Published 12 November 2026
How to lose weight without feeling hungry: The best method for fat loss without dieting and counting calories
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Why are you not losing weight?
Many of us ask this, and the advice on how to lose weight often leaves you feeling hungry. We’ve been told weight loss means eating less, moving more, but for lasting fat loss, dieting, calorie counting, and willpower may not be the answer.
In today’s episode, Professor Giles Yeo, who has spent his career decoding the biology of appetite and body weight, and Dr Federica Amati explain how to lose weight in a healthier way, and why it’s harder for some people than others.
You’ll learn how more than 1,000 genes shape the way your brain responds to food, and whether there’s really an "obesity gene."
We also explain why a calorie deficit stops working over time and how your gut microbiome affects your weight. We also ask: Can you lose weight without exercise, and are weight loss drugs an easy fix?
The episode provides simple steps for healthy, lasting weight loss. And, by the end, you’ll know which foods to reach for to help keep you fuller for longer.
If you can’t stop snacking, even when you want to diet, this episode will help you lose weight while eating MORE.
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Actionable takeaways
Is weight down to willpower?
No. Over 1,000 genes influence how your brain responds to hunger hormones and the food around you, making weight loss much harder for some people. But your genes aren’t your destiny – small changes to what you eat can make a real difference.
Do I need to count calories to lose weight?
Not necessarily. Cutting calories can leave you hungrier and is often hard to sustain. Instead, focus on food quality and what you can add. Fiber-rich whole foods like beans, whole grains, veg and nuts can help keep you full and satisfied.
Should I exercise to lose weight?
Exercise is brilliant for your health, but on its own it won’t lead to much weight loss. It can help you keep the weight off, though, so find ways to move that you enjoy.
Where should I start?
Start with one meal, rather than trying to change your whole diet at once. Breakfast is a good place to begin: try adding fiber, protein, and healthy fats, like Greek yogurt with fruit, nuts, and seeds.
What if my weight loss slows down?
That’s normal. Weight loss isn’t linear, and plateaus are part of the process. Try weighing yourself less often, and remember that slow, steady changes are much easier to stick with.
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Our new app reveals what the food labels won't, using data from the world's largest nutrition study run by ZOE.
Jonathan: Is weight gain due to poor willpower?
Giles: No.
Jonathan: Is how much weight we gain purely due to our genes?
Giles: No.
Jonathan: Federica, does calorie counting work for sustainable weight loss?
Federica: No.
Jonathan: Do all ultra-processed foods lead to weight gain?
Federica: No.
Jonathan: Is it possible to lose weight without going on a restrictive diet?
Federica: Absolutely, yes.
Jonathan: And finally, Giles, what one thing do most people get wrong when they're trying to lose weight?
Giles: That the people who are trying to lose weight obsess about every single meal, and I think that is the biggest mistake to make because then that removes the joy of life. You need to think about your diet as a whole, but not every single meal.
Jonathan: We all know that obesity is a huge concern, right? With this amazing shift, even in my lifetime, from the number of people living with obesity when I was a child to today, and most people I know either have tried to lose weight or are trying to lose weight, right?
Like, this is a massive thing in our population. And at the same time, the stigma that surrounds weight, you know, is really heavy and harmful and tough for people. You know, when I was growing up as a kid, I was told that being overweight was just a lack of willpower. Is that true?
Giles: It's not true. It's interesting.
I'm a geneticist, so I study the genetics of body weight, and we now know the genetics of body weight is actually the genetics of how our brain influences our eating behaviour. So when I say I study the genetics, people think I'm anti-physics. I am not anti-physics. I do understand that in order to gain weight, there needs to be an energy differential.
You need to eat more than you burn, and therefore, the solution to obesity is to burn more than you eat. This is the eat less, move more argument, and people are going, "Why have I... How come this is... Why you having me on again?" But that's the how. So how you get to the body weight you are, whatever size you are, small, medium, or large, is going to be down to physics because it's a fundamental law, okay?
The question is the why, and that is where the genes come in, and why do people behave so very differently around food? Why do people appear to be more efficient when they actually deal with the calories? So the genes that are involved in body weight pretty much exclusively sit in how our brain influences our feeding behaviour, and that, that's where the genes come in.
And just to give you an idea of what I mean by behaviour, because people are thinking, is it because you're more hungry? Is it m- I think it's slightly more nuanced and actually more complex than just simply being more hungry. So the scenario I always bring up is the Monday morning meeting scenario, all right?
And you know, we've all been there. We've all been around some hideous board table, and then suddenly someone on a Monday morning brings in a plate of cookies. Now, I would argue that as the plate of cookies is sliding down the table, that there are four, at least four different types of behaviours that kind of emerge.
So the first, as the cookies are sliding down the table, there's someone there who's already picked up the cookie and started chewing on it. Behaviour number one. Behaviour number two are the people who long for the cookie. They desire the cookie. They want the cookie. But for whatever internal algorithm, they don't pick the damn cookie up.
But as a result, they're now obsessing about the cookie the entire time, and they have missed the whole damn meeting. The third behaviour is people who are just the most annoying people. They don't even know the cookies have arrived. They're all going... And they ignore the cookie. And then the fourth, interestingly enough, are sort of the people who pick up the cookie and eat the cookie.
They don't even know they're eating the cookie. There are probably going to be other behaviours. These behaviours are not mutually exclusive, but that is what I'm talking about. It's the complex scenario, other foods are available, of what you do with a plate of cookies as it is sliding down the table in your normal life.
The genes that are involved in body weight sit around these behaviours, and pretty much some people are more drawn to the cookie and other foods than others, therefore eat more, therefore are larger than someone else, broadly speaking.
Jonathan: That's super interesting. You've gone straight to the brain and, like, this idea that there are all these different behaviours as the cookie arrives.
Why isn't it just a question of, well, if you just had a little bit more willpower and it wouldn't be a problem?
Giles: But what is willpower? Obviously, willpower, it depends on sort of, like, the behaviour, the trait we're actually talking about, but let's talk about the cookie scenario. What is willpower, right? If we're talking about willpower, meaning that either the person who picks up the cookie or the person who longs for the cookie and doesn't do it, you might say, "Oh, that's willpower."
