The Obesity Debate: Breaking Down the Science | Dr. Faidon Magkos

Summary

The Dr. Gabrielle Lyon Show: The Obesity Debate – Breaking Down the Science with Dr. Faidon Magkos

Host: Dr. Gabrielle Lyon
Guest: Dr. Faidon Magkos, Professor of Obesity and Metabolism, University of Copenhagen
Release Date: December 31, 2024

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1. Introduction

In this insightful episode of The Dr. Gabrielle Lyon Show, Dr. Lyon welcomes Dr. Faidon Magkos, a distinguished metabolic expert and professor at the University of Copenhagen. With over 200 publications and a profound impact in the fields of nutritional science and exercise physiology, Dr. Magkos brings a wealth of knowledge to dissect the complexities surrounding obesity.

2. The Core Debate: Energy Balance vs. Carbohydrate-Insulin Models

Dr. Lyon and Dr. Magkos delve into the two predominant theories explaining the pathogenesis of obesity:

• Energy Balance Model: This traditional model posits that obesity results from consuming more calories than the body expends. Dr. Magkos illustrates this with an analogy:

  "[14:04] Dr. Fadan Makos: So you have an expansion of adipose tissue..."

• Carbohydrate-Insulin Model: Contrarily, this model suggests that obesity arises from how the body processes carbohydrates, leading to fat storage and subsequent overeating due to perceived energy deficits. Dr. Magkos explains:

  "[17:55] Dr. Fadan Makos: To put it back in the analogy of the car..."

3. Insights from the Perspective Paper

A highlight of the discussion is Dr. Magkos' recent perspective paper published in Nature Metabolism, co-authored with notable experts like Kevin Hall and David Ludwig. This paper emerged from a collaborative workshop aimed at reconciling differing viewpoints on obesity's causes.

"[07:14] Dr. Fadan Makos:...we have summaries of discussions that..."

Dr. Magkos emphasizes the paper's goal to find common ground between opposing models, fostering a more unified scientific understanding of obesity.

4. Challenges in Obesity Research

The conversation sheds light on the inherent difficulties in obesity research:

• Limitations of Human Studies:

  "[20:56] Dr. Fadan Makos: But this is not possible in humans to do."
  Dr. Magkos discusses how long-term, controlled studies are unfeasible, making it hard to definitively prove or disprove prevailing models.

• Variability Among Individuals:

  "[102:48] Dr. Fadan Makos: Some of it could be genetic..."
  The multifactorial nature of obesity means that factors like genetics, environment, and lifestyle interplay, complicating research outcomes.

5. The Role of Muscle Mass and Body Composition

A pivotal part of the discussion revolves around muscle mass versus adipose tissue:

• Quality of Weight Loss:

  "[70:59] Dr. Fadan Makos: ...it's about 75% fat and 25% lean mass."
  Dr. Magkos explains that effective weight loss strategies should prioritize fat loss while preserving muscle mass.

• Measurement Challenges:

  "[74:45] Dr. Gabrielle Lyon: What do you see as the problem in that."
  The duo discusses the complexities in accurately measuring muscle mass, underscoring the need for advanced methodologies like CT or MRI scans for precise assessments.

6. Diet and Exercise Strategies for Weight Loss

Dr. Lyon and Dr. Magkos explore practical approaches to managing obesity:

• Personalized Diets:

  "[89:27] Dr. Fadan Makos: ...there is no ideal diet. There is no perfect diet."
  Emphasizing the importance of individualized dietary plans, they advocate for trial and error to find what best suits each person's lifestyle and needs.

• Exercise Modalities:

  "[108:55] Dr. Magkos: ...high intensity interval exercise, which is a great way to exercise."
  They discuss the benefits of various exercise forms—endurance, resistance, and high-intensity interval training—and their roles in weight management and metabolic health.

7. Communicating Complexities to the Public

Addressing the challenges of translating complex scientific debates to the general public, Dr. Magkos highlights the importance of avoiding oversimplification and recognizing the multifaceted nature of obesity.

"[111:54] Dr. Magkos: ...the public discussions typically take the form of..."

They stress the need for balanced communication that acknowledges multiple contributing factors rather than attributing obesity to a single cause.

8. Future of Obesity Research

Looking ahead, Dr. Magkos expresses optimism about leveraging big data and artificial intelligence to unravel the complexities of obesity. However, he also acknowledges that obesity's multifactorial nature means research will remain challenging.

"[114:38] Dr. Fadan Makos: ...we might be able to mine this data in a more effective way..."

9. Concluding Thoughts

Dr. Lyon and Dr. Magkos conclude with a mutual appreciation for the collaborative efforts in the scientific community to better understand and address obesity. They advocate for a holistic approach that integrates diet, exercise, and personalized strategies to promote long-term health and wellness.

"[116:23] Dr. Gabrielle Lyon: Well, Faden, thank you so much for sharing time and your brilliance. You are an amazing human and a phenomenal academic."

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Key Takeaways:

• Obesity is a complex, multifactorial condition with ongoing debates about its primary causes.
• Energy Balance and Carbohydrate-Insulin Models offer distinct but potentially overlapping explanations for obesity.
• Research Limitations make it challenging to definitively prove or disprove prevailing models.
• Muscle Mass Preservation is crucial in weight loss strategies to maintain metabolic health.
• Personalized Approaches to diet and exercise are essential given the variability among individuals.
• Effective Communication must convey the complexities of obesity without oversimplification.
• Future Research holds promise with advanced technologies but will continue to face challenges due to obesity's multifaceted nature.

Notable Quotes:

• "If you can make people lose weight in a controlled environment, but we cannot replicate that in real life, then how much does that effect our understanding?" – Dr. Faidon Magkos [24:23]
• "There is no ideal diet. There is no perfect diet. And when I say that to people, most people get sad and disappointed." – Dr. Faidon Magkos [89:05]
• "Obesity itself is not necessarily associated with increased risk for disease." – Dr. Faidon Magkos [61:17]

This episode offers a comprehensive exploration of obesity's scientific debates, emphasizing the need for nuanced understanding and individualized health strategies.

Transcript

[Dr. Gabrielle Lyon]

Welcome to the Dr. Gabrielle Lyons show where cutting edge science meets innovation and practical application for everyone. In this episode, I sit down with Dr. Fadan Makos. Now, you may not have heard of him because he is not on social media and in fact he is one of the most well published, well researched, well respected metabolic experts in the nutritional science and exercise physiology space. He is a full professor at Copenhagen and he is in the Department of Nutritional Sciences. He's also published some of the most well respected hallmark studies. In this episode we discuss the true cause of obesity, both sides. You've heard about calories in, calories out, and you've also heard about the carbohydrate insulin model Faden. Dr. Fadin breaks it down from two sides of the coin, both perspectives, to bring you the commonalities and the differences. Now join me in this conversation with Dr. Vadan Makos. Vaden Makos. We go way back and you laugh at me. And I said, vaden, We've been friends for, you know, we've been friends for over 10 years.

[Dr. Fadan Makos]

Yeah, that's about right.

[Dr. Gabrielle Lyon]

That's. That is about right. You are a professor in obesity and metabolism at the Department of Nutrition, Exercise and Sports at the University of Copenhagen in Denmark. Which, by the way, your flat looks amazing.

[Unknown]

Oh, thank you.

[Dr. Gabrielle Lyon]

I, you know, it's really interesting because I met you at Washu. You were a professor at Washu. You, let's see, there's Harvard Medical School here. You have published over 200 papers, you know, with their impact factor of an average of 6.3h index is 54. And for those who are not academics, basically I'm talking to a genius.

[Dr. Fadan Makos]

Thank you. Probably those who are not academics, they believe you. So.

[Dr. Gabrielle Lyon]

But you know, you said something to me that really struck me and I don't, I'm sure you don't remember this, but I am, you know, I would normally say this would embarrass you, but it's not going to embarrass you because probably most things don't. But you said to me something that I've taken with me for over 10 years and you said, when you are average or mediocre, nobody cares about what you're doing. Do you remember saying that? But when you are great, people have these expectations. So how I took that was basically, if you're functioning at a level and not producing and not providing, you know, it's kind of like great, whatever. But when you are exceptional, there's a lot of criticism and there on your work. Do you remember telling me that is That a fundamental.

[Dr. Fadan Makos]

I honestly don't, but it sounds about right.

[Dr. Gabrielle Lyon]

And you do not have a Instagram YouTube channel or probably not even a Twitter account.

[Dr. Fadan Makos]

But I do not. Yeah, I do not. I typically don't disseminate my research in those channels.

[Unknown]

So this is an exception.

[Dr. Gabrielle Lyon]

Well, I feel very special and I. You didn't really have a choice but to say yes, there was. There was no choice. And if someone were to Google your name, they will find a ton of citations, they will find a ton of papers. But I do want to mention that the quality of these papers, these are hallmark papers. They are, they are literature that has moved the field of obesity in ways that is so meaningful. And I don't know if anyone has ever said thank you, thank you so much.

[Dr. Fadan Makos]

I mean, I think that you're too kind, but thank you so much for your kind words. I mean, some papers are better than others. I mean, that's a reality, right?

[Dr. Gabrielle Lyon]

Here's how I've been using AG1 with my unsweet Texas tea and half a shot of ketones. I have to tell you, I feel really good about that kind of decision. AG1 covers what I lack in my diet. It comes from whole food sources that are synergistic. It is the difference between eating components of a stew, for example, rather than the entire cooked stew itself. AG1 has vitamins, minerals, adaptogens and bioactive ingredients from whole foods like citrus, bioflavonoids. The synergy of the parts amplifies the effectiveness of AG1. It contains prebiotics, probiotics, gut supporting ingredients. In fact, in a research study, 97% of participants felt digestion improved after 90 days of drinking AG1. In another clinical trial, AG1 was shown to increase healthy bacteria in the gut by two point. AG1's formula takes a dual approach supporting the gut microbiome and also overall health and wellness. I know because I feel it myself. What I love about AG1 is that it has a commitment to research and furthering the science around nutrition and gut health. AG1 uses research backed ingredients and they even take it a step further by conducting multiple research studies on the complete formula. They continuously publish their findings curated across many disciplines and are deep in the research testing, validation now. It's a great first step to investing in your health and that's why I'm so excited to be partnering with them. Try AG1 and get a bottle of vitamin D3K2 free and five free AG1 travel packs when you first subscribe at drink ag1.com lion that's a 48 value for free if you go to drinkag1.com DrLion check it out. And I was so excited to see this, this paper. This is, I'm sorry, it's not a paper. This is a perspective, perspective piece. And this was published August 2024 in Nature Metabolism and it's on the pathogenesis of obesity. Causal models and missing pieces of the puzzle. You are the first author in this perspective piece. There are really juggernauts. Got Kevin hall, we have, you know, Arnie Astroff, the list goes on. And basically I want to know why you wrote it. I mean, why did you take this beast of a perspective on and what was the perspective? And by the way, I know it, but hearing it from you is way more interesting.

