Paul (00:03.164) Hello and welcome to this episode of the Curious Advantage podcast. My name is Paul Ashcroft. I'm one of the co-authors of the book, The Curious Advantage. And today I'm here with my co-authors, Simon Brown and Garrick Jones. And today we are delighted to be joined by Dr. Giles Yeoh. Hi Giles.

Simon Brown (00:14.325) Hello?

Garrick (00:17.047) Hi there.

Giles Yeo (00:23.859) Thank you for having me. Well, don't thank me till after this, but thank you for having me.

Garrick (00:27.115) Yeah

Paul (00:27.931) Well, you're very, very welcome to the Curious Advantage podcast. And have to be honest, we were very excited to have you on the podcast. And just a bit of a plug straight away. And I was enjoying this recently over the holidays, but reading Giles' book, Calories Don't Count is a brilliant read. And I'm going to encourage everyone to read it, but we're going to find out all about it and about Giles through this podcast. So really excited to have you here with us talking today, Giles.

Let's get straight into it. Charles, you wear a lot of hats. You're a geneticist, research leader, author, science communicator. There's a lot we know going on in your life. Can you tell us a bit about your journey into the world of genetics and how did it all begin for you?

Giles Yeo (01:16.115) I mean, I did my, by chance, I think all of it as these things are. I always knew I wanted to be some kind of biologist. I was good at biology. So I ended up doing just a standard molecular biology degree at UC Berkeley in California, which is where I'm from. But I specialized in genetics in the last two years. I had done a practical on fruit flies, know, Drosophila things. And, you know, it was a standard kind of thing. You had to sex the flies, you had to cross them to see why some had red eyes and some, but...

Actually, was the first time I had direct sort of input into genetics, so to speak, you practical input. And so I really loved it. And so I specialized in genetics and then ended up doing a PhD in Cambridge on molecular genetics of Japanese pufferfish. Once again, that's a very niche topic. it is a niche topic. But these pufferfish are fugu. So I don't know if you guys are into

Garrick (02:06.594) I've eaten though.

Giles Yeo (02:15.087) expensive sashimi. Yeah, I never actually eaten it because even though I eat pretty much anything, anything that relies on whether or not the chef was well enough trained to not kill me seems a little bit stepping over the... Don't you think? It's not... I mean, it's a neurotoxin as well.

Garrick (02:29.55) You

Simon Brown (02:31.133) I was going to say it's a high risk endeavour to eat that, yes.

Garrick (02:32.782) I was in Japan and staying in a ryokan and it was a place where you had to have breakfast and lunch and supper and it was served in your room by lovely people and it was all amazing and after day three I said to them I think I'm going to go out into Kyoto and have a meal and they said but Mr. Jones we've already been to the market and we've got a guy in and he's doing fugu for you tonight

And I was like, well, thank you very much. I then looked up online what fugu was and they said it was the most highly toxic thing on the planet. And it's been known to kill restaurant loads of people. So I survived though, thankfully. They haven't changed chef. But so this was your area of specialty, was it?

Giles Yeo (03:20.807) The genetics of it, this is pre-genome project and we were using the puffer fish sort of as a model. It's without boring anyone silly. They got a very small genome. Okay, so one tenth the size of humans, one tenth the amount of DNA as humans do. Pre-genome project and we're both vertebrates, a fish is a vertebrate, humans are vertebrates. And so therefore we actually have the same number of genes. And so if you have the same number of genes but the genome is 10 times smaller,

Garrick (03:23.608) Uh-huh.

Giles Yeo (03:49.415) then what you can do is do compare and contrast to find the really important bits of it. So that's what I ended up doing for my PhD. But it was, and I'm well-trained as a molecular geneticist, but I think the fugu thing ended up being, or at least I felt that it was a bit too niche to pay my mortgage. And so I then used my molecular genetics skills, which I then picked up my PhD and then I moved into the...

Garrick (04:09.326) Thank

Giles Yeo (04:18.141) genetics of severe childhood obesity and from then on into body weight in general and that's how, that's the genetic story and why I ended up doing body weight.

Garrick (04:27.82) I saw at the top of our script today that the title for this is curious about genetics, the brain, and the science of eating. But I really think it's basically curious about weight loss.

Giles Yeo (04:38.791) For most people, yes. I think for most people, I'm interested in body weight in general. Most people are not interested in why they're fat. They're interested in how they can become unfat. So yes, I think I probably agree with you.

Garrick (04:40.078) Garrick (04:52.056) So you've described your work as exploring how the brain influences our eating behaviours. How does the brain influence our eating behaviours,

Giles Yeo (05:01.287) I mean, that's how long a piece of string is. think because the brain does most of the command control of pretty much anything. first of all, what's an eating behavior? So I think people think about eating, they think, well, I'm hungry or I'm full. Yes, those are probably behaviors. I think a good example, which I've used previously, is the Monday morning eating, Monday morning meeting scenario.

We've all been there, it's Monday morning and we all sat around a table and someone has brought a plate of cookies. And so, and I would argue that in this meeting room that we're in and the cookies have arrived, that there are four, at least four different feeding behaviors, okay? And so the first one is before the plate even stops sliding down the table, someone, me, would have already picked up a cookie and started munching on it. So there's behavior number...

Simon Brown (05:34.507) Yeah.

Giles Yeo (05:53.127) Behaviour number two are the people who long for the cookie. They desire the cookie. They want the cookie. But some internal algorithm stops them from having the cookie. But they obsess over the cookie the entire meeting and ignore the rest of the meeting. Behaviour number two. Behaviour number three are the people who eat the cookie without even knowing they have a cookie in their hand. They're going munch, munch, munch, munch, munch. How's the cookie, Joe? And go, what cookie?