Or is willpower simply some form of manifestation of some internal hormonal state? And I think ultimately that's what willpower is, the desire or the difficulty someone finds to say yes or no to the cookie, I think reflects an internal hormonal state, and that's the behaviour. So I think willpower is simply another behavioural output of the internal pieces of information that are communicating with your brain.
Jonathan: So you're saying that, you know, we use this word willpower, but actually there's all these hormones and things that are going on inside me. Could you just help me try to understand what you're saying is going on?
Giles: So feeding behaviour is a brain control thing, okay? It's a top-down thing.
Unsurprising, your brain controls many things, but feeding behaviour. So your brain needs to know broadly two pieces of information in order to influence your feeding behaviour. Internal information. There is lots of extrinsic information, the environment, which we'll get to undoubtedly, but let's speak internally first.
Your brain needs to understand how much fat you have, because that's your long-term energy stores, how long you last without any food. And your brain needs to understand your short-term energy stores, so i.e. what you're currently eating and what you've just recently eaten. And naturally, these signals are going to come from your gut, your gastrointestinal tract.
And so these are largely hormonal, okay? Not exclusively, but largely hormonal, so you're going to have hormones that are some, secreted from fat, hormones that are secreted from your gut, many hormones. And so your brain then senses this milieu of this repertoire of short and long-term signals and understands how much fat you have, have I eaten or not recently, and then some internal algorithm then influences your next interaction with a menu, with a refrigerator, with a restaurant.
And so that willpower will then be speaking about... Because after all, you can have a lot of fat but still be hungry because those are short-term signals, or you can be very, very, very full but tiny and skinny, okay? And so those are the two extremes. But after, it's going to be a spectrum, right? And it needs to be an interaction between the two to then say cookie or not.
And so that's what I mean by the willpower. Now, clearly then the willpower then depends on is it a plate of broccoli that's sliding down the table, or is it a plate of cookies that are sliding down the table? And then that willpower conversation becomes a little bit more complex because now you're in- you're interacting with the type of food that is there.
But that's what I mean. So there's some hormonal mix. First of all, people, when they... when we talk about hormones, think we're talking about sex hormones, which they do exist, but hormones exist for many other behaviours, including feeding as well. So that's what I mean by the willpower. The output of whether or not I can or cannot say no to the cookie is the interaction between all of these hormones that are sloshing around in your bloodstream.
Jonathan: It feels like something is going wrong for many of us today because it seems like we're eating more than in fact we need to if our body's just telling us, you know, what's needed to sustain and that that is different than it was 100 years ago.
Giles: So I think the concept of someone eating too much has been around a long time.
The prevalence of obesity is the contemporary problem, okay? Our genes haven't changed. The obesity rates have rocketed throughout our entire lives, and then we haven't evolved a second head, right? So ultimately our genes haven't changed, and so undoubtedly it's the environment. But let's go back to that cookie scenario, all right?
Where with the cookie there, there are gonna be more people reaching for the cookie and eating it than not, even with whatever internal hormonal state we're talking about. But say what slides down the table is not the cookie. I joked about broccoli, but let's imagine that there is a Monday morning meeting scenario in which suddenly we have crudité, you know, instead of cookies.
You're gonna change the number of people who pick up the carrot or the broccoli, or at least you're gonna be picking up fewer sticks of carrots or florets of broccoli than someone might be for the cookie. I think that probably is the explanation for the rise. The internal hormonal state is there.
The drive to eat is there. Now you need to interact with the rewarding elements of the food, the ease of which that you're getting the food. So back to the Monday morning meeting scenario. Now, imagine if before you actually eat the cookie, you need to log in, okay? So suddenly you put a hurdle actually in front of it, fewer people are gonna do it because, you know what?
Or at least the people who eat without knowing are now not going to do it because now they've realized something because now, "Oh, I've got to log in to get my cookie." And so I think the issue is the fact that it is a cookie rather than crudité, problem number one. The issue number two is ease of access to the cookie.
All right, where before, way back when we had to chase after the antelope, we certainly don't have to do that anymore. And then even 50 years ago, we would have actually had to go to a grocery store in order to actually buy the food. We now don't have to get off our couches. We can go beep, beep, beep, beep.
Someone will deliver the cookie to your door. So it's that mix, the internal hormonal drive, which is biology, and then the interaction with the cookie and everything that comes with it.
Federica: I think it's really nice. What you've basically touched on is this idea of different types of hunger as well. So what Giles is sort of talking about here with the cookies, really, that's hedonic hunger.
Your body's not lacking cookie. It's just that it's delicious. It's in front of you.
Giles: Some people are lacking cookie.
Federica: Some people are lacking cookie. And then there's homeostatic hunger, which is this actual need for food. So this is where perhaps your fat stores have gone down because you haven't eaten much recently, or there's nothing in your gastrointestinal tract, and so your gut is not releasing those satiety hormones.
And I think once we start to separate hedonic hunger from homeostatic hunger, you're able to see, like, do I... Am I actually hungry because I'm lacking in energy and nutrients, or is it because the cookies are always served? It doesn't matter where you have meetings. There's always biscuits, cookies, cake.
It's this interplay of the foods that are presented stimulate our brain to respond with a hedonic hunger response, which is, as Giles said, very genetic. So some people are just more prone to want to have the cookie, whereas others might be like, "Eh, actually, I've had breakfast, and I'm not that bothered by the cookie."
So I always think that when speaking to people, it's useful to frame them as different types of hunger. There's too much stimulation for hedonic hunger. There's too many options that tap into that separate circuit that isn't really strictly about nutrition.
Jonathan: And Federica, you know, I know you see a lot of patients as well as overseeing a lot of what we do at ZOE.
One of the things I'm struck by is how much people feel that weight gain is a personal flaw. But the conversation that both of you are having is the way in which these are hormones, and this is your brain chemistry. Like, why is it that people feel this so much as a personal flaw in the way in which, you know, many other cases, you know, you'd go and see a professional, and you say, like, "I've got this-"
Federica: Yeah.
Jonathan: "-condition," and you don't feel that same level of guilt?
Federica: Yeah, it's so true. I think there's just so much societal pressure to be a certain size, and you know, historically actually, having a bigger body was celebrated. In some countries and some cultures it still is. Especially in women, it was a signal that you might be more fertile.
