Jim Hill:

Welcome to Weight Loss And, where we delve into the world of weight loss. I'm Jim Hill.

Holly Wyatt:

And I'm Holly Wyatt. We're both dedicated to helping you lose weight, keep it off, and live your best life while you're doing it.

Jim Hill:

Indeed, we now realize successful weight loss combines the science and art of medicine, knowing what to do and why you will do it.

Holly Wyatt:

Yes, the “And” allows us to talk about all the other stuff that makes your journey so much bigger, better, and exciting.

Jim Hill:

Ready for the “And” factor?

Holly Wyatt:

Let's dive in.

Jim Hill:

Here we go.

Jim Hill:

Holly, today we're tackling one of the biggest questions that I think we hear over and over. Is it really about calories in and calories out? Can it be that simple? Is there more to the story?

Holly Wyatt:

Yes, Jim. This is one of my favorite topics because I do think it's confusing to so many people. We hear so much conflicting advice. Some say weight loss is all about energy balance, all about calories in and calories out, while others argue, no, it's not that simple. It's about hormones. It's about metabolism. It's about genes.

Holly Wyatt:

All these things play a bigger role than just calories in and calories out. So who's right? What do we actually know? And more importantly, what does it mean for the people who are trying to lose weight and keep it off?

Jim Hill:

Yeah, Holly, and we have a guest today. And, you know, one of the fun things about doing this podcast, we can reach out to people whose work we've admired. And this guest is someone whose work I've admired over and over. And for whatever reason, maybe they don't know us very well, but they agree to come on and have a conversation with us.

Holly Wyatt:

I know. Can you believe that? They actually agree.

Jim Hill:

I can't believe it. They don't know any better. But anyway, I want to introduce Dr. Keith Frayn. Keith is Emeritus Professor of Human Metabolism at the University of Oxford. He's an internationally recognized expert in human metabolism and energy balance, Holly, and you know this is my world here, energy balance. He studied how the body uses fuel for energy and for storage. He's focused on metabolic changes associated with conditions such as obesity and diabetes. Now, Keith has a lot of scientific publications, but the other thing he does, he has written books for the public. And you and I know how tough it is to really communicate the science. He has a new book just out called A Calorie is a Calorie, and I just read it. And I highly recommend it. I don't think it's quite available yet in the U.S., but it will be. And the beauty is it's written. You don't have to be a scientist to understand that He explains this stuff in really, really clear and easy terms. So, Keith, welcome to the show.

Keith Frayn:

Thank you, Jim. And hello, Holly. I'm very pleased to be on your show. Thank you.

Holly Wyatt:

All right, Jim, let's kick it off. I've got a whole list of questions.

Jim Hill:

We've got more questions than we can possibly ask in a day. You want to go first?

Holly Wyatt:

No, no, Jim, you got so excited about this. I'm going to let you go.

Jim Hill:

I am very excited. And so I'll ask an easy one. Keith, why did you write this book? Why do you think we need a book like this?

Keith Frayn:

Jim that's a very good question there's a lot of science out there which has interested me, as you say, and you for decades about energy balance. And I think we've always thought, well it's rather obvious what energy balance is all about. But in the last what five years or so people have begun to question this. And they've begun to question it because they're really saying if it's as simple as we make out, calories in and calories out, and you've got to eat less and exercise more, why are we getting fatter? And so people are saying, maybe we just haven't understood it properly, and maybe there's other things at work. As I've tried to explain in the book, and we'll be happy to talk about here, I think we have to see energy balance as the sort of umbrella within which all these other things, hormones and genes and the environment, within which they work.

Jim Hill:

Keith, I couldn't agree more. People have asked me, do you believe in this theory of energy balance and energy balance isn't a theory. Energy balance is an explanation of how energy comes in and goes through and exits the body.

Jim Hill:

So, let's hit that one. If it's energy balance, why is it so hard for people to maintain a healthy weight?

Keith Frayn:

Jim, I want to take us back to when I was, I suppose, a PhD student, you know, after my undergraduate years. And I think probably you'd be about the same. And it really was not an issue we talked about. So say, late 1970s onwards, I think most people would say that's when things changed. If we remember that, it just tells us a lot. So our genes haven't changed in that time. Our hormones haven't changed, except they're being influenced by everything that's around us. Everything that's around us is food, it's labor-saving gadgets. It's so many things in our world that have changed. Not our bodies, except they've had to respond to this, and they have responded. I think what makes it so difficult, as you put it, is the environment around us. I'm sure that's something we'll talk more about.

Jim Hill:

I love this, Holly, because again, And when I started out, Keith, I wasn't studying obesity because obesity wasn't a very big problem. I was studying how body weight's regulated. And I remember reading statements like, it's amazing that people are able to maintain a constant weight throughout their lives. And yet it isn't happening now. And so the question is, is there something wrong with our bodies? Or, as you said, is our body working fine for the environment that we've created?