And then there's the fourth and that's the most annoying person and these are the people who are not even tempted by the cookie. The cookie comes by and they're not even looking at a cookie. And slightly facetious I know, but actually if you consider those four different behaviors, we all know where we sort of sit. know, sometimes we overlap and we know where our wives, our partners, our family members, where they would sit as well. That is feeding behavior. It's not only how hungry you feel, it's the general drive.

to pick up the cookie or not pick up the cookie and put it or not put it into your mouth. That is what I mean by feeding behavior. And our brain plays a very big role in pulling the strings about how we actually end up eventually picking up the cookie and munching on

Simon Brown (07:04.476) that a fixed behaviour? if I probably in that category would be in reaching and trying a cookie and then once you've had one then it's like they tasted really good I might have to have a second and a third. Is that then a fixed behaviour that sticks with me or is this something that I can influence and change over time over yeah how fixed is it I guess?

Giles Yeo (07:30.555) I think that's an excellent question. don't think it's... It's a difficult question to answer. I think what you're asking is what the genetic versus the environmental contribution to such eating behavior is. I think... I mean, there is a number actually. Now, I don't know if this is true for... If we parse every single behavior, is this necessarily true for every single act?

Simon Brown (07:41.163) Yes.

make it sound a lot better than how I asked it.

Giles Yeo (07:56.883) One really doesn't know because we don't know it to this level of granularity. But if we ask the question about, what is the heritability, I guess is the term we're going to call it, the heritability of body weight, and we know that genetics of body weight is the genetics of eating. So heritability of body weight. If you actually look at twin studies, so the study of twins, either identical twins who are genetic clones or non-identical twins who have 50 % of genetic material, and you study tens of thousands of twin pairs, then you can actually ask the question about

any trait. What happens when you share 100 % of genetics versus 50 % and you work out heritability? And if you do that for feeding behavior, then it turns out to be around 40 to 70%. There's a very big range. But if we take the middle of that, the average of that, then it tends to be 50-50. Learned versus nature versus nurture or nature and nurture, shall we say. It's roughly 50-50. It's slightly more complex than that, but broadly speaking, that is what it is. 50-50.

Simon Brown (08:57.803) So if half of me genetically is saying I should eat the cookie, then the remaining half I can then influence through my willpower, through my environment, through those other pieces.

Giles Yeo (09:09.747) You see, willpower is an interesting word. mean, what is willpower? I mean, if willpower is your ability to stop eating after one cookie, then I'd argue it's part of the feeding behavior, you know, of that. I'll give you, let me answer the question in another way in terms of learnt versus genetics. so for example, if anyone can tell, I'm Chinese by ethnicity, so East Asian. My wife's English. My wife's a white Caucasian.

Now, we both love carbohydrates. Now, my, without backing myself into a stereotype, my favorite type of carbohydrate is rice. It just has to be rice. I eat it all the time. You know, this is just what we will. My wife's to be, my wife's favorite carbohydrate is bread or pastry or anything flour-based. And once again, so that is a situation where it's taught.

Okay, the reason why I like rice is culturally ingrained in me. The reason why my wife likes bread and pasta, whereas I can take neither take nor leave a bread or pasta, that is ingrained and culturally ingrained. The love of carbohydrates, however, that is something which is genetic. This is what I mean by saying that it's very difficult to parse it specifically, but something like the having a sweet tooth versus a savory tooth or a fatty tooth. You don't have a fatty tooth, but you know what I mean.

Garrick (10:31.639) Mm.

Giles Yeo (10:31.795) That is likely to be heavily genetics influenced and less taught. Whereas the type of sweets or carbohydrate or body part you eat, whatever it is, that tends to be culturally ingrained and that tends to be taught.

Garrick (10:47.564) I'm wondering whether I'm a one or a three. Do I eat the cookie immediately or do I eat and not even be aware that that is going on? You make me think about my DNA from a genetics perspective. How do we understand the role of DNA in shaping our response to that, the eating of the cookie?

Paul (10:47.766) See you next week.

Giles Yeo (11:10.387) So I'll give you, we know some pathways, the circuits better than others. So the two pathways we understand that, so your brain needs to know two internal pieces of information rather than the pieces of information from around the world. Okay. So, so internal pieces of information in order to influence our feeding behavior. And the first piece of information it needs to have is how much fat you have. And that's because fat,

is your long-term energy stores, and so that's how long you would last without food. So your brain needs to know how much fat you're carrying. So that's the first piece of information. The second piece of information, your brain needs to know what you have just eaten and what you are currently eating. And these are going to be your short-term energy signals, and this is going to come from your gut, your stomach, your gastrointestinal tract. And so these are all hormonal. These long and short-term signals from the gut and from fat are all hormones, so they circulate in the blood.

your brain picks up on these long and short-term signals and then essentially then integrates them and influences your next interaction with the cookie, with the refrigerator or with a menu. I want this instead. So some of the genes, for example, that we know about, and we know of over a thousand genes that play a role in this feeding behavior, abacus, whatever we want to call it. Some of them,

make your brain feel less sensitive to the circulating hormones. So for example, if I were carrying 20 kilos of fat, which is like roughly what I'm carrying at the moment, but your brain is only sensing 18 kilos of fat because it's slightly less sensitive, then it's going 18, 18, I thought I had 20. And so it'll then drive you to eat more to sort of make up the rest, but you already have 20 kilos. Then another example, imagine if you've had a thousand calories for lunch, just as an example, even though they don't count.

but a thousand calories for lunch, but your brain only senses 800 calories. You get where I'm going with this. So, these are some of the pathways. Other genes might influence your ability to ignore yellow M's on the side of the motorway, just as an example, whereas other people are more drawn to that. So that is where these probably sit. There's gotta be more subtle, more nuanced.