When food was scarce, having enough fat was very important to actually be able to produce. But as time has gone on, you know, there's been this switch, and it was-- it's really interesting when you look at the history of body weight and body size, and there was this whole period of time where basically having tuberculosis was the ideal beauty standard, which is mad, really. But being thin and slim and not having fat became the desirable body type, and so there's this huge pressure societally to be slim and to not have any fat. And even until recently, not even be muscly if you're a woman. I mean, I remember growing up, I loved horse riding and ballet, and I was told, "You shouldn't do both. You'll have big legs." So there's this huge pressure, and so you feel this personal guilt. There's a huge industry around it. There's a lot of pressure from social media and the fashion industry. And so as a society, we've created this sort of- individual blame issue. And policy has as well, because for many years policy has focused on the individual.
It's like, "Oh, we'll give you more exercise classes. What we'll do is we'll make vouchers to buy fruits and vegetables," putting the onus back on the individual when, as we've discussed actually, if more than half of adults are overweight or have obesity, that's not an individual failure. That clearly shows you that the environment we're living in actually promotes weight gain.
And so the individual pressure people feel is actually really unfair because it's not an individual concern. It's not something an individual can beat by themselves.
Giles: And there's also the other problem. So all of this is true, but then we have to go back to sort of our, the humans, right? I mean, we're like half a step away from a chimp brain, which we are, right?
And we sort of model the world, right? So red berry, poison, you know, blue berry, lion, and that's what's kept us surviving. And so we tend to model the world based on our own personal experiences. Okay, so if I'm hungry, this is how much food. And obesity is an interesting human trait. It's not unique, but it's very unusual in a sense where first of all, it's very public, so in other words, we can tell when someone has obesity.
But substantially, it's different actually to other cosmetic traits. It's not gonna- but cosmetic traits like hair color because now we have an obesity in which we can point someone out, "Ooh, look, that person has obesity." But we can link it to a behaviour that's intimately associated with that specific trait, such as body weight, because it's public.
When you go to the grocery store, the supermarket, you know exactly what's going into the shopping trolley, the shopping cart, okay? If you're in a restaurant, I know exactly what you're eating. We go, "Ooh, how come she has three slices of pizza? I only need two slices of pizza." So I think now compounding the problem, we now have very public behaviours because we eat in public, we eat at home, but we eat in public.
Our body weight is public. Our chimp brains then are putting the two together. She's fat because she's eating too much. And I think that is also part of the problem in which everything is so public.
Federica: Yeah, 'cause it's true. So if you suffer with a mental health condition or perhaps even heart disease, it's not visible.
So you can go to the doctor, get your statins, and carry on with your life, and nobody's going to comment on-
Giles: Or your cholesterol levels or anything like that. No, no one can tell...
Federica: Exactly. Have you thought about not eating that bacon sandwich? So, like, no one will do that to you. But when you're living with obesity, people always feel like they can comment.
It's a bit like, the only thing I can compare it to, I haven't lived with obesity, is pregnancy.
Giles: How far along are you?
Federica: It's like, well, really none of your business.
Giles: Yeah, no.
Federica: Exactly. So like, are you making sure that you're not doing too much? So there's, as soon as something's very visible, and I have to say I feel like for women it's more so.
So when I work with people one-on-one, the thing I'm always struck by is the level of shame and guilt and desperation where they've tried everything, and this is especially people who have lived with obesity for the majority of their lives, so since they were young. And it has taken over their lives in a way that it's hard to imagine unless you've been through that.
It has consumed their thinking. They think about it every single day, and they try so hard to reach a body goal. And it's usually body weight, so it's usually something to do with the scales. So much so, Jonathan, that they forget about the rest, how they feel. Are they enjoying their food? Like, what would they like to be doing with their children?
What is it about their lives that they look to improve? 'Cause it becomes so much about that body weight and size that you lose sight of, like, the enjoy- the joy of life, and it's really sad.
Jonathan: I think that's a really powerful way to describe it, Federica. You know, I feel really moved just hearing about it.
I think the next thing I'd love to discuss as well, so is it all your genes? And so Giles, I've got one of the world's experts on this topic in the room. Can you start by just saying, like, you know, how much does genetics influence weight compared to other things?
Giles: We actually have a number. Well, it's not a single number, it's a range, but we actually have a number of this.
I think the term we're looking for is heritability, which is in other words, for the yin to the yang, how much is genes, how much of it is environment? Like with most human traits, it's come from the study of twins. I realize Tim Spector works with you, but just to briefly précis twin studies, you have identical twins and non-identical twins.
Identical twins are genetic clones of each other, 100% of genetic material. Non-identical twins, as much material as we would with our siblings or parents, 50%. So in a large enough set of twins, tens of thousands of twin pairs, you can then say, 100%, 50%, you can calculate heritability. And if you do so, then the heritability of body weight sits between the 40 to 70% mark.
So it's quite a big range. But I guess if you sort of split the difference, then roughly speaking, it's probably safe to say that for most people it's a 50/50 thing. So that's the number. 40 to 70%, split that difference, that's a 50/50 split.
Jonathan: And Giles, you touched on this in the questions right at the beginning, but I've seen all these headlines, you know, over the last few decades, scientists discover the obesity gene.
Is there like one or two genes that, you know, you and other scientists have found that explain that 50%?
Giles: No, there's actually more than 1,000 genes.
Jonathan: More than 1,000?
Giles: So there are gonna be more than 1,000 genes that have been associated with obesity, but we have found, we the community rather than me personally, we have found about 30 of them, of these 1,000, that when you have a whacking great big mutation, so in other words, when you actually have a bona fide something wrong with that gene, causes severe obesity.
0.3% of the general population will have these whacking great big mutations, okay? In one gene in particular, but broadly speaking around this area. A broken fat sensor. That does mean that 99.7% of us don't, and with about 50% of the population having obesity or being overweight, then clearly 99.7% and 50%, there's got to be somewhere in the middle.
And that's where the other 1,000 genes actually come in, where they're not whacking great big mutations, but actually are very subtle variations. And imagine of these 1,000 genes that there are two... Now, these are not mutations. All of us have these genes, right? It's just that if you might consider for each gene, there is a, make you, an influence so that you are lighter version versus you are heavier version.
Let's just simplistically put, okay? So in other words, you have genes that either you have one version that you are more likely to be lighter and one version you are likely to be heavier. And so you can then take the 1,000 genes and almost sum them up. Now, in normal biology, we all have an average number of these genes, broadly speaking, but some are going to have more, some are going to have less of the heavier version, which is why we are, is, which is why it's a spectrum.
