Weight loss surgeon explains the real reason you're always hungry

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.

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Jonathan Wolf: Andrew, thank you for joining me today. 

Dr Andrew Jenkinson: It's a pleasure. Jonathan. 

Jonathan Wolf: 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? 

Dr Andrew Jenkinson: Of course. 

Jonathan Wolf: 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 inevitable? 

Dr Andrew Jenkinson: No. 

Jonathan Wolf: For most people, will calorie counting work for long-term weight loss? 

Dr Andrew Jenkinson: No. 

Jonathan Wolf: Can our hormones cause us to overeat? 

Dr Andrew Jenkinson: Yes. 

Jonathan Wolf: Should obesity be considered a disease? 

Dr Andrew Jenkinson: Yes. 

Jonathan Wolf: If we are living with obesity, could many of us lose weight and keep it off without drugs?

Dr Andrew Jenkinson: Definitely. 

Jonathan Wolf: Does your metabolism slow down when you lose weight? 

Dr Andrew Jenkinson: Yes. 

Jonathan Wolf: And finally, what's the most common myth about obesity that you hear? 

Dr Andrew Jenkinson: That losing weight is all about calories. 

Jonathan Wolf: 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 topics 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. 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 eat less, move more, and the problem's solved. What does the latest science say about that? 

Dr Andrew Jenkinson: The popular opinion is that 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, politicians, and policy leaders, which is a big problem. 

The sort of myth that it's all about the calories is, 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 is 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, there used to be probably in each year, one pupil living with obesity, really big, struggling, et cetera, et cetera. 

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. You know, so we've had a massive change over the last, you know, 30 years or so. 

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 addicted. 

You know, these are the questions we've gotta ask about why suddenly the population is really struggling with obesity and its consequences. 

Jonathan Wolf: I guess when I was growing up, I think just as you described, in the schools that I was in, there were very few children living with obesity, maybe one or two in a year. 

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 explains everything. 

How much are genes the answer to what's going on?

Dr Andrew Jenkinson: Well, you know, those children living with obesity, 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 struggling with their weight as well.

But when you look at the actual figures, the risk of developing obesity from a genetic standpoint is about 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 had been separated at birth because whatever family problems and brought up in different households. 

Then they looked at them as they were adults, and they found a correlation, you know, 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. 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, you know, those families were still in the same country, so they had a similar food environment, but there's definitely a 70% correlation genetically. 

Jonathan Wolf: 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 a hundred might end up with obesity.

And you're saying now it's a third, but the genes haven't changed. 

Dr Andrew Jenkinson: Yeah, but it's the genes plus the food and stress culture that we've got nowadays. 

So, 30, 40 years ago, the obesogenic 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, you know, home prepared foods and don't snack and things, those obese genes aren't triggered.

When I was at school a long time ago, the food culture was much different.

Jonathan Wolf:  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.

Dr Andrew Jenkinson: Exactly. Yeah. 

Jonathan Wolf: 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. 

Could you tell us a bit about that and also explain what epigenetics is? 

Dr Andrew Jenkinson: 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 us, that's our phenotype, whether we've got blue eyes, we're tall, whether we have obesogenic 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.

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. 

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.

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 other 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 to the women that were in their first and second trimester 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. 

They found that that offspring were much more likely to be seriously obese and centrally obese, and diabetic. 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 hungrier, 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 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. 

Jonathan Wolf: The fetus is there, its genes are set anyway, from there.

Dr Andrew Jenkinson: The DNA is set. 

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Jonathan Wolf: The DNA is normal. But actually, while the fetus is in the womb, it's sort of getting this information about Wow, I'm not getting enough 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'd be great if actually you spent 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 your brothers and sisters because you're sort of preset.

It's changing your behavior. 

Dr Andrew Jenkinson: 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. 

Jonathan Wolf: That's amazing. And I guess that's a great counterexample to the idea that weight gain is simply about willpower, because this has nothing to do with these children having different willpower than their brothers and sisters.

This is the marination as they've been grown. 

So, Andrew, why don't diets work for long-term weight loss for most people? 

Dr Andrew Jenkinson: 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 worried about diet or, you know, pretty much healthy eating when we were younger.

But I obviously did surgery, went through my training, and ended up as a bariatric surgeon, which is really interesting, you know, surgery on the stomach. 

But the consequence was that 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 as I got more experienced of chatting to 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. I've lost a ton on their 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 because I'm from a family that live with obesity, I think my metabolism's low, I compare what I eat to my flatmates, my flatmate eats twice as much as me, but they have no problem. 

So all of these comments really stimulated my interest in weight regulation and metabolism, and thinking, you know, 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.

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 appetite, 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 at 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. 

So you can lose 20 pounds, 5 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 ultimatums.

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 know, never going to be able to stop breathing. 

Jonathan Wolf: 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.

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. 