Garrick (13:11.64) Yeah.

Giles Yeo (13:31.347) ways that we actually end up affecting our feeding behavior, but generally speaking that is what we're beginning to understand. It's a wired network of these more than a thousand genes, which then, and these are not mutually exclusive, clearly you can have some or all or none of these different behaviors, but ultimately they make you more or less likely to say no to the cookie.

Paul (13:58.003) So Charles, does the brain then in some way get confused as to whether you're hungry or you're just craving something or actually you want more food? So I get to the end of my meal and I have my dessert, my pudding or whatever we want to call it. I might choose a healthy one, but I might just choose something unhealthy because actually I always do, right? I was full, but now I was quite happy to eat the extra ice cream or something. So how does the brain, you know,

Can we confuse our brain in this way? Does it get confused? What happens there?

Giles Yeo (14:30.003) So the way that I conceptualize, so what we're talking about is appetite for food, right? So appetite is an interesting term, I think, because it's an integrative word. So it integrates at least three different concepts, at least three. It integrates how hungry you are, we understand what that feels like, how full you are, which is a completely different set of circuits to how hungry you are, I wanna point out, and a different part of the brain, okay? And...

how nice you feel when you're eating. Because for most of us, eating feels nice, some feel more nice than others. And imagine that triangle of those three different concepts with appetite sat in the middle. Now you can tug at any of the three points of the triangle and it changes the shape of the triangle, but the area still roughly remains the same. So in other words, your appetite is influenced by all three points. So now we get to the dessert stomach.

Okay, that you were actually bringing up. So for example, your appetite is here. Now, the hungrier you are, the more likely you, okay, if you're really, really, really hungry, you know that the simplest foods taste the nicest. So you can just a bit of rice, a bit of bread, a bit of cheese, the fuller you become, the more picky you become with your food. You have to, there's a far...

Paul (15:26.823) you

Paul (15:50.613) I'm gonna make it worth a while.

Giles Yeo (15:50.963) bigger hurdle to jump over to make it worthwhile to actually reach down and actually eat the food. So therefore, the fuller you become, you need foods that wallop a great big hit on the nice bit of the brain. And this tends to be foods that are high in sugar and fat, because why would it not? And so actually, your dessert stomach is a physical manifestation, so to speak, of this triangle where you're tugging the ends. And so the fuller you are,

The higher the hurdle you need, sorry, that's right. The higher the hurdle you need to jump over to make eating feel just as nice. And so we turn to high fat, high sugar, high caloric dense foods when it comes to desserts because we tend to be full of protein or fish or whatever it is we're eating already.

Simon Brown (16:39.177) So I remember someone telling me in the past, and I don't know if this is true, be good to know that it takes sort of 20 minutes for your stomach to register that you've eaten something or something. So in that situation, if you're eating, you're eating, eating, it's 20 minutes after you've eaten it that you realize I was actually full 20 minutes ago and I shouldn't have eaten that dessert or whatever. Is that, is that, is there truth in that? there's this sort of lag between, yeah, your...

your sense of eating and actually your brain saying I'm full, you should stop eating now.

Giles Yeo (17:10.257) Yeah, there is truth in that. mean, it's not... It clearly depends what you're eating. And sugary drinks, you don't have to wait 20 minutes. It goes right through and it gets absorbed. Whereas something complex and starchy or protein-y is gonna take... It's probably gonna take the full 20 minutes before it actually emerges out the other side. know, just enough time for you to finish your sort of main meal before you do things. But no, it is absolutely right. It does... There is a physics...

that your food needs to get past a certain level before the gut hormones begin, the relevant gut hormones are then released as your food sort of moves down the tube. Now, there are learned things, obviously, because we're not, we have most things we have eaten, barfugu, we have decided this, but most things we've eaten, we have eaten before. And so we registered the fact that I'm going to have a bowl of strawberries and ice cream, just as an example, and already,

If you like strawberries and ice cream, then salivation has begun. So you do learn of that. But yes, there is definitely a delay. so the old wives' tale, for lack of a better term, that says, you should choose more slowly or you could do things, that's where it emerges from. Because typically, if you end, before you decide if you're at a buffet or something, that you're going to go back for a second one, if you sit there for 15 minutes, and if you need more food, by all means. But typically, if you sit there for 15 minutes, you probably will say, know what?

I'm okay now. So no, it's a real thing.

Garrick (18:42.2) So we should slow down when we eat. I guess that's a precursor to my real question, but this is amazing. It's fascinating that the weight is a relationship between my genes, my DNA, and the hormones, and then how those are influencing what my brain is telling me and then my behaviors. But what does this mean for us, for those of us who are wanting to lose weight or are constantly losing weight?

while trying to remain slim. What are the implications for all of this, for how we should control our behaviour?