So some people are going to be small, medium, or large.
Jonathan: I'm really interested how, firstly that how complex this is. You know, just like thousands of genes coming together. You know, it's not like there's just like this one gene that explains something, but also that the example you gave is right straight back to sort of how your brain is sensing your body weight and adjusting what you want to eat.
But it also made me think actually about my children as you were saying this. My daughter, ever since she was very little, has never really wanted to eat breakfast. She just hasn't been interested. And my son, who's much older, always really liked breakfast. Could those be examples of these subtle genetic differences that you're talking about?
Giles: Absolutely. That's pretty much what we're talking about here because some people might be more hungry all the time, some people might need more food to get filled up all the time. But it is far more often more complex. When you're driving down the highway or the motorway, does the yellow M shout at you, whisper at you, or do you not see the yellow M at all?
There are huge complex interactions, internal hormonal state with yellow Ms on the side of the highway that have to sort of meet in order for you to take the next exit, right? Because ultimately that's what it is. Whatever s- thing is going on, what makes you reach for the cookie?
There is still something, nerve still has to go hand cookie two, right? And all of these things, but it is all a response of this internal hormonal state interacting with the cookie, interacting with the yellow M on the side of the motorway.
Federica: What's also interesting is that the interplay of how these genes are then expressed and how they interact with our biology changes throughout our life course.
So your daughter might love breakfast when she turns into a teenager, and it will be the same genes. She has the same genes. But perhaps her hormones or her lifestyle will change how she experiences her hunger and her satiety.
Jonathan: So I'm really struck that as you talk about the genes, it feels like so much of what you've been talking about is how we respond to the food environment around us, and you're saying there's a big genetic difference, right?
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So half of people end up living with obesity or being overweight, half don't today. You're saying that, and part of that is the genes that influence how easy it is to resist the environment around us, is what I'm understanding. Is that the heart of what you think is going on in terms of the genetic, the genes, right?
Giles: It is, and it isn't. So let me answer this obliquely, if I could. One in eight people in the world have obesity, about 50%, certainly in the UK, United States, Australia, Northern Europe, places like that, have, are either overweight or have obesity. But hidden under that average is the fact that it's unevenly distributed.
I mean, obesity and overweight aren't evenly distributed throughout the world, but actually even within a singular country, it is unevenly distributed. So if you look at the bottom quintile, 20% socioeconomically, in many of the countries we've talked about, rates of obesity, certainly in children, 11-year-olds, 12-year-olds are more than twice if you are in a bottom 20th centile socioeconomically versus top 20th centile socioeconomically.
All right? The differences are stark. If you look at 10, 11-year-olds leaving primary school, elementary school, grade school, okay, 10, 11-year-olds, if you look at top 20% rates of obesity, 13, 14%, too high, but that pretty much is it. If you look at the bottom 20% rates of obesity, north of 30%. I've got a colleague of mine, Professor Clare Llewellyn, she works at UCL, and she has a cohort of twins as well.
It's called the Gemini Study. Uniquely, unusually, her cohort of twins has socioeconomic information underlying. So 40 to 70% heritability of body weight. Here's the interesting, well, it's interesting to me as a geneticist. If she goes to the households that we would be more familiar with, so top 20th centile, then she actually finds that the heritability of body weight sits at about the 40% mark, okay?
Now, if you go to the households, lower socioeconomic status, more food insecurity, the heritability maxes out at 70%. Hang on a second. I thought we were talking about genes, right? And there's no genetic difference between rich or poor people. It's an accident of birth. So how come when you go to different households of different socioeconomic status, your heritability can change?
And so the answer is because while your genes can't change, your environment does. So yes, it is access, but then you then layer on this complexity of socioeconomic status, of how much the food costs, of where you live, of where fast food shops are concentrated in, whether you have a kitchen in your home.
Jonathan: If someone has the genes that are predisposing them to gaining more weight, does that mean there's nothing you can do about it? Are you sort of doomed by your genes?
Giles: I will never be able to run as fast as Usain Bolt, okay? And it is because of my genes, I'm sticking to that. But actually it doesn't mean that if I train harder, I won't be able to run faster.
So I think your genes do set some parameters. Why do I look Chinese? Because of my genes. Why I don't have any hair? Because of my genes. Why am I more likely to pick up the cookie? All right. There are going to be genetic drivers that make it more or less likely, more or less difficult than someone to do it, but it doesn't mean you can't do anything about it.
I think there are going to be some people that because of their genes are never going to be stick thin. Okay? Probably. And there are going to be other people who are, without any effort at all because of some internal hormonal state, won't actually gain a great deal of weight, unless you have these rare mutations I'm talking about, but let's put that aside.
If you have some mix, then there is something you can do about it. It's just that it's going to be harder for some people than others.
Federica: I think it's empowering when I think the point of this information is that you realize, okay, it's not your fault. It is a hard environment to stay healthy in.
So you- we're slightly swimming upstream as a bunch of salmon. That doesn't mean you still shouldn't try and swim upstream, right? You still want to get up that waterfall. We all have different bodies, we have different genes, we respond differently to environment. What can you do to help yourself get to the healthiest possible state? And throw away this notion that if you just starve long enough and run for long enough, you'll look like someone else.
Giles: I wish I looked like Brad Pitt, but you know.
Federica: I wish you did too, Giles. But no, it's really empowering, I find. So as, again, when I work with people and we talk about this, they feel very bad. They're like, "Thank you. When..." We say, "It's not your fault, actually. There's all these conditions, but let's work together to get to a place where you can improve your health and improve your body size, if that's a goal."
So certainly we're talking about fat loss reduction here. We're trying to reduce fat mass because that can be harmful. And instantly it's like, "Oh my gosh, thank God you've said that. It's not my fault, but there is a lot we can do." There's some fascinating studies that show how gut microbiome composition can predict weight loss more strongly than your genes.
So there are things you can do to harness the power that your diet has on other systems in the body to essentially help you to lose weight in a healthy way.
Jonathan: Actually, Federica, you just mentioned the gut microbiome. We obviously talk about that. We've rarely talked about it in regards to weight loss.
Like, how important is it?