Dr Andrew Jenkinson: So yeah, I mean your weight set point will change in response to your environment. 

So basically, your weight set point… 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. 

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, or 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 set point 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. 

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.

Jonathan Wolf: You're saying that there's part of my brain, the hypothalamus, that basically knows what my weight should be. 

Dr Andrew Jenkinson: So it is calculating what weight it thinks you should be taking into account all the data, either genetically from your ancestors or your current 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.

Jonathan Wolf: And so how does it change what's going on in our body, if we end up going either below or above that setting? 

Dr Andrew Jenkinson: So, I mean, 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 are anchored in a harbor and your ship's just there. It's hovering, you know, up and down around that anchor, five, 10 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. That's 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. 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. 

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 for the understanding of weight regulation, will collapse. 

Eventually, you’ll give up. The elasticated rope is going to pull you all the way back to the waters you are in normally. And probably a little bit further up the obesity waters. 

Jonathan Wolf: 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.

Dr Andrew Jenkinson: 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, I do LighterLife, whatever. But then I put the weight back on. And more, they all say and more, two, three pounds more.

When you look at it from a 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 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. 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 if there is another perceived harsh winter, we need not 60 days of energy, we need 90 days, maybe we need 120 days.

So recurrent, low-calorie dieting is detrimental. It's very difficult to do these studies on humans because 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. 

Jonathan Wolf: They're sort of alternating between what I consider the McDonald's diet half the time, and then sort of starvation the other half. 

Dr Andrew Jenkinson: Yes, 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 four cycles of this because, you know, rodents don't live very long, so it's actually quite a big part of their life. So the graph of the healthy eating ones is sort of low, and then the ones on the McDonald's diet is a bit higher. Clearly. 

But the ones on the intermittent fasting is jagged. It goes up and down and up and down and up and down. And actually, at the end, they're higher than the ones on the terrible McDonald's type diet. 

Jonathan Wolf: And just to clarify, because when you say intermittent fasting, I think some people here, will be thinking about time-restricted eating per day.

But you're actually saying it's jumping between getting McDonald's and being starved for a long period of time and then jumping…

Dr Andrew Jenkinson: Yeah, like a low-calorie diet.

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 diet. 

But then when you looked at the progress of the ones that have been starved and on calorie-restrictive terrible diets for four days now, actually for 50% of their lives it was a jagged curve. 

So they go up 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 results, they were heavier than the ones that had always been on the terrible Western diet.

Jonathan Wolf: They were heavier. So the ones that actually were getting starved regularly actually ended up having more weight.  

Dr Andrew Jenkinson: So it's this weight rebound. This thing that, you know, the hypothalamus understands you are in a harsh environment and wants more weight on, 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 the starvation diet guys were heavier. 

Jonathan Wolf: It's really remarkable, isn't it, Andrew, that these rats, 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. 

Dr Andrew Jenkinson: This whole misunderstanding, Jonathan, is the joker in the pack, which is our basal metabolism. 

This is 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 to towards your weight set point. 

All of my patients say they've been dieting their whole lives, you know, 10, 20, 30 years and it doesn't work and it's because of this joker in the pack: your basal metabolism. 

Jonathan Wolf: What is basal metabolism? 

Dr Andrew Jenkinson: 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, breathe, and your heartbeats, and you heated your body, and your immune system was working.

Actually, that's quite a lot of energy. That's 70% of all the energy that you would've used if you'd been up and doing whatever you're doing today. 

Jonathan Wolf: 70% of my energy be used just by lying in bed. 

Dr Andrew Jenkinson: This is just the basic stuff. 

Most of the other is passive energy expenditure, which is your day-to-day activity. So geing to 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 bigger scheme of things. 

Now, the basal metabolic rate, so your basal energy expenditure is massively variable. And if we 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, you know, 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 could be really sort of glowing and hot and your heart's 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 undereat and calories restrict, that metabolism will follow us.

This is why diets don't work. So normally people would take in over 2000 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, it'll take about a month. You may lose, you know, 10, 15 pounds. But you're then on the scale as you're still on your diet, you've been happy because you lost a bit of weight, but it stops. Your body has adapted to the low-calorie intake by turning that dimmer switch down.

Jonathan Wolf: Does that tie back to what you described about feeling listless and tired? 

Dr Andrew Jenkinson: 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 starvation, irritability, and 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 under our control, but is really powerfully turned up or down. 

Now, a 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 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've 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 if you had a situation where you were faced with a pack of dogs in the street you would certainly 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.

And this is like turning on the afterburners, and it's something that 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 taught in medical school, that 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 the 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, 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. 

Jonathan Wolf: So that is then an increase in my basal metabolic rate. 

Dr Andrew Jenkinson: Yeah. So if you look at the amount of calories that Americans consumed over the last… I think from 1990 to 2010, their 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 and energy out, one pound of fat is 3,500 calories. So you're going to put 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? 

