Nutritional Revolution Podcast

Deficit Without Decline: How Low Energy Rewires Muscle Protein and Mitochondria

• Season 6 • Episode 174

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In episode #174 we discussed Dr. Jose Areta's latest research, including:

  • How energy deficits influence muscle protein synthesis and quality
  • The role of mitochondrial proteins and their upregulation during energy restriction
  • Practical implications for timing and periodization of caloric deficits in training cycles
  • Hormonal signals and their interaction with muscle adaptation during energy deficits

Associate Professor Dr. José L. Areta is a leading scholar in Exercise Metabolism and Nutrition in the School of Sport and Exercise Sciences at Liverpool John Moores University (LJMU). His research investigates how nutrition and exercise interact to influence both performance and health. He focuses on the timing and composition of macronutrients — carbohydrates, proteins, and fats — and how they affect training adaptation. José also examines the role of dietary supplements in optimizing athletic performance, as well as the endocrine and metabolic consequences of energy restriction, particularly low energy availability. He has contributed influential studies on how severe calorie deficits combined with exercise can alter muscle quality and metabolism. José’s work links cellular-level changes in muscle to practical nutrition strategies for athletes facing weight-sensitive sports or energy restriction.

Please note that this podcast is created strictly for educational purposes and should never be used for medical diagnosis or treatment.