Keith Frayn:

Well, when you say, is there something wrong with our bodies, we've got to go back into evolution of it, haven't we? And human evolution goes back so far. If we look back in human evolution, many things have shaped the way we are now. Andjust to take an example, most of us will have accumulated more genes that produce the enzyme that digests starch in our saliva, salivary amylase. That gene has replicated itself because most people in the world today come from stock who began to grow crops. And this goes back, I don't know, a few tens of thousands of years. So our evolution has been changing. But if you go further back than that, probably well before we diverged from chimpanzees, we're going back millions of years, you know, one constant in the environment which our genes were adapting to help us defend ourselves against was starvation. It wasn't plentiful calories, it was starvation. And so everything in our bodies is attuned to gathering calories and holding onto them where we can. And now, of course, we have an environment around us where calories, for most people in the world now, are plentiful. And that's what our bodies are not adapted for.

Holly Wyatt:

I'm just going to play devil's advocate because I'm totally on board with you. And I totally always want, I want us to dive deeper into this environment stuff, but not everybody struggles with their weight in this environment. There's definitely a group of individuals that don't have to work as hard maybe at some of the behaviors. And so how would you explain what's going on with that group?

Keith Frayn:

Well, you're absolutely right, Holly. And I think there isn't enough attention drawn to that. So as Jim said, when he and I set out to study energy balance, we were thinking, oh, there's these few odd people who accumulate weight. And now we're thinking, well, there's a very small number of people who actually don't accumulate weight, and they're the real oddities, and we ought to be studying them. But I think we can say fairly clearly, there is a major genetic influence as to those who will struggle with their weight and those who won't so much. What those genes are doing, of course, isn't in any way changing the overall pattern of energy balance. It's just making it more difficult for some people to resist all the things that are tempting them in the environment around them.

Holly Wyatt:

Yeah. Jim, did you hear this idea? We did the National Weight Control Registry. We need a registry for people who can maintain their weight in this environment and study them.

Jim Hill:

Yeah, I agree.

Keith Frayn:

I've actually pointed that out in the book because I think the National Weight Control Registry, and I'm sure we'll refer to it again, is a brilliant source of data about how those people who have managed to lose weight and keep it off, how they manage that. But I do think we lack a comparison group of people who haven't put on weight in the first place. And they're the interesting group.

Jim Hill:

No, I agree. And actually, what you said just raised a question in my mind, or at least a hypothesis that I have. We started looking at these weight loss maintainers back in the early 90s, and some of them were actually maintaining weight far beyond that. I think, Keith, that people that are successful now may be different. I think obesity is changing. I think... That there are factors that lead one to become obese, but I think being obese actually changes things. So, obesity today may not be the same as obesity in 1980 or 1990.

Keith Frayn:

Jim, you could be right in some ways. I'm not sure we could discuss that more. I still don't think any of that contradicts our ideas about energy balance as the overriding principle that governs it.

Jim Hill:

Totally agree. So why do people question energy balance, Keith? Why does, you know, there's the insulin model out there, people saying, oh, it's not calories in and calories out. It's a type of calories and how it affects insulin. Why do you think there are what I would call challenges to the energy balance model?

Keith Frayn:

I think the answer to that, Jim, is that all of us find it difficult to understand energy balance in our daily lives. We meet people who don't seem to obey the same rules. And I've given anecdotes about that in the book, and I might have time to talk about those. People who seem to be able to eat anything and yet not put on weight, and others who have the opposite problem. I think experience of everyday life is that we all know that we should be eating less and exercising more. And yet, we as a population continue growing. And so that I think is, and people want a simple answer, an easy answer, which is not just, well, you do have to eat less and exercise more. People want an easier way of doing that, which is absolutely understandable. But in my mind, that is the basis for people questioning the energy balance model.

Jim Hill:

I constantly run into people that say, "God, there must be something big we're missing. How can you explain all this obesity with what we know? There's got to be some factor out there that we have no clue at that's driving weight gain."

Keith Frayn:

If you went back probably 20 years, I think, Jim, and you'll know this, in the scientific literature, there was a fairly plausible, strong body of opinion that there was a virus causing obesity.

Jim Hill:

I totally remember that.

Keith Frayn:

And the way obesity has spread around the world, it looks like a virus. And yet that theory has really died away. And I think it's unnecessarily complicated. I think there are such obvious things in the environment that are causing this issue that we have to deal with. You don't need to look for more mysterious causes.