Federica: Yeah, so actually it seems to play a big role in understanding who's more likely to lose weight with a dietary intervention, and there's a few studies that have been done that aren't our own, Jonathan. So other scientists have looked at gut microbiome composition as a predictor of successful weight loss, and they've all been published in the last sort of five, six years.
Couple of studies that have really shown that when you analyze the gut microbiome composition, you can predict which group is going to lose weight more easily with a dietary intervention. In our own data, using our gut microbiome score, we can predict someone's BMI just by looking at the composition of their gut microbiome across other people's data sets.
So not even just ZOE members. So what we're starting to see is that gut microbiome composition is a piece of the puzzle to how your weight trajectory is looking. And then one of my favorite studies, which was published in thinking '23, did an intervention in a closed clinical setting. So where they keep people in a lab for a long time, and the intervention group had, they had a calorie-matched diet, same food, but the intervention group had more fermentable fibers, so more fibers that our gut microbes love.
And that group, the microbes were so happy and fermenting away that they actually used some of the energy from the diet for themselves, for their own biomass growth, so to reproduce. And so that intervention group, the people lost 100 calories a day to their microbiome, which then resulted in weight loss, but the calories were matched, the expenditure was matched, so they weren't burning any more energy.
It was their gut microbes that were doing it for them. It's one of my favorite studies, and it's, it needs to be replicated. But how exciting to think that in certain individuals, just by ramping up their gut microbiome activity, where the microbes are so happy and replicating, they're using energy from the diet to replicate themselves and then you poop it out.
You're modulating this energy balance with your microbes. Again, we did a recent analysis which we presented looking at people in our co- in our study. We found about 5,000 people who were living with obesity or with overweight, right? And we wanted to understand, okay, can we see any interesting change without calorie restriction?
Like, what is helping these people lose weight just doing ZOE? So just by following the advice in the app, right? And of those 5,000, we saw that actually a large percentage, more than 80% were losing some weight, which is encouraging, and about 35% of those were losing significant amounts of weight. So we're talking like a stone, so like six kilograms per plus.
When you look at that group and you're like, "What's going on there?" They were highly adherent, so they were really following the advice. They were getting their scores up, which means they were eating lots of plants, whole plants, a lot of the advice we give. And of the highly adherent group, more like 50% of them were actually losing a stone, six kilos more or more, up to 7.5.
They weren't eating fewer calories than people who didn't lose the weight. They just ate more of the foods that we think are culturing the microbiome and helping with that weight loss in that way. There is of course, as well, it's worth noting, whole plant foods act very differently with our physiology than, you know, a highly processed food.
So if you're eating lots of nuts and seeds and berries and lots of broccoli, then the way we actually break that food down and absorb the nutrients and the energy from that is entirely different to something that has the same calories but is in a different format. I remember hearing you talk about the difference between eating a raw celery and a cooked celery.
I will let you tell the story, but how we eat is so important.
Jonathan: Tell me about the celery.
Giles: No, no, how we eat and how we process the food. Yeah. So pe- okay, look, first of all, just to... Let's debunk some myths here. People think that celery is negative calories. Yeah, I love that. So in other words, you're actually losing weight.
It's not... So an average stick of celery probably sits at around a six-calorie mark. It's not negative. It's pretty close to zero. What's interesting, however, celery, as we know, it's fibrous, it's stringy, there's a lot of chewing involved, it's mostly water. But what actually happens is if you cook the celery, if you chop it up and put it in a stew or a gumbo or whatever the hell it is you're eating, actually you increase the number of calories you can get from a celery from six to around 30.
There's a fivefold increase in the amount of calories. I haven't added calories. This is not, I'm not anti-physics with this. We've established this. But actually, the cooking makes it easier, takes less energy for you, and you can actually extract more calories from it.
Jonathan: You're like pre-destroying the food matrix before you even eat it.
Giles: You're pre-digesting it.
Jonathan: Yeah, yeah. Amazing. So it sounds like food quality is a very important thing that's overlapping with sort of the genes in terms of understanding weight loss.
Giles: I think I would go further. I would say food quality is the most important thing. People think it's the amount of food we eat.
This is the calorie argument. There is something to be said for the amount of food. You could have a wonderfully healthy diet but just eat too much of it. But I really do think that a primary problem is the quality of the food that we have largest access to at the moment. So I would go it's the primary problem.
Federica: Yeah, and it's exactly what we saw in our trials. So when we did the intervention of ZOE versus standard diet, the calories were the same. People ate the same amount of calories. There was no difference. But people who were eating the ZOE way lost weight and lost waist circumference and re- improved their blood markers, and it was the quality of food that changed.
It wasn't the calories.
Jonathan: So were they on a calorie-restricted diet?
Federica: Nope. Neither of the groups were on a calorie-restricted diet. One group was on a recommendation, sort of public health recommendation, the US, USDA guidelines, and the other group was given the personalized advice through our app. And they actually looked at calories.
They-- no one changed their calories. There was no calorie restriction, but the group who ate more quality, high-quality foods in the ZOE group lost weight. So we might both eat two thousand calories, but if what I'm eating two thousand calories from whole foods, my body is not gonna be able to as quickly extract as many calories.
Even if the actual food contains two thousand calories, I won't be absorbing all of them. If you're eating two thousand calories in a ready-to-drink shake throughout your day, you will absorb all of it because there is no work for your body to do. It's going straight into the hepatic portal vein to your liver, boom.
So what we ingest in terms of calories is not the same as what we absorb, what our gut microbes use for us, and we poop out. It's just not the same. So it's not... I'm like Giles. I'm not anti-physics. We all understand what calories are, but they are just not the only factor to consider when we're considering healthy weight because it's just not the same thing.
Also, if I'm eating two thousand calories from whole foods, I'm gonna be satiated. I'm gonna be full. My stomach is stretched. There is stuff going on in my gastrointestinal tract. There is fiber in my colon. My gut microbes are busy. There are hormones like GLP-1 being fired back to my brain for the day.
If you're drinking your meals throughout the day for two thou- the two thousand calories, you're gonna be really hungry, and you're not gonna have any of that lovely satiety response that happens with whole foods. Very different experiences. Calorie restriction works. You will lose weight, but you're ignoring everything else that's happening in terms of food matrix, nutrient density, and actual gastrointestinal activity.
Jonathan: And when you say calorie restriction works, I mean, I think, like it works for a little while-
Federica: Yeah, then you get hungry...