[Unknown]

I get you.

[Dr. Fadan Makos]

I mean, just to give you a little bit of a background, back in 2023, like in the fall of 2023, the Nodis foundation, which is a research foundation that we have here in Denmark, they took the initiative of putting together a two day workshop in Copenhagen. And they invited people who have very different perspectives on the pathogenesis of obesity from all around the world. And of course there's a lot of different ideas and thoughts and models and hypothesis about how obesity develops. But they kind of chose the two most popular ones or predominant ones, let's put it this way. So they invited everybody to Copenhagen. It was about 15 or 16 people, pretty much as many authors as you see in that paper. And the, during these two days we had a lot of interesting discussions. Some of them were more heated than others. There was a lot of agreement, much more disagreement. So at the end of that workshop, we kind of thought that it would be a good idea to summarize, you know, what came out of this. I mean, did we spend those days in a meaningful way? Did we manage to achieve anything? Or did we just go to a very nice place that novel foundation kind of rented for us and we just wasted our time pretty much, you know, because generally speaking, scientists tend to support their hypothesis quite a lot. So it's, it's, it's always difficult to have people with very different perspectives and ideas to kind of get together and discuss in a way that is also very open, easygoing and transparent. Right. Because that was not a conference, so nobody really had to defend anything.

[Dr. Gabrielle Lyon]

And, and I have to say, to interject, you've played a huge role in the way that I think. I don't know if you know that, but you, I'm sure you do, because I, I do call you freaking out on numerous occasions. And you always say to me, number one, science is a science of uncertainty.

[Dr. Fadan Makos]

Yes, absolutely.

[Dr. Gabrielle Lyon]

And you always challenge me. Why Muscle?

[Dr. Fadan Makos]

Why.

[Dr. Gabrielle Lyon]

Why this?

[Dr. Fadan Makos]

Yeah, yeah, you're absolutely correct. When we say in science and in our research that something is happening, we always say that with a certain level of being uncertain, which means that it might not always happen this way and it might not always happen for everybody in the same way. Right. So going back to the, to the, to the workshop, I consider myself relatively, I mean, nobody can, can really be completely neutral. Right, in this debate. But I, I'm one of the people who kind of understand the arguments from both ends. And then I took on the task of putting all these discussions into a paper that everybody would agree on and then getting it out there for the public to kind of read.

[Dr. Gabrielle Lyon]

Oh, sorry, go ahead. I'm sure you're going to tell us the arguments and, and why.

[Dr. Fadan Makos]

Well, I will, I will. I was about to tell you the process. So it took us many, many months and drafts and back and forth because, you know, everybody needs to be, to agree on the final version of the paper and on the actual words, not just the meaning, but we had back and forth in terms of trying to find the correct words to portray what these people believe and agree on. So that task was not particularly easy. So it was one of the more difficult papers for me in terms of getting together all the authors to agree on writing a paragraph. And sometimes it took us forever to write the paragraphs, but thankfully it all culminated in a nice paper that was published.

[Dr. Gabrielle Lyon]

Well, and now it's out there and give us the overarching themes of what people disagree on, what people agree on it. And this really was. What is the cause of obesity? Is this a energy balance issue? Is this a carbohydrate issue? Insulin issue? And I have to say, looking at the authors, when I saw this, I couldn't believe it. As you'd mentioned, you have Kevin hall, you have David Ludwig. There are people that have drastically different views and they're all very well respected.

[Dr. Fadan Makos]

Absolutely, yes, absolutely. There's no question about this. And if you look individually at, you know, in the literature, there is evidence to support arguments on both ends.

[Unknown]

Right.

[Dr. Fadan Makos]

I mean, that's the reality of human research. But, but going back to, to the, to the, to the two different ideas or two different models, let's say that, that, that these two camps represent, one of them is, I would say, the most, the one that we were all pretty much brought up with and the one that we are or more or less familiar with, which is energy balance model. And what this hypothesis states is that obesity generally develops as a result of people eating more food, more calories than the amount of calories that they burn. The main reason why this happens is that the modern food environment, predominantly the modern food environment and the characteristics of the modern food supply, what they do is that they facilitate overeating below the level of your conscious awareness. So you eat more without even realizing it. Right? So that's the general idea. So the excess calories, regardless of whether you eat more carbs or more fat or more protein, when you do not burn them, the body typically eventually tends to convert them and store them as fat, right?

[Dr. Gabrielle Lyon]

Yes.

[Dr. Fadan Makos]

So you have an expansion of adipose tissue. So in the energy balance model, overeating or positive energy balance precedes the adipose tissue expansion and the development of obesity. So that's what I would say most textbooks on dietetics and nutrition and obesity kind of portray as well.

[Dr. Gabrielle Lyon]

And that's what we've all been taught, correct?

[Unknown]

Correct.

[Dr. Fadan Makos]

So to try to give you an analogy, right, imagine that you go, let's say on a Monday morning, you go with your car to the gas station and you put 10 gallons of gas, right? And then you take your car around.

[Unknown]

And as you go around, of course.

[Dr. Fadan Makos]

You burn some of this gas, right? So at the end of the week, by Sunday night, you pretty much are empty. So the next Monday morning, you put again 10 gallons of gas. And that goes on, on and on. But on every Sunday night, you are always at zero, so you are always empty, right? So you are in an energy balance in this case. But imagine now that you know, you decide to change gas station, right? And this new pump that they are using, it kind of works a little bit in your favor. Meaning that it reads that you are dispensing 10 gallons, but in reality you are dispensing 11. Okay? So now you go around your daily life and whatever you do during the course of the week, but now at the end of the week, on Sunday night, you are left with one gallon in the tank, right? Now you think, however, that you are left with nothing. So next morning you put again another 10 gallons of gas, as you think, but in reality, another 11. So, you know, if this goes on, you accumulate one gallon of gas every week.

[Dr. Gabrielle Lyon]

So gallon is fat or this gallon. Are we're talking about fat? Are we talking about.

[Unknown]

Correct.

[Dr. Fadan Makos]

If you do not. If you do not, let's say, strive to, to do something with physical activity, most of the excess calories are being stored as fat. Nonetheless, as the time goes on and your weight increases, imagine this as a form of passive training. So obesity is also associated with an increase in lean mass and muscle mass because you need the additional muscle to carry the much more weight of your body.

[Unknown]

Right.

[Dr. Fadan Makos]

So most of the weight gain is fat, but part of it is lean mass and muscle.

[Dr. Gabrielle Lyon]

Lean mass and muscle. But that. And I'm just going to mention this, and you and I certainly discuss this, it doesn't necessarily reflect the health of that tissue.

[Unknown]

Absolutely.

[Dr. Fadan Makos]

But I will get back to that. We can get back to that. But let me. So this is. So this is the energy balance model. And the idea is that because of the food supply has changed and now we have these ultra processed foods which are calorie dense and they have a lot of other ingredients in them that, you know, kind of mask or saturate the ability of our brain to understand how much we eat. That's the general idea. So it all starts with eating more than what you need in the energy balance model. And then the end result is an expansion of adipose tissue.

[Dr. Gabrielle Lyon]

Obesity and muscle.

[Dr. Fadan Makos]

Correct. And muscle to some extent. So also energy expenditure goes up in, in along these lines.

[Unknown]

Right.

[Dr. Fadan Makos]

So the total energy expenditure of the body goes up simply because you have a larger body right now. So for any sort of activity you do, you burn more calories. Right. Now the other model that is, let's say the contender is the carbohydrate insulin model of obesity. Right. And that model suggests that the primary defect is not really the brain that does not understand how much you eat, but it's something that happens in your body in the peripheral organ, say in the liver or in the adipose tissue or the skeletal muscle. So the handling of the incoming nutrients and the incoming food is changed and is changing the way that you cannot utilize all the calories that you ingest for doing all sorts of things that you want to do.

[Unknown]

Right.

[Dr. Fadan Makos]

To put it back in the analogy of the car, let's assume now that the, the pump is functioning correctly. So you put in 10 gallons. But the tubes that transfer the gas or the fuel from your tank to the engine, they have leaks. So you cannot take advantage of all the fuel that you entered in your car.

[Unknown]

Right.

[Dr. Gabrielle Lyon]

Chicken or the egg, what came first? Is it, are we over consuming food and then getting an increase in adipose tissue? Right. It would be considered hyperplasia. Would that be considered hyperplasia or.

[Dr. Fadan Makos]

Well, hyper. Hyperplasia and hypertrophy refer to two characteristics, ways by which tissues typically increase and grow hyperplasia is that I am making more cells. And if we are talking about adipose tissue hyperplasia, then you would make more adipocytes. So the number of cells increases hypertrophy, meaning that it means that the cells themselves grow bigger.

[Unknown]

Right.

[Dr. Gabrielle Lyon]

And is that what happens when someone.

[Dr. Fadan Makos]

Typically both happen in obesity, although hypertrophy is more pronounced. So typically you develop larger adipocytes rather than more cells when you develop obesity in your adult life. But, but going back now to the carbohydrate insulin model, so what this suggests is that if since your body cannot, let's say, take advantage of all the calories that you just ate, it signals to the brain and it tells your brain that, you know what, I need more food. Right. Even if you have it in your body, but you just can utilize it. So the brain, then what it does is that it tells you that you either need to burn less, so it will make you make your energy expenditure lower to match what you have or what you think you have, or most.

[Unknown]

Commonly, it will make you overeat.

[Dr. Fadan Makos]

So in the carbohydrate insulin model, the causal chain is reversed, meaning that you start first from depositing more of the ingested calories into fat, and then this.

[Unknown]

Leads you to overeat.

[Dr. Gabrielle Lyon]

Right. I see.

[Dr. Fadan Makos]

So in that, in the, in the carbohydrate insulin model, it's a, it's a, it's something that happens in your periphery that then signals the brain to eat more. Whereas in the energy balance model is quite the opposite. Try to the first eat more and then you deposit those calories into fat.

[Dr. Gabrielle Lyon]

I see.

[Dr. Fadan Makos]

And, and as you mentioned, the chicken and the egg, that's something that is extremely difficult to, to dissect in humans. Right. Because we would have to take people who have normal body weight and then perhaps overfeed them for a prolonged period of time until they become obese and see what comes first.

[Unknown]

Right.