Holly Wyatt:

I've struggled with my weight my whole life and it's the reason I went into this field. And exactly what you said, I was sure there was something different, even when I was young, about what I could eat and what my friends could eatand all of that. So, I think when you live it, when you're experiencing it, you really think it's true because it seems so real to you. And the struggle that, I think, some individuals have to eat less is a big struggle. And so really understanding why that's the case. Energy balance may be, you know, that may be true but certain people are struggling more to stay in energy balance than other people.

Keith Frayn:

Indeed, Holly. And we know something about those people. And part of my understanding of this comes from the National Weight Control Registry. And so if I may quote the data that comes from the two of you on that wonderful database, you know, if you look at people who are keeping their weight down, having lost it, one of the things that characterizes them is they become more physically active. They also change what they eat, and I'm sure we're going to come on to that. But physical activity has decreased, and maybe for some people that's easier than others. We know a lot more, really, in the genetic side, we know a lot more about factors that control appetite. But I'm sure there are other factors that control how easy we find it to be physically active, for instance, things that we just don't yet understand in detail.

Jim Hill:

Yeah, Holly and I, Keith, are very interested in weight loss maintenance and believe that physical activity is a key part of it, and actually quite a lot of physical activity. I believe someone maintaining a significant weight loss, it's not fair, but they have to do more physical activity than their neighbor who's never been obese. And we actually did some studies and showed that. And the reason is what still strikes me as crazy is weight loss is still focused on food restriction. And food restriction is a great short-term tool, but it's not a very good long-term tool because exactly what you said, our bodies are geared to preventing against starvation. And so what we try to tell people, not that diet isn't important, it really is important, but what physical activity does, it get your energy expenditure up to a level where it's reasonable to match it with food intake without being hungry all the time.

Keith Frayn:

Jim, I would love to get your view on an idea that came to me as I looked at all this information and was writing the book. And it seems to me that perhaps what physical activity does, of course it burns calories, but it also perhaps resets the way one views food and changes one's relationship with food. That's what I've really begun to think must be the case.

Jim Hill:

What we're focusing on, Keith, it's real interesting. People talk about, well, physical activity, it burns calories, and it clearly does burn calories, but there are a couple of other things it does, and we can talk about this too. I'm really very enamored with this concept of metabolic flexibility, how metabolisms may vary a little bit and how physical activity might affect that, maybe in small but important ways. And the other thing, and I know you're familiar with a lot of work John Blundell's group has done on how physical activity may feedback and help us better match appetite to our state of energy balance.

Keith Frayn:

Holly talked about personal experiences. And so this is anecdotal, but I certainly feel this. And I know other people who feel it. We've been out for a jog and then we don't need to eat because we're feeling high after, you know, run as high as they call it, which we understand scientifically. It's a flood of hormones in our bodies that just makes us feel good. And we just don't feel the same need to eat immediately. It may catch up with us later.

Jim Hill:

Yeah, and again, you hit on it too, is even though we can talk about the need to increase physical activity, we do not have an environment that is conducive to physical activity. In fact, you know, as a lot of people say, we've re-engineered movement out of our lives. You go from the bed to office chair at work, back home to the lazy boy to bed, and you can really go through the day without being very active and be on some level what looks like being productive.

Keith Frayn:

Jim, I think this is all pervasive and perhaps more than we even realize because it creeps up. And the COVID epidemic didn't help that because we got used to working at home. So lots of people who would have gone into the office five days a week now spend two or three days at home. And…

Holly Wyatt:

Yeah.

Keith Frayn:

Sorry, Holly.

Holly Wyatt:

No, I do want to bring up one thing because I know what some of the listeners are thinking. And I think it's true. But I think also some people respond to physical activity. Some people feel the runner's high, and I think some people don't. For some people, it's a positive experience, and for some people, it may not be. So we've got genetics kind of coming into that too. So many different ways that individuals can be in a positive energy balance for so many different reasons. But I just always want to be sensitive to people out there saying, you know what, I don't even know what that runner's high is. I don't feel that, you know?

Keith Frayn:

Yes, sure. No, I completely agree. And I've tried to say this in the book, you know, there are people for whom exercise doesn't have the same effects. And those of us who can get out and do a run or whatever and feel good afterwards, we're the lucky ones. And I do appreciate that.

Holly Wyatt:

Yeah.

Jim Hill:

I remember from work again with the National Weight Control Registry, we ask people those kinds of questions. In general, there's some variability, but they report, "No, I don't learn to love physical activity, but it's become an important part of my life. I would miss it if it weren't there, but I can't tell you that I live to exercise kind of thing." Again, I don't think that people have to get to the point of where they live to exercise, but I think they have to get to the point of where exercise is a key part of their lives.

Keith Frayn:

I'm sure that's right, Jim. I think the key thing is to find a way of building it into your daily life.

Jim Hill:

Exactly.