Giles Yeo (19:18.163) You see, I had its implications on any number of different levels. Let's start with the smallest unit, so our homes, broadly speaking. And I think there is where we have the most control, for lack of a better term. You at least know what you're buying to bring into the house. And so that's pretty much one of the only places you have where you can say, okay, now you can sit now and then you sort of reflect, right? Assuming you're honest with yourself, well, where do I sit in

in that feeding behavior, that cookie scenario. And then there's another one, right? Do I eat when I'm stressed? Do I not eat when I'm stressed? Once again, another split. And then you can then make some decisions about what you might or might not have in a house. Okay? The problem with that is that we do eat at home, but we have to then interact with the world to bring the food into the house, like in the supermarket, like everywhere else. And there is where I think the big weakness of...

pushing purely personal responsibility comes in. Because if you have some internal drive or socioeconomic drive, because remember it's not only the internal drive, it's what you can afford, what choices you can or cannot make as a human being, and then you step into the supermarket. Now then suddenly there you're stepping into a place where people's jobs who are inventing the foods is to attract you to buy me, buy me, buy me, buy me, like in Alice in Wonderland.

And so you then begin to interact with the world of marketing, the world of the food manufacturers, the world of policy. Where do they put chocolate? Do they put it by the tills? Where do they put the sale items? Exactly. So you can control your household to a degree, but the implication is if you are susceptible for any number of different reasons to eating, but we don't, as a society, fix the food environment or the built environment.

Garrick (20:53.678) the psychology of thinking about this.

Giles Yeo (21:13.275) Okay, then it's very difficult to try and keep the weight off because you have to interact with the world in order to carry carry your day-to-day carry out your day-to-day living

Simon Brown (21:27.094) And what would fixing that food environment look like?

Giles Yeo (21:32.819) Look, mean, if I really had that answer, no, that's not true. I probably do have some kind of an answer. I think the difficulty with fixing the food environment is there is no one single answer. And depending on who you are or what culture you're in, public health is an interesting thing to my mind, okay, because there is always a tension in public health between what liberties are you willing to lose

for the greater good. We drive on one side of the road, we stop when a traffic light goes red. We can't do whatever the hell we want. We lose liberties. But in return for that, we don't die as much in a traffic accident. I don't think we have got to that stage, at least with this food environment we've been in, of finding that balance. Because some people are libertarians and says, to death, you put this Mars bar out of my hand.

And then they're going to be the people who want to keep all the food like the way they sell cigarettes, which is behind a glass cabinet. Both are ridiculous to my mind. And clearly, it has to sit somewhere in the middle where if I need to go to my children's birthday party, then we can have a cake, whereas I'm not having cake every day. So the answer is I don't know the answer because it's got to be whatever the answer we find, it's got to be accepted by society, that tension.

Garrick (23:02.382) Hmm.

Giles Yeo (23:03.155) And it's going to differ from society, society. It's going to differ here to America to China. And that's fine. That's absolutely fine. But we're nowhere near there yet because we, think our discussion, the tenor of the discussion around nutrition and food, certainly in this country, or at least in the higher income countries, I think borders on hysterical. And so,

without, we need to remove the hysteria from it in order to come to some kind of society acceptable position to take to sort of be able to go to our children's birthday party, but not all die of heart attacks. You know, there's going to be a middle ground.

Garrick (23:42.572) That's right. There has to be a middle ground and I can hear your response is extremely pragmatic and also diplomatic because you want to prepare, you want to have a solution that has some chance of being accepted. But we do exist within some kind of obesity epidemic, if you like. There's way more obesity around now than there was before, say, 50 years ago. And as I think you're saying, that's partly to do with

with the environment, the food environment we've made for ourselves. I want to ask you, I really want to get to what's your view on the injections and Azempec and Wigovi and Mungaro and these, if you have one and their impact. But before we get there, I wanted to just tackle the issue of highly processed foods and what's going on and the impact that highly processed foods are having on us.

regardless of calories as you say. Do you have a view about those?

Giles Yeo (24:47.211) I do. So these are the so-called ultra-processed foods. So I guess a couple of things. What is the problem with ultra-processed I'll get to my reservations about the term ultra-processed a second, but just for some definition. So ultra-processed foods are different from processed foods. the vast majority of foods we eat, aside from if you walk into your garden and pluck an apple of a tree, are processed. Cooking is a process. Fermentation is a process. Curing is a process.

There's nothing inherently wrong with processed food is what's kept us alive. Now ultra-process begins to introduce issues because it is a relatively contemporary process and it's industrialized. So it's industrialized processes that we cannot replicate domestically. We just can't. So what's the problem with ultra-processed foods? Before I get to the caveats, I think a couple of things.

Because of the ultra-processing, it is inherently lower, the food item is inherently lower in protein and or fiber, depending on what we're talking about. Fiber is only found in plants because everything is just in the stripped out. That's problem number one. And so the foods are very calorically available, which means that a protein and fiber slow down the release of calories of food as we actually digest them.

And so if you strip something out, then that food is very, very calorically available. All the calories are accessible to us. number one. Problem number two is the ultra-processing process that was not good, but the ultra-processing also strips out flavor. Now, where does flavor comes from? Flavor comes from the Holy Trinity, sugar, salt, fat. Okay. So now if you take out sugar, salt, fat, you have to replace it with sugar, salt and fat. so ultra-processed foods tend

to be low in protein and fiber and high in salt, sugar and fat. That's a toxic mixture. for many ultra processed foods, we should eat less off. The issue I have with ultra processed as an umbrella is it's too broad a church. It covers too many foods. I think they are uncontroversial foods that we should stay away from or least eat less off. And I think most of us can point them out, turkey twizzlers or whatever. But they include yogurt.