[Dr. Fadan Makos]

But this is not possible in humans to do. The best model that we have so far for weight gain and obesity is these overfeeding studies where we experimentally feed people more than what they need. But this is typically very large extent of overfeeding. So let's say we feed them 1,000 or 2,000 calories per day more than what they need for a few weeks. That's not typically how obesity develops.

[Unknown]

Nobody goes to bed being lean and.

[Dr. Fadan Makos]

Wakes up the next morning being obese. Typically, obesity develops by at least what, that's what we think is by eating a few more calories than what you need on a daily basis for years. So we do not have really a very good model for human obesity in research.

[Dr. Gabrielle Lyon]

We don't. I want to restate that because many of us who are not academics and as you know, well, you might not know because you're not on the social media circuit or sphere, but there's a lot of information out there and the discussion is stated in ways that it seems as if these are absolutes that this is will review literature and then you'll have influence or influencers or scientific educators then speak to the public. And a fundamental concept is that I think it's important to highlight is we don't actually have a good model of obesity to study. And the foundation of the work is built on the best that we could do is. Is that fair to say?

[Dr. Fadan Makos]

Yes. And I would say it, you know, all the. So one thing with the, with the social media and the influences and all these arena is that, you know, but you have to always defend or try to convince people why things are not necessarily as stated in the social media. You know what I mean? And that's a little bit tiring.

[Dr. Gabrielle Lyon]

Tell. Explain to me a little bit more. I, I agree.

[Dr. Fadan Makos]

So, you know, there is a lot of, A lot of the new trends and the fads and the diets that come up from time to time stem, for instance, from studies in animals or from a single study in humans. And, and their results are very good because they are very good to make a headline. But nobody really digs deeply to understand the limitations of the study. What does one study mean? Nothing really.

[Unknown]

Right.

[Dr. Fadan Makos]

There is no definitive study research in humans at least, or generally speaking, science. You have to consider every study as a little brick. And we are trying to build a building. So if you take a brick and you focus on that brick and you tell me, look, the story that brick tells you, it's really relevant for the whole building. Right. So that's, that's kind of the analogy that I try to, to, to give to my students as well when it comes to a single study versus understanding what the whole literature shows. And now coming back to obesity in humans, for instance.

[Unknown]

Right.

[Dr. Fadan Makos]

To give you an example, in the overfeeding studies, we are very successful. We take people in the lab, we can overfeed them, we can make them gain 5, 10 kilos, right.

[Unknown]

But remarkably, when we send them home.

[Dr. Fadan Makos]

And the study is finished, the majority of them within a few months lose that additional excess weight effortlessly without even doing anything according to their testimonials. This is completely different to the model to the real obesity that we have in real life where people struggle to lose weight, right?

[Dr. Gabrielle Lyon]

Yes.

[Dr. Fadan Makos]

So how good, how good of a model? That is probably not so good. And of course, you know, there is not even a point in discussing the animal studies because it's also different species, right? Completely different.

[Dr. Gabrielle Lyon]

And whether you're ad libitum feeding them.

[Dr. Fadan Makos]

It'S very easy to pick up the results, you know, to cherry pick and make a story. That's not a difficult thing to cherry pick different findings and make a story. What is difficult is to say that, okay, if this, if all of these, let's say, magical diets or reasons why we get obese and why we lose weight and don't lose weight, if these were true, we would have solved the problem already. We wouldn't have obesity. But we still do have obesity and we are very much unsuccessful in treating it.

[Dr. Gabrielle Lyon]

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[Unknown]

Well, you know, I'm, I'm, I'm, I'm.

[Dr. Fadan Makos]

I would say that the US as neutral as I try to be, I think that the major factor is that, you know, food is nice and eating is really, it's an enjoyable Activity. Right. For you, for pretty much everybody, I would say. And, and you know, the, the fact that the modern food supply helps you overeat. So you eat a slice of pizza or a hunger and that's 500 calories. If you eat it in vegetables and fruit, that will be a bucket of fruit.

[Unknown]

Right. Or, or vegetables and volume.

[Dr. Fadan Makos]

So energy density is a major factor. But there is a lot of other reasons why we eat food.

[Unknown]

So eating or eating humans is not.

[Dr. Fadan Makos]

Just a homeostatic response, meaning that it's not just when my brain understands that I don't have enough energy, I go and eat. I mean, in Copenhagen, to give you an idea, I'm running in the mornings and in the mornings all the bakeries are baking their, you know, croissants and bread and da, da, da. And you know, I love carbs.

[Dr. Gabrielle Lyon]

Yeah.

[Unknown]

I struggle to not stop and just.

[Dr. Fadan Makos]

Not go in and just eat something. Right. Yes, I know better. But, but what I'm trying to say with this example is that there is a whole lot of, you know, other socio cultural factors that drive eating behavior in humans.

[Dr. Gabrielle Lyon]

And let's say we were to take that out though. And for those of you listening, or I'm really hoping you get to watch this, because I've never seen Faden wear a suit ever. I've seen him wear lots of T shirts and running shorts. He will run for hours and then would go to the store Straub's and get an entire baguette and I would call him and he would be sitting there eating the entire huge loaf of bread and him and I would go back and forth about, do you need carbohydrates? Could someone just eat protein? And you know, one of the other things is, and I don't want to get too off track, but I do want to have you be humanized. You are an incredible researcher and even you, with all of this knowledge, it's not so cut and dry. And when I think about these two competing ideas, this energy balance or carbohydrate insulin model, I wonder when did these first come, you know, when was there an idea that perhaps there was an emergence of two models?

[Dr. Fadan Makos]

Well, as I said at the beginning, Gabrielle, there is more than two.

[Unknown]

Right.

[Dr. Fadan Makos]

So there is a. There are theories that obesity develops because of viruses. There are also theories that obesity develops because of environmental contaminants.

[Unknown]

Right.

[Dr. Fadan Makos]

And that's. That may well be relevant. To give you an example, there is evidence that the basal metabolic rate of humans, there is evidence that it has been decreasing over the past 100 years. 100 years is much prior to the emergence of the obesogenic environment, as we call it today. Right. And the, and the McDonald's and the fast food chain. So we're talking about back to 1910.

[Dr. Gabrielle Lyon]

So there was no change in activity. This is.

[Unknown]

Well, I would say, I mean, of.

[Dr. Fadan Makos]

Course, you know, going back and looking into what happened historically, the quality of the data that we have is not so good. But, but I would say that the majority of evidence would suggest that up until maybe the 60s, 70s, there has been decreases in activity level simply because of the industrialization and the, and the changing in the type of jobs that we do. From the 60s, 17 onwards, I don't think that there has been so much change because focus also has been put on having people do more leisure time, physical activity. And you have to also remember that it depends on. So if you are bigger, you burn more calories. So maybe the reduction in the level of activity count is counterbalanced to some extent by the increase in our body weight, which burns more calories. Right, but what I want to say by that is that there is evidence that our metabolism has been changing way before the obesogenic transformation of society where we start blaming the, you know, modern food for all the bads and all the obesity and all the diseases that have been happening.

[Dr. Gabrielle Lyon]

Is it possible then, if, if we were to think about and expand a larger view there. Carbohydrate insulin model, energy balance model, these are the ones that are most robustly discussed. You mentioned environmental contaminants. We do see this in my clinical practice. We do see environmental contaminants. You know, to what degree these environmental contaminants play a role, I can speculate. There seems to be a disruption in potentially thyroid regulation. We do see these contaminants and to what the mechanism is. I remember that. I'll just give you an example, is that I had a military family, a commander who was living on a golf course and his dog dramatically gained weight and it was over. I mean, we are talking about this dog went from a normal lean animal to a very obese dog in a matter of two months. And it wasn't that he was changing anything. It was that he had actually gotten into some of the pesticides.

[Dr. Fadan Makos]

Okay, so he was not eating more. You mean he was, he was being fed the same amount of food.

[Dr. Gabrielle Lyon]

He was being fed the same amount of food. And it turned, it turned out that he had been exposed to all of these chemicals. He also lost vision in his eye. There were other things that happened.

[Unknown]

Yeah.

[Dr. Fadan Makos]

So one thing that is very, very possible is that all of these factors can operate in tandem. Right. Or at the same time. Meaning that some individuals may be more prone to the, you know, energy balance type of obesity. Meaning that they tend to overeat. Some individuals, maybe because of genetics or other factors or where they live, as you say, may have problems with their peripheral metabolism and handling of the ingested food. And then, you know, the sim like model may be more relevant. It is. It is possible that, you know, more than one factors or model or contributing pathways account for obesity in different individuals.

[Dr. Gabrielle Lyon]

And would you say that there are other models before we go back to this, you know, this perspective paper that maybe we're going to begin to hear more about?

[Unknown]

Well, about the fact that you can. Even if you identify the cause of obesity, removing that cause doesn't mean that you're going to treat obesity. Right.

[Dr. Gabrielle Lyon]

That is a way to think about it, though, because if, for example, if excess calories, if that was the cause of obesity and then you remove the excess calories, one should be able to treat it, no?

[Unknown]

Well, you know, not necessarily. Because if, let's say the alterations that, or the adaptations that have happened in the body in the obese state are resistant to change, then this does not necessarily mean that you will be able to treat obesity effectively. Meaning that physiology is not linear. Right. That's something that happens in pretty much all physiological responses. Our body doesn't respond linearly to increases or decreases in stimulus, such as calorie intake.

[Dr. Gabrielle Lyon]

Where do you think the divergent pathways came from? People historically focused on this energy balance model. Then somebody must have had an opposing view.

[Unknown]

Yeah, yeah. So I think that, you know, evidence or at least focus on the amount of calories that we eat being responsible for obesity dates back maybe to the early 1900s, 1910 or 1920. There were booklets about, you know, calorie counting. So the focus on calories was there over 100 years ago, I would say say. So, you know, that that's, that's where I can identify the root of the energy balance model. Now, the carbohydrate insulin model kind of emerged from the realization that all efforts that we do to try to treat obesity by energy restriction don't really work in the science.

[Dr. Gabrielle Lyon]

In the randomized control trials.

[Unknown]

Yes. So, you know, in randomized controlled trials, you can have people lose weight for the first maybe, you know, three, six, nine months, then they reach a plateau and then they just start regaining weight. Even though you're still supposedly trying to calorie restrict them. So, you know, the body is very, very good in defending that obesity. We don't lose weight so easily, so the body perceives that as a threat, I would say. But you know, starting from that realization that if energy balance is correct, then by removing the excess calories we should lose weight. Right. And if this doesn't work, then something else must be happening. And that something else is what eventually led to the formulation of the carbohydrate insulin model. And I would say that at least some indication that calories may not be the culprit dates back to the 40s, 50s or something like that. But as a model, the carbohydrate insulin model was formulated relatively recently, maybe the past 20 years or so.