Jonathan Wolf: And everyone in America hasn't become 400 pounds heavier. 

Dr Andrew Jenkinson: No. So they've put on one pound a year on average in that period of time. So you've got to think about, hang on, where has that energy gone?

You know, I've taken in 500 kilo calories a day, but actually only 11 kilo calories, when you work out, the maths has been stored. So what happens to the other 489 calories? 

And that's where the sympathetic afterburner comes in. The fact that that metabolic rates, you know, that dimmer switch has been turned up 

Jonathan Wolf: And this is back therefore to why calories in minus calories out doesn't work because your body's changing the amount of calories that it’s burning each day. Is that what you're saying? 

Dr Andrew Jenkinson: Totally. But you know, the really intriguing thing is, 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.

Jonathan Wolf: You're teasing me now, Andrew, what's the answer? 

Dr Andrew Jenkinson: This is where we come onto 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.

Jonathan Wolf: 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. 

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 it up a little bit. So in that situation, the set point is not stable. Did I understand that? 

Dr Andrew Jenkinson: Yeah. I mean, most dieters that you speak to, from teenage years, maybe when they're only size 10 or 12, were not really struggling. 

Being their peer pressure and whatever media, they want to be a size eight or a size six, start going on a diet, and they'll have the same jagged weight gain, weight reduction curve over the years, over 10, 20, 30 years, that those mice in the experiment.

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, seriously, you would put weight on. 

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Jonathan Wolf: The best way to put weight on is to go on a diet.

Dr Andrew Jenkinson: Low-calorie diets, long-term, long term. 

Jonathan Wolf: You were about to say that the hormones that sort of control my appetite are a central part of understanding this. 

Dr Andrew Jenkinson: 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 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 into our muscle and whatever, and start to become very, very sick. 

So 60 days is what a human is hardwired to carry. We are 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 an 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, 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'll think, okay, the leptin level is quite high, 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 thoughts, your weight will go back down towards the weight set point basically. And the same thing happens the other way. If we lose weight, if we go on the 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 they'll suddenly be an alarm.

So that the hypothalamus will dip into the blood, it'll see the leptin levels has gone down,  think, Oh God, okay, we're in a famine situation, 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 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. It's blocked, it's leptin resistant.

Then you get the opposite signals or responses from the hypothalamus that you should get. Because it can't see 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 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 rate 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 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.

Jonathan Wolf: 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, yu've got the 60 days you're talking about, I don't need anymore. 

It's not able to see this anymore. And they say, I need to eat more food, because clearly we haven't got enough storage to be safe for the next famine. 

Dr Andrew Jenkinson: 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, I’ve got to fill up in the same way as if your hypothalamus wasn't seeing leptin, it thinks 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 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.

Jonathan Wolf:  It's a brilliant explanation that I've just been hearing about why these calorie-counting diets don't work. 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 going to push 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 are eating affect this story?

Dr Andrew Jenkinson: 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.

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 that type of low-ish 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, 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 habitually take.

But if you 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 eat really well and enjoy food when you're having the meal. 

Constantly snacking is something that is new. Something that only in the last sort of 20, 30 years or so has just become a norm. Eating, you know, confectionary 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-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 really embrace healthy old-fashioned food, you know the food that your grandmother would've cooked. Fish, meat, any type of vegetable and dairy products. 

Jonathan Wolf: Why are processed foods something that you are worrying about for someone who's looking to lose a significant amount of weight?

Dr Andrew Jenkinson: The problem with processed foods is, you know, they metabolically cause chaos in your body. 

They really encourage high insulin levels, sluggish insulin, and the weight set point goes up because you've got leptin resistance. So when you get rid of them, it's not to do with the calories, the weight will go down.

Jonathan Wolf: We talk a lot about mindful eating at ZOE. In fact, 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 across your books. 

What does mindful eating mean to you, and why does it matter? 

Dr Andrew Jenkinson: Yeah, I mean this is something that we've probably lost in Western societies, and that actually other societies still have it, particularly the French.

You look at the opposite, so mindless eating, which is what you know, actually we very habitually do. Eating processed, highly sugary, highly fatty foods mindlessly, and it's making them feel good. It's almost like a drug. They're stimulating their dopamine, they're relaxing.

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This becomes a habit. The brain wants to do these things because it makes you feel okay, you know, it makes you feel, you know, at ease and safe. So that's mindless eating, 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 savor before you eat. You know what you're going to eat, how are you going to prepare it, or which restaurant you're going to go to, you know, really look forward to your meal.

Really taste every mouthful, really, really savor it. 

Jonathan Wolf: And this can really make a difference to what you eat and ultimately your ability to adjust the set point. 

Dr Andrew Jenkinson: I think so. I think if you're really mindful about actually how some processed foods really taste and what they make you feel, you know, 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. Food becomes part of you. That’s a really important part, part of it.

