This week on the podcast I speak to Dr Catia Martins about metabolic adaptation and weight loss. Catia has spent her research career answering questions around why some people experience a greater reduction in basal metabolic rate (BMR) than others when they lose weight, and how this impacts on overall weight loss success and the timing of that success. She has also studied the effects of the ketogenic diet on weight loss and how ketosis may impact this relationship. This is such a great conversation and, while a bit scientific, is interesting for general audience and practitioner/scientist alike.

Dr. Martins has been investigating over the past almost 20 years how exercise and energy restricted diets impact on energy balance and body weight homeostasis, in particular their impact on appetite control. 

She holds a first degree (honor) in Nutrition and Dietetics from Oporto University (Portugal), a M.Sc. in Clinical Nutrition (distinction) from Roehampton University, London (UK) and a Ph.D. from University of Surrey (UK). She has received an awards from the British Nutrition Society in 2007 and Association for the Study of Obesity (ASO) in 2008 in recognition of her research on the effects of exercise on appetite control.
In 2008, after completion of her Ph.D., she was awarded a Post Doctoral fellowship (from FCT, Portugal) to investigate the effects of exercise-induced weight loss on appetite-related peptides and motivation to eat in individuals with obesity, at NTNU, under the mentorship of Prof. John Blundell (University of Leeds, UK). Two years later, in 2010, Dr. Martins was awarded a research grant from Central Norway Regional Health Authority/NTNU to lead a project on “High-intensity intermittent training to maximize metabolic and cardiovascular protection in individuals with obesity” in collaboration with Dr. Neil King (Queensland University of Technology, Australia) and Prof. Linda Morgan (University of Surrey, UK).

She is at the moment at the University of Alabama at Birmingham (UAB) investigating the physiology of the reduced-obese state in collaboration with Dr. Barbara Gower, Dr. Gary Hunter and Dr. James Hill. Dr. Martins is particularly interested in understanding the phenomenon of  metabolic adaptation (a reduction in energy expenditure below predicted levels) and its clinical relevance.
Dr. Martins has published several original papers and reviews on the impact of exercise and energy restricted diets (namely ketogenic diets) on appetite control and energy metabolism and is a regular speaker at the European Congress of Obesity.

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Mikki Williden

What is Mikkipedia?

Mikkipedia is an exploration in all things health, well being, fitness, food and nutrition. I sit down with scientists, doctors, professors, practitioners and people who have a wealth of experience and have a conversation that takes a deep dive into their area of expertise. I love translating science into a language that people understand, so while some of the conversations will be pretty in-depth, you will come away with some practical tips that can be instigated into your everyday life. I hope you enjoy the show!

Transcription generated using AI transcriotion services, errors may occur. Contact Mikki for clarification.

Welcome, hi, I'm Mikki and this is Mikkipedia, where I sit down and chat to doctors, professors, athletes, practitioners, and experts in their fields related to health, nutrition, fitness, and wellbeing, and I'm delighted that you're here.

Hey everyone, it's Mikki here. You're listening to another episode of Mikkipedia and this week on the podcast, I speak to Dr. Catia Martins about metabolic adaptation and weight loss. Catia has spent her research career answering questions around why some people experience a greater reduction in basal metabolic rate than others when they lose weight and how this impacts on overall weight loss success. She talks about, or she's researched,

metabolic adaptation and the thrifty genotype and what impact this has on long term weight loss. She's also studied the effects of the ketogenic diet on metabolic adaptation and whether this impacts on someone's ability to lose weight and keep it off. She's done so much in the body composition space and has worked with a lot of huge names in the field. So it was a great opportunity to talk to Catia and

get some insights from her as to how much of an issue metabolic adaptation actually is, in terms of how meaningful it is for someone wanting to drop body fat. Dr. Martins has been investigating for over the past 20 years on how exercise and energy restricted diets impact on energy balance and body weight homeostasis, in particular their impact on appetite control. So she studied her undergrad at

Porto University in Portugal and then in London she did a clinical nutrition masters and PhD at the University of Surrey. After 2008 she was awarded a postdoctoral fellowship in Portugal to investigate the effects of exercise induced weight loss on appetite related peptides and motivation to eat in individuals with obesity and we discuss that research as well.