[Dr. Gabrielle Lyon]

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[Unknown]

Yes, yes, absolutely.

[Dr. Gabrielle Lyon]

And you'll hear many scientists say, well, the carbohydrate insulin model, that's been disproven. And what would you say to that?

[Unknown]

Well, as I said, it's very difficult to prove or disprove something in humans. Right. So how do you prove the energy balance model are there? We should. So we should take people who have normal body weight, put them somewhere in a hotel, isolated, Right. Then try to, to have, or to mimic the normal food environment where there is all these ultra processed foods and all those things, and then keep them there for years, right?

[Dr. Gabrielle Lyon]

Yes.

[Unknown]

And then have another control group where they would be in another hotel where the food resembles the minimally, perhaps, or low, little processed food that we had in the, in the beginning of the previous century. So these studies are impossible to do. And of course, when I say isolated, you know, you have to think, as I mentioned, obesity has a very strong sociocultural copy component. Right. Because, you know, I remember when we were doing studies, you remember at Westview, that we had some TVs in these.

[Dr. Gabrielle Lyon]

Rooms and I was just having flashbacks to the, the metabolic ward, the unit, you know, we should.

[Unknown]

You remember that all, all these people were watching the Food Network.

[Dr. Gabrielle Lyon]

I know. Did you guys do that on purpose?

[Unknown]

So what I mean is that, you know, the influencers, the, the amount of food advertisements, what you see, this is impossible to replicate in a controlled environment and see what is the effect of that on eating. Right. So in the same way that I cannot answer you whether the carbohydrate insulin model has been disproven, I can also not answer whether the energy balance model has been proven. Right. Because what does disproving mean? I mean, you would. People would say that. Let's say if you give people a low carb, low GI diet and they don't lose weight, that that kind of disproves the carbohydrate insulin model. But the reality is that all our diet intervention studies are either too short or they have too little intensity. Right. And the reason, of course, is feasibility and funding. Just to give you an idea, when you test weight loss drugs, for each person that we recruit in a study, we spend about 40, $50,000 in weight loss studies with diet, exercise, and these lifestyle behaviors, we spend about $2,000. So we just can do these studies so far, at least in humans in a way that it will be a definitive answer to whether this works or the other thing works.

[Dr. Gabrielle Lyon]

Have there been particular hallmark studies that we can pull information from? The. I think it was the ABC trial in humans.

[Unknown]

In humans, you mean?

[Dr. Gabrielle Lyon]

Yes, yes.

[Unknown]

I think that. Well, on the energy balance side, the Kevin Hulls group, they have this setup where they actually have some sort of a hotel, like clinical research center where they can actually Control the food supply with vending machines. And you know, they keep people isolated and they have compared in a randomized design. What happens when you put people in vending machines that offer only ultra processed food versus vending machines that offer only minimally processed food or stuff like that. And they have generally seen that under aglibutum conditions, meaning that people were allowed to do and eat whatever they wanted on the ultra processed food. They tended to eat a little bit more. Right. And then they tended to gain weight. Of course, these are like two week studies. Right. So what can two weeks tell you about obesity that develops over a time frame or a time scale of decades? It's very difficult to answer this question, unfortunately. So even the very well publicized studies, they, they, in reality, they tell us very little. They give us an indication, but they tell us very little in terms of definitive proof.

[Dr. Gabrielle Lyon]

And if you look at this paper that you wrote, the key differences between the energy balance model and the carbohydrate insulin model. Energy balance is the energy balance model. The causal direction is positive energy balance results in net fat deposition and then the carbohydrate insulin model is altered. Fuel partitioning results in net fat deposition and then subsequently positive energy balance.

[Unknown]

Correct. Because in the latter case, because you actually store more of the ingested nutrients as fat and you don't utilize them, let's say, to fuel your movement, your brain tells you that you need to eat more. I don't have enough energy to do what you want to do in your life, so that's why you overeat in that case.

[Dr. Gabrielle Lyon]

And it's interesting because if I were to think what are, what are the components that these two models have in common? The primary dietary driver for both for the energy balance model is increased availability, which you know is clear and marketing of a wide variety of inexpensive. These are the highly palatable foods that are high in portion size, fat, salt, sugar, low in protein and fiber. And then the carbohydrate insulin model, it really points to carbohydrate rich foods with a high glycemic index and fructose rich beverages. The energy balance model, point of entry into the regulatory system is the brain versus the carbohydrate insulin model being the periphery. And really the brain's response which you had mentioned for the energy balance is that we're there's a. Impaired appetite is not the right word, but an impaired response in the brain. And the carbohydrate insulin model seems to not have anything to do with the brain.

[Unknown]

Yes. So in the in the energy balance model, the brain is really tricked, right? To to not see how much you eat or to not understand how much food and energy you need. So that's why the brain has a central focus in that model. Because the characteristics of the food themselves or something else in the food environment or the non food environment either saturates the ability of your brain to sense how much you eat and how much you need, or it kind of impairs it, right? On the other hand, the brain, the carbohydrate insulin model is functioning very well. It's just that the brain in that case cannot see all the nutrients that you just ate. So it actually correctly tells you that you need to get something more because I cannot see it. Go back, going back to the analogy with the tank, right? If you have a leak in the tubing that transports the fuel from your tank to your engine, then you will still have that fuel somewhere in your car, but you would not be able to use it. So you will be forced to actually put more gas next time, right?

[Dr. Gabrielle Lyon]

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[Unknown]

Correct. Let me just take a step back.

[Dr. Gabrielle Lyon]

Thank you.

[Unknown]

So in humans there is a lot of evidence suggesting that our total energy expense expenditure, meaning the amount of calories that we burn right, on a daily basis for maintaining, you know, our basic metabolic and physiological function. So our heart pumping blood, our lungs exchanging oxygen and carbon dioxide, all of those things that maintain us alive are a function of body weight. The same thing is true, true for the calories that we burn with all sorts of weight bearing activities, which for all intents and purposes are all sorts of exercises and physical activities that we do. Right, Unless you are in space for instance. But at least, you know, running, cycling, walking, the amount of calories that we burn are a direct function of body weight. Okay? So the more body weight you carry with you, the more calories you burn. To understand that, think how easy it is to walk around in the gym and then grab two 20 pound dumbbells and walk around again. You can understand that it's a little bit more difficult, you're burning more calories.

[Dr. Fadan Makos]

As you carry more weight.

[Unknown]

So this is what the energy balance model tells you, that as you gain body fat and your weight becomes greater, then you start burning more calories. That's why energy expenditure, the total energy expenditure for the whole body goes up. However, if you take a piece of muscle tissue or a piece of liver tissue, or a piece of adipose tissue, then the metabolic activity of that tissue per unit of mass is not altered. It's just that you have more of that tissue in your whole body. That makes a greater energy expansion would make sense.

[Dr. Gabrielle Lyon]

Yes, that makes sense. Would one be able to argue, looking at the commonalities between this, that if we had a low energy environment, that would solve the problem? If we had limited access to food? If. Right. Versus let's say someone has a virus but no access or environmental contaminants?

[Unknown]

Yes, let Me, I will get back to that. That's a very good point, and I will get back to it. But just now to explain you what happens energy expenditure in the carbohydrate insulin model. So what the carbohydrate insulin model tells you, remember, is that since your brain cannot see all the calories that we just ate, right? It tells you that you need to eat more. That's what it tells you. It drives you to eat more. If you do not act on that drive and you do not eat more, then the second option for the brain is to shut down your energy expenditure so it will make you feel more tired, for example, so you will not go for a run. So that it will decrease your energy expenditure in order to match with the amount of calories or the amount of energy that your brain thinks you have available. That's why it decreases if you do not eat. But of course, in the modern environment, most people would eat. That's why most commonly, the end result of the carbohydrate insulin model is also overeating or positive energy balance. Let's put it this way, and going back, I'm sorry, now let me now go back to what you just said. So there is no question. This is something that of course needs to be clear. No matter whether we are talking about genes, environments, type of food, amount of food, whether I am feeling good or bad or sad or happy, all of these factors that affect my drive to eat, they must manifest by known biological mechanism that affect either energy intake or how I handle the food that I just ate. And you are correct, if I take people in the lab and I just remove their access to food, they lose weight, as expected, right? Like textbooks. So there is no magic there. But that is not something that we can do in humans. And it does not really prove that either model is correct. What?

[Dr. Gabrielle Lyon]

Were there any surprising points during this conversation, during this. Would you call it a debate?

[Unknown]

Yes, to some extent I would. I think what was surprising actually satisfying to me was to see these very good scientists come in the same room and during, let's say, breakfast on day one, you could actually cut the tension with a knife. But I think that as the day progressed and then as we had the second day at the end of the workshop, you know, everybody was so much better and, and the environment and the climb was so much better. So for me, that was satisfying to see that, that we can achieve that. Because as I said, as humans, as scientists, we also have our egos. And these are not easily. These are not easy to Kind of put on the side.

[Dr. Gabrielle Lyon]

Were there any insights from either party? Because really, this debate between the energy balance model and carbohydrate insulin model has really been robust within the scientific community. And the only way that we have any kind of mental flexibility is if we're willing to acknowledge or hear from the other side. Do you think? And also, is there a place where these two models work in tandem versus it's this or that?

[Unknown]

Yeah. So I think that, you know, if you. If you also read the paper, a lot of. Of the. How the normal physiology and the normal regulation of energy intake and expenditure is regulated in humans, both models agree to that. Right. So there is a lot of overlap and a lot of agreement. It's just that it's not highlighted anywhere. But again, both camps and everybody, I guess, no matter what kind of model they back, you have to agree that it will operate under known mechanisms of energy intake, energy expenditure, peripheral metabolism, and all the things that we know that operate in humans as a species. It's unlikely that you will find someone that will suggest something different. I think that the realization that they have actually a lot of points where the two models converge is something that the two camps also realized during the workshop, and that was a pleasure to see as well.

[Dr. Gabrielle Lyon]

And what was their big takeaway that we need also longer human trials.

[Unknown]

Yeah.

[Dr. Gabrielle Lyon]

What were the big.

[Unknown]

So my feeling, first of all, is that even though they acknowledge that there is a possibility that, you know, I may be wrong or something else may be happening, you know, they went back home and they're still believing what they believe. Right.

[Dr. Fadan Makos]

And that's.