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Hello everybody and welcome back to the Nutritional Revolution podcast. Today we have for you guys Jose Areta and this is a fascinating episode. I really enjoyed it. He is a leading scholar in exercise metabolism and nutrition in the School of Sport and Exercise Science Liverpool John Moores University. His research investigates how nutrition and exercise interact to influence both performance and health. He focuses on the timing and composition of macronutrients, carbohydrates, proteins and fats. and how they affect training adaptation. Jose also examines the role of dietary supplements in optimizing athletic performance as well as the endocrine and metabolic consequences of energy restriction, particularly low energy availability. And he has contributed influentially on studies on severe caloric deficits combined with exercise and how they can alter muscle quality and metabolism. Jose's work links cellular level changes in the muscle to practical nutrition strategies for athletes facing weight sensitive sports or energy restrictions. This is an amazing episode, very fascinating. I enjoyed it. I know you guys will too. Hello everybody and welcome back to the Nutritional Revolution podcast. We have for you guys Associate Professor Jose Areta. I'm so excited to talk to him about all things protein and we got a really fascinating study we're gonna dive into with Jose today. thank you so much for joining us. Oh, pleasure, Kyla to be here with you and to share the insights of our study. Yeah, I'm excited. Before we dive into the nitty gritty of some some research here, I'm going to have you break down your tutors and a lie for me. So, all right, so number one, I am a black belt in Taekwondo. Number two, I've competed at a national level in road cycling in Australia and Norway. And number three, I fought a bear in the mountains of Colorado. Oh, okay. These are good. These are good. My immediate reaction is to say the fought a Bear is a lie. I mean, immediate reaction. m Yeah, but if you did, that would be a very, I can't wait to hear the story. um That's pretty impressive. Black Belt and Taekwondo. I don't know a whole lot about Taekwondo. I imagine they do the belt system similar to karate and maybe Jiu-Jitsu. I'm not sure how that. That could, that's a tough one to road cycling. I feel like maybe you could have been like, that seems reasonable to be considering the research avenue direction you went. So I think I'm to go with my initial gut reaction. The bear fighting in Colorado was a lie, but we will wait to reveal the answer for our listeners at the end of the episode here. So we're going to dive into a piece of literature you put together here today. But first, can you share with us and our listeners a little bit about you and your research focus and how you ended up studying energy deficits and exercise together? Yeah, for sure. It is a bit of a long-winded sort of, could be a long-winded answer because there's a lot to say how I ended up doing what I do today. Originally I'm trained as a biologist, like a zoologist and throughout my PhD in Australia and a postdoc then in Norway and so on, I sort of got more and more into this topic. know, broadly speaking, ah we study how manipulating... carbohydrate, fat and protein intake can sort of interact with their training stimulus to drive training adaptation and optimize performance. And I ended studying energy deficit and exercise together because I was fascinated by the idea that energy deficit could generate a very particular sort of physiological state and affect many systems in the body in ways that maybe some people think of negative and some people think as positive. Oh yeah. And it seems that, know, like many people, like high level athletes and general population alike, they are exposed to energy deficit, but we have a rather limited understanding of how our bodies respond to it. So I was like, this is really fascinating. You know, it's very relevant to a lot of population, but there's a lot to discover here. So, yeah, that's kind of like took me in that direction. Yeah, this is very fascinating because to your point, certainly in the women's specific like research area in the deficits, we see a lot of conversations around relative energy deficiency in sport and effects to that degree for over longer term. So this is going to be very interesting to talk about. I know the paper we're going to talk about today was done solely on men, correct? OK. Okay. So yeah, I'm curious to hear what your thoughts are when we can get there as we get further down. But for our listeners or endurance athlete population, if you had to explain kind of like a quick summary of what this paper is diving into and as we will get into the nitty gritty here shortly, how would you explain what you were looking at here in the paper? Yeah, so basically we're looking at how the quality of the muscles changed when people were exposed to a degree of energy deficit. with concomitant exercise. We know that muscle protein synthesis tends to be reduced sometimes when there's a degree of energy deficit, but we don't really know what happens to the more qualitative part of the muscle. hasn't been a lot of analysis of how different parts of the functional machinery of the muscle changes with energy deficit when there's an exercise stimulus at the same time. Okay. Yeah, this is, I think this is so fascinating. So we can start to get into a little bit of the study design, the participants, how many maybe first you want to tell us what the question was that you're looking into in the paper. And then if you could break down kind of who you were looking at for how long, what did you, you know, study, what markers, et cetera, were you? be looking into in the paper. for sure. So when you do a study, you always have primary questions or main questions and main points, hypotheses and so on. And you have secondary bits of hypotheses that you want to add. address sort of thing. The main point of this study, the main question of this study was like how energy deficit or low energy availability affect skeletal muscle phenotype. The phenotype is the visible characteristics of the muscle. Visible as oh I mean, like, you know, in this case, we were looking at specific proteins, how many proteins, we're going to talk about the methodology soon, but you know how the characteristics of the muscle were changed when concomitantly exposed to energy deficit and exercise. Then the secondary aim of the study was to understand better how males when exposed to energy deficit. respond in terms of like the physiological markers that are typically attributed to like low energy availability. As you said well before, this area is being more studied in females than in males in the past. it's probably the only area in sports science and in sports nutrition, that's been studied more in females than in males. But we were like curious about, you know, because there's the whole idea of the female and male athlete triad and this whole idea of like REDs and so on and say like okay how are males affected by energy deficit we don't have a lot of information about that you know when people are exercising at the same time so that was you know broadly speaking what we were trying to study in this research Awesome. I'm so excited to learn. um what was, we mentioned it's males, but how many participants were you looking at and kind of rough age and what was the duration of the study? Yeah, so uh this study, we studied 10 fit young males. So these were not like high level athletes or they were not untrained individuals. We picked individuals that... would be familiar with the type and amount of exercise that we were going to expose them to because we didn't want the exercise to be like a novel stimulus. But we wanted the main stimulus, the main stressor, not to be exercise, but the energy deficit that was the novelty. So this is not like a training study or anything like that. uh Because these studies are very, very well controlled and it's very hard to control humans tightly. These are not like... rats that you put in a box and you can just control everything what they do for like weeks on end. People have lives and so on. We did a protocol that was rather, you know, how do you say, drastic in terms of the energy deficit because we wanted to look at the physiological effect of energy deficit, not replicate what people are doing in sort of in real world scenario because we are more interested about the mechanisms. So we expose them to like five days of energy balance with concomitant exercise followed by five days of quite a pronounced energy deficit. Wow, okay. And with the type of movement they were doing, the exercise, what did that exercise look like? So the exercise, so I must clarify that all food and all exercise was 100 % controlled. So we had a very, very tight control. We put together their meals, we gave them their meals, everything was custom made, pre-packaged. em And so exercise was very well controlled as well. They only did the exercise that they did in our labs. So every time that they were doing exercise, we controlled the power output on an ergometer in the lab. cycling type exercise in a commenter, were, you know, a lot of the time that they were exercising, they were also hooked to an indirect calorimeter. So we were measuring the respiratory gases that they were inhaling and exhaling. So we could measure contributions of fat and carbohydrate during exercise and so on. the exercise was cycling, was three times, around 90 minute sessions. em So three times every five day period. they had like two consecutive five day periods of control of exercise and nutrition. On each of those five days, they exercised three times. So they had two days rest, three days exercise. And yeah, it was about 90 minutes. And when I say about 90 minutes, it was because we want them to do an exact amount of exercise to burn an exact amount of energy and most people took around 90 minutes. Okay. And what level of energy expenditure were you wanting to achieve in that 90 minutes? So they were exercising at around 60 % of VO2 max which is sort of a moderate intensity exercise. They were doing it in the morning. And the amount of energy that they expended was 15 kilocalories per kilo of fat-free mass per day, which is roughly about, it depends on the size of the individual, but would be between 1,000 and 1,200 calories, roughly. Okay. And with the energy intake, so monitoring that, having them at maintenance needs in the first five day block, I should ask too, was this a crossover? Do we crossover study design? It's not a crossover design. The name of the experimental design is called a quasi-experimental design because it was the energy balance followed by the energy deficit. And this is because if to do a crossover design would have been a bit tricky because we gave our participants a type of tracer which is deuterated water which is very, very expensive. uh And we would have to do that like twice and that increases the cost of the study a lot. So we put first the intervention that was likely to have the lesser uh effect on whatever we were looking at, which is the energy balance intervention followed by the energy deficit. So uh we didn't have like a washout period in between. So it's not a crossover design, but it's a quasi experimental design. That's what it's called. Yeah. the deficit that they went into, tell us a little bit about that. Yeah, so we purposefully put them in a quite severe energy deficit. If you are familiar with the literature on low energy availability and so on, typically see that all the