Katie has spent a number of years following, working with top names in the field of obesity research, such as Professor John Blundell, Dr. Barbara Gower, Dr. Gary Hunter and Dr. James Hill, where she is currently based actually at the University of Alabama in Birmingham, investigating the physiology of the reduced obese state, which is just someone who has lost weight, in collaboration with those names that I just mentioned.

and they are particularly interested in understanding that phenomenon of metabolic adaptation. So that is a reduction in energy expenditure below predicted levels and how relevant that is and this is basically what our conversation is today. Dr Martins has published several original papers and reviews on the impact of exercise in energy restricted diets, namely the ketogenic diet and is a regular speaker at the European Congress of Obesity.

So I will pop a link to Dr. Kadia Martin's research gate in the show notes so you can get a better understanding of the papers that we have discussed. Before we crack on into it, I'd just like to remind you the best way to support the podcast is to hit the subscribe button on your favourite podcast listening platform because that increases the visibility of the podcast out there and amongst the literally thousands of other podcasts so more people get the opportunity to learn from the guests that I have on the show.

Alright team, please enjoy this conversation that I have with Dr. Catia Martins.

Katya, thank you so much for taking the time to speak with me this morning. Your research is in an area which I'm super interested in, metabolic adaptation and just how this might influence weight loss or long-term success or what might influence just our metabolism in general. Obviously, we're going to do a deep dive into that, but can we first begin with your background

Education and your postgraduate work, how you got involved in this type of research? Okay, well, I'm a registered dietician. I have done my first degree back in Portugal, where I'm originally from. Then I went to England, to London to do a master in clinical nutrition. I did a PhD on the impact of exercise on appetite regulation. I then took a professorship position in Norway, where I was for 11 years.

And then I decided to do a sabbatical leave at the University of Alabama in Birmingham to work with Dr. Gary Hunter and Dr. Barbara Goer. And I had worked before in trying to understand how weight loss impacts appetite and how that can modulate weight regain. And so when I came to the United States, I had the opportunity to look into the other side of the energy balance, so to look into energy expenditure.

and metabolic adaptation as a potential determinant of weight regain in the long term. And then my husband got a job here and we decided to stay. So that was already, it's going to be four years ago. And I have continued doing research in that field. Nice, can we actually start on sort of from where you originally came from with your PhD research looking at exercise and appetite regulation. Yeah, so can you tell us a little bit about that study and what you did and what you found?

Yes, definitely. We have looked into how performing exercise can improve your appetite control. So we use the method that is called the preload test paradigm. So basically the participants come in fasting, we give them a milkshake. One of them is low energy and the other one is high energy. And we do this difference by using a product that is called maltodextrin, it's a carbohydrate and it doesn't have any taste or any color.

And the participants think that it's the same milkshake that is just, you know, a repetition. And they come different days of the week. And then after one hour, after they finish consuming the milkshake, we present them with an ad-libiton meal and tell them to eat as little or as much as they want until they feel full. And what we found is that if we do this experiment in individuals that are sedentary, they are

and they eat the same at the ad libidon test meal, regardless of the milkshake that they drank first. But then if we put them through, we have tried six week in normal weight individuals and then 12 weeks in individuals with obesity, and we perform the same measurement, these changes, and it's amazing that from a physiological perspective, somehow the body is able to detect this difference in energy and compensate for that.

in the right direction so that the individuals eat significantly less after the high energy milkshake compared with the low energy milkshake. And so that's so interesting because I've seen research where people talk about the uncoupling of exercise and appetite for people who are very sedentary. So are these the type of people that you're talking about? Well

I think that is a different type of experiment. We are talking about then how if a person spends energy by exercising, is the body then going to be able to compensate for that by increasing energy intake? Is that what you are talking about? Yes, yeah, yeah. Okay, so here is different. So it's a different mechanism by which exercise can modulate body weight.

Right? First, by the ability to be able to sense the amount of energy in food and to compensate for that at the following meal. And second, by being able to sense the energy that is spent during an exercise bout and how much of that is going to be compensated at the level of energy intake. Yeah. Okay. So it's two different mechanisms. Yeah. And with your research, was it

What type of exercise did you get your participants to do? Was it high intensity or was it moderate? It was aerobic exercise. And it was continuous moderate intensity. Yeah, so this was already 10 to 15 years ago. Yeah, yeah, yeah. So the high intensity interval training was not yet as popular as it is today. But I believe that the same would be seen with high intensity interval training. Yeah. And.