Keith Frayn:

I've been lucky. I live in the UK in a city where I've been able to cycle to work. You can't do that in many cities. That's how the environment is affecting us.

Jim Hill:

And if you don't like it, you aren't going to stay with it. I mean, again, every January, people go and join the fitness clubs and everything else. And by March, they're all empty. I think the key is finding some way of moving that you actually like.

Keith Frayn:

And I do think that modern city life, and perhaps if I dare say it, particularly in the U.S. compared with some of Europe, does encourage this lack of activity even in getting to work, getting to your desk.

Jim Hill:

Oh, absolutely. You know, every time I go to Europe, Holly, the steps on my step counter go up all the time.

Holly Wyatt:

Well, you know, I move. I live in downtown Birmingham, so I can walk to work, so I can walk places. So you can still choose to live places where you get more physical activity in, but you got to work at it.

Jim Hill:

But in most of Birmingham, you couldn't do without a car.

Holly Wyatt:

Oh, absolutely. But I'd move specifically where I could do without a car.

Jim Hill:

Well, that's the idea of you modified your own environment a little bit, pushing back against the bad environment.

Holly Wyatt:

Yeah. Jim, I want to switch questions one minute, though, and make sure we get… I only want this answer about macronutrients. Is a calorie a calorie? Is a carbohydrate calorie the same as a protein calorie? There's so many people that believe if we would just cut the carbohydrates, that would be the solution. So I really want to make sure we get your answer. Do you believe that all calories are metabolically equal or does the macronutrient composition, whether it's carbs or proteins or fat in the diet, alter energy balance through other mechanisms? How do you explain that?

Keith Frayn:

Well, the title of my book is a bit provocative, A Calorie is a Calorie. But basically, I do largely believe that. We might say to a first approximation. If I had to single out something, I'd say that protein has some different effects. When we eat protein, we get this small, small rise in metabolism, what some people would call diet-induced thermogenesis or postprandial thermogenesis, which you don't see to the same extent with carbohydrates or fat. But it's a small effect. I'm a metabolic scientist. I study how these nutrients work in the body. And in the end, they all feed into exactly the same mechanism in our cells for producing energy. And then it's very difficult for me to see how they can be very different. So I am basically of the opinion that they're not different to the extent that would affect our daily lives.

Jim Hill:

And in the book, Keith, you go into a little bit more detail on why things like the insulin model aren't really the long-term answer and even though it may sound easy and different, at the end of the day, it's still about energy balance.

Keith Frayn:

That would be my way of looking at it, Jim. I'm not saying insulin doesn't have a role. A lot of my research has been about how insulin affects fat storage, for instance. But I see insulin as the intermediary, what makes our body respond when we have an excess of calories and store them away in our fat cells and so on. Whereas other people are saying insulin is the primary driver of obesity or putting on weight, which I would definitely challenge because I don't think the evidence is there to support. I think this is so clear. So if you really believe that insulin causes obesity, and that phrase, insulin causes obesity, I could point to several books that say that, or papers in the literature. If you really believe that, let's imagine we had a drug that increases insulin production from the pancreas. That ought to make us fat, right? So do we have such a drug? Actually, we do. There's a new class of drugs. They're called GLP-1 agonists, and they were introduced to treat diabetes because they make the pancreas produce more insulin. And do they make us fat? No. These are the wonder drugs that are making people thin. And if you can tie that into the insulin causes obesity hypothesis, I'd be very interested to know how.

Jim Hill:

Great point. These have really, I think, been a wake-up call for the obesity field because I think they're making us think differently. From an energy balance point of view, what do you see maybe in the benefit plus minus for these drugs in the short and the long term? And what do you think the still challenges about how we use these are going to be?

Keith Frayn:

Well, Jim, they're not entirely clean drugs. So I've been asked several times, what's the difference between a weight loss drug and say a statin, which we use to lower cholesterol? And the answer is the statins have been in use now for several decades. And we know a lot about their safety profile, and they're extremely safe drugs and very effective. It's not the same with these weight loss drugs, the GLP-1 agonists. They don't have a completely clean safety profile. They work for many people without problems, but not for everybody. They're expensive drugs, unlike the statins, which cost a few cents per pill. I think they have a place in medical treatment of severe obesity. There's a big worry in Europe, and I don't know if it's quite the same in the USA. People are getting these drugs online without a physician being involved at all. And some of the people who are getting these drugs have perfectly normal body weight, and there may be people with body weight issues. And this is not a good thing at all. So I think it needs to be very carefully regulated. They have a place in the medical management of severe obesity, which is causing medical problems. But I don't think we should regard them as a panacea for the whole population, not like statins.