[Unknown]

I mean, we did not expect that something else would happen, but something that the. Emerged from that workshop is that now that, you know, we have. We started having collaborative ideas and perhaps designing projects in common. Right. To try to test some aspects of these models or some predictors, predictions of these models, there is no way that you can have a single study, as I said, that can prove or disprove one or the other, but at least now they are open to the possibilities. And that's. That's a wonderful thing to see that it happens even at that level of science, which you would think that this is the norm, but it is not really the norm.

[Dr. Gabrielle Lyon]

You actually mentioned this in the paper. The paper mentions that the debate has often led to controversial discussions in both parties, in both scientific and popular media. And you are a phenomenal scientist. We. I could speak with you for hours, which I do, but for the podcast particularly, I was so excited that you wrote this paper. Because again, and I do want to touch on what you have seen in randomized controlled trials and some of the work that you have done in effective ways to lose weight. I do, I want to discuss diet, exercise. I know we didn't really decide that we were going to do that before, but I do want to make sure that we have tangible items that people can take away. And you've done a tremendous amount of research.

[Unknown]

So of course, I mean, that's the reason why we are really interested in that. In what sense? No matter how obesity develop, people, or let's say the majority of individuals right now are interested in trying to figure out ways to effectively lose weight. Right. So it doesn't really matter how you put that weight on now you're interested in losing that weight.

[Dr. Gabrielle Lyon]

It doesn't, doesn't matter the speed. If we were to think about. And I just want to pause there, it's an interesting mental exercise when it comes to obesity. Does it matter the swiftness at what's at which someone puts on weight? And the reason I ask this, because in my mind, I think that the distribution of fat would be variable over time. For example, if someone has been obese for an extended period of time, now you're not looking at just peripheral adiposity, but you're looking at intraorgan adiposity. And perhaps that might take longer to then course correct metabolic outcomes.

[Dr. Fadan Makos]

Yes.

[Unknown]

So one thing that I'm not sure how much known it is to the wider public is that perhaps during the past 20, 30 years, we have had a lot of evidence and we realize that obesity or having excess weight and total body fat is not necessarily associated with metabolic abnormalities and metabolic disease and increased risk of diabetes and cardiovascular disease. Right. And vice versa.

[Dr. Gabrielle Lyon]

I have to push back on that. I'm sorry, so your students would never push back on that. So you are, what you are mentioning here is a phenotype of obesity that would be metabolically healthy.

[Unknown]

It's metabolically healthy relative to the majority of obesity. It's not the same as being lean and metabolically healthy. Right.

[Dr. Gabrielle Lyon]

Okay. I, I just want to say.

[Unknown]

Right, so, Right. So that if you just focus on body weight and total body fat, that doesn't tell you much in terms of risk of disease. That's what I want to the point that I want to get across and vice versa. You can have a normal body weight and a normal total body fat, but if you have accumulation of fat in specific locations around the body, then you can have increased risk of metabolic abnormalities. And this is the fact that typically people refer to as visceral fat, which is the fact that we have, let's say, around our bellies, but also fat that we can store in our muscle or in our livers or in our pancreas. And then that fat really affects the function of those organs which are critical for metabolic homeostasis. And it is remarkable. If you think that you can have. You can be a person with obesity, right, in a BMI of 40 or 50. So you can have 50 kilograms of extra fat in your body, but that doesn't necessarily tell you much, as if you accumulate only, let's say, 5 kg as visceral adipose tissue or 200 grams of fat in your liver. This is remarkable. So the location of where you store that fat, fat seems to be way more important for your metabolic health rather than the total amount of fat you have in your body. Now, why people tend to accumulate fat in this or that or in the third organ, it's something that we do not really know. Genes definitely affect or play a reason, but they are probably other reasons as well. So diet could be a reason. Exercise and physical activity habits definitely have a reason on body fat distribution, and they have a big role. So generally, yes, obesity itself is not necessarily associated with increased risk for disease.

[Dr. Gabrielle Lyon]

And I think that there's a bit of a spectrum on that. Again, just to take it back, I was reading another paper and one of the things is potentially it's on a continuum we might not be identifying. It's almost on a spectrum. So we might see an obese, metabolically healthy person, but it's at that point in time. And I would argue that obesity is never going to be healthy. We might just not have the science yet to put into words. And, you know, potentially it's just that the body is able to manage and mitigate negative outcomes for a period of time. Or let's say we're not measuring the myokines appropriately or the inflammatory markers. We just are not identifying it from a clinical.

[Unknown]

You are totally correct, because one of the commonest things about metabolically healthy obesity is that these individuals tend to be younger. Right. And we know for a fact that as we age, the chances that you're staying metabolically healthy are diminishing almost linearly, even if you. Even if your weight does not increase. So definitely, it seems to be. It is not a shield against the metabolic abnormalities. That is a permanent sealed. Right. It's just a temporary seal that. It's exactly what you said. Your body, because of your age or your other functional Capacities has the ability to kind of withstand or mask the metabolic complications of excess weight and fat.

[Dr. Gabrielle Lyon]

If you were to.

[Unknown]

Let me touch up. Let me. I'm sorry, I just remember you mentioned also the rapidity at which we put.

[Dr. Gabrielle Lyon]

Gain or the period. Yes, the period in which you gain.

[Unknown]

Don't really have a very good. We don't have good studies that. That made people gain the same amount of weight with different rates. Right. Because in a study like that, in order to be able to get a good answer to your question, you would have to have the same amount of weight gain with different rates. So in different time frames. Right. But we do not have studies like that. What we do have, however, is the opposite. So we have studies that compared what happens if you lose the same amount of weight with different rates. So lose it fast or lose it slow, right?

[Dr. Gabrielle Lyon]

Yes.

[Unknown]

And generally these studies suggest that if you look acutely, so if you look on the day that you reach the target weight loss, then losing it slow is generally better. Right. But this is a little bit of a confounding interpretation of the data because you do not allow the body to stabilize at your lower body weight if you do that. So if you do the measurements after one month of stabilization at that new lower body weight, then it doesn't really matter whether you lose it fast or slow. For all intents and purposes, all the metabolic effects of weight loss are the same, no matter how fast or slow you lost it. And if anything, just as a last point to this point, we have data to suggest that people who for some reason lose weight initially at a faster rate are those who are more successful in long term weight loss, whether it's biological, whether it's something else. We do not know the mechanisms. But this observation comes again and again that rapid initial weight loss predicts longer success.

[Dr. Gabrielle Lyon]

I was so hoping you were going to say that. And remind me, that came out of. Was that the. It's the abc, was it?

[Unknown]

I think so. And also the Look Ahead trial. It was the Look Ahead several others. I think you know it. It is remarkable to say that the rate at which you lose weight in the first week, one month or two months of a diet predicts what you do four and eight years later. But because what I mean is that in the first month or two months of a diet, everybody is excited. Right. So there is no issue of compliance over there because you can easily say that compliance is a major factor that predicts weight loss success. And that's true. Two of the main predictors of weight loss success is compliance to the diet and then the initial rate of weight loss. So the initial rate of weight loss must be something that has to do with the biology. Right. Because everybody's excited and they are very compliant to the diet in the first few weeks.

[Dr. Gabrielle Lyon]

And this is all without medication because.

[Unknown]

Yes, yes, yes.

[Dr. Gabrielle Lyon]

When you use GLP1s or GIP, some of these dual. Agnes. And I'm sure that I know that they will have multiple generations of these agents coming out. You know, I wonder where that plays a role, because the recidivism rate, the regain weight of individuals just in general who struggle with obesity is. I mean, it's over 80%, right? It's higher than that.

[Unknown]

Yes. It varies, but generally it's not satisfactory because if it were, we would have treated the problem. Right?

[Dr. Gabrielle Lyon]

Yeah.

[Unknown]

So clearly weight loss drugs, and especially these GLP1 agonists and the dual agonists kind of help quite a lot. And actually, you know, results for these dual agonists suggest that you can reach, you know, bariatric surgery levels of weight loss. Really the point is that, you know, you need to get these drugs forever, meaning that if you stop taking these drugs, you go back to your initial weight trajectory. And I think that there is some studies published recently on clinical practice in real life effectiveness. And it seems that like with most other medications, the majority of patients are just not compliant to their medications, even if it has to do with, you know, these GLP1 and GIP agonists. And of course you take into account the cost. Right?

[Dr. Gabrielle Lyon]

Yes.

[Unknown]

And that brings also then the other question of insurance and politics. Because if we take consider obesity as a disease, globally speaking, and then these medications need to be reimbursed by the insurance companies, then this would bring most national economies to their knees with we have 1.8 billion people who struggle with excess weight globally. Right. So there are a lot of other factors involved when you talk about, about how to treat obesity medically.

[Dr. Gabrielle Lyon]

Yes. And if one of the other things that we haven't spoken about is the quality of the weight loss, rapid weight loss typically seems to be lower quality. It is lean tissue as well as fat tissue. And I'm curious from your work and some of the things that you've been involved in, ideally, if you were to think, okay, based on evidence, how would I personally design a diet, how would you do that?

[Unknown]

Yeah. So let me just say something about the composition of weight loss. Right. When we lose weight, generally speaking, it's about 75% fat and 25% lean mass. What this means Is that If you lose 10 kilos, about 7.5 kilos is F fat mass and about 2.5 is lean mass. Out of those 2.5, most but not all is muscle. But not all. Okay, so when we say lean mass is not just muscle, lean mass is everything else other than fat and water and bone. Now in terms of, of, of rapid weight loss, you are right. When we lose weight rapidly, it seems that we tend to lose more lean mass. But this is what happens. If you measure people body composition acutely, if you allow them to stabilize it up at that new lower body weight, then these differences are actually minimized. And I'm not sure if they are clinically significant anymore.

[Dr. Gabrielle Lyon]

Say that again. That's a very important point.

[Unknown]

Yeah, so you know, if you, if you do your body composition measurements at the, you know, end of the weight loss treatment, where people are, are just coming out of their negative energy balance. Right. A lot of the changes in body composition that you see also have to do with water fluxes around the body. So they are not really true. When you repeat those measurements one month later, when you have stabilized those people at that new lower body weight, then the composition of lost tissue doesn't differ that much between slow and fast weight loss.

[Dr. Gabrielle Lyon]

That, that is an inter. It's just interesting because oftentimes, even in the literature, we think about rapid weight loss being extremely negative for muscle.

[Unknown]

Well, correct, but that's what I mentioned, that this probably is not true, which.

[Dr. Gabrielle Lyon]

Is incredible to think about. The next obvious question is how good at actually measuring skeletal muscle and differentiating between lean mass are we?

