidden metabolic 'dimmer switch' 27:53 The mystery of the missing calories 32:35 Why dieting can actually raise your weight set point 34:31 The master hormone that tells your brain when you're full 36:08 The hidden reason your brain can't tell you're full 37:35 Why feeling hungry and lazy are symptoms, not causes, of obesity 39:00 The 'broken gas tank meter' analogy for weight gain 41:26 Step 1 for resetting your weight: the 30-day challenge 42:07 Why you need to stop snacking between meals 43:50 What is mindful eating and why does it matter? 46:22 Can time-restricted eating lower your set point? 48:37 The truth about new weight loss drugs like ozempic 50:28 The surprising impact of stress and sleep on your weight 51:42 The single most important thing to understand about weight loss 📚Books by our ZOE Scientists The Food For Life Cookbook | https://amzn.to/4amfIMX Every Body Should Know This by Dr Federica Amati | https://amzn.to/4blJsLg Food For Life by Prof. Tim Spector | https://amzn.to/4amZinu Free resources from ZOE:Live Healthier: Top 10 Tips From ZOE Science & Nutrition |  https://zoe.com/freeguide Gut Guide - For a Healthier Microbiome in Weeks | https://zoe.com/gutguide

Welcome to Zoe, Science and Nutrition, where world-leading scientists explain how their research can improve your health. Dr. Andrew Jenkinson is a highly respected bariatric surgeon, an international authority on weight regulation and metabolism, and the best-selling author of Why We Eat Too Much. With over 100 scientific publications and two decades of experience treating obesity, His insights combine cutting-edge science with deep clinical expertise. Andrew, thank you for joining me today. It's a pleasure, Jonathan. We like to kick off our show here at Zoe with a rapid-fire Q&A with questions that come from our listeners. Are you willing to give it a go?

Of course. And we have some quite strict rules. We need you to say yes or no, or if you have to, a one-sentence answer. Is gaining weight as we age in? inevitable? No. For most people, will calorie counting work for long-term weight loss? No. Can our hormones cause us to overeat? Yes. Should obesity be considered a disease? Yes. If we aren't living with obesity, could many of us lose weight and keep it off without drugs? Definitely. Does your metabolism slow down when you lose weight? Yes.

And finally, what's the most common myth about obesity that you hear? The losing weight is all about calories. Well, I can't wait to get into this. And we have discussed weight loss on the podcast before, but it's still one of our most requested topic from listeners, which tells you how much we all feel that it's really important to us as individuals. Many of us are fighting with it, even if, you know, in fact, we aren't viewing ourselves as overweight. and we're all desperate, I think, to understand what's going on inside our bodies and how to make lasting changes. When I was brought up, I was told that weight gain was all about willpower.

So it was like, eat less, move more, and the problem is solved. What does the latest science say about that? The popular opinion is that, yeah, it is all about willpower. It still is, you know, this is the popular opinion. And this is the opinion amongst a lot of doctors and, you know, politicians and, you know, policy leaders, which is a big problem. The sort of myth that it's all about the calories is, you know, when you look at the very, very basics of thermodynamics, i.e. how big an object is, how much energy it stores, it's sort

of, it chimes, it's okay, the first law of thermodynamics, energy in minus energy out equals energy stored, but it's a lot more complicated than that. We need to take into account negative feedback systems and what we call in medical terminology homeostasis, so the body trying to keep things on an even keel. Now, I think I might be a little bit older than you, but when I was at school, they used to be probably in, no, in each year, one pupil living with obesity, really big, struggling, et cetera, et cetera. Now, when I took my daughters to look around secondary school a few years ago, it's now about a third of those children are living with obesity. So we've had a massive change over the last, you know, 30 years or so.

And the question is, what's caused that? Is that a sudden lack of willpower amongst that population? Is the food suddenly so much tastier, it's got us, it's got us addicted? These are the questions we've got to ask about, you know, why suddenly the population is really struggling with obesity and its consequences. I guess when I was growing up, I think, just as you described, in the schools I was in, there were very few. children living with obesity, maybe one or two in a year. And I had thought this was all about

genes. And I was also growing up in the period where we were being told that sort of genetics explain everything. How much are genes the answer to what's going on? Well, you know, those children living with obesity, you know, when we were children, they were the extreme because, you know, the food wasn't quite as bad then. Probably if you visited their family, their family would be, you know, struggling with their weight as well. But when you look at the actual figures the risk of developing obesity from a genetic standpoint. It's about a 70% risk. Now, you have to have the genetic predisposition and the environmental, the food and the stress culture together to actually trigger the obesity. So, you know, if you have a population that's living

and eating home-prepared natural foods from their local area without any processed foods, even those people with the obesity genes aren't going to become obese. However, when you transfer them to a culture with Western food or the Western food comes to their culture, that triggers that time bomb, as it were. And we know this from really, really eloquent identical twin experiments. So there are a number of experiments around the world where they took identical twins that have been separated at birth, because whatever family problems, and bought up in different households. And then they looked at them as they were adults, and they found a correct. correlation within 10% of their weight. So one may have been in a pretty healthy eating household and one may be put into a terrible eating household. It didn't matter. Within 30 years, their weight

was within 10% whether they're from a naturally slim family or a family that suffers with their weight. Obviously, those families were still in the same country, so they had a similar food environment. But there's definitely a 70% correlation genetically. I think you're saying that 70% of what explains your weight gain is your genes, but you've also said, hang on a minute, 30 years ago, only one kid in 100 might end up with obesity, and you're saying now it's a third, but the genes haven't changed. Yeah, but it's the genes plus the food and stress culture that we've got nowadays. So 30, 40 years ago, the abysogenic genes weren't triggered, as it were.