Holly Wyatt:

We think of them as tools and definitely certain individuals, I think that they are changing the game for them and the people who've struggled to lose weight, they definitely can play a role. I don't think it's like, let's put it in the water, you know, let's put it in the drinking water. And people have talked about putting statins in the drinking water. So I don't think we're there yet. But I want to come back to one thing because you really got me thinking when you said, okay, a drug that increases insulin, I'm an endocrinologist, so I think in hormones, that's where I think everything happens. And yes, you're right. The GLP-1 drugs, you know, increase insulin secretion. But here's where I think there's a difference. They also, in addition to increasing insulin, block appetite, decrease appetite. So I think if you had a drug that increased insulin but didn't block appetite, you could potentially gain weight like crazy. And we tend to see that in conditions that are hyperinsulinemic, especially if you tend to be sensitive or resistant. But I think why the GLP-1 drugs work is in addition to the insulin property and the secretion of insulin are causing that, not the secretion, but the causing of that, they actually also at the same time keep your appetite low.

Keith Frayn:

Holly, I would agree. That's one argument. Certainly with semaglutide, the first one, the one that's in widespread use, that's true. It's acting directly. We know this on the brain, on the pathways that regulate appetite. But the new drugs that are coming in, like tirzepatide, they're acting on other receptors which are not known to have the same effect. So tirzepatide also targets the hormone known as GIP. That's not known to be involved in appetite regulation. It's known to be involved in insulin secretion. And then we have new ones coming along targeting other hormones in the body that are not known to affect appetite secretion. So we may be uncovering new layers of appetite regulation, or it may be there's something going on that we really don't understand.

Jim Hill:

Interesting.

Holly Wyatt:

I agree. There's a lot we don't understand for sure.

Jim Hill:

Holly and I sort of recognize these meds as very, very useful new tools. But one of the things that bothers me is, and you alluded to it a little bit, they're oftentimes prescribed without any other advice. So you don't have to exercise to lose weight on these meds. And you don't necessarily have to worry too much about your food intake because you eat so little that you're going to lose weight. So I worry in the long term about whether maybe this thing makes us rethink success. Is success really that number on the scale? Or is it other things? Is it fitness? Is it some of the other things that don't just come from weight loss alone? And for the first time, we're seeing a lot of people that actually hit their weight loss goals. So maybe there's an opportunity to help people maybe rethink what success and weight management looks like.

Keith Frayn:

Well, I think you're bringing us to one of the other drawbacks of these weight loss drugs, Jim. And that is that so far as we know, and we don't have many long-term studies, you have to keep taking the drug for as long as you want to keep the weight off. And so what we're coming down to is this thing that this period that you and Holly have done so much work on, the transition to maintaining that weight loss. And the drugs aren't necessarily helping us there. They're going to require a whole different approach that we really haven't worked out, I think, yet.

Jim Hill:

Yeah. I told him, Holly, that we've written a book about how to help people keep the weight off without the medication. And again, we say in the book, if people want to continue them forever and they're okay with that, that's fine. But what we're seeing is enough people don't. And if they don't have a plan when they stop the meds, they regain the weight. So what we want, I mean, think about this, you lose 20, 25, 30% of your body weight, and then you regain it when you go off the drug. So what we want to do is to start providing people with options that hopefully will prevent some or all of that regain if they choose or have to stop the medications.

Keith Frayn:

I think that's so important, Jim. And there's a study going on in the UK led by Roy Taylor and Mike Lean, which is looking at very low calorie diets, these soup and shake diets, typically 800 kilocalories a day for people with type 2 diabetes. It brings their weight down sharply, and many of them will go into remission of the diabetes, which is absolutely wonderful. Something we recognized before with bariatric surgery, gastric banding and that sort of thing. But it can be done with diet, and that's what they've shown. But what they've really done, these investigators, that was in a way straightforward. What they've really done is put a lot of work into this period of then people adjusting, going back to eating normal foods and keeping weight off.

Jim Hill:

That's always been the problem is, you know, in some ways, the weight loss is easy because you just give up and follow. And people can do that. But it's a very short-term process. And where people get into trouble is trying to go from that food restriction to now achieving a lifestyle that keeps you in energy balance.

Holly Wyatt:

It's from being in a negative energy balance to being in energy balance. So really the key is how can you help your body stay in energy balance at a healthy body weight? That's really the key. You could get the weight off many different ways, but then you've got to do something to stay there and calories in matching calories out. So that's the big question.

Keith Frayn:

We have to recognize that these ways of losing weight rapidly, like the soup and shake diets, they're not healthy in the long term. I mean, one thing is they lack fiber. And I gather that some people just need to add fiber so they have fairly normal intestinal function. Recognizing that means you really have to change what you eat to maintain that long term.