Was there any analysis done on subsequent meals and whether across the course of the day the participants would eat these? Yes. In our experiments in normal weight individuals, we have not looked into that. It was only six weeks. And then during my postdoc, I tried to do the same, but in individuals with obesity, and it was a 12-week exercise program, moderate intensity.

four times per week, spending 500 kilo calories per day. So it was a lot. Sorry, what was your question? Yeah, that's okay. Did it impact on their overall energy balance and did they lose weight? On the second experiment in individuals with obesity, we not only monitored what they eat at the meal immediately after the milkshakes, but we also gave them...

like a food diary, and we asked them to report everything that they ate until the end of the day, so until midnight. When we analyzed that data, the same trend appeared. They were able to compensate throughout the day. At the end of the day, those that ate the high energy milkshake ate significantly less compared with the other. Oh, interesting. With the other arm of the study.

match much more the energy that was in the milkshake because they had exercised? Yes. But when it comes to impact on weight, I think that was where we wanted to go, they lost on average 3.5 kilograms. And that was what was expected given the amount of energy that was spent during the exercise program. But there was a large inter-individual variation, which has been reported in

in many different studies. Yeah, because the purpose of it wasn't weight loss either, was it? It was looking at appetite. No, exactly. Yeah. Catia, can we sort of shift into metabolic adaptations? So, can we start with you just defining what that even means? Yes. So metabolic adaptation is a reduction in energy expenditure with weight loss that cannot be explained.

by the changes in fat mass and fat-free mass. So when a person loses weight, of course there's going to be a reduction in energy expenditure because that person has a lower body weight, right? And so it needs less energy to perform basic functions and also to perform exercise, right? But if that reduction cannot be accounted for by the loss in tissues, so fat mass and fat-free mass,

then we have what is called metabolic adaptation. So it's like the body going into a hibernation or saving mode in terms of energy expenditure. Yeah. What is thought to account for this? We really don't know. Potentially mechanisms that have to do with energetic energy metabolism and coupling proteins. So really, deep.

biochemistry inside the mitochondria, and in terms of generation of energy. That is what we believe at the moment accounts for that. Okay, I remember seeing a study on the biggest loser participants. Yeah, yeah. And that they, they were like, their predicted resting metabolic rate was maybe 500 calories higher than what

actually their metabolic rate was at the end of that study. This is what we're talking about, isn't it? Yes. So in the biggest loser competition, of course, the participants had severe obesity and they lost a huge amount of weight. If I remember correctly, 58 kilograms over the 30 week weight loss camp. And when they measure rest metabolic rate, the rest metabolic rate was approximately 250 kilocalories lower than predicted.

And then they called the participants back six years afterwards and they had regained, I think around 70% of the initial weight loss, even though they were still below baseline. And what was really surprising, and nobody can explain that, even though I have my own theory, there was in fact an increase in metabolic adaptation. It went from an average of 250 to an average of 500 that you just mentioned, even though they regained most of the weight. Okay.

Obviously, you just said you have your theory. So we are all very aware that this hasn't been studied. But I mean, what do you speculate is going on? Well, the studies that I have performed here at University of Alabama in Birmingham point out that the energy balance status, or if you want, if the person is weight stable or is not weight stable, is very important when it comes to magnitude of metabolic adaptation.

So we have done a study where we measure participants after a 12 kilogram weight loss on average, just when they finished the day after, and there was metabolic adaptation, approximately 200 kilocalories per day at the level of resting energy expenditure. And then we put the participants through a four week weight stabilization period, and then they came back, we repeated the same experiment, so they still had 12 kilograms weight loss, and they maintained their body weight over those four weeks. And then we measured again,

and we had less than half. We had 45 kilocalories per day metabolic adaptation. It was still there, but it was very small. So this experiment really showed that energy balance of the participant is important in modulating metabolic adaptation. Now, going back to the Biggest Loser, my theory is these individuals were told that they could come back.

to repeat a set of measurements and I believe that that changed their behavior. I mean, they started losing weight from that time point that I don't know where it was, maybe one week before, two weeks before, I don't know, one month before. And so when they came to do the measurements, they were not in energy balance. They were in negative energy balance, right? They were losing weight. And that exaggerated.

the magnitude of metabolic adaptation that was present. Okay, so essentially the participants were on a weight loss diet, so therefore they were not eating as many calories as they needed to sustain their weight. So it appeared that their metabolic adaptation was a lot greater. Yes, definitely. Yeah, interesting. So with regards to the transient nature of it then,

I've read your studies and it's so interesting to have a look at the numbers of what the metabolic adaptation is. In that study you mentioned, was it around 90 kilocalves per day immediately post their diet? Yes. It depends on, because on that study that I mentioned that we repeated the measurements after four weeks, we first looked into every one and I think we had around 70 participants.