And if you put a population into an environment where there isn't processed foods and people eat natural home-prepared foods and don't snack and things, those obese genes aren't triggered. You know, when I was at school a long time ago, the food culture was much different. Got it. So I think you're saying that if I'm eating really terrible food, how I respond to that, my genes are going to have a lot of influence on it.

But on the other hand, if I'm eating the sort of food that maybe our grandparents ate, then I'm probably not going to be a beast despite having the same genes. Exactly, yeah. Now, you just mentioned epigenetics, and I think you might be talking about something in the book that I found fascinating, where you're talking about this Dutch famine study. Yes. Could you tell us a bit about that and also explain what epigenetics is? Yeah, I think it's absolutely fascinating. So we have a DNA template, half from our mothers and half from our fathers, and that's our phenotype, you know, whether we've got blue eyes, we're tall, you know, we have obisogenic tendencies or whatever.

But there is a lot of emerging interest in this field of epigenetics where that DNA can be altered within the womb in response to a predicted future environment. And various different genes are turned on and off by a process called methylation. So a chemical process actually changes the way that your body works. And as I say, this is something that occurs in the womb in response to what the current environment of the outside world is

in relation to what the baby is sensing. And a really interesting study that sort of highlighted the importance of this to our health was the Dutch famine study. So this is a study actually that was conducted in 1975. But it looked at the offspring of children who were born to women who suffered in the 1944 famine in the Second World War in Holland. So to put into the context, this was a time when the German army were retreating. There was all the counterattacks and attacks. the canals were frozen, food couldn't get in, and people were on 500 calories of food a day for about nine months. And they looked at the women that were in their first and second trimester

of pregnancy during this time, starving during pregnancy. And they looked at their offspring 30 years later and compared them to their offspring when they weren't in a famine. And they found that that offspring were much more likely to be seriously obese and centrally obese and diabetic. And now you think, well, why is that? So the changes in the genes to prepare those fetuses, those babies for a predicted environment. The predicted environment was famine. So if you epigenetically have had your genes manipulated so that you become a more hungry, a more food-seeking baby, then actually you're going to do better. If you are born into a famine, you have a preferable survival advantage. However, if you're

gamble that the environment is going to be the environment that your mother was in doesn't pay off, And actually, it's an abundant environment. You're going to struggle. The fetus is there. Genes are set anyway from their, from your mother and father. Your DNA is normal. But actually, while the fetus is in the womb, it's sort of getting this information about, like, wow, I'm not getting enough, you know, calories as I'm growing. So the outside world is going to be tough.

There's going to be famine. So I need to be adapted to try and grab as many calories as I can. So that would be great if actually you spend the next 50 years living in an environment of famine. But actually then you're in Holland. There's lots of food after because the war is over. And so you tend to put on a lot more weight than like your brothers and sisters because you're sort of preset. It's changing your behavior. The genes, the genetic makeup actually changes during fetal growth.

An eloquent way that it's been described before is the fetus is marinating in preparation for the environment that it predicts. That's amazing. And I guess that's a great counter example to the idea that weight gain is simply about willpower because this is nothing to do with these children having different willpower than their brothers and sisters. This is the marination as they've been grown. Yeah. So, Andrew, why don't diets work for long-term weight loss for most people? I'm glad you said long-term because, you know, they do work short-term. I'm from a family that's naturally fairly slim, so we never worry about diet or, you know, pretty much healthy eating when we were younger. I obviously did surgery, went through my training, and ended up as a bariatric surgeon, which is really interesting surgery on the stomach.

But the consequence was that, you know, all of my patients were living with obesity. And I, like actually, most doctors, didn't know a great deal about it, apart from, you know, go on a diet and go to the gym, you know, pull yourself together. But the really interesting thing was that as I got more experienced of chatting to, you know, hundreds of patients, the stories were really, really similar. So they all said, yeah, I can lose weight on a diet. I've been doing it for decades, you know, I've lost a ton on a diet if you count up through the various different diets, but they always put it back on and more. You know, you'd have

hundreds of people saying almost identical things. I think it's in my genes. I think it's like because I'm from a family that live with obesity. I think my metabolism's low. I compare what I eat to my flatmate. My flatmate ate twice as much as me, but, you know, they have no problem. So all of these comments really stimulated my interest in, you know, weight regulation and metabolism and thinking, actually, maybe our understanding of weight regulation is flawed, and these people actually are correct. Well, they're not making it up. That is their experience, you know. There was no collusion between them. So this is when I got really, really interested in the causes of why people struggle so much with losing weight through diets. And I came across a lecture where the

weight set point was mentioned. This was many years ago, maybe 20 years ago, this idea that every individual has got their own weight setting where the part of the brain that controls our appetites and metabolism and basically our weight, the hypothalamus, will try and fix your weight at that particular point. Now, that's good if your individual weight set point is in a healthy level, but actually, if it's been set at an overweight or an obese level, it's a real problem. Because your brain's going to defend that set point. You know, so you can lose 20 pounds, five kilograms, whatever, on a diet, but you're going to put it back on because these subconscious urges that are driving us

were almost like automatoms, you know. Not much of it is conscious. We can try and override it, but the hypothalamus is going to win in the end. It's like breathing. You can hold your breath for a while, but you're never going to be able to stop breathing. And Andrew, can you help me to understand this a little bit more? So you're saying there's a part of my brain that sort of knows what weight I, should be, but you're saying if I go below this number, then suddenly your body is saying,