Giles Yeo (27:05.147) which in of itself is a fermented product, so it's not ultra processed. But if you have those, I don't know if we can mention brand names, but those square yogurts with the little corner, okay? Now, the yogurt in of itself is fine, but the moment you tip whatever is in that other half of it, be it crunchy, be it a jam, what have you in, suddenly the whole yogurt becomes ultra processed. Really? I do think there is a difference between an item of food like a nugget or something like that, that's been sort of

molecularly constructed from meat of provenance that is, shall we say, a little bit doubtful versus yogurt with a bit of jam in it. And the jam is the ultra processed food. So that is my issue. think my issue is I don't people, whenever I speak like this, you call me a pragmatist. Thank you. Most people who are not pragmatists call me in the pocket of big food. I am not in a pocket of big food. I just am a pragmatist. So I think that

Given that we know what is actually bad for us, we need foods that are of better quality, higher protein, higher fiber, we need to eat less salt, sugar and fat, all of this is true, then let's use terms that are more precise about the quality and the type of food, as opposed to something like ultra processed, which to me includes a lot of foods that while off putting too many, because it's definitely not grandma and apple pie, right, because it's an industrial process,

doesn't mean it is inherently bad for you. That's my, sorry, that was my opinion.

Simon Brown (28:37.873) And you said something in there around things being calorifically available. I got that right. you made a passing comment earlier around calories don't count. we've been, well, at least I've grown up to think things that are high in calories are bad, things that low in calories are good, but it sounds like that's maybe not the thinking anymore.

Giles Yeo (29:02.531) I, well, there are some people who still think that and some people who think I'm anti-physics. I'm not anti-physics. So I think my issue with the calorie is that it gives you only one real piece of information, the amount of food you're eating. So clearly 200 calories of chips is of course twice the portion of 100 calories of chips, but so is 200 grams of chips, twice the portion of 100 grams of chips. And no one's trying to compare 200 grams of chips to 200 grams of carrots. And ultimately,

That is the point, all right? Where calories will tell you the amount of food you're eating, but otherwise nutritionally blind. It doesn't tell you anything about what is in the content. So if you're calorie counting to lose weight, clearly you need to achieve an energy deficit, calorie deficit to lose weight. That's physics. But there is a big difference between choosing to do that. If say your diet included a 400 calorie lunch, just as an example.

where if you ate a steak of 400 calories, I'm being slightly facetious here, but imagine if you have 400 calories of steak or 400 calories of sugar. You know, that's an extremis, but that's what I'm talking about, where we need to consider calories as one piece of the information, but the quality of food is calorie blind.

Simon Brown (30:23.669) sense.

Garrick (30:23.81) Question I've got then, Gels, is there an alternative to counting calories? I mean, if I want to lose weight, if I want to watch what I eat, I need to have high fiber, I need to have protein, I need to not worry about calories, but what should I be concerned about?

Giles Yeo (30:40.679) You see, the main issue is that I do have a solution, or at least what looks like a solution, but no one's listening to me. So it's very difficult to do that solution in isolation. I think the problem is, you know, we have these traffic light signals on our food, the prepackaged foods. Traffic lights in the front, if it's in color, and then whole reams and reams of nutritional information at the back of the...

Now what they do is they highlight specific things, including the number of calories in red, amber or green. I think we're highlighting the wrong things. So I do think what I think we should be thinking about is the quality of food. And in shorthand, that is highlighting how much protein is in the food. Okay, that's the first thing. That's the most important thing. There is also a sweet spot for protein. You don't want to eat too much or too little. You need to highlight the amount of fiber in the food.

the more the better. That needs to be highlighted as well, depending if you're talking about plant foods, not about fiber. And I think you probably need to be talking about the amount of free sugars in the food. Now, free sugars are sugars that have been added as opposed to sugars that are stuck in a fruit. All right, so anything which honey, sugar in of itself, obviously maple syrup, algarve, nectar, whatever it is, they are all free sugars because you add them. Whereas a sugar in a prune or something like that, that...

it's tied up in the fiber and the amount of free sugars, maybe the amount of saturated fats. But that is what I would do actually. would traffic light those four items, three to four items. And then when you go in and shop, rather than saying that, I need to match my protein, you need to say, well, does this say green, amber or red for protein? And if I have two items of red for protein, because I am buying a pie or something like that, then I better get some items that are green for protein instead.

That is the way that I would reset up the system. I would focus on the nutritional content that really, as a shorthand, reflects the quality of the food and highlight those instead so that when you're walking through, you still have the traffic lights, are a universal number that we can in our head, not number, a universal signal without us having to put our glasses and look at font zero and able to then shop properly. But then we need to change the whole food system.

Giles Yeo (33:01.595) and I don't know when that's gonna happen.

Paul (33:03.872) Hey Joe, so I certainly agree with the quality of the food thing, although I suspect we end up in a sort of ability to pay for it conversation. I'll give you one specific example though. Greek yogurt. Now I can choose to go on, but which I think is a healthy choice, having a Greek yogurt. I won't mention any particular brands, but I eat it every day. Now, I originally was, went down the middle and you could buy 0 % or 5 % Greek yogurt.

And I used to go down the middle and go up 2 % and that seems a good balance of not too fatty and not too anything else. Then I thought, oh no, I'll be healthy and go for 0 % fat. But then I realized that 0 % fat means that a load more sugar has been added into it so that it can become 0 % fat. So now I'll switch back to 5 % fat. And I'm trying to be an educated buyer of Greek yogurt, right? So what should we do about the signage of these foods?

what actually is better for us?

Giles Yeo (34:05.469) So I think there is another, I think the main issue is we should not be, okay, I'm not giving you the easy solution. I'm just telling you what I think, okay? I think the main issue is we shouldn't be looking at the Greek yogurt specifically. Because once again, what you choose to do, there's a flavor element as well. I think you need to look at your whole diet over a period of time. I think a week seems to be a good type of period of time to go because you have work days, you have weekends, you have the odd.