And then we did a subgroup analysis in participants that had data at all time points, including the one year follow up. And I think we had only around 45. And so there is a small difference in one, we had an average of 100 and the other one we had an average of 90 because the group is different. So that is the reason. Yeah. And is this just like how meaningful is that number Katya? Because I like would... Yeah. So does that...

Is it an appreciable difference that we would notice in everyday life? Because people often talk about the number of calories it takes to maintain your weight as being more of a range than a particular number anyway. So can you speak to that at all? Well there has been a lot of controversy as you potentially are aware about both the existence of metabolic adaptation.

and second about the implications of metabolic adaptation. So before I run these experiments, there was this big theory that the body fights back to weight loss by the activation of compensatory mechanisms on both sides of the energy balance equation. So on one hand, there is a reduction in energy expenditure, potentially larger than expected. And on the other hand, and despite this, people feel more hungry.

And that these would then favor a positive energy balance. So they would start eating more, overeating, and in the long term, would lead to weight regain. Now, my experiments in Norway showed that the increase in hunger and grelling that occur with weight loss are not drivers of weight regain and are, in fact, a normalization towards a lower body weight. Because individuals with obesity have lower

levels of ghrelin that is a hunger hormone, not higher compared with normal weight. And so when they lose weight, the levels of ghrelin just increase because in normal weight individuals, the levels are higher. That's what I mean? So we have compared appetites, so subjective feelings of appetite and hormones after weight loss. And then we had a control group that had never lost weight, but had the same amount of fat mass and fat-free mass.

And when we compared the different appetite markers, there was no differences. Again, suggesting that this increase in hunger and growling is a normalization. Then when it comes to metabolic adaptation, again, there was this theory that metabolic adaptation would be a risk factor for weight regain in the long term, but we have shown in two different studies, one with a dataset from Norway, another one with a dataset from the United States.

two slightly different populations. In Norway it was men and women with obesity. In the United States it was women, postmenopausal women with overweight, both European Americans and African Americans. And we showed that metabolic adaptation was not a risk factor for weight regain. In saying this, I'm not saying that metabolic adaptation is not important, but it doesn't seem to be a risk factor for weight regain.

published another two papers more recently, where we tried to investigate if metabolic adaptation could contribute to resistance to weight loss, to the fact that in certain individuals they lose some weight but then, you know, they cannot move forward. It's very, very hard. So we have looked into that potential mechanism and indeed we found in two different

that those individuals that experience a larger metabolic adaptation during the active weight loss phase are those that lose less weight and less fat mass, this was in one experiment, and are also those that take longer to achieve their weight loss goals. Now, the contribution is not major, but it can be important,

metabolic adaptation. Because we are only talking about average values, but there is a very large inter-individual variation in metabolic adaptation, potentially genetic. So some individuals have very little or nothing, and other individuals, for example, in our studies are reported that the average was 100, but we have individuals with almost 300.

A participant or client was advised to follow a diet that is 500 kilocalories lower than what they need to maintain their body weight. And then if they have a metabolic adaptation of 300 kilocalories, then the deficit is only 200. And it's going to produce very little results. So I think that from a practical point of view, this just is important to make both patients and professionals aware.

that there are some individuals that are going to experience a large metabolic adaptation during weight loss and that they are going to struggle to reach their goals. And that does not necessarily mean that they are non-compliant or not adhering with intervention, but it might be that they have experienced a very large metabolic adaptation. Yeah, so interesting because you do see people and, it's almost like sometimes,

adaptation, metabolic adaptation is pitted against adherence. And it's like, well, which one makes the biggest difference? Whereas obviously, as you've just pointed out, it could be super individual and it is individual with the extent of it. I wanna pick up on something you were talking about earlier, Catia, with obesity and appetite hormones, just to sort of, and it makes sense, I think, is that hunger isn't necessarily determined by body size. That's basically, you know, like, it's not like,

people who have obesity are always hungrier all of the time, I guess. So it makes sense that there's a normalization. We have also done experiments, and in fact, we published a systematic review on metanolase last year, where we compared both subjective appetite feelings and appetite hormones between individuals with obesity and individuals with a normal weight. And there are no significant differences in hunger.

in hunger feeling or desire to eat in fasting, ghrelin, that is this hunger hormone, is lower, not higher compared with normal weights. But what we see is that individuals with obesity, they have a weaker satiety. What that means is after they eat a meal, they tend to feel less full. And that happens potentially, is what we believe,

that results from the fact that the production of satiety hormones, such as glucagon like peptide 1 or peptide Y1 or CCK, calcistocinine, are much lower after a meal. And that may contribute to the fact that they feel less full and therefore that they need to eat more to reach the same level of fullness as an individual with a normal weight. Yeah. Because Grelin, not Grelin, I'm sorry, leptin got a lot of...