oh, your weight's too low, you need to eat more food? So yeah, I mean, your weight set point will change in response to your environment. And everyone will understand this, because everyone sort of knows what their weight set point is. They may be going to the gym and they may be dieting constantly, but they know that when they just eat normal food, they're going to be whatever weight, and that they're trying to manipulate their weight with a conscious effort to a different one, okay? And the weight set point is calculated by the hypothalamus via a number of things. One of the main ones is genetics, which you can't change, and your epigenetics, which you can't

change. But then there are aspects that you can change. And really, if you understand how your own weight set point is calculated by your brain, you can change the factors that it's looking at, and your weight will come down, and your weight will come down, and you'll lose weight seamlessly. And those factors that are external, and we can change, include mainly the diet, but also things like stress, sleep, and a little bit exercise, but diet is the most important thing. And going back to this calorie thing, it's not the calories in the food. It's the food in the calories that are important. It's what the food does to you metabolically. So you're saying that this is part of my brain, the hypothalamus, that basically knows what

my weight should be. So it's calculating what weight it thinks you should be, taking into account all the data either genetically from your ancestors or your current sort of external environment. It's taking all of that data in and it's saying, okay, we want a weight setting, maybe in a normal range, but it may be overweight. And so how does it change what's going on in our body if we end up going either below or above that setting? So you're going to go into a metabolic response. It's not just if you starve yourself. It's actually also if you overeat, your brain is going to stop you increasing too much weight too fast. And you can sort of imagine it a little bit like a weight anchor. Okay. So you've got this, you're anchored in a harbour and your ship's just

there. It's hovering, you know, up and down, around that anchor, five, ten pounds here and there over the years. Now, if you try and think, okay, I want to get to the healthy shallow water and you're going to drive your engines, you're going to go to the gym, you're going to starve yourself. You can imagine the anchor, the rope on the anchor being an elasticated rope, you're going to push the engine, you're going to really go for it, you're going to get almost towards the shallow water, the slim water. But the more you try, the stronger the pull back, you know, from that elasticated rope. That's exactly what happens when your weight set point is at the unhealthy angle. You could reach it, you know, but it's a major struggle. It's almost like a light, you can't do

a full-time job and, you know, be able to do that. And eventually you'll give up because you'll feel terrible. You'll be absolutely starving, which is one of the responses of the brain, starvation, food-seeking behavior, being really, really irritable and not enjoying life, thinking about food all the time. That's one response. And the other response is this low metabolism, feeling very, very listless and not wanting to do anything. And, you know, your basal metabolism, which we'll talk about, because this is very important part of the understanding of weight regulation will collapse. Eventually you'll give up. But the last schedule rope we're going to pull you all the back to the waters you were in normally and probably a little bit further up the obesity waters.

And that last bit is often after you finish this cycle of calorie control weight loss and eventually get so starving that you have to eat, that you often end up slightly heavier than when you start it? Yeah. I mean, this is what so many patients tell me. I can go on a diet. I can really, really push it. I can go down. You can do light to life, whatever. But then I put the weight back on, and more. They all say, and more to three pounds more. And when you look at it from probably an evolutionary standpoint, you know, the brain can't differentiate between a low-calorie diet that you've consciously gone on and a famine in the food environment, you know, from our ancestral times. So it's thinking, well, hang on, we've just been through a famine, a low-calorie

diet for three, four months. We need a little bit more insurance this time. A human body on average will carry about 60 days worth of energy within it, usually in the form of fat, a little bit in the liver, you know. If you've been sort of manipulating your diet to such an extent where, you know, you're starving yourself for periods of time, your hypothalamus is going to pick up on that and it's going to want that insurance that, you know, if there is another perceived harsh winter, we need not 60 days of energy, we need 90 days, you know. Maybe we need 120 days, you know. And so recurrent low-calorie dieting is detrimental. It's very difficult to do these studies on humans because, you know, dieting is so difficult. But there's a really interesting

rodent study from Bergen in Norway, actually, where they looked at three groups of mice. They put one on a normal diet. They put one on a Western-type diet, high-fat, high-calories. And they put the third group into the Western calorie diet, but intermittently fasting them and starving them. But they're sort of alternating between what I sort of consider the McDonald's diet half the time and then sort of starvation the other half? McDonald's rubbish sort of Western food for eight days and then four days of 70% of that. So like a semi-starvation, whatever. And they did the four cycles of this because rodents don't live very long. So it's actually quite a big part of their life. The really interesting thing was that, you know, when you looked at the three groups, so the natural fed mice, their weight gain was nice and normal, the Western. food diet, McDonald's, Burger King, whatever, they obviously were much, much bigger than the

natural food diets. But then when you looked at the progress of the ones that have been starved and on, you know, calorie restrictive terrible diets for four days, actually for 50% of their lives, it was a jagged curve, so they'd go out quite fast, and then they'd come down on the diet, and then it was like a sort of sore tooth type weight progression. But when you look to the end result, they were heavier than the ones that had always been on the terrible Western diet. They were heavier. So the ones that actually were getting starved regularly actually ended up having more weight. So it's this weight rebound, this thing that the hypothalamus understands you're in a harsh environment and wants more weight on, you know, wants that insurance.