Paul (34:29.424) If you're a good actor, you can work a year weekend at your work week party. So you can invest in the same thing. Over the weekend, you need to take a good look at the amount of time you've got to work on your And if we can achieve that on the weekend, then that's true for you to have.

Giles Yeo (34:35.099) a workmate party or even your child's birthday party. Okay, so you can imagine that fits within sort of like a week. And over the week, I think we need to hit specific targets about the amount of saturated fats, sugar, protein and fiber that we want that we need to hit. And if we can achieve that over the week, then that leaves room for you to have 5 % fat Greek yogurt. It leaves you room to have a chocolate bar. But then...

Also it leaves room for you to make sure maybe you have a salad on Thursday night and maybe you don't have meat on a Tuesday at lunchtime. See what I mean? And so that is, to my mind, it's a far more healthy way of thinking about the food because now I can enjoy any food I want as long as I don't eat 5 % as long as I don't eat, you know, fatty food or whatever you like that every single meal of my life. So that is probably where I sit.

and with what we should be doing with an individual food item.

Garrick (35:31.746) Giles, I've just had an idea. I think you can make a fortune. You need an app that kind of allows me to manage my fat, protein, fibre and sugar intake over the week and just keep track of things. I'm sure there's a solution there somewhere.

Giles Yeo (35:47.443) Do you know, do you know, we look, won't, I won't mention the name. am advising, once again, as a consultant, an app that are doing that and what they're doing, they collect some information as well. Well, what they do is they have with the birth of AI and I have not seen, they will reduce, release the app. They have a paid version. They will release the app actually free to the world, but it is one of the most remarkable. So what do you do is you take your phone, you take a picture of whatever the hell it is you're eating.

And because of AI, it's not perfect, but it's as good as it's gonna get. my God, I had fried rice. I thought this is gonna be complex. Like fried rice in a Chinese restaurant. I said, okay, everything is mixed together. Let's see how many items it picks up. So I took a picture. It got pretty much every item up. It got the carrot, there was the chicken, it was char siu. It got the char siu. It's a char siu. And then the only downside is you have to sort of indicate the...

Garrick (36:23.512) enough.

Giles Yeo (36:46.323) portion size, so that's probably one of the weakness. But in terms of the percentage of averaged fat, carbs and proteins that you're getting, and then it then does a weekly tally. So you get to the end and you go, do you know what? Last week I really had way too much fat, way too much that this or that.

Garrick (37:03.842) That's amazing. And here's my question. Would I have to start, if I use that app, would there be a genome test first to determine what my optimum percentages that I should be managing over the week?

Giles Yeo (37:19.997) So there would be, I didn't come on this to sell this, okay, but there will be a number of tests that you can take upfront. However, speaking as a geneticist, the tests that claim to be able to find your optimum percentage of your macronutrients, shall we say, are probably jumping ahead of the science at the moment. So I think we know very good averages.

Garrick (37:32.014) Mm.

Giles Yeo (37:46.737) But you're absolutely right. It's probably going to differ very subtly between you and me and Simon and Paul. I think that's probably true. But I think the broad strokes are going to be true for all of us as well.

Garrick (38:00.878) That's right. This is probably where we headed in the 21st century, is it becoming more and more specific as the science becomes more and more clear and the more and more data is accumulated. I mean, I did do a very expensive DNA test, which wasn't about my heritage or my history. It was about the macro sort of components of my DNA. And for all of that money, it told me to eat more broccoli and eat less bread, which was not very helpful.

It also told me I was lactose intolerant, which was new for me. I didn't know that. it seemed very fuzzy, just looking at the results. But I'm sure we're going to get better and better at it.

Giles Yeo (38:42.035) So I took a similar test, wrote a piece for one of the major newspapers actually paid for one of these tests for me to take so I could write a review on it. And I thought I was going to poo poo the whole damn thing. much like you, they came with a lot of personalized information that was so personalized it was bland. I also learned I was, and I don't want you to judge me looking at the color of my skin. I also learned that I was lactose intolerant. I am as it turns out. Therein lies the problem with these tests.

Garrick (38:49.582) Mm.

Garrick (38:57.729) Mm-hmm.

Giles Yeo (39:10.567) there are traits which are genetically predictable. So for example, lactose intolerance, one gene, one marker, and it can tell, can you digest lactose? This is the same for alcohol, famously. This is the same for your ability to metabolize caffeine and a couple of other things. Now, all of these genetic tests incorporate these tests, incorporate these specific genetic markers. The problem is they mix it together with

whether or not you are more less likely to respond in a Mediterranean diet. There's a big difference between the biochemical ability to chop lactose into glucose and galactose, which is one enzyme, and your ability to handle an entire diet. So the main issue, I think, with these genetic tests is they mix in truly predictable traits with others that have minor genetic influence. But if I suddenly realize,

Garrick (39:43.267) Mm-hmm.

Giles Yeo (40:09.305) I am lactose intolerant. Everything in this test must be true. That is my problem with these tests, I think.

Garrick (40:10.861) Mm-hmm.

Garrick (40:15.714) Yeah. It was interesting for me because I didn't know I was lactose intolerant. The problem is I like milk and dairy and cheese, but it did have an impact on, well, I clearly should be eating less because it's not doing any good for my body. So small steps, but here's what I want to ask you. What's your opinion on the weight loss injection trend? Everybody's on We Govy or Mungaro, which is...

another one, what's the other one? Azempic, you know, do you have a view on these? I know that some are impacting two of the hormones in the body, some are impacting one, you know, how do they work, I think is my first question.