[Unknown]

Yeah, we don't really have that good of methods. If you really want to be very specific about muscle, you would probably have to resolve the methods, including either CT like computer tomography or magnetic resonance imaging, and you would have to do it at the whole body level. Right. So you have to scan head to toe because, you know, muscles we have. Muscle is an organ that is not anatomically defined, like your heart. Right. Muscle is a tissue that is interspersed in various parts of our bodies. Right. So you would have to scan the whole body and that would give you the best, let's say, measure of muscle mass. Most studies that we do in nutrition research and obesity treatment, we use techniques such as bioelectrical impedance analysis, which kind of tries to take advantage of the fact that fat tissue is a good insulator, whereas the rest of the body is a better insulator. So it kind of gives you a guesstimate of body composition. We also use another type of Skin scanning with dual X ray absorptiometry, which gives you, you know, fat mass and lean mass, but it cannot separate muscle mass. So I would say that the majority of the studies that you see out there, they do not use a particularly robust method for muscle mass.

[Dr. Gabrielle Lyon]

What do you see as the problem in that.

[Unknown]

Of not being able to quantify muscle mass, you mean? Well, clearly you could. You could argue that if I cannot get a good measurement of muscle mass, then I do not get a good estimate of what is the effect of weight loss on body composition. And it goes back to what you said, right, the quality of the weight loss. Because if you lose more muscle, theoretically your resting metabolic rate would go down. You would have alteration in the amount of all these myokines that you have circulating your bloodstream. And this could, of course, affect metabolic function. But of course, we. We have some, let's say, indirect ways that we can probe that. Meaning that you can actually measure myokines. Right. In the bloodstream.

[Dr. Gabrielle Lyon]

Are you guys doing that a lot in Copenhagen? Which, first of all, I know that you are, and if I could, maybe I'll put in a good word for me at Bente Penderson's lab.

[Unknown]

Yeah, yeah.

[Dr. Gabrielle Lyon]

But over here, we.

[Unknown]

Linda does, though. Yeah.

[Dr. Gabrielle Lyon]

Yes, she does. There. I was actually trying to set you up for a softball. I was trying to pitch you a ball. I was going to see if you were going to bite on this or.

[Unknown]

I don't even know what softball is.

[Dr. Gabrielle Lyon]

Yeah, soccer, soccer, football, none of those things. Completely complete, terrible joke. If we don't do a good job at, number one, identifying and quantifying skeletal muscle mass loss as well as gain, in my mind, it stands to reason this has been a huge disservice. I know that that is not scientific. But then we will fail to see, number one, the potential importance and the potential impact the loss or gain of muscle is in overall health in general. You and I were talking about something else. And 10 years ago, when I was in fellowship, it was just the start of getting better at identifying and measuring skeletal muscle mass with CT, MRI. And that was 10 years ago.

[Unknown]

Yeah, but, you know, these. These pieces of instruments are very expensive. I mean, I understand what you're saying, but generally we do the best we can do. And, you know, the majority of studies, I would say that focus on the data, the treatment of obesity, they are not so muscle centric, to put it this way. So, you know, you have to allocate your resources in a way that is equitable for the outcomes that you want to measure. Right. I'm guessing that you would have to do a specific study that focuses on the amount of muscle mass in order to engage and utilize those technologies, techniques that are more accurate. Still, muscle mass in itself doesn't necessarily will tell you everything. Right. Because you have muscle function on top of muscle mass. You have fiber composition. Right. So you can have the same amount of muscle, but depending on the composition of these myocytes, the function and their metabolic effects might be different. So I mean, we see that in professional athletes. Right, Right. Whether they are endurance train or resistance train, they have different metabolic profiles and they have different changes in their metabolism during their training. So clearly mass is an important factor. It's definitely not the only thing that that matters. I would say for, for health. Right. You have to take into account how.

[Dr. Gabrielle Lyon]

That mass functions when it comes to health. What works for someone else may not work for you because we are unique. We have unique genetics, habits and health goals. That's why I'm so excited to tell you about InsideTracker. You've heard me talk about it before. InsideTracker is a way to get your blood work which shows you exactly what your body needs and gives you a personalized plan for strength, hormone, balance, overall health. You name it, they get it done. There are plenty of companies that just look at blood or just look at DNA, but I use InsideTracker because it's the only one that looks at everything, including your blood results, DNA, fitness tracker inputs and other health information. It's a 360 degree analysis that provides incredible visibility on what is going on inside your body. InsideTracker Analytic centers on what calls your 10 healthspan categories. This includes a whole host of things like fitness, hormone, health, you name it. When you become a member, you'll get an individual score for each of your healthspan categories and you'll learn what you need to do to drive your score high. Your personalized recommendations will include things like food supplements, exercise and sleep tips. And by tracking your healthspan category score scores and blood results, you'll be able to confirm what is working and what is not. Now it's time to start your personalized health journey. Especially because InsideTracker is dropping prices by 30% for this year's Black Friday sale. Get after it. Year long membership plans will start at $104. You can also purchase discounted blood tests, DNA, biological age analysis. It's everything that you need to fast track your health. Mark your calendars because instead of buying that new Tupperware or that new Coffee mug. Get your blood work done. Starts Wednesday, November 27th. And you want to act fast because you want to make this happen. Go to InsideTracker.com to get your health journey started. That's inside Eye Tracker.com and use the code. Dr. Lyon, do you think the oversight in skeletal muscle or the lack of skeletal muscle is in part due to its complexity because it is heterogeneous versus adipose tissue, which is homogeneous? And I'm just referring to circle back to what Faden was saying about muscle mass. No two people have the same muscle fiber type composition intra muscular fat. It's a very complex tissue. And the composition of the fiber throughout the body potentially can be different.

[Unknown]

Yeah, not potentially, we know that different fibers.

[Dr. Gabrielle Lyon]

You were the one who taught me to speak like this, to not speak in absolutes. This is your fault.

[Unknown]

But this, but this we know because we have actually taken biopsies from different tissues around the body of the same individuals. And you see that there are differences, let's say between the fiber composition of your soleus vs glute vs gastrocnemius vs so on and so forth. There is also differences in the rates of protein synthesis and, and all those things. Whether or not these are clinically significant, we do not know. Right. But statistically you can see differences anyway.

[Dr. Gabrielle Lyon]

And maybe it. We're just too early. I think that we're just too early in the research.

[Unknown]

Yeah, yes, yes. The other thing is that as you said on, as another. On average you're right that adipose tissue, at least white adipose tissue, subcutaneous white adipose tissue, is a more homogeneous tissue compared to muscle. Right. But you know, you have visceral adipose tissue, you have adipose tissue or fat inside organs. So I do. What it means that, yes, probably on average the remark that muscle is much more complex is true. Now if you approach the diet, right, which you have to approach the whole body, you cannot really approach the diet in an organ specific way. Typically people get obese and this affects all organs and the same thing as they lose weight, this affects all organs. So you know, if you, if you go back to the 30,000ft viewed and try to see, you know, what can we do, you know, for obesity, you know, we have at least ideas about the characteristics of a healthy diet. And again, I'm going, I'm using the term healthy because I think that obesity treatment has over focused on the skin scale rather than on the outcomes. What I mean is that would we care about obesity if it were not for the increased risk of disease. No. Obesity would not even be considered by the WHO health organization. Right. Because obesity is defined as the amount of excess fat accumulation that may impair health. If it was not for the complications for obesity, we would not mind so much. Nobody would care about the aesthetics. Right? And historically, if you see this, there was a time where obesity was considered a favorable trait in humans. But anyway, so we know that some characteristics of the diet that are conducive to good health are, you know, be prudent in calories, have variety, eat the mostly plant based diet, but with enough protein, not vegan.

[Dr. Gabrielle Lyon]

I'm just kidding.

[Unknown]

You know, I'm from Greece, right? We like the Mediterranean diet. So the Mediterranean diet is a mostly plant based diet, but we eat meat, we eat protein, we eat dairy. So you know, I would say eat everything in moderation is a trick here. Right? So we know most of the characteristics of, of a healthy diet, but yet it's very difficult to adhere to that diet because that requires that you go to the grocery shop. You know, it's not convenient with everyday life to go to shop and cook and do all those things at home. We, it's much more easy to get a ready made food and heat it in the microwave and eat it. So it's, it's, it's, it's really tricky. And of course I know you're interested in exercise, right? We know that doing exercise or exercising, being active is good. And what is the best exercise? Well, it's the one you do. That's very simple.

[Dr. Gabrielle Lyon]

The answer to that, not the one that Satan does. This guy runs. He just runs.

[Unknown]

No, not like me. No, I don't. Yeah, but what I mean is that it doesn't matter if you lift, if you run, if you cycle, if you swim, as long as you do something right or you walk your dog. All these are behaviors that we know are healthy. We know that they help you maintain a healthy weight or reduce a little bit the oxygen, excess weight that you may have. We definitely know that they will keep you healthier for longer, which is important, right? Because it doesn't really matter if you have 1, 2, 3 more kilos in your body, as long as this doesn't affect you and you can still go around and do the things that you want to do with your life.

[Dr. Gabrielle Lyon]

From. I agree with you. And for history's sake, you guys listening again? Finn and I have known each other for over 10 years. When we think about the percentage of. And we've worked together, actually we've worked on multiple studies together. He's much more published, I think. I have two papers and a book chapter published. But I did write a book that. That did well. Which you. I think, pretty much.

[Unknown]

Congratulations. I remember that.

[Dr. Gabrielle Lyon]

Yes. Because I think that you refused to review it because it was for general consumption and not in the white tower of academia. I'm totally kidding, you guys. I. I am kidding. But our perspective on muscle, I think, is very similar. Although I would say I tend to be very dogmatic in my thinking, and I. I definitely recognize this. If I were to. To really think about where does obesity, where do these problems begin? For, for me, it's muscle. I appreciate my biases from a dietary perspective. If one were to set up from a giving actual number perspective, and there is variation. For example, Faden does a lot of endurance training. He does. He weightlifts two to three days a week. At least he did. And he's a creature of habit. I'm assuming you still do that, right?

[Unknown]

Yeah.

[Dr. Gabrielle Lyon]

Go to the gym, you spend like three hours training, and then you're ready to go to bed. By I mean, you train at night. It's a whole thing. The listener wants to know, how do they design a diet? And let's say they're very prudent about protein. We know that 0.8 grams per kilogram is the minimum to prevent a deficiency. It's probably not enough to support aging. One probably requires more if they are in a catabolic condition or even with obesity.