And, you know, the really interesting thing about that study is when they looked at the total calories consumed by the two top groups, so the Western diet and then the semi-starvation diet, they consumed the same amount of calories, but, you know, the starvation diet guys, were heavier. It's really remarkable, isn't it, Andrew, that these rats that half the time are on this calorie restriction getting much less food, you would expect them to weigh a lot less than the ones who are constantly getting access to all of this Western diet? This whole misunderstanding, Jonathan, is, you know, the Joker in the pack, which is our basal metabolism, and this is, like, so interesting this science. It's massively dynamic, and, you know,

it's not under conscious control, but it will drive your weight up or down. It will always win in the end and it will get you back towards your weight set point. All that my patients said they've been dieting their whole lives, you know, 10, 20, 30 years and it doesn't work. And it's because of your basal metabolism. What is basal metabolism? Very good question. So we'll get started with energy expenditures. So the amount of energy that we use every day is divided into three main elements. So the first is our basal metabolic rate. So imagine if you just stayed in bed all day, you just laid down in bed. All you did was think, actually, and breathe, and your heartbeat, and you heated your body and your immune system was working. Actually, that's quite a lot

of energy, you know. That's 70% of all the energy that you would have used if you'd been up and doing whatever you're doing today. 70% of my energy will be used just by line in bed. Basal metabolism. This is just like the basic stuff. Most of the other is passive energy expenditure, which is your day-to-day activity. So get into the office, if you've got a more active job, if you're a cleaner or a builder, doing that stuff, you know, you're going to use a little bit more energy. And then a very, very small aspect is active energy expenditure, which for most people is walking upstairs or running for the bus. But occasionally people will go to the gym, you know. But it takes quite a lot of activity to actually even use up a small amount of energy.

in the biggest scheme of things. Now, the basal metabolic rate, so your basal energy expenditure is massively variable. And if you actually look into the concept of how much energy does it take to run a human body, okay, it's about 120 watts, which is the same energy as a light bulb, but it's very variable. So on average, it's 120 watts. It can go from 60 watts to 240. So you've got to think of that basal metabolism as almost like a dimmer switch. So the human body can be turned up and down as far as metabolism. And this isn't in our conscious control. You can be, you know, really sort of glowing and hot and your heart's, you know, going fast and your immune system's really firing sometimes a little bit too much. Or you can actually be very, extremely sluggish, your heart's

going very, very slow, you feel a bit cold. We can't consciously affect this. But when we either overeat or under-eat and calorie restrict, that metabolism will follow us. So this is why diets don't work. So normally people would take in over 2,000 kilocalories a day, if you go down to 1,200 kilocalories a day, which is what most diets go towards. You will lose a little bit of weight at first, but then that metabolic dimmer switch is going to be turned down and your body is just going to adapt to 1,200 kilocalories a day. you're going to be on the scales

probably after it'll take about a month you may lose you know 10 15 pounds but you know you're then on the scales you're still on your diet you've been happy

because you lost a bit of the weight but it stops your body has adapted to the low calorie intake by turning that dimmer switch down and does that tie back to what you described about feeling like listless and tired yeah what normally happens is so you'll be on the scale for a week or two

you'll still be on the diet and the consequences of the diet are you know starvation, irritability, tiredness, you'll go to your doctor and you'll say, look, this diet's not working anymore. Your doctor will not believe you. It will think that you're sneaking in Mars bars and biscuits and whatever. We don't learn about this stuff in medical school. It's only when you're exposed to it in your day-to-day life and you get really, really interested in it that you really understand it. But it totally explains why diets don't work. A basal metabolism that's not in the end of our control, but it's really powerfully turned up or down. Now, really

interesting factor is how is it turned up and down. And I think there's two areas that probably account for it. So the first is what we call the autonomic nervous system. Medical terminology is the sympathetic nervous system and the parasympathetic nervous system. But we, you know, in day-to-day life, it's the fight or flight response. And this is the thing that keeps us safe in times of danger. So in primordial times, if we got a predator around or there is a tribe coming to attack us, our fight response will come in. This is a sympathetic nervous system response. We all experience this, you know, every day, but it's not always danger. It's like perceived danger or whatever, or just worry. But, you know, if you had a situation where, you know, you were

faced with a pack of dogs in the street, you know, you would suddenly become very, very aware, more blood to your brain, your heart's beating faster, you feel a little bit hotter, and there's a lot of energy going to your muscles and you can run, you can really run or fight, you know. And this is like, you know, it's like turning on the, you know, the afterburners, you know, and it's something that, you know,

is a survival thing for humans and actually all mammals, you know, it helps you. But we can't turn on the afterburners all the time because we're going to be burning too much energy and it's going to be like a real hassle getting too much food in, you know, going to take up all that time. So this is something that is just intermittent in

periods of danger. And that's what we're in medical school, the autonomic nervous system is to do with protecting us from danger and also in times of relaxation, letting us relax. But actually, probably the primary function of the autonomic nervous system is maintaining a healthy weight, maintaining that weight set point of what should be around 60 days of energy storage. So the autonomic nervous system will turn up or down your basal metabolism depending on whether your brain wants you to increase weight or defend a weight or if it wants actually you to decrease weight because you're eating too much. If I gave you a Burger King on top of everything else every day, okay, you would actually put a little bit of weight

on, but actually you wouldn't balloon. You wouldn't put on as much weight as would be expected from 500 kilocalories a day because your body would actually adapt just as it would if you're calorie restricting, if you're overeating, it's going to turn on the afterburners. It's going to turn on the autonomic nervous system, the sympathetic nervous system. Your heart's going to be racing a little bit faster, you're going to feel a little hotter, probably you're going to be thinking quite clearly, lots of energy in your muscles, you're going to feel good, but actually you're burning a lot of energy that you don't really need. So that is then an increase in my basal metabolic rate? Yeah. So if you look at the amount of calories that Americans consumed over the last, I think from