airtime a few years ago, I remember, and being a med-rep bullet for obesity, which is another satiety hormone, isn't it? Yes, but leptin is more a long-term signal. Leptin is produced by the diposide, so by the fat cells, in direct proportion to the amount of fat stores. So an individual with obesity has high levels of leptin circulating in the blood compared with a person that is normal weight.

that somehow signal the brain regarding the amount of fat stores that that individual has. So in theory, leptin acts in the brain and it should reduce food intake. But we know that in practice is not working. And we believe that in a similar way as insulin, that individuals with obesity become insulin resistant, that the same happens for leptin.

So there are high levels of leptin in the circulation in individual zero obesity, but somehow leptin is not acting as it should. Okay, and then the other hormones you mentioned, glucagon and CKK. Glucagon like peptide one or PLP one, peptide YY or PYY and called C-stap.

calcistocin or CCK. These are more what we call episodic or short-term signals. So they go up and down every time we eat. So they signal the brain that we have eaten a meal. The circulating levels of course depend on the macronutrient composition of the meal, but also on the amount. And they would signal the brain that this person has eaten a certain amount of food and should stop eating.

It's what you call association or meal termination. And also it regulates intermeal interval. When are we going to feel hungry again? Yeah, yeah. That's interesting, I was chatting. So I'm a twin and my sister and I, we are not identical twins. And we're very different in our habits and behaviors and in our adult life, we're very different in our size as well. And we accept it's funny because I...

say that I eat like a bear, like I need large amounts of food in order to feel satisfied at a meal. And until I get that volume, then I'm just going to be hungry, whereas she is very, she's very different. Like she can have a small amount of food and feel quite satisfied, whereas I would be still scratching at the kitchen cupboards looking for something, which I think speaks to the impact, our differing impact of those satiety sort of hormones. Yes, yes. But.

I don't know if it is the case, but maybe you also exercise much more than your sister. Yes. So that explains almost everything. Because, you know, as I told you before, exercise sensitizes the appetite control system. So people become, and I think that is pretty easy to understand, you know, we know exercise is good for everything. You know, it improves the respiratory system, it improves the heart, it improves the muscles, it improves almost everything.

So in that way, it also improves the appetite control system. And if your body was not able to sense the amount of energy that you were spending and then increasing your energy intake, you would basically die because you would lose weight. So it's because of that. You need to eat. You have what is called a high energy flux. Yes.

A lot of energy going out, a lot of energy coming in, but they are matched. Yeah, yeah, yeah, yeah. No, that makes sense. And I also want to pick up, Katie, on what you were talking about with that individual variation in the adaptation, because I think all like, I'm a nutritionist, and so I speak to clients all of the time. And I speak to, I have one client in particular, and she's on her calorie intake is quite low, yet she's still.

unable to lose weight, yet her thyroid function is fine, her sleep is fine, and there are no other indicators that she might be, that there's anything else sort of going on. Do we know any of the risk factors that might put someone at risk of having greater adaptation?

It's an excellent question, Miki. I don't know the answer. I don't think we have the answer for that. Unfortunately, we know very little about what modulates the magnitude of metabolic adaptation and what explains inter-individual variations in response. Now, what I would say is, first, of course, there is the issue of adherence to the intervention. And second, I would say if this maybe an approach would be...

to ask your client to stop the diet and just maintain body weight for a couple of weeks and then try again. Because as I mentioned to you, by stopping the diet and maintaining body weight, metabolic adaptation is going to go away. Okay. Right? Yeah. And then she can try again. Yeah. And will it not just come back? Well, during the active weight loss phase, yes.

but maybe she's able to lose some more weight. I see. So it's, yes, yes. So it's almost like you have this little plateau, but if you maintain your weight, then you're able to push a little bit more. And I suppose it's just managing expectations around weight loss. I know it's funny because people are often in a hurry to lose all of the weight rather than looking at it as, you know, if you just look at it as this is, you know, this is a long-term thing because you want, it doesn't.

shouldn't really matter how long it takes you to get there as long as you sort of end up getting to where you want to be. Yeah and that is the big challenge right losing weight is relatively easy you know there are different approaches different types of diets diet plus exercise diet plus behavioral intervention now we have pharmacotherapy but for how long can you do that right and then you need to go into a maintenance phase and you know most individuals will regain