[Unknown]

Correct? Yeah. Yeah. So now let me just say, of course there is. There is a lot of different ways that you can design a diet. So I believe that, you know, if you think about drugs versus food. Right. Drug is a very specific compound. It's one compound that targets one specific metabolic pathway. Let's say in the body, diet or food has like thousands, if not millions of compounds that act on everywhere and interact with each other. Right. So each one affects the effects of the other. So I like to think that there is no ideal diet. There is no perfect diet. And when I say that to people, most people get sad and disappointed. But I try to give it a positive spin. In what sense? That there is so many degrees of freedom for you to go out, choose, experiment, and find out the diet that works for you. As you said, I like pasta. My. My diet is 70% carbs. I've measured that. So I'm. I'm 70% carbs, 20% fat, and 10% protein. But I cover my protein needs because of all this exercise that I do. I eat a lot of Calories. Right.

[Dr. Gabrielle Lyon]

And you, you definitely have to, to expand on that.

[Unknown]

Yeah. What I want to say is that I have found a diet that works for my lifestyle.

[Dr. Gabrielle Lyon]

And your body type though, you're very lean.

[Unknown]

Yeah.

[Dr. Gabrielle Lyon]

And I, I'm sure that there is a variation, just as some people do better on a higher protein diet, which I am one of them.

[Unknown]

Absolutely. Yeah, absolutely. Yeah, you're absolutely correct. Some people do better on different diets. And that's what, that's, that's the positive spin for me. That diet has a lot of degrees of freedom and you have to find a person who is a little bit knowledgeable, like me, you or whoever, and help you identify what are, let's say, the mistakes that you may do. Because you know, sometimes when you know a lot of things, like if you are on the academic side of things, you take some knowledge as granted. And that's not true. I can see that whenever you have a new input of students, we also have to kind of deal with all the ideas that they come in the university and then I get to remind myself of, oh my God, how is it possible that you don't know this? But that's the reality out there for the general public. So you have to find somebody who is a little bit knowledgeable and they can help you identify some errors that you may be doing and then try to experiment and you know, trial and error. It's all about trial and error and finding something that works for you. That's, that's how I managed to do it anyway.

[Dr. Gabrielle Lyon]

Well, you're also very evidence informed. Evidence based and evident. You're evidence based, but you're evidence informed. For you to get 10% of your calories from protein. The reality is you counterbalance that by your activities. Extreme. I, I think that you're also at a standing desk. You have enough.

[Unknown]

Well, everybody in Denmark has a stand. You know, this desk that goes up and down.

[Dr. Gabrielle Lyon]

Yes, well, we don't have that here in the studio. Denmark, everybody moves around and by the way.

[Unknown]

Well, let me just correct you. In Copenhagen, everybody moves around and because, you know, bicycles is, is so much into the culture. So I bike to work every day, right? Yes, back and forth. In addition to the other stuff which. But everybody does that.

[Dr. Gabrielle Lyon]

Everyone does Rural, rural Denmark is not the same. But again, from a, a larger view, Copenhagen is really the Mecca. It's like the Harvard outside of the US Especially for anything metabolic, exercise related and skeletal muscle and just really this nutritional perspective. However, one thing that you have to take into account is their lifestyle Is not an American lifestyle. People are.

[Unknown]

Of course, absolutely.

[Dr. Gabrielle Lyon]

So the perspective is, you know, that is what the exposure is. The individuals could get away with a lower protein diet because they counterbalance with a way of life that is extraordinarily active. And you're.

[Unknown]

Yeah, but as I mentioned, you know, if you, if you think 10% of calories over 3 or 3, 500 calories on a daily basis, this is about 300 calories from protein. Divide that by four. Right. You get about 90 something.

[Dr. Gabrielle Lyon]

Which is low. Well, from my perspective is low. And you and I definitely.

[Unknown]

But I'm weighing. But I'm weighing 70 kilos, so I'm eating about 1.3. You know what I mean?

[Dr. Gabrielle Lyon]

I do, I do.

[Unknown]

So the, the percent of the calories seems or sounds low, but the actual.

[Dr. Gabrielle Lyon]

Amount is not low, is not low. If.

[Unknown]

And I'm. I'm. I'm lifting for maintaining. Right. I'm not weightlifting to be a bodybuilder.

[Dr. Gabrielle Lyon]

So you could be if you decide.

[Unknown]

Not if you wanted. If your target is that, then yes, of course, you need much more protein.

[Dr. Gabrielle Lyon]

There's no question if someone wants to build muscle, how much protein?

[Unknown]

Well, I think that you should go up 1.6, but definitely no, I don't think there's any need for more than 2.2, 2.3. I think that that's where you saturate the system. And that and all the studies that we have so far where they, where they measure muscle protein synthesis in response to, you know, different types of exercise and different forms of feeding amino acids, insulin and all those things, the response is always the same. You have a linear increase and then a plateau. So there is definitely a point where you saturate the system. And then any more than that, you will obviously either burn it or for energy or store it as fat. And so you should not overdo it. That's what I mean.

[Dr. Gabrielle Lyon]

And I want to pause there and interject what he's saying is that from a. If your goal is muscle hypertrophy or repair, skeletal muscle repair, anything above 2.2 grams per kilogram might not be necessary.

[Dr. Fadan Makos]

Right.

[Dr. Gabrielle Lyon]

And that's definitely the upper limit from a overall calorie perspective and an overall intake, there's no downside. And Finn and I may disagree here, but, you know, one gram per pound, ideal body weight, I find is safe. I think it's easy to do. Assuming so 2.

[Unknown]

So 2 grams per kilo, approximately. Yeah.

[Dr. Gabrielle Lyon]

At the upper limit, you know, there's. I haven't seen any evidence to suggest that that, oh no, there is no.

[Unknown]

There is no downside as long as your total energy intake is kept like under control, no problem at all. There are no side effects really, if you are healthy and you don't have any sort of kidney problem problems.

[Dr. Gabrielle Lyon]

Correct. And you had mentioned insulin and these other hormones. Where do you think that that plays a role from a obesity perspective? Because if insulin and other hormonal responses to food play a role in the carbohydrate insulin model, do you think that, say, having a diet high in carbohydrates would be obesogenic or is it a genetic and activity related question?

[Unknown]

So, I mean, I, I obviously don't have the exact answer to your question. But, but let, let me just say that, you know, we are talking now about building muscle, but if you are talking about building muscle in the context of losing weight, so losing weight and building muscle, then that is very difficult to do. So you have to actually be going to the gym almost daily for like 15 hours a week. I only know one or two studies in the literature with professional athletes where they were losing weight because they were trying to make, to make competition weight. Right. And they were training about 15 hours a week. And only in this population under this condition do they manage to gain muscle while they are losing weight. For all intents and purposes, for the average person, I would say that when you lose weight, you cannot avoid losing muscle. You can minimize that muscle loss by exercising and eating more protein, but you will not be able to avoid a complete loss of muscle. And now the protein that you have in your diet as a percentage of your calories should go up if you are calorie restricting yourself. Right. So maybe because I'm eating 3,500 calories a day, I can get away with 10% protein. The person who is actively in calorie restriction and eating 1,000 calories a day to lose weight, the percent protein should be 20 or 30 if it was higher.

[Dr. Gabrielle Lyon]

Remember the protein sparing fasts? Do you remember those? The modified protein sparing fasts?

[Unknown]

Yeah, yeah, yeah. So all the, now the commercial VLCD products, you know, the very low energy diet products, they're like the Nupo and I don't know what you have in the States, but all these now are about 50 protein, right? Because you eat only 800 calories a day, then protein is the most important nutrient to match and to meet your body's needs. So as a percent of calories, the less you eat, the more you need.

[Dr. Gabrielle Lyon]

And then aging as well.

[Unknown]

Yes, with aging as well, and that's true aging. So aging has been associated with a little bit of an anabolic resistance, as we call it. Meaning that. I'm going back to your insulin question. Right. So the main effect of insulin is that it kind of stops muscle breakdown. So when you exercise, you increase muscle breakdown. Really, that's the effect of resistance exercise or weight lifting on muscle. But then when you eat after that exercise, the insulin, what it does is that it stops muscle breakdown. And then the additional protein that you have eaten is being used to stimulate protein synthesis, so your balance becomes positive. It seems that aging is associated with a little bit of anabolic resistance, meaning that for the same amount of protein, people who are older, they do not respond very robustly in terms of muscle protein synthesis. What you can do to circumvent that problem is to feed them a little bit more protein. If you flood the system a little bit more, then you get the same response that you would get. That's easily solvable with aging.

[Dr. Gabrielle Lyon]

When your students are coming in, again, you're a full professor. When your students are coming in, are you seeing trends? Are you seeing trends of incorrect thinking or perspectives? And what are those?

[Unknown]

Well, you know, instead of rather than incorrect thinking. Because again, I would say that I can never be 100% sure in research. Right. But there is definitely thinking that is not supported by the weight of the evidence. Right. Things like eating both carbs and protein in the same meal. Things about what the effects of exercise are. Things about when you should eat, like the time of the day.

[Dr. Gabrielle Lyon]

Tell me. We all want to hear. We're all dying to hear. I just want to hear the highlights where it's not supported by evidence.

[Unknown]

Well, I wouldn't say it's not supported by evidence, but for instance, there is this idea that, say, eating earlier. Right. Or breakfast skipping or breakfast eating is associated with more or less body weight and obesity. Right. So generally, if you go out in a population, you will see that people who typically habitually tend to avoid breakfast, they are more obese or they have greater body weight. So this has led to the assumption that breakfast is important to. To kind of treat obesity. However, if you take people who are habitual, not breakfast eaters like myself, and you put them in a study and you tell them, now start eating breakfast. We gain weight, we don't lose weight. So breakfast is bad in that scenario. Right.

[Dr. Gabrielle Lyon]

So complicated. Yes.

[Unknown]

So that's what I mean. So observation in the population is very difficult to different from what happens when you actually put it to the test, because there's a lot of other factors that could be responsible for that relationship. You saw another thing is that we know also that people who tend to eat or to spread their calories around the day have better weights, body weight, than those who pack more of their calories in fewer meals. Right. So that's why we say it's better to eat more meals rather than pack all your calories in a single meal or two meals. Right. You've heard that.

[Dr. Gabrielle Lyon]

I guess I, I'm trying to think where. What I hear. I mean, I have seen people try to, you know, I don't know. I don't know if I've heard that some people try to do one meal a day or. Okay, yeah.

[Unknown]

I'm not sure generally, however, that I think that, at least in my students, because that's who you asked about. The general perception is that eating fewer calories spread out evenly throughout the day is better for body weight homeostasis. But again, when we put this to the test and we bring people and we randomize them on one, one month to eat one meal, all calories of the day in one meal versus spread out in six meals, we do not see any differences. Again, kind of mute. Right?