Jonathan: And then you get really hungry, and then you binge on some food, and you feel really bad about yourself.
Federica: Your body adapts, right? So however you're restricting your calories, your body interprets it as some sort of famine.
So back to what Giles was saying in terms of fat hormones, right? If we lose loads of fat, then our brain gets the signal that, oh my gosh, we have decreasing fuel gauge, fat mass is going down. We have less and less energy stored. When you then start eating again, your body will store as much of it as quickly as possible into fat just in case another famine is around the corner.
So metabolic adaptation, hunger, and frankly, misery if you're doing calorie restriction without the support of medicine, so just by dieting. It's hardcore, and it's hard to do, and it's not a very happy experience for most people.
Giles: Agreed a hundred percent everything there. I guess everyone just remember, we eat food.
We do not eat calories.
Jonathan: Federica and Giles, I have two absolute experts with me today.
I'd love you to unpack my own experience around weight, if that's all right. I was always told as a child that I was actually very thin, and I was small, and if anything, I would have liked to put on a bit more weight and of course a bit more muscle. That was also true sort of throughout my 20s. And then around my mid-30s, I started to sort of very slowly put on weight.
So it wasn't like I suddenly noticed over six months. But the net result of that is that when I met Tim Spector in my very early 40s, I'd probably put on about six or seven kilos over the previous decade, and I was interested in nutrition because I'd been suffering from these food intolerances for a long time.
But I just never thought about weight. But suddenly I was like, "Oh, wow, I actually don't fit into the same jeans that I had." And that's a bit of a shock. But after about two or three years, I'd actually made a really sort of profound change in terms of what I was eating. And as part of that, I was actually probably eating more food than I was eating before.
So like big volume of things at breakfast, lunch, and dinner, 'cause this is all like really good stuff now. It's like, wow, like extra virgin olive oil is good for me. So like- I'm splashing it all over. And what I realized like after a couple of years is actually I ended up losing about four kilograms. And the reason I knew is I was able to wear these jeans from my 30s that I couldn't wear.
And I think the thing I'm most struck by is that about six years later on, I haven't put any more weight on. So could you tell me basically what is going on?
Federica: What you probably noticed is your waist circumference changed.
Jonathan: That's right.
Federica: And what tell- that tells us is where your fat was distributed. So actually, one of my favorite metrics for metabolic health is waist-to-height ratio.
Understanding where your fat is distributed is very important. So by any kind of stretch, if I had to guess, Jonathan, your BMI would still have been within normal range even when you were a bit heavier. But your waist may have gone up, and your waist-to-height ratio may have changed, and that is more of a pr- more of an issue when we're predicting cardiometabolic health, your risk of heart attack or anything like that.
You want your waist to be about half your height. And the fact that you can now fit your jeans again tells us that you probably lost the weight where we want you to lose it, which is the fat that stores around your organs, which is the most dangerous type of fat. It's called visceral fat. You also didn't mention anything about still having these food intolerances, which is another hint.
So you've fixed those, you're eating more, and your visceral fat has gone down. And that is all thanks to an improvement in your dietary quality, and it's critical to improve your cardiometabolic health. People often say, "Well, I can't believe she's saying I need to eat more food." I'm not suggesting that to improve your cardiometabolic health and improve your weight, you need to eat just more of any food.
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But eating more of the right food groups is critical to improve your health, including losing the weight that you want to lose, which in your case, visceral fat.
Jonathan: How is that possible that I'm not putting on the weight that I was putting on a decade ago?
Giles: So I think ultimately changing what you eat for higher quality is what is doing the job.
And I think that has got to be the biggest message. Now, once you've actually fixed your diet, and if you're still gaining weight, then maybe you're eating too much of this wonderful diet. But, you know, that is a secondary problem. Fix the quality of your diet first, and then if issues are still there, then you can begin to think about actually the amount of that specific diet you're eating.
But with this kind of whole foods diet where there's a lot of fiber, it's actually relatively difficult to overeat beyond what you... Because this stuff is naturally more satiating and actually bulkier, right? So in other words, you get... You just... Everything gets filled up faster. So I think there is an internal sort of control that you can actually get once you actually get to a whole foods diet.
Federica: Your diet, Jonathan, made up of these whole foods, and what I love about beans and legumes and whole grains is that once we learn how to cook them, they're affordable and they can be cooked in batches so you can have them ready to go. So when you're eating those, as Giles said, you have this volume of food, right?
So your broccoli, your cauliflower, you're eating these big plates of fiber-rich, voluminous foods. Hits your stomach. Well, first of all, you're preparing them at home, which is fantastic. You see them, you interact with them. That helps your brain prepare for food. That's actually the first phase of satiety is in your brain.
Then when you eat it, your stomach has these stretch receptors, much like your bladder, and when it stretches, it sends a message to the brain to say, "Okay, we've got food coming. You can ramp down the hunger sort of responses and looking for food." And then as it travels through your small intestine, where a lot of the fats and the proteins and the carbohydrates are absorbed, that sends another message to your brain, "We have nutrients."
And thanks to it being so fiber-rich, it reaches your large intestine where your gut microbes have an absolute field day. And a lot of the cells that are involved in making hormones like GLP-1, GIP, PYY, all these satiety hormones, they live in your colon, and they're sitting there waiting for a signal that means that nutrients have arrived.
And a lot of them are concentrated in your large intestine, and it's your gut microbes that break down the fiber, and they also love things like omega-3 fatty acids, and they then release short-chain fatty acids. They make short-chain fatty acids that interact with your L cells and I cells that help the release of these satiety hormones back to the brain.
And if you think about your breakfast or your lunch, two, three hours later, you're getting this lovely response in your colon thanks to your high fiber diet. So you have this sort of nice sustained messaging from your gastrointestinal tract being like, "Hey, we're good. We don't need to look for food because we're actually still going through what we ate."
So that's like a way of thinking about how can you eat so much but then feel so satiated and still not put on weight.
Jonathan: What I'd like to talk about now is what people can actually do to lose weight or indeed, as we sort of discussed, like, to maintain their weight so that it's sort of static over time rather than that sort of slow and steady rise.
Are there any other easy and healthy ways to lose weight? When I was growing up, everyone talked about exercise as a solution. I seem to remember Coca-Cola advertising, like, all sorts of exercise activity.