I know. Yeah. And it's that ability to, to set yourself up. So you've got the habits and behaviors that allow you to maintain that lower body weight rather than the quick fix. Six week juice cleanse or whatever that some people might take. Definitely. I agree completely with you. Katja, what about, so was the speed of weight loss, like a factor at all? Like I'm thinking about the biggest loser, like it was quite an extreme.

camp that they went on, you know, like hours of exercise from memory. I mean, I watched a couple of shows, but I did read the research papers much more recently. It was a very extreme intervention, no doubt, you know, 58 kilogram weight loss over a 30 week camp. And they exercised every day and they had coaches there. And of course they only ate what was provided to them. So from a physiological...

perspective is an important study, but when it comes to practical implications, it's harder to extrapolate what happened to that population, to your client, for example. Now I have done a study where I looked into speed of weight loss. So we had a group that both groups lost exactly the same, but one group lost it over four weeks and the other one over 12 weeks.

and they're looking to, you know, changes in appetite and also reduction in energy expenditure, and we found no differences. Interesting. And in fact, the largest study in that field was done in Australia, in Monash University, and they had almost 300 individuals, they randomized them again to losing weight fast or losing weight slowly, and then they followed them up.

to three years and they found no differences when it came to loss of lean tissue, that it was at least in the past one of the concerns. They found no differences in weight regain. Both groups regained similar amounts of weight, but they found that in the group that lost weight fast, more individuals were able to reach the target weight loss compared with other group.

I believe there are two mechanisms that explain this. One is behavioral. Individuals see changes very fast, and that motivates them to keep going. So seeing in the scale that you are losing 1.5 kilos every week is different from seeing half a kilo, right? And the other one is that the studies that have looked into fast weight loss, they have used low energy diets with commercial products.

And these diets induce ketosis. And I have shown and others that when individuals are ketotic, they don't feel hungry. Opposite with a standard diet, low fat or even a balanced diet that does not induce ketosis. And so in some individuals that may also help them to continue in the diet because they don't feel hungry. Okay, yeah, I saw that you very recently published on that, Catia. So...

Can you just describe your research trial actually? Yes, definitely. For example, we did experiments where we put individuals in a very low energy diet and then they lost, I don't remember, we have one where they lost up to 17 kilos. It was an eight-week very low energy diet. Then we measured appetite at the baseline. We measured appetite immediately after the end of the intervention. Then again, we had a four-week

maintenance phase, we called them back and we repeated the measurements. And so what we saw was that when we did the measurements of appetite while they were cathartic, there was no increase in ghrelin, that is his hunger hormone, and there was no increase in hunger. But then when we repeated the measurements four weeks after with the same weight loss, but they were not cathartic, hunger jumped up and ghrelin jumped up. So,

We can say that being cathartic prevents the increase in grellian and hunger that would otherwise be seen with weight loss. Yeah. So what, did you also use commercial products to induce hypnosis? Yes, we did. Yeah. And what was the energy value and matched for protein or did they have protein?

for women and 650 for men. But then they also had an allowance to eat 100 grams of low carbohydrate vegetables, just to have something to chew on. So maybe they reached around 650, 750 with allowance. We have another study where it was 750 for both males and females plus the allowance.

And in fact, we have another one where we try to identify what would be the threshold. I mean, how much can we eat of carbohydrates and how low is the level of beta hydroxybutyrate that is a ketone body, but we still have beneficial effects in terms of appetite control.

So this was an RCT where individuals with obesity were randomized to diets that were 1,200 kilocalories per day, but they had either 70, 100, or 130 grams of carbohydrates. They were matched for protein, and then fat was adjusted. And what we saw was that even at 130 grams of carbohydrates per day, there were still approximately half of the participants in that group that were cathartic.

And so it's possible to achieve benefits even at a higher level of carbohydrate when we are talking about energy restricted diets. Of course, if we're talking about a weight maintenance diet, then the restriction of carbohydrates that is needed to achieve ketosis is much, much larger. Yeah. And was exercise controlled for it all? Well, in all the studies that I have done back in Norway,

we ask participants not to change their physical activity during the intervention, during the active weight loss, then during the weight maintenance phase, then we advise them to increase. But during the active weight loss phase, we ask them not to change their physical activity behaviour. And we use either we have used armbands or we have used heart rate monitors, usually for four days at the baseline in the middle of the intervention and at the end.