1990 to 2010, the calorie intake increased by 500 kilocalories a day on average, which is equivalent of a Big Mac and chips and a Coke, extra to what they were doing before. And they weren't doing any extra activity, so they weren't burning off more. Now, if you look at very simplified energy in, energy out, one pound of fat is 3,500 calories. So you're going to put it on one pound of fat every week. So that means over a year, you're going to put on 50 pounds. And over that 20-year period, you're going to be massive. You're going to be like 400 pounds or whatever or more, you know. And everyone in America hasn't become 400 pounds heavier. So they put on one pound a year on average in that period of time. Not 50 pounds for a year. So you've got to

think about, hang on, where is that energy gone? You know, I've taken in 500 kilocalories a day, but actually only 11 kilocalories when you work out the maths has been stored. So what happens to the other 489 calories? And that's where the, you know, the sympathetic afterburner comes in, the fact that that metabolic rate, that dimmer switch has been turned up. And this is back, therefore, to why, like, calories in minus calories out doesn't work, because your body is changing the amount of calories that it's burning each day. Is that what you're saying? Totally. But, you know, the really intriguing thing is, you know, if weight regulation is that accurate to within 0.4% of your intake, or actually another study, which looked at

even more accurately, 0.2 of intake, why do you put any weight on? If it works, why doesn't it work fully? We know our hydration system works absolutely perfectly. You know, you've got the same amount of fluid percentage wise that you had 10 years ago. Okay, you're teasing me now, Andrew. What's the answer? This is where we come on to leptin resistance. Leptin resistance, again, is another one of the real pillars of understanding of weight regulation. And when we get it, that really empowers us to lose weight. I think what you're saying is to really understand weight gain, you need to understand this idea of a set point.

And there's a part of our brain that is making sure we're at that set point. And so if you start to calorie reduce, your body says it's starvation, it does all sorts of things to stop you losing too much weight. You end up coming back. And then I think you said often you actually end up putting a few pounds on, which makes it sound like your set point in that situation has actually shifted up a little bit. So in that situation, the set point is not stable. Did I understand that?

Yeah. I mean, most dieters that you speak to from teenage years, maybe when they were only size 10 or 12, we're not really struggling. Be no peer pressure on whatever media. They want to be a size 8 or a size 6. Start going on a diet. And they'll have the same sort of jagged,

weight, gain, weight reduction curve over the years, over 10, 20, 30 years that those mice in the experiment had. You know, they will lose weight, they'll put it back on, and more. And as we said before, it's this response from the hypothalamus that wants more insurance because they perceive a famine environment. So, yeah, you get this sort of slow increase in your weight set point in response to recurrent dieting. The best way of putting weight on, we're both a little bit slim, Jonathan, is probably to start going on diets, you know. Seriously, you would put weight on.

The best way to put weight on is to go on a diet. Low calorie diet, long term. You're about to say that the hormones that sort of control my appetite are a central part of understanding this? Yeah. So there's one hormone, the master controller, leptin. Again, skimmed over in medical school, not too many doctors really understand it too much, but it's like absolutely crucial in human weight regulation and mammalian weight regulation. If we're in an environment where there's no food, we're sort of okay for 60 days. That's a long time to try and find some food. And then we start eating in. into our muscle and whatever and stuff to become very, very sick. So 60 days is, you know, a human is hardwired to carry. We're not hardwired to carry 120 days. We don't need it.

It's going to drag you down. You're not going to be as fast. You're going to be, from a, you know, evolutionary point of view, at risk of predation. You know, so those people who were big, they didn't pass their genes on. So how is that regulated? Because it is. Because it's really, really important from a survival perspective, this homeostasis, It's this regulation of that 60 days.

Basically, it all evolves around leptin. And leptin is a hormone that is produced by our fat cells. And the more fat cells that we have, the higher the leptin level. So leptin comes from the fat, goes into the blood. And that really important area of our brain that we discussed before, the hypothalamus, which is the master controller of our weight, will sense the level of leptin in our blood. And it will think, okay, the leptin level is quite high.

high. You know, I think we've got maybe 70 days or 80 days storage. The tank is really, really full. We can ratchet down the appetite. We can be not that interested in food. We can increase the metabolism, that dimmer switch. Seamlessly, without any, you know, any thoughts, your weight will go back down towards, you know, the weight set point, basically. And the same thing happens the other way. If we lose weight, if we go on a calorie restriction diet, or if we get sick and we don't eat much and we lose weight or if we're in a famine environment, that level of leptin will decrease because our fat has decreased and there'll suddenly be an alarm. So that the hypothalam will dip into the blood. It will see the leptin level has gone down. I think, oh God, okay, we're in a famine

situation. We ratchet down the metabolism so we don't burn off too much, go into battery saving mode, but actually be looking for food. And this, you know, from an evolutionary perspective, is the thing that kept us within that target range of around about 60 days of energy storage. Now, if that's working, why does anyone become fat or store far too much energy? Sometimes a year's worth of energy. What is the point of that? That is a disease. Something's gone wrong.