[Dr. Gabrielle Lyon]

Yeah. And I just want to put a little caveat on here. What he's talking about is really thinking about things in population base. This would not be, for example, that would not be a strategy. A one meal of the day kind of a thing would not be a strategy I would use for an older person, someone who's trying to build muscle, someone who's trying to protect muscle. But again, this circles back to the beginning of the conversation that I had with Faden is there are population studies, we're doing the best we can. But it, when it comes to individuals, it's.

[Unknown]

There's variation, clearly, and it also will depend on the characteristics of the person. Right. Because we know that even if you. So if you, if you prescribe the same diet and exercise regimen for, you know, a group of 100 people, you will get a hundred different responses. Right. Depending on your outcome, these responses may vary from, you know, a little improvement to a lot of improvement. But for some outcomes, they may vary from improvement to getting worse. So, you know, the variability between people to the same diet and exercise is humongous. Some of it could be genetic, some of it could be compliance to your instructions. Right. Because people also are not particularly compliant. And we see that when we bring people in the lab and we actually house them in the lab, so we are responsible for feeding them for telling them, now rest now, hop on the treadmill. Now, rest now, eat. The variability is much less than what we see in real life.

[Dr. Gabrielle Lyon]

I didn't know that. The variability is much less when we study that. You mean their response to exercise? Because there's some data out there that talks about exercise. Non responders, there's.

[Unknown]

Yeah, yeah, yeah, yeah. What I mean is that, of course you see that in the lab as well. It's just a range of responses is smaller because you take the compliance part out of the equation. Clearly, if you just prescribe an exercise treatment in real life, then compliance to that exercise regimen will be a big factor in mediating the individual differences in response. But when we take that out of the equation, we still see some level of individual responses. Right.

[Dr. Gabrielle Lyon]

What about, what about exercise that you are seeing? Your younger students come in thinking that is potentially not following the literature?

[Unknown]

Well, you know, unfortunately, the, most of my teaching is in the nutrition field, so my students don't feel strong about exercise. And that's, I think it's a pity because, you know me, I mean, I always, I'm 50% diet, 50% exercise. And I think that, you know, these are two sides of the coin that you cannot consider the effects of exercise without knowing what you are eating and vice versa. You cannot evaluate the effects of eating without knowing whether or not I exercise.

[Dr. Gabrielle Lyon]

Yeah, Right. From a nutrition perspective, I'm sure you get ketogenic diet questions. And even with the, the energy balance model and the carbohydrate insulin model, where does a ketogenic diet play a role? And does it prove or disprove one or the other?

[Unknown]

Yeah. So ketogenic diet, and if you mean by strictly ketogenic, so I eat less than 20 or 50 grams of carbs per day. These are very, very effective diets in the, in inducing weight loss. So actually you, if you do a real two ketogenic diet, you can, cannot, even if you feed people, you cannot maintain their weight because they tend to lose weight. Of course, the majority of this initial weight loss is more water rather than fat, for instance. Right. But the point is that these diets, they are not diets that you can maintain in the long term. And by long term, I mean years or for the rest of your life. And that is a problem whenever we talk about diets. So it is not difficult to make people lose weight in soda. What is difficult is to change their habits so that they can do that effortlessly for the rest of their lives. That's the, the, the, the big obstacle that we have with the treatment of obesity. Right. You mentioned that before. If we take food away, people lose weight. Thank you very much. But we cannot. This is not life. Right?

[Dr. Gabrielle Lyon]

Yeah, it is certainly. When, when everyone was together, was there a discussion about muscle, about exercise? I know that this is, you know, and I bring this up because you said diet is 50% and exercise is 50%, but, you know, they are tackling the pathogenesis of obesity. But where was the conversation about muscle and exercise?

[Unknown]

Well, back then, you know, I think that again, the. Where we both were, we were mainly focusing on diet and weight loss and obesity in regards to diet rather than exercise. But, you know, to put it this way, you cannot over exercise yourself out of a bad diet in the same way that you cannot, you know, eat your way out of being sedentary. There is no question.

[Dr. Gabrielle Lyon]

That's a. Let's say that again. That. That's fascinating. I don't think we've ever heard anyone say that. That you cannot eat your way out of being sedentary.

[Unknown]

Yeah. Meaning that if you are sedentary, it doesn't mean that you can follow like, you know, prudent diet and then be in optimal health. Right, that's what I meant by that. In the same way that you cannot eat whatever you want to and then just exercise yourself out of it. So you have to pay attention to both. Clearly, there is no question that being active helps you stay healthier for longer. And that's important, I think, as a message, because aside from what the scale says and all those things, you know, as we grow older, we realize that, you know, we want to be healthy, we want to be functional, and we want to be independent and exercise and being physically active is a critical component of functional independence as you age. There is no question about it, and.

[Dr. Gabrielle Lyon]

I know that you will tell me. It's whatever anyone will do. And that's the kind of exercise. How do you place the importance of endurance resistance, high intensity interval training? Where do you think about that from a health, longevity, obesity prevention standpoint?

[Unknown]

Well, all of these things that you mentioned are probably different because let's say from the energy balance perspective, clearly endurance exercise predominates simply because for the amount of time that you spend during exercise, you burn more calories with endurance and resistance exercise. Right. At least acutely during the exercise session, which again, is not that much. Meaning that if you see how many calories you burn by running for an hour, it's 500 calories. If you run at the moderate to high pace, 500 calories is you know, a slice of pizza, so. Or a Danish. So it's really disappointing to see how many calories you. But the point with exercise is that it puts you in a positive mindset, right? And in a positive feedback circle that, you know, you exercise, you feel better, you pay attention to what you eat, and then you keep this going and then you, you enter a healthier way of living. That's, I think that's the main value of exercise. Now again, if, if your main focus is calories, then I would focus predominantly on endurance type of exercises. If your main focus is to build muscle or to maintain functional capacity, then definitely resistance training is important. So for aging, I would say I would put more emphasis on weightlifting and resistance training rather than endural training, because this is mostly what you need to maintain your functional capacity. Capacity.

[Dr. Gabrielle Lyon]

And that's. I. Ultimately what people want, they want to age.

[Unknown]

Well, yeah, I think so too. Of course. I think so too. And you also mentioned the high intensity interval exercise, which is a great way to exercise. As long as you can do it, of course. It's a way that you can reach your goals at a smaller amount of time. Right. So it depends. Some people have more time to spend in the gym, some people have less time to spend the gym. So with high density interval exercise, you do not increase your biological ceiling, you just reach it faster.

[Dr. Gabrielle Lyon]

Do you think that there is a biological ceiling?

[Unknown]

Well, I think so. You know, as long as you do not. If you, if you are trying to maintain all other parameters the same meaning that if, if you do not want to increase your weight, then yes, of course, there is a biological ceiling in terms of what you can achieve. And we can see that in, even in, as you said, in the response to exercise, Right. We see some people who double or triple in capacity and some of them who increase only by 10 or 20% and they do the same amount of exercise. So there's definitely some sort of ceiling in all of their responses. The human body is not endless.

[Dr. Gabrielle Lyon]

I absolutely agree with you. And there are foundational principles that everyone, from my perspective, should be doing. I think that you.

[Unknown]

I agree.

[Dr. Gabrielle Lyon]

Yeah.

[Unknown]

And we know most of that stuff, right?

[Dr. Gabrielle Lyon]

Yes, we know most of that stuff. When you were in this room and you're seeing researchers and I, I'm not sure if there were any clinicians in there, but obviously, if the smartest people in the world are struggling to have these conversations, how do you suggest that we, as science communicators, as academics, as clinicians, as trainers, as coaches, communicate the complexities to the public.

[Unknown]

Well, I'm sorry, let me just mute my phone because it just told me that I need to get my medicine.

[Dr. Gabrielle Lyon]

Also, we're, by the way, we're wrapping up anyway. You want me to ask you that again?

[Unknown]

I know, I, I remember that.

[Dr. Gabrielle Lyon]

Okay. Medicine. Okay, I'll talk about that later.

[Unknown]

You know, I, I, I, I didn't tell you I was in Beijing and then I was running like crazy and exercising like crazy and I got an exercise induced asthma attack. So I was hospitalized in China.

[Dr. Gabrielle Lyon]

You didn't tell me that.

[Unknown]

Yeah, that was an experience. That was a surreal experience. So I had to stay like, I had to go to the hospital, like for six consecutive days.

[Dr. Gabrielle Lyon]

Oh my God.

[Unknown]

Yeah, yeah, yeah. But the Chinese were really detailed about how to treat it. Anyway, so now they, I'm pres, I have been prescribed, you know, an inhaler. Oh like inhale the brood dilators for like three months.

[Dr. Fadan Makos]

Oh my God.

[Unknown]

Okay, so going, going back to how do we communicate? I think that what is important is to avoid being absolute and to avoid placing foot, focusing on a single topic, a single finding, a single food ingredient, a single diet. Because, you know, focusing on, on a leaf or a leaf, it's, it makes you lose the tree, let alone the forest. Because that's what, you know, the public discussions typically take the form of. Right. We focus on just a small, like tiny little thing and then we forget the, the, the, the whole idea of the forest behind that leaf. So, you know, I think that taking a perspective that is, you know, trial and error and you know, we know basic things about healthy diet and healthy lifestyle, but we tend to not even doing those because we are focused on.

[Dr. Gabrielle Lyon]

Other things that makes sense. And I have one last question, and that is, where do you think the future is going, the future of obesity research?

[Unknown]

Well, I wish I knew because had I known, I would be very successful in getting new grants in the future. Right.

[Dr. Gabrielle Lyon]

Yeah.

[Unknown]

But, you know, I, hopefully, you know, now we are entering an era where we have big data. So because you have huge studies around the world with thousands of people which are deeply phenotyped and genotyped, now with the advent of AI and all these artificial intelligence systems, we might be able to mine this data in a more effective way that can possibly give us some ideas or some better ideas about possible causative factors or possible ways to treat obesity. But it's not that I will see that this will go away relatively fast simply because again, obesity is so multifactorial that is very difficult to kind of understand all of these factors in a comprehensive way. So on one side, that's good for me because I will have work to do in the future. Again, on the other side, I don't want this to sound as pessimistic in a sense that, again, we know a lot about what you can do right now already to be healthy, even if you maintain 1, 2, 3 more excess kilo. So you should not be focusing on the scale so much. You should be focusing on your health and all on all those other aspects that make living worthwhile. Right. To So I think that's an optimistic note to end this discussion with you, Gabriel.

[Dr. Gabrielle Lyon]

Well, Faden, thank you so much for sharing time and your brilliance. You are an amazing human and a phenomenal, phenomenal academic. And thank you so much for coming on the show.

[Unknown]

Thank you so much for having me. And thank you for your kind words.