And usually we see no changes over time. Yeah, okay. But we are talking about individuals with obesity and we have excluded those that were active at baseline because the amount of energy restriction would not be adequate for that subgroup of individuals. So we are talking about sedentary individuals. Yeah, and I get that makes sense as well because you're looking at the mechanisms behind, you know, like that would definitely add confounders. So I'm just thinking about that 130 grams

carbs and whether they were probably people who were a little bit more active than your group that was on. Yes, that would be a different answer for sure. I agree with you. Yeah. Oh, so interesting. And then with their maintenance diet, you didn't keep them in ketosis or you didn't just adjust calories up and add more fat? So what we did is that we always measure resting metabolic rate after four weeks of weight stability.

reduction in energy expenditure would be exaggerated. We would have metabolic adaptation if we measured it immediately after. So you measure it after four weeks and then we multiply by a physical activity factor that we have from the physical activity monitors and then we prescribe a diet that match their energy needs. I wonder how did you measure RMR? Is that through guess? Indirect calorimetry with a canopy. So they lie down on a bed and then we put the canopy

and we usually measure them for at least 15 minutes. Sometimes it needs longer. We need at least five minutes of stable data. Yes. Okay, thank you. And sorry, what were you saying in terms of, so you had that number and then you sent them off and they...

I was just going to say that in Norway we use the recommendations from the health government when it comes to a healthy diet with a standard macronutrient composition 50, 30, 20, and advise them to increase physical activity also. Yeah, nice. And Catia, I find it so interesting with the ketogenic diet, of course, because practically speaking that's one of the benefits that people say is that they...

they can follow it much, they can adhere to it much better because they're just not as hungry. So foods are just more satisfying. Yes, definitely. Of course, my experiments have been done only, not only, but mainly with very low energy diets. But there are different ways of achieving nutritional induced ketosis. It can be with a very low energy diet because the amount of energy is so little that

Even though we have 50% carbohydrates in grams, it's very little. Right. But we can also reach ketosis with a maintenance diet that has 5%, for example, carbohydrates. Right. So a very low carbohydrate ketogenic diet. Or we can also achieve ketosis with a low energy diet. As I told you, 1,200 kilo calories, 70 grams of carbohydrates. Almost everyone is going to be ketotic.

even at 100 grams of carbohydrate. So, you know, it can be achieved through different types of dietary approaches. And I think it will be something that would benefit particularly those individuals that mention that they cannot follow an energy restricted diet because they are very hungry. Yeah, yeah, for sure. Yeah. Right.

I'm going to ask you a question and you'll be like, that's not my research though, which I totally appreciate. But high protein, what do you think about the role of protein with metabolic adaptation? Or do we know, not necessarily your research, but has there been research looking at the role of protein? Well, from my understanding, there are no studies that have compared metabolic adaptation after different dietary interventions in terms of macronutrient composition of the diet so that we could...

conclude what is the independent effect of protein or metabolic adaptation. I believe that metabolic adaptation is mainly related with the magnitude of weight loss and not so much with the type of diet that was used. When it comes to protein, I think protein is very important and potentially explains also why ketogenic diets are easy to follow because they are high in protein and protein is more satiating.

compared with other myconogens. So it's more potentially metabolic adaptation occurs with a, it's not about the speed of weight loss, which you mentioned earlier with your studies, but it's more than the amount of weight that's lost. There potentially is more adaptation. Yes. Yes. Yeah. And then it would just be trying to, I guess for those individuals as the solution, if we know this about somehow they've, I don't know, been involved in your study,

somehow or else other know that they've got this going on, then we just have to find a livable solution for them to allow them a diet that they can sustain to lose the weight, to keep the weight off, and then also probably exercise a bit more to allow them more opportunity to eat more food. Yes. You know, all the research points out to exercise being, you know, a very important tool to maintain weight loss in the long term.

And one of the mechanisms is, as you say, if you increase energy expenditure, then you are able to have a much more flexible diet compared with a person that does not exercise at all. Yeah, yeah. And I think I've seen research that the non-exercise activity diminishes when we lose weight as well. So, you know, is that the part of your resting metabolic rate that sort of drops a little bit, I guess? Yeah. Yes, definitely, definitely. Yeah.

Katja, so what are some of the areas that you're looking at now with your research? What research studies do you have going on now? Yeah, well, metabolic adaptation is of course very complex. We have now been talking only about studies that have measured one component of total energy expenditure, that is resting energy expenditure. Very few studies have measured total energy expenditure.

and looked into how metabolic adaptation at the level of total energy expenditure impacts on long-term outcomes. So that is something we want to do to look at the whole picture. The second part is we know that the equations that we are using to predict energy expenditure are not the best. So basically we are adjusting for usually age, sex, race, if we have different races, and then fat mass and fat-free mass.