The other thing about mindful eating is this awareness of hunger, awareness of your hunger gauge. We, in our western societies, well, if you've got a hunger gauge of zero to 10 where you're getting a little bit hungry when you're four, you're sort of starving when you're seven or eight.

Actually, you should be eating when you're about seven. We start to have a coffee when we're at three. 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 sauce. It makes the food taste so good. 

Jonathan Wolf: 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? 

Dr Andrew Jenkinson: I think it's very good, and it fits in with the weight set point theory and leptin resistance.

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 five two diet where you have 500 kilocalories, 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 rather sleeping, or you're consuming water or black tea, black coffee. So zero calorie beverages. 

Now that time that you're not eating is going to, your interesting 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 are carrying and have an appropriate response to that weight.

The more you fast per day, the more effective the time-restricted eating will be. The ideal thing is to have one meal a day, but you can have a very, very, very large meal. 

But if you can do eight hours a day or six hours a day, or play around with it.

We all have lives though, so there's going to be some days where you're going out, you're meeting people on a social occasion,

Jonathan Wolf: And this is guidance for people who are looking to lose a significant amount of weight.

Is that right Andrew? 

Dr Andrew Jenkinson: So if at the moment you have breakfast and then you eat all the way to 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 what my dietary advice would be apart from time-restricted eating.

So we'd said give up sugar, which said give up snacking. We'd said, try and give up processed foods. 

But the final thing is to reduce the amount of carbohydrates you take in. 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 down towards a hundred grams of sugar a day in our foods and maybe even less, maybe 80 or 60 before we get terrible carbohydrate cravings, this is going to have a really good effect on our in insulin.

So low-ish carbohydrate dieting that is tolerable. Yes, if you combine that with time-restricted eating as well. Fantastic. 

Jonathan Wolf: 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 Ozempic. 

Dr Andrew Jenkinson: 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. 

It's called GLP-1. It comes from the intestine and you know, after you eat, it's released after about half an hour and it's a signal that goes to your brain, 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, 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. Now, my new area of advice is actually use the drug the smart way. So maybe use them over a year to really understand things like the leptin resistance, the way it's set points. 

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. 

Jonathan Wolf: We didn't really talk about things that were outside 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?

Dr Andrew Jenkinson: Good question, Jonathan. And there is, because you know, 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 unpacking work or family issues or being able to have relaxation techniques is really important for weight loss. So you'll decrease your cortisol level, your insulin level will normalize. Leptin signal will be released.

Exercise has a similar thing. You don't lose weight via 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, et cetera, et cetera.

So these things: de-stress, little bit of exercise that you enjoy and sleeping well. 

Jonathan Wolf: 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? 

Dr Andrew Jenkinson: I think it's really to understand that it's not the calories in the food, i's what the food does to you metabolically. 

So avoid sugar, avoid refine carbohydrates, avoid processed food. Don't snack all the time. You'll lose a lot of weight just by doing that. 

Jonathan Wolf: 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 starved on and off for half their life ended up fatter than any of the other ones, including the one on this 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 weight and it's this beautiful analogy I think to the culture that we've all been living in for the last 50 years of short term, get your body ready for the beach, you know, restrict your calories, actually ending up damaging you.

That's because, 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're going to start to feel terrible. 

And all of this is about understanding this set point inside our body and how we respond to it. And so we have this hypothalamus in our brain, basically this measure that knows you are 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. Hence you feel tired. 

And you talked about this basal metabolism, which is 70% of all the energy I use, is just this background and that's going to reduce. 

And you gave me this beautiful sort of visual metaphor of a boat at anchor, you know, with this elastic rope. And you can try and pull it towards the shallow end, but the further you pull it, the tightre 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 my 60 days of energy, you talked about, I need to store steadily more and more of that.

But the other thing you said to understand is that our food environment is broken and as a result, our internal gas tank meter can very easily be broken. 

And you described 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 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.

You were describing about, maybe 40 years ago, where there might be just one kid in a school who's living with obesity, and now it's now it's a third.

And then you said, What can you do? And you know, your own program based upon seeing all of your patients over decades who want to lose a significant amount of weight, is sort of a step-by-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, 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 as a way to control the amount of time that you want to eat. You talked about quite short time periods. I know that at ZOE, our advice tends not to be as short as the one meal or six hours, but I know what you're talking about. 

People who are living with obesity, mindful eating, so being really aware of what you're doing is sort of sitting underneath this. 

Last but not least is not only about the food that we eat, you're saying de-stressing, sleeping well can also have a profound impact through these different pathways, not just through the leptin you were talking about.

And if you put all of this together, you've seen real success with people able to shift the set point, reduce their weight in a sustainable way. 

Dr Andrew Jenkinson: 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 tax 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.