Holly Wyatt:

Yeah. The quality of your diet becomes important once you're in the long term. I need to maintain this. Short term, to get the weight off, the quality may not matter as much because it's short-term. But the quality does become important when you're now thinking about this for the rest of your life.

Jim Hill:

Well, that's how our work with the National Weight Control Registry years ago led us to understand that weight loss is a different process than weight loss maintenance. It requires different skills. If you think about it, it's like you can hold your breath for a short period of time and do almost anything. But if you live your daily life, you can't avoid social situations. You can't involve all these other things. And what we hope is with the meds getting the weight off, we can actually help people learn some skills for weight loss maintenance that might allow them to be a little more successful.

Keith Frayn:

Well, I think it's wonderful that you're doing this and that you've written the book, you and Holly, because that's really what's needed. If these meds are going to be used effectively, we need to work on that transition. And that would be very, very helpful that you've been thinking about that.

Holly Wyatt:

So I have a question based on thinking about this from an energy balance, a calories a calorie standpoint, do you think that we will ever have a cure for obesity? A cure. Not just, you know what I mean.

Keith Frayn:

You're putting, because I can see your hands, Holly, you're putting cure in inverted commas. And I guess I have to say, what do you really mean by a cure? I would love to think we could prevent it by changing the environment around us. But I accept you can't uninvent things. You can't uninvent the motor car. You can't uninvent home working. And so maybe we never will reverse those things. And then what are you talking about? Are you talking about a cure in the sense of a drug we all take? Or are you talking about a cure in the sense of some magic thing we were going to eat? And I can't really imagine what that looks like. But I could imagine that we could find a lifestyle that most people won't find possible. Lifestyle in the sense of a combination of exercise, what we might think of as sensible eating that will keep us satisfied. I could imagine we could come up with that. But I don't think there's any, I don't think there's going to be a magic thing. Like, as you said earlier, something we could put in the drinking water.

Holly Wyatt:

Got it.

Jim Hill:

Wow.

Keith Frayn:

Something in the drinking water could be very dangerous because, of course, if we go back to the people who are not having a problem with their weight, if they start losing some, we could be in trouble. It would be like putting a blood pressure-lowering pill in the drinking water, which has been mooted too. And it worries me as somebody with rather low blood pressure. I don't really want that.

Holly Wyatt:

Yeah. People have talked about putting an ACE inhibitor in the in the waters before. Yeah.

Jim Hill:

So one of the big areas that's pretty hot in nutrition research here, I think it's the same in the UK, is this idea of precision nutrition. That if we understand how people differ in physiology, behavior, et cetera, we're going to be able to target that perfect diet that's going to make it easy for them to maintain weight and be healthy. Thoughts on where you think this might go?

Keith Frayn:

It's a very interesting area, Jim. But, you know, I was working in medical research at the time when genetic medicine was all the rage. And we were told in 10 years time, everybody will be treated individually because we'll know what their genes are like. We'll be able to treat them individually. And how many times is that true? Now, there are some good cases. There are some individual cases, you know, genes that cause breast cancer. We can act proactively on that. But there aren't many. And I think we're a long way off that, even in general medicine. And the other thing I'd say, you know, so it may come, it may come with diet and maybe exercise too. But on the other hand, I'm not sure we need it particularly because, you know, there's nobody for whom a low calorie diet won't reduce weight. And so in a way, what are you learning by the precision medicine? So I think there may be something there to come. I don't think it'll dramatically change the way we do things.

Jim Hill:

Even if we identify the best diet for someone, we have to get them to actually eat it. And we haven't made very much progress in changing dietary behavior.

Keith Frayn:

It's just like we say about medicines, they don't do much unless you actually do it.

Jim Hill:

Exactly. Oh, man. Holly, should we get some listener questions? Do we have time?

Holly Wyatt:

Yes. And I have one because this is a question that they always ask me. So I want to get Keith's answer on this one. So how do you feel about artificial sweeteners or non-nutritive sweeteners for weight loss? Are you okay with it from an energy balance standpoint? Do you think it does something and messes up the metabolism or kind of what are your thoughts on that?

Keith Frayn:

Could I give you an anecdote? And I'll mention a name. I hope that's okay. Michael Gorin, whom I'm sure you know, professor of pediatrics in University of Southern California. He was my first PhD student.

Jim Hill:

I didn't know that.

Keith Frayn:

There you go. He came over to spend a year in Oxford about 10 years ago. This was about the time I was winding my research down. And we were talking about these issues and I said to him, "Of course, diet colas, diet drinks, they're the way to go forward. That's going to help everybody, isn't it? And he said to me, and I quote this in the book with his permission, he said, "I wouldn't give those to my kids. They're full of chemicals." And I thought, "Come on, Michael, what are you talking about? They're going to be the answer to obesity." But I have to say the evidence that it seems so obvious that replacing the sugar, which is calorific, with a non-calorific sweetener, it seems so obvious that will help. The evidence that that is helping people control their weight is not really there. And increasingly, there are reports of potentially bad effects of some of these chemicals. So I don't think they are the answer. I'm not saying there's anything wrong with having a can of diet cola each day, and I drink it from time to time. But I don't think you should. I've known people who kept a little fridge beside their desk full of cans of diet cola. Doesn't the president of the USA do this?