Now the problem is, or the challenge is, that fat-free mass is not a homogeneous component. It's very heterogeneous. And the metabolic rates of the different components of fat-free mass are very, very different. And up to now, we have not been able to capture that. Because most of the studies looking into metabolic adaptation have either used the air displacement

that is a two compartment model that divides the body in fat mass and fat free mass. Or you have DEXA, that is a free compartment model where you have fat mass, you have bone mineral content, and then you have the rest, we usually call it lean body mass. But again, there is no separation between skeletal muscle and organ mass. Now we have a couple of small studies that have been published suggesting that if we

to measure these different compartments, measuring skeletal muscle, measuring changes in the liver, in the pancreas, even at the level of the brain, with weight loss and we adjust for those differences, that their metabolic adaptation is not there at all. So some have suggested that metabolic adaptation is just a methodological artifact.

But we need more research to really clarify that. So in the research that I'm applying for at the moment, I'm writing a grant for, we aim to measure total energy expenditure instead of just measuring resting. And we aim to look into a detailed body composition assessment and how that changes over time. So we are aiming to use MRI to look into changes in skeletal muscle, liver.

pancreas, kidney and brain so that we can then adjust for these differences because the metabolic rate, for example, of the brain is like 20 times larger than the skeletal muscle and the same applies for the liver and for the pancreas. And so assuming that these changes are just skeletal muscle is wrong. And there are a couple of studies that have shown in fact a reduction in organ size with weight loss. Yeah.

So potentially, so maybe there are just dramatic reductions in brain mass, for example, or liver. And I have seen those studies that, no, that makes sense, yeah. It sounds like a very expensive study, if I'm honest. It is. It is, because measuring total energy expenditure, we wanted to look into double labeled water, for example, or metabolic chambers, and then you have the MRI. It's very expensive studies indeed.

Yeah, yeah. But we need those types of studies to really be able to conclude once and for all if metabolic adaptation really exists, first. And second, what are the practical implications of this phenomenon? Yeah, totally. And it's interesting what you say about that energy expenditure calculation, because I've been working with a group of people, we're just looking into this stuff, you know, the people that I'm working with. And from a practical perspective, you

calculate calories, then you say, track and measure in that for two weeks to see what happens to your weight. Like that is actually probably the best way to determine whether we're accurate because there are so many different calculators out there. And they come up and the differences are quite wide in terms of the recommendations they provide. Yes, yes. And the data, the databases that they use to then transform food into nutrients and how easy or

it is to estimate portion sizes is extremely complex and errors can occur at all levels. No, for sure. Catia, well, that's super interesting research that you're involved in and I'll be really excited to see some of that emerging over the next couple of years, two to five, five to ten.

can, they're just the normal person who might want to lose weight. Are there any practical applications in the here and now that we can provide people? The evidence that we have for today and maybe things change in the future is that some individuals will experience metabolic adaptation during active weight loss and that those individuals will take longer to reach their weight loss goals.

But when it comes to long-term weight loss maintenance, metabolic adaptation does not seem to play a role. I think that is the overall message when it comes to metabolic adaptation. No, that's good. And then potentially people who struggle with hunger might want to look at ketogenic approach. Definitely. Yeah, interesting. Keriya, thank you so much for your time today. And I'm going to pop in the show notes links to...

your research gate that has all of your research in there. You've got a number of such interesting studies and we only really touched on a few of them today, but it's been really insightful. So thank you so much for your time. My pleasure, Miki. All the best.

Alright team, hopefully you got a lot from that interview. I really loved talking to Catia and am super excited for the research that will be coming out of her lab in the next few years. And as I said, we will post links to her research gate in the show notes for you to be able to dive a little bit deeper, as I know some of you will want to. Next week on the podcast, I have a conversation with Zoe Harcombe, a nutritionist out of the UK.

Great conversation. I know some of you are familiar with Zoe. It was a really good opportunity to chat to her. But until next week, you can hit me up in the DMs on anything podcast related over @mikkiwillidennutrition, that's on Facebook, @mikkiwilliden on Instagram, Twitter and threads, or head to my website, mikkiwilliden.com to book a one-on-one call with me or sign up to my recipe portal access.

That's $12 a month, super cheap for recipes that are regularly updated. I am putting a ton of new stuff out there every week. So you also get access one-on-one to me as well. It's a great deal, actually. All right, team, you have a great week, and I'll see you next week.