Okay, so something's gone wrong with leptin. It's called leptin resistance. So if you measure someone who's really suffering with obesity, and you measure their leptin level, it is sky high. It's like triple what ours would be. So why is that not working? Why is the hypothalamus not able to see it? And it's because it's being blocked by this other hormone that we all know, insulin. Insulin and leptin share a receptor pathway in the hypothalamus. So the more insulin we have, the more dilute the leptin signal. So you can be

walking around with very, very high leptin levels, but actually because your Western diet has foods that stimulate high insulin, so sugar, highly refined carbohydrates, and a snacking culture, which we have, your insulin levels are, you know, on average, raised. That dilutes the leptin signal, and the brain can't see the leptin anymore. Despite you carrying far too much weight, it can't see it. You know, it's blocked. It's leptin resistant. And then you get the opposite signals or responses from the hypothalamus that you should get, because it can't leptin, it thinks that you're fading away rather than you're carrying far too much weight. So you will get totally inappropriate signals of hunger and low metabolism.

And this is the crucial thing, Jonathan. So, you know, when you understand leptin resistance, these factors that society and doctors blame on obesity as, you know, poor character traits. So being a little bit too hungry, a little bit too greedy and a little bit too lazy. That is not the cause of the condition. That is the symptom of the condition. So when you've got leptin resistance, you become hungry and you become quite tired because your metabolic raise has been turned down.

It totally flips the whole concept on its head, you know. Actually, this is a symptom. This is not the cause. And that symptom then drives up the, you know, the weight set point. And this is the reason that people's weight set point will go from normal up, up, up, up, up. because leptin has been diluted by the insulin signal. It's also diluted by inflammation, but that's a separate thing. If you understand the insulin blocking leptin side of things,

you're going to start to empower yourself to be able to change your weight set point. And so I think you're saying that the food that we're eating has a really important impact, not thinking of it now in terms of calories, but actually the sort of food we're eating is leading to much more of this insulin in our blood, and therefore our brain is sort of not sensing anymore. Hey, you're carrying around enough fat, you've got the 60 days you're talking about, I don't need any more.

It's like not able to see this anymore. And they say, oh, like need to eat more food because clearly we haven't got enough storage to be safe for the next famine. So this is really explained, I think, in a lovely analogy called the empty gas tank. So imagine you're driving along the highway and suddenly your gas tank meter is flashing red.

And it's like, oh, God, you're going to run out of gas or petrol. And you start panicking a little bit and thinking, God, they've got to fill up in the same way as if your hypothalamus wasn't seeing leptinot think I'm starving. You get to the gas tank, you start filling up, and you realize, well, hang on, the gas tank is already full. Now, the problem is, the gas tank meter is broken. And this is what leptin resistance is. So you've got these people with full gas tanks, but the gas tank meter is broken. They feel like they need to fill up. That warning light is flashing all the time.

But unlike a car where you can't fill up more than full, you can in a human. It's a brilliant explanation that I've just been hearing about why these calorie counting diets don't work, sort of how our environment is against us and how our set point is basically not only preventing us from losing weight, but actually if we try these sorts of calorie deficit and eating the sort of food that's generally around us, it's sort of pushing us in the wrong direction. On the other hand, it's all quite bleak. I would love now to talk to, like, what could listeners do to actually either achieve sort of sustainable long-term weight loss or ensure that, like, their set point remains stationary? So could we maybe start with what people are eating? How does the food that we're eating affect this?

story. The first thing that we've nailed is it's not about the calories. You need to understand that it's all about your set points. So you can try and calorie count. You can try and go to the gym. You can lose weight for a month or two months or you can lose weight for six months, but you're going to feel terrible and it's all going to come back on eventually unless you understand why your set point is set so high. And you've really got to address the amount of insulin that you're taking in. So if you can decrease the amount of insulin you're taking in, you will release that leptin signal. So if it's working, you will get back towards a normal weight. We've got to go on a sort of that type of lowish carbohydrate diet that is doable that we can live with.

My book goes through various different phases of that diet. And the first thing would be, you know, the real enemy is sugar. That's the first enemy anyway. So if you can maybe do a 30-day giving up sugar and sugary food challenge, that would be the first thing. It's going to take a little bit of willpower because we haven't even gone towards, you know, the dopamine reward pathways and what sugar does to us and how it is basically a legal drug that we're all addicted to and, you know, habitually take. But, you know, if you can get your head around all those things and actually give up sugar for a month, that's the first thing. You will lose some weight. Your insulin levels will increase slightly and you will release.

that leptin signal a little bit more and naturally your weight will come off okay so first thing give up sugar second thing second month maybe don't snack between meals just have three square meals a day try and embrace hunger you know do what the french do don't snack between meals but like eat really know really well and enjoy food when you're having the meal constantly snacking is something that, you know, is new, something that only in the last sort of 30 years or so has just become a norm, sort of, you know, eating, you know, confectionery or crisps or whatever on the tube or whatever in the street because you're starving. The reason you're starving is because your glucose levels are going up and down because we're on a very high, high carbohydrate

diet. So we're off the sugar, we're off the snacking. Third thing, processed foods. If you can then give up the processed foods and, you know, really embrace healthy, old-fashioned food, you know, the food that your grandmother would have cooked, fish, meat, any type of vegetable and dairy products. Why are processed food something that you're worrying about for someone who's looking to lose, you know, a significant amount of weight? The problem with processed foods is, you know, they metabolically cause chaos in your body. They really, you know, encourage high insulin levels, sluggish insulin, and the weight set point goes up because you've got leptune resistance. So when you get rid of them, it's not to do with the calories, the weight will go down.