Jim Hill:

Oh, yeah. Yes, he does. He has a button at his office to call for them.

Keith Frayn:

I'm not sure that is going to be good for health in the end. I think we don't really know the long-term effects of these non-calorific sweeteners. The World Health Organization has pronounced on this and said these are not the answer to anything. And the problem is, I think maybe, and this is what the World Health Organization says, from which the USA has just withdrawn, by the way, says that they encourage a sweet tooth. And what we've really got to do is get used to having a less sweet tooth.

Holly Wyatt:

Yeah. I'm drinking a diet soda right now. I believe that they're a helpful tool in some people. Some of us want to have something sweet and just to get rid of everything sweet in our diet. I don't know if that's effective or helpful for everybody. But I do think we don't know everything and to look and see and make sure they're safe. But for me, I drink them. I feel like they're pretty safe. I don't drink a gallon a day, but I probably have a diet soda every day or so.

Keith Frayn:

Oh, yeah. I don't think there's any evidence that that's harmful, of course, Holly. I mean, for you, it's obviously helpful. But on the whole, I don't think, you may correct me, I don't think the evidence is there that these drinks are helping generally with controlling weight.

Holly Wyatt:

You're absolutely right. And I think that kind of comes back to not any one thing is going to move the needle because there's so many issues involved. If people think just substituting something for something they're drinking is going to solve the obesity problem, I think that's not true. As you've talked about, there's just the environment in so many different ways pushing and our metabolism in so many different ways pushing us.

Keith Frayn:

And do you know, at a local bus stop, because I use the local buses quite a lot, there's a big advert for a local fast food takeaway, a well-known brand all over the world. And it's got a picture of some fried chicken nuggets, got a picture of a burger dripping with cheese melting out of it. And at the bottom, it's got a can of diet cola. And I thought, what's that doing?

Jim Hill:

The diet cola doesn't counter the other negative aspects.

Keith Frayn:

But it gives that impression.

Holly Wyatt:

Right.

Jim Hill:

I've got one for you. There's a lot of interest now, Keith, in the gut microbiome and how it may play a role in obesity. How do you see that? And in particular, how does that fit into the concept of energy balance?

Keith Frayn:

Yeah, Jim, this is a very interesting area. And I have said in this book that it wasn't an area of interest when I was starting in research. And so it's come upon me, and I haven't worked directly in this area myself. And I might be a bit more dismissive of it than I should be. If you look at small animals in the laboratory mice, for instance, there's a clear relationship between what's going on with with the bugs in their gut and their body weight. And if you take the droppings from one mouse, the feces, from a thin mouse and you give it to a fat mouse, the fat mouse will begin to lose weight. Because you've changed the bugs in its gut. The same effect has not been found with humans although people would love it to be so. And I do think, as I'm always saying to people, energy balance in small animals like rats and mice is regulated in a very different way from humans, just because of body size. And so I don't think we have the evidence on this in humans. It's not impossible. I don't think it's going to defy the laws of energy balance. But I think it's not impossible that bacteria in the gut are producing something that gets into the bloodstream and changes our relationship with food. But I really don't think we have that evidence as yet.

Jim Hill:

No, I agree with you. And I think this concept of people are looking at things like the gut microbiome and say, "Well, it can't be energy balanced because of the gut microbiome." In fact, the gut microbiome can fit very well with the concept of energy balance because it influences the flow of energy through the body. So you don't have to throw the concept of energy balance out when you look at some of these things.

Keith Frayn:

No, I completely agree. They're part of the whole system.

Jim Hill:

Part of the whole. I see the microbiome as very much part of metabolism and part of energy balance.

Keith Frayn:

Absolutely. Yes.

Jim Hill:

Holly?

Keith Frayn:

It's a fairly small part, I might say.

Jim Hill:

Right.

Keith Frayn:

Not a big part.

Jim Hill:

Right. But small differences could be important in body weight regulation.

Keith Frayn:

Yeah. I quite agree.

Jim Hill:

Holly, you want to do a vulnerability question or two?

Holly Wyatt:

I do. I have one.

Jim Hill:

Okay, go for it.

Holly Wyatt:

So, what's one common weight loss myth you wish we could eliminate forever? If you could say, let's just get that one off there where no one believes that, what would you do? What would you say?