Giles Yeo (41:02.065) Okay, so Ozempic and Wigovia are actually the same drug. They're called semaglutide, or it's called semaglutide. Ozempic just happens to be the diabetes version of the drug, and Wigovia is the obesity version of the drug. So it's slightly marketed differently, but chemically it's exactly the same compound. Now, the drug that hits two hormones, so semaglutide hits one hormone, and the hormone is called GLP-1. Mungiro hits

mimics two different hormones, GLP-1 and JIP. So, but JIP and GLP-1 are both gut hormones. So these are some of the, we know of 20 different gut hormones that go up as we eat and food kind of goes through our gut. And so JIP and GLP-1 are two of these drugs. Now they do two of these hormones. They do two things. Both JIP and GLP-1 are also called incretin hormones. And why they call that?

If you inject yourself with glucose, like in an IV for example like that, your insulin goes up. We understand that biology. When you eat sugar however, and it passes through the gut wall, there is a six to eight fold enhancement of insulin secretion. Because as it passes through the gut wall, JIP and GLP-1 goes up. And so JIP and GLP-1's job is to hit the pancreas, which is where insulin is produced, and increase, enhance insulin secretion.

which is why these drugs I'll use as diabetes drugs first. The second, sorry, go, go.

Garrick (42:31.736) So just to understand, so they're actually causing the body, the bodily response by causing the insulin to be produced by the body rather than an artificial injection of insulin, for example. The body is responding.

Giles Yeo (42:47.581) Correct, correct. So your natural hormone is to sort of enhance the insulin secretion for that. The drug hijacks this. The drug hijacks the system in order to prolong the enhancement of insulin because you are diabetic or something and you need more insulin. It's designed to prevent you. Now, this is not true for type one diabetes in which you don't have the cells that produce the insulin have been killed, all right?

Garrick (42:55.757) Yes.

Garrick (43:04.184) comment.

Garrick (43:09.154) Okay.

Garrick (43:12.94) Yes.

Giles Yeo (43:16.465) The job of the drug within the context of diabetes is to minimize the amount or exclude you from having to need insulin to begin with, to try and make use of your local machinery to produce more insulin. So that's the diabetes side.

Garrick (43:32.142) And how does it cause us to lose weight then?

Giles Yeo (43:35.963) So because the other place that it hits is the rear of the brain and the center of the brain, and it makes you feel fuller. Because most of the gut hormones that make you feel fuller, including JIP and GLP-1. And these drugs are, but the problem is the native hormones don't stick around for very long. The native hormones only last a couple of minutes before they're chopped up. And so the superpower of these drugs are...

they've sort of been decorated, molecularly decorated, so they stick around the blood for a week or two, which is why they're now once weekly injections. They do exactly the same thing. They enhance insulin secretion, hence diabetes drug, and they sit around the blood for longer and make you feel fuller. And what happens is, mean, full disclosure, because we're talking about this, you don't know him, so I can talk about him. My son. So my son, I...

I put him on Mungaro, so this is the drug which hits Jyp and Jyp1, at the beginning of the year. He's in his 20s now. went to, look, I'm not a skinny person. He's the same kind of build as me. But he went to uni and suddenly, whoop, you know, get the freshers 14, he got the freshers 30. Anyway, so he got quite large. But I put him on the drug and he suddenly said, he talked to me because he loves food like I love food, but I love exercise.

Okay, so that's one mind, one little tiny saving grace. He hates exercise and loves food, toxic mixture. And what he said is that the moment he took the drug, and I saw it actually, it was, we started on, through some reason he wanted to start on a New Year's Day. So he started the first injection on January 1st, 2025. And we were in Wales for just a family vacation and we were having a walk. And you know, we bring sandwiches for a walk, eight mile walk, that kind of thing.

And he had some small tiny candy bar in the morning. And then we walked and we did the thing, we got to the end. And I just came to ask him, well, how much did you eat? He goes, no, I didn't eat anything other than the candy bar in the morning. So which reflects the good and the bad thing about this drug. The fact that, first of all, the effect was immediate. He injected himself in the morning and he didn't eat anything but a sandwich all day. He didn't even eat a sandwich for the day. And I could tell you, I make the sandwiches. He would have scoffed half of them. The second thing.

Giles Yeo (45:56.911) And this is where I'm not on this to sell the drug. There are negatives to it. And one of the negatives is that these drugs, they're not negative. It's not a negative. You just need to consider this. These drugs make you feel fuller and therefore you eat less and so you lose weight. They do not improve your diet. And so if my son had not been thinking about it, you could just have a couple of chocolate bars a day and he'd go, you know what? I'm full. And yes, you would lose weight.

but at what cost to everything else in your system. So these drugs should be used by the people who need them, but they need to be prescribed with some kind of wraparound care. They need to be prescribed with a dietary intervention. They need to be prescribed with an exercise intervention actually, in order to maintain your muscle mass. So that's my opinion. I think these drugs are super powerful. In fact, let me sum up. They're super powerful because they work.

pretty much immediately. They're bad because they're super powerful and they work. they will work whether or not you are a 350 pound man looking to lose 100 pounds and that's fine, or a 16 year old girl who's 75 pounds. It doesn't matter what your starting weight is, the drug will work. So you need to be bloody careful about who gets the drug and you wanna aim and you wanna make sure the person that gets it needs it.

Paul (47:08.759) It doesn't matter what you're gonna be. You're a cool guy.

Giles Yeo (47:23.427) It's feeling ill from it. I mean, it's feeling... It's ill because of their obesity and needs to the drug or diabetes or something like that. You can't have people using this, as a lot of people are using it at the moment, as a cosmetic drug. That's what it shouldn't be used as.