Giles: They still do. Exercise is probably the best thing you could ever do about pretty much anything you can think about.
Your mental health, your physical health, everything about it, except, oddly enough, weight loss. Okay, now- Do not read this as don't exercise, okay? But don't use it primarily for weight loss. I mean, undoubtedly, it plays a role because obviously there's the energy balance issue. In principle, you could lose weight just by exercise if you were an Olympic athlete.
Okay, in other words, you're exercising so much that you don't have to think about your diet at all. For the vast majority of us mere mortals, if you don't change your diet, exercise is not going to shift your body weight, even though it's actually going to improve all the rest of your markers and everything.
It is, however, really quite effective at helping you maintain the weight loss. So if you get to the weight maintenance stage and what we're talking about, actually exercise helps. So exercise, wonderful for everything but weight loss, but actually really quite effective for weight maintenance once you've actually lost the weight.
Federica: And I'd like to also add that movement and exercise can be treated slightly differently. All the, like, bits we do throughout the day, the walk to the station, the gardening, the walking your dog. Like, moving throughout the day is a really important part of maintaining health and of maintaining weight, but can actually be helpful in your weight loss journey.
This is especially important if you're somebody who is very sedentary. So if you're starting from a point where you really don't move much, you don't get out and about, then integrating movement with the dietary change is important to help move the weight loss along and keep it healthier. Daily movement is another slice on top of exercise, so do both.
Jonathan: Other than exercise, are there any easy, healthy ways to lose weight? And I guess the thing that springs to mind obviously is like, how could we not talk about all of these, you know, new weight loss drugs, the Ozempics and the Wegovy?
Federica: I wouldn't consider those drugs an easy option. They require work.
You need to improve your diet. You need to keep moving. You need to really bring resistance training into the picture if you want to maintain healthy lean mass. We should never frame medicine as like an easy option. You have to be screened appropriately, make sure that it's the right medicine for you, and then you have to be followed up closely to make sure that there aren't any adverse effects from taking the medicine.
So I would take that out of the easy box. But it's definitely one of the new tools we have, which is very exciting for treating people who've lived with obesity for a long time.
Jonathan: Let's say you're listening to this podcast, you're thinking about trying to lose weight. What is the most important thing that you should be thinking about as you think about food?
Giles: I think I would do two things. So first of all, the first, slightly depressing, look at your parents. At the moment, that's the best predictor. What shape are they? If they're alive, are they healthy? If they're not, or are they ill? It gives you a really good idea about what's coming down the road, okay, before you get there, and you can begin to think about mitigating things.
So that's the first thing I would do. The second thing I would do is now consider why you think you eat more than you need to, and this answer is gonna differ depending on who you are. Do you eat because you're stressed? Are you the eating the cookie person? What do you actually eat? It's the big, bad world out there.
It's very difficult to control the environment outside in the world, but you can control the environment within your four walls that you call your house. So be honest about why you eat and what you eat, and I think most of us can know that, and then mitigate against what you let in the front door. If it's cookies, cookies.
Just don't do that. If it's chocolate... In our household, for example, my wife refuses to let me bring chocolate into the house, except maybe when I come back from Belgium and I buy some. But she says, "Look, don't," because the moment there's chocolate there, she cannot just leave the chocolate alone. Once she's had a piece, the whole bar is gone.
She has to tell me to hide it. So I don't bring chocolate into the house unless I'm... There's a special occasion. My problem is potato chips, all right? Where I will just finish this, so I don't have potato chips in the house. My pe- my friends come around the house, "How come there's no potato chips?"
Because. So think about your household, why you eat, what you eat, when you eat, and try and mitigate against that in your household.
Federica: Learning how to cook is such an underrated life skill. If you can learn how to cook foods that you love to eat at home, it unlocks freedom, so you don't have to depend on the ready-made foods or deliveries and things like that.
And then make it really easy to snack healthily. So for example, I keep mixed nuts in lovely little Kilner jars from Amazon on my counter, and I have fresh fruit bowl out, so that if I'm walking through the kitchen and I'm like, "Oh, I just kind of fancy something," I'll grab a handful of nuts and a piece of fruit.
Yogurt in the fridge, things like that. The other thing to consider is to really don't try to tackle your entire diet in one go because it can be very overwhelming. Begin with breakfast. Make breakfast so nutritious, like get all of your whole foods in there. You've got the most control. You're at home.
It's before you leave the house and tackle the big, bad world. Make it so filling and satiating and delicious that it makes it a lot easier in that 9:00 AM meeting when they bring out the pain au chocolat, you might be like, "Actually, I'm good," or, "I'm gonna have a bite and then leave it." And then one last thing, I really recommend being honest with yourself about what you're drinking.
Often people overlook the sodas, the alcohol. Alcohol is not your friend if you're trying to lose weight. It's not your friend for lots of reasons, but if you're trying to lose weight, consider that a glass of wine or a pint is 300 calories, zero satiety, and it's bad for lots of other things. So be honest about how much you're drinking, where can you reduce it, and then Bob's your uncle, you're on your way and you're gonna feel better.
Jonathan: Giles, what are your thoughts listening to that?
Giles: No, I think that's absolutely right. Look, I think the real solution to actually sustainably tackle obesity has got to be done societally, ultimately, because if we look at what we've been talking about, right, the fact that there are biological drivers to eating that we're trying to control the environment we can control in the home.
But we're at home, particularly if you work, we're at home for a minority of the day, the most of our day is spent in the world outside. So the real answer is that we need to tackle the food environment outside, which cannot be done by individuals. We can do grassroots as a collective, but ultimately it's policymakers.
It's interesting, we talk about these drugs, okay? Are they a shortcut? Are they easy? And what have you. I don't think they're a shortcut or easy for the person with obesity. I think it offers for some people the specter of hope. I do, however, think it could be used as an excuse by our policymakers, whatever color they happen to be, okay, as an excuse not to take the often politically inexpedient choices you need to make to improve the food environment, education, legislation, all the -tions, in order to actually do that.
So I think we need to sort of take a step back and look, I don't think obesity is a choice from a biological perspective. Currently, I don't think it's a choice from the environmental perspective either, because it's a driver to do it. So don't use any of these drugs or anything else here as a shortcut.
We still need to fix the food environment.