Do you know someone who's trying to lose weight? Perhaps they're trying to decide whether to use these new drugs or if there's other options that could work. If so, why not share this episode with them? We talk a lot about mindful eating at Zoe. It's actually central to the new app that we've been working on over the last year and I feel like this concept comes up quite a bit sort of across your books.

What does mindful eating mean to you and why does it matter? Yeah, I mean, this is something that we've probably lost in Western societies and actually other societies still have it, particularly the French. You look at the opposite, so mindless eating, which is what actually we're very habitually do,

eating, processed, highly sugary, highly fatty foods mindlessly. And it's making them feel good. It's almost like a drug. It's like it's stimulating their dopamine, they're relaxing, you know. And this becomes a habit. You know, the brain wants to do these things because it makes you feel okay, you know, makes you feel, you know, at ease and safe.

So that's mindless eating, you know, this habit that makes you feel good, but actually metabolically is very, very bad for you. So the opposite would be mindful eating where you actually really do not only, savor your food, but actually savour before you eat, what you're going to eat, how you're going to prepare it, or which restaurant you're going to go to, you know, really look forward to your meal, you know, really taste every mouthful, really, really savour it. And this can really make a difference to what you eat and ultimately your ability to adjust this set point? I think so. I think if you're really mindful about actually how some processed foods really taste and what they make you feel inappropriately good, it can change your mind. you know and if you understand exactly how good well-prepared natural foods can taste but actually

how good they are for your body because they become part of you you know food becomes part of you you know that's a really important part of it the other thing about mindful you know eating is you know this awareness of hunger awareness of your hunger gauge you know we in our western societies well you know if you got a hunger gauge in zero to ten where you're getting a little bit hungry when you're four, when you're sort of starving when you're seven or eight. Actually, you should be eating when you're about seven. You know, we start to have a coffee when we're at three.

You know, we never get even close to five in our Western societies. You need to not snack between meals. You need to really actually start to embrace hunger because, as the French say, hunger is the best source. It makes the food taste so good. What about time-restricted eating, which has come up on a number of podcasts that we've done, and actually there's been quite a bit of Zoe research about it. What's your experience there?

I think it's very good, and it fits in with, you know, the weight set point theory and leptin resistance, you know, the defense of the, well, the reason that the weight set point in some people goes up because there's too much insulin around. If you time-restrict eating, so we're not talking about the 5-2 diet, where you have 500-cala calories two days out of every week, I much prefer time-restricted eating where you're eating for a window of maybe six hours or eight hours

and the rest of the time you're either sleeping or you're consuming water or black tea black coffees and zero-calorie beverages now that time that you're not eating your insulin levels are going to go down after a couple of hours of eating and that's going to release that leptin signal again suddenly your body's going to see the amount of weight

that you're carrying and have an appropriate response to that way. the more you can fast per day, the more effective the time restricted eating will be. If you can do, you know, eight hours a day or six hours a day or play around with it, we all have lives, though, you know, so there's going to be some days where, you know, you're going out, you know, you're meeting people on a social occasion. And this is guidance for people who are looking to lose a significant amount of weight. Is that right, Andrew?

So if at the moment you have breakfast and then you eat all the way to, you know, 11 o'clock when you go to bed. If you then go towards time-restricted eating, you will lose some weight. But we haven't got to the final part of, you know, what my dietary advice would be, apart from time-restricted eating. So we'd said give up sugar, we'd said, give up snacking, we'd say, try and give up processed foods. But the final thing is to reduce the amount of carbohydrates you take in, you know, basically we're taking 300 grams of sugar a day. It may be, you know, from vegetables to bread or whatever. If we can go to, down towards 100 grams of sugar a day in our foods and maybe even less, maybe 80 or 60 before

we get like terrible carbohydrate cravings. This is going to have a really good effect on our incidence. So lowish carbohydrate dieting that is tolerable. Yes, if you combine that with time restricted eating as well, fantastic. What about these new weight loss drugs? I think you couldn't have a conversation about late weight loss without talking about all of these GLP-1 drugs like a Zem-Pic. Yeah. It's extremely interesting, extremely topical. I mean, these drugs are based on a natural hormone that is the increased after we do

a gastric bypass, so this is very topical for me. This is called JLP1. It comes from the intestine, and after you eat, it's released after about half an hour, and it's a signal that goes to your brain to say, we've been eating for half an hour, stop eating. Now, the pharmaceutical companies have managed to copy that hormone, and, you know, produce it in a weekly injection where you get that feeling all the time that you don't really want to eat, the appetite's turned off. That has a big consequence on your weight,

maybe not your weight set point, in that you will lose maybe 15, maybe 20% of your weight over a year on these drugs. There are side effects and there are risks, but generally they're pretty good drugs. Now, the problem with these drugs is when you come off them, you will gain at least two-thirds of your weight within the first year and probably you'll end up heavier than you were before you started them. So it's almost like an ideal drug for a pharmaceutical company. You've got to be on them all the time. And my new area of, you know, advice is actually use the drug the smart way. So maybe use them over a year to really understand things like the leptune resistance, the way it's set point, change your eating behavior and change your habits,

make your insulin start firing and become really efficient. Then you're more likely to be able to come off the drug and not regain weight. We didn't really talk about things that were outside of sort of the food that you eat. Is there anything else that's important that could really support this sort of long-term reduction of your set point and reduction of your weight? Good question, Jonathan. And there is, because cortisol is very, very important. Cortisol is the stress hormone.