Keith Frayn:

Lots of people will hate me for saying this, Holly, but it's the idea that we gain weight because of a slow metabolism. So, there's lots of anecdotal evidence of, as we've said, people who seem to be able to eat anything and not put on weight and vice versa. But there are quite a large number of studies where those people, big eaters and small eaters with the same body weight have been brought into the lab and studied and it's never been possible to show this supposed difference in metabolism. And what that highlights, really, is how very, very bad we all are at judging what anybody's eating, including ourselves.

Holly Wyatt:

Yeah.

Jim Hill:

Okay, I've got one for you, Keith. The people that I've admired in our field from back when I was a graduate student is a researcher named John Garrow. John was a mentor of yours. So, the vulnerability question is, what did you learn from John that has really influenced your career?

Keith Frayn:

So I have some personal dealings with John. I was going through a difficult period when there were pressures on me to join a particular research group within the university where I now am. And I talked to John and said, you know, what would be your opinion? Should I stick it out on my own with a small research group of my own or merge into this bigger group? And he was very definite because it was the way he always worked. He said, get your own group, you know, and do it your own way, which I did. And I've always been grateful that he said that. As you'll know, this book is dedicated to John Garrow. But he also wrote what could be seen as the predecessor of this book, although it was written for professionals. It was called Obesity and Energy Balance in Man, and it reviewed a lot of the ideas that I've reviewed here, although I've taken different viewpoints and I've tried to write it more for anybody in the population. But he had a very, very common sense way of looking at obesity. And he had techniques such as putting a band around somebody's stomach, a band that wouldn't expand. It was like a piece of wire. And that just made them keep their weight down. Otherwise, it got very, very uncomfortable. So he had these very practical techniques, but in a very nice way, very, very gentlemanly person and always very kind to his patients.

Jim Hill:

Yeah, and if you haven't read his work, it's just he's... And I read the book you were talking about years ago and just fascinated stuff. And I think he was one of the people that I really admire in this field.

Jim Hill:

Well, Keith, it's been a great discussion. Before we leave you, we're going to ask you to give our listeners one takeaway message that you want them to remember about energy balance.

Keith Frayn:

I think one thing that throws us all when we think of energy balance is that our weight can vary such a lot from day to day or week to week. And actually, when you look at this metabolically, what you're probably looking at is just water balance in the body. So I think what we have to do, if we want to think about weight regulation, I think you have to take a long-term view. You don't weigh yourself on the scales every day. But I think your work with the National Weight Control Registry absolutely chimes with me that people who manage to control their weight weigh themselves regularly. And I'd suggest weighing regularly, maybe once every two weeks or something like that, not more frequently, and perhaps even plotting a graph. I used to do that. And when you see that graph is going upwards, you'd do something about it. If you see that graph is going downwards, just be happy and just keep it going downwards. It doesn't take a big adjustment to do that.

Jim Hill:

Yeah. Holly's big on telling people that if your scale's five pounds up from yesterday, that's not five pounds of fat that you've gained.

Holly Wyatt:

Yeah. So, I think we're in agreement about this. But the way I kind of handle is I do have them get on the scale every day, but we average it each week. That helps take that water up and down out of the picture and we look for new highs and new lows. So we kind of look at the data differently, but I think we're agreeing that that water weight is something you have to understand and it can really make things difficult if you don't.

Jim Hill:

Keith, thank you for sharing your expertise today. And to our listeners, what's been your biggest challenge with weight loss? Have you found energy balance to work for you? Or do you think there's more to the story? We'd love to hear your thoughts. And Holly, we're getting more and more of our listeners that are actually sending in questions and comments. So that's good because we'll use those. And we've even had suggestions for other podcasts. We want to hear from you. Let us know what's going on and what your big questions are.

Holly Wyatt:

Absolutely. Send us the questions. Tell us what you like, what you want to hear more of, and we will answer as many as we can. And people on, I love that we get to bring experts on and really hear from so many people, no matter where they are, all across the world.

Jim Hill:

Thanks, Keith. Thanks, everybody. See you next time on Weight Loss And.

Holly Wyatt:

Bye.

Jim Hill:

And that's a wrap for today's episode of Weight Loss And. We hope you enjoy diving into the world of weight loss with us.

Holly Wyatt:

If you want to stay connected and continue exploring the “Ands” of weight loss, be sure to follow our podcast on your favorite platform.

Jim Hill:

We'd also love to hear from you. Share your thoughts, questions, or topic suggestions by reaching out at [weightlossand.com](http://weightlossand.com/). Your feedback helps us tailor future episodes to your needs.

Holly Wyatt:

And remember, the journey doesn't end here. Keep applying the knowledge and strategies you've learned and embrace the power of the “And” in your own weight loss journey.