Paul (47:35.381) Yeah. And for sure we're seeing that, right? It's all kinds of ways that people are getting access to these drugs at the moment, which perhaps could be another subject of another podcast. Although it is very interesting how it's impacting your behaviour. friend of mine says it feels like the army is marching with you. So it's in some way, back to your appetite triangle, Charles, I guess.

Giles Yeo (47:57.171) It is our appetite triangle. So where it pulls on the appetite triangle is the fullness side of things. And so you can imagine that it almost shores up the fullness triangle. So you can pull with the reward and the hunger without worrying about the full. So you can eat less, you know, everything and more, because it kind of almost like puts a bit of foundation up at the fullness side of things. That's where it acts on the triangle.

Paul (48:20.044) But does it wear off? So if you've gone through a course of this and you've lost this dramatic amount of weight, are you stuck with the drug forever? Because presumably somewhere along the line, you still need to change your own behaviors if you want to maintain the weight loss.

Giles Yeo (48:37.745) Yeah, absolutely right. So look, it is a drug and like all drugs, they only work when you're taking the drug, which means that if you stop, yes, the weight will come back on. So it does appear that many people, although not all, will need to be on some version of this drug for a long time. I think there is an opportunity. You know, I think it was earlier on in this interview where it says how much of this is learnt.

What can we learn? Simon, you were the one that was asking me. How much of this is learnt and can you change? So can one take the opportunity during the period of time where you're taking it for two years or whatever it is you're supposed to be taking it for, where you're losing the weight, where because now you don't have the hunger monster behind you, it means that you can try better exercise regime because then the problem with exercise is that we exercise and we feel hungry. This is less so because of this drug.

Garrick (49:34.36) Mm.

Giles Yeo (49:36.975) And can we practice, learn different habits? Instead of cooking four chicken thighs, we cook two chicken thighs or whatever it is you actually cook. I think it will be difficult for many people, but I think it will work for some people. However, for most people, I think there's going to need to be some kind of maintenance dose. And all of these drug companies are now exploring. I don't think anyone thinks within the pharma space, thinks that the weight maintenance stage

is going to be the same as the weight loss stage. That requires heavy banging on the door with the drug in order to get you to get there. But the moment you're at maintenance, all the drug companies are testing one of three things, either reducing the dose, increasing the space in between the injections, or testing oral versions of the drugs. So all of which results in less efficacy, but actually at the maintenance stage is probably more than sufficient.

And so let's see where things go as more and more people take it and more and more people reach the weight maintenance stage of these drugs.

Paul (50:43.638) Charles, this has been an amazing conversation. I'll try and give a bit of a summary of what we've been talking about. And then I'm going to ask you, just give you a moment to think about it. What would be, all the things we talked about, what would be something you would want to leave our listeners with? But just some of the things that I've really taken away from this. How we've talked about what really is an eating behavior and how the way we eat is really sort of informed by our genetics, our own behaviors, and even our neuroscience.

to what extent we can already help it or we're just suffering from our own nurture. I very much like the four behaviors of the cookie story. I'm still trying to think where I sit on there. Somewhere between grabbing and eating the cookie and trying to stoically refuse it, I think. Very much learned a lot about appetite and how appetite is this triangle between how hungry we are, how full we feel and how nice food actually feels for us.

But also what that means in terms of what are some of the levers we need to pull in the food environment and that we're living within that's helping us make smarter choices, particularly around some of the more problematic foods like the ultra processed foods that are presented to us every day on the supermarket shelves. And then the third thing that is about our own diet. I personally love the book about why calories don't count and about the availability of the calories in the food that we're eating.

but also what we should actually pay attention to. Not just the signage, the low fat, the low sugar, but also the actual quality of the food that we're going to be eating. And then how we can use that to assess our diets. Perhaps I'm going to try this myself on a weekly basis, thinking about, have I got a good balance of quality food across the macronutrients through that throughout the week? And then of course we've touched on obesity and the obesity drugs and why these drugs work, how they impact our behaviors. And perhaps one of some of the

the longer term impacts of these both for ourselves and perhaps for the pharmaceutical industries as well. Giles, it's been, and I'm sure on behalf of Garak and I want to thank you very much for a brilliant conversation. If there's one thing you would like to leave our listeners with, what would that be today?

Giles Yeo (52:56.499) I think for those of you listeners who are larger than someone else for any number of different reasons, then I think the message which I bang on all the time is, look, there should be a space in the world to understand, you know, a socially mature society, that obesity, carrying too much fat is a problem. It's impacting health. I think we should be able to accept that because it's true, but also not blame the person suffering from the condition. I think, you know, people with obesity are not bad.

morally bereft, they're fighting biology. And so I think that's the message we want to take away. And so because they're fighting biology, then we need to make sure that in order to actually fix obesity long-term for everyone, then I think we not only need to look at ourselves, we need to look at the entire society and entire community in order to do so. That's my takeaway.

Paul (53:48.955) and sounds like there's still quite a lot of work to be done in that space. Thank you so much for joining us. You've been a brilliant guest. You've been listening to the Curious Advantage podcast. We're curious to hear from you. If you think there was something useful or valuable from this conversation, we encourage you to write a review for your podcast on your preferred channel saying why this was so and what you've learned from it. We always appreciate hearing our listeners' thoughts and having a curious conversation. Join today, hashtag curious advantage.

Curious Advantage book is available on Amazon worldwide. your physical, digital or audio copy now to further explore the seven seas of curiosity. Subscribe to the podcast today and follow the Curious Advantage on LinkedIn, Instagram and keep exploring curiously. See you next time.