If we have too many stresses at work or at home, that's going to increase our insulin. You can do everything, but if you're one of these very, very stressed people, it's almost like you're a scared animal, your body doesn't want to lose weight. So de-stressing, either by unpecking work or family issues or being able to have relaxation techniques is really important for weight loss. So you'll decrease your cortisol level, you know, your insulin level will normalize. Leptin signal will be released. Exercise has a similar thing. You don't lose weight by exercise by burning off the calories, you lose weight by making insulin more efficient and decreasing cortisol. That's why gyms are popular. It's not to do with burning off calories.

And the third thing is sleeping really, really well. So sleeping again is really important for our relaxation, our cortisol, etc., etc. So these things de-stress, a little bit of exercise that you enjoy and sleeping well. Finally, if you could give one piece of advice to anyone who's listening to this who's trying to lose a significant amount of weight, what would it be? I think it's really to understand that it's not the calories in the food. It's what the food does to you metabolically. So avoid sugar, avoid refined carbohydrates, avoid processed food. Don't snack all the time. You will lose a lot of weight just by doing that. Andrew, thank you so much. I'm going to try and do a little summary and correct me where I get any of this wrong. So the first thing that springs to my mind is this

amazing rat study you were talking about where they had different groups, but the rats that were actually being sort of starve on and off for half their life ended up fatter than any of the other ones, including the one on this sort of like Western McDonald's diet. I think that's really amazing, this idea that basically doing these cycles of calorie restriction actually made them put on more way. And it's this beautiful analogy, I think, to the culture that we've all been living in for the last 50 years of like, you know, short-term. and get your body ready for the beach, you know, restrict your calories, actually ending up damaging you.

And that's because, you know, in human beings, calorie counting is going to fail eventually. You're going to start off good. You're going to lose some weight. And then after a month onwards, you're saying you can start to feel terrible. And all of this is about understanding this sort of this set point inside our body and how we responded. And so we have this hypothalamus in our brain, basically this measure that knows, you know, you're supposed to be 130 pounds or whatever it is. And if you go below it or above it,

it's going to make changes. And if you go below it, your brain starts to think, wow, we're in a famine. You might die. So try and put on weight as much as possible and try and reduce the amount of energy that you're using up. And hence you feel tired. And you talked about this like basal metabolism, which is like 70% of all the energy I use is just sort of like this background. And that's going to reduce. And you gave me this beautiful sort of visual metaphor of a boated anchor, you know, with this elastic rope, and you can try and pull it towards the shallow end, but the further you pull it, like the tie to the rope is and eventually you get pulled back unless you can actually move sort of where that boat is

anchored, which I thought was really powerful. And one of the ways to understand this is that after I lose weight, actually, my body is saying, oh, wow, we're in more of a famine environment than before. So actually, I better move my set point up a little bit. And so instead of storing like my 60 days of energy you talked about, like, I need to store steadily more and more of that. But the other thing you said to understand is like our food environment is broken. And as a result, sort of our internal gas tank meter can very easily be broken. And you describe this leptin as this key hormone to help to understand this. But with all the food that we're eating and the processed food and all the rest of it,

actually our brain sort of can't measure the gas tank, which in this example is like, how much fat am I carrying. And so it's like, oh, I'm hungry, let's get more, even though actually I'm already full up. And that it's our diet is really the thing that's different between now and the description you were describing about maybe 40 years ago where there might be just, you know, one kid in a school who's living with obesity and now it's a third. And then you say, well, what can you do? And, you know, your own program sort of based upon seeing all of your patients over decades

who want to lose a, like a significant amount of weight is sort of a step-to-step plan to say, how can you actually shift the set point? And you start by saying, try giving up sugar for a month, then try giving up snacking. Eat your main meals, like fill yourself up. Don't worry about calories, but do that. Then go on to processed foods, give them up as well. On the back of all of that, you're going to really reduce the amount of carbs and particularly all this sort of highly processed carbs that get turned into sugar. That is already going to make a big difference. Think alongside this. Time restricted eating is a way to control the amount of time that you wanted to eat. Mindful eating. So being really aware of what you're doing is sort of sitting

underneath this. And, you know, last but not least, it's not only about the food that we eat. You're saying de-stressing, sleeping well can also have a profound impact through like these different pathways, not just through the leptin that you were talking about. out. And if you put all of this together, you've seen real success with people able to shift this set point, reduce their weight in a sustainable way. Fantastic summary. Now, if politicians could get this, they would understand it's not about the calories, actually it's about processed food and sugar. If these types of food were taxed as much as alcohol and tobacco, and that taxed revenue then went into an education campaign so that people understood what the hell's going on

with their bodies, actually obesity would start to come down naturally. But the real problem is we don't understand obesity. I'll end this episode with something I think you'll like, a free Zoe gut health guide. If you're a regular listener, you know just how important it is to take care of your gut. Your gut microbiome is the gateway to better health, better sleep, energy and mood. The list just goes on. But many of us aren't sure how to best support our gut. I wasn't sure before doing Zoe, which is why we've developed an easy-to-follow gut health guide. It's completely free and offers five simple steps to improve your gut health. You'll get tips from Professor Tim Specter, Zoe's scientific co-founder and one of the world's most cited scientists, plus

recipes and shopping lists straight to your inbox. We'll also send you ongoing gut health and nutrition insights, including how Zoe can help. To get your free Zoe gut health guide, head on over to zoey.com slash gut guide. Thanks for tuning in and see you next time.