Jonathan: So listening to like, you know, Federica's list of advice, like it's really powerful. Giles, I'm really interested in going back to the people who've been listening to this and saying, "You know what? I'm pretty convinced that I have some of those genes that you were talking about, that, you know, I find it harder to resist the cookies that goes by, or maybe I'm a little bit hungrier, and that is what I've sort of been living with for a long time."
Is there any particular advice that you would give them about how you should think about, you know, the foods you're eating and all the rest of it that, like might really help for people who are like, "No, tho- I feel like those, you know, I've got those genes"?
Giles: Yeah. So I think as I said, try and control your household, but what happens in a big, bad world out there?
So I think the first thing is to try and think about your diet as a whole rather than an individual meal. So if you think about your diet as a whole week, then I think that's a healthy way, healthier way to do it, where if you've got sort of like a birthday party and what have you, then you can think about foods that are then healthier elsewhere.
I think we need to think about eating enough protein for sure. I think we need to eat a hell of a lot more fiber. The more fib- and fiber only comes from plants, right? And grains. So you need to add, eat a hell of a lot more of that. And I think you can then use those general rules and think about your diet in terms of over a period of a week rather than in an individual meal.
But if you find it difficult, don't think it's because you are bad. For those people finding it difficult, it's because you're fighting your biology one step at a time. The thing about weight, weight is cumulative and weight will come off with small changes, and that's what you've got to think about. You don't have to think about tackling all of the problems all at once.
Jonathan: If people start to eat better, start to, you know, eat in a way that's supporting their microbiome and the other things that you were talking about, Giles, start to do at least the movement, like how quickly might they start noticing a difference?
Giles: I don't think this is a question of speed. The problem is the only way to do it quickly, leaving aside the pharmaceutical aids, the only way to do it quickly if you want to do it by diet is if you do something extreme, and the problem with extreme approaches is that they're nearly, if not impossible, to stick to.
Whereas if you're doing something in which you are trying to achieve some kind of energy deficit but it's tiny each day, you're taking small steps, and oh my God, it's only, it's been a full year and I've only lost 10 pounds. Do you know what? Your chances of keeping the 10 pounds off are just far greater than if you lost the 10 pounds off in the first two weeks, literally.
Federica: And I think it's really important to note that weight loss is not linear. So what tends to happen is people will lose an initial amount of weight, feel really good, then it will stall a bit, and they'll be like, "Oh, no, it's not working anymore." It's actually normal for weight loss to be very staggered, and that is part of that metabolic adaptation.
It's also because initially we really kind of lose water weight. So remember, it's a long journey, and it's not a linear one. So I also really recommend not weighing yourself every day. Like actually spread it out a bit and just see that you're going in the right direction. Use waist-to-height ratio to see your fat distribution is a really good marker as well.
And, you know, I think most people will see if they change their diet and they ch- start to change their lifestyle, and they do integrate the movement, better sleep, then you will start to see weight loss within about six weeks. And you want to sort of, back to Giles's point, you don't want to have a massive crash.
And same on the medicines, actually. So people who lose, who are overresponders and lose a lot of weight on these medications are less likely to be able to then maintain and sustain. So slow and easy wins the race, I guess. That's the best- Yeah- way to think about it.
Jonathan: Finally, Giles, if someone is feeling motivated right now on the back of this wonderful podcast to embark on a weight loss journey, what's the one piece of advice that you would, you know, give them at the very top of this list to take away at the end of today's episode?
Giles: Variety. Variety. I think most of us do the same damn thing all the time. How we move, how we eat, where we get our veg from, where we get our meat from, and I think that's part of the problem. I think if you could every single week decide I'm going to try a bit something new. I'm going to try a new bean.
I'm going to try a new way to work. I'm going to try a new movement. I'm going to try a new piece of a protein. And I think that if we actually try and bring something new into our life once a week or something, that variety, I think because then you're thinking about what you're doing, I think that is a first step to try and improve your health.
Variety.
Jonathan: I love it. I'd like to try and do a little summary of what we've covered. But before I do that, I wanted to say that if you've enjoyed listening to Giles, and I have to say, I always absolutely love doing these podcasts with you, Giles. It was wonderful last time. Wonderful again. Giles actually has a brand-new podcast of his own called A Matter of Fat.
So if you would like to get more of Giles, then you will find that, I presume, on all good podcast-
Giles: All the normal places...
Jonathan: Exactly, where you're listening to this show. So what have I taken away from today? I think the biggest thing by far is if you're living with obesity or if you're overweight, this isn't just all your fault.
This isn't just because you don't have willpower. We now understand, firstly, that there's at least 1,000 genes that influence obesity, and that all of these genes, in fact, what they're doing is really adjusting the way that your brain is responding to all these hormones you're getting from different parts of your body.
And so it's the brain that is really driving the hunger, and you are going to be responding differently to the same, like, weight and food, depending upon, you know, your own genes. But critically, genes are not destiny. Just because you have these genes, that doesn't mean you're forced to see that. And one of the reasons we know that is, like, everybody had the same genes 100 years ago, and very, very few people were living with obesity.
And now we have this crazy thing where, you know, half the population is, and that's because the outside environment has changed. We then talked about what can you actually do about this? And the first thing I think, which I always find really shocking, is exercise is great for your health. You should do it, but you won't actually lose any weight with it.
Which is like, so it's not willpower, and exercise doesn't solve it. But you did both say that if you've lost weight, exercise can help with weight maintenance. Yeah. You can get to a healthier state. And I think both of you focus also that it's a lot more about your health than it is about like a number on a scale.
And to do that, you need to actually embrace food as a solution, not as the problem. I loved what you said there, Federica. Try to learn to cook a bit. Transform what's in your house because you have control. Get lots of healthy snacks. Don't try and fix everything in one go. This should be a step-by-step program.
And Federica, you were saying start with breakfast. Be honest with yourself about what you're drinking. Sugary sodas are terrible. Alcohol is also going to be a real problem if you're trying to lose weight. So be honest about that. Think about your diet across the whole week. Forgive yourself.
Everything is okay occasionally. This is simple, but not easy. So like, it's not that there's some super complicated thing that you have to do, but it's gonna be hard. Don't blame yourself. And finally, what I took away is successful weight loss is slow and steady.
Federica: Yeah, beautiful.
Giles: Lovely summary. Yeah. I need you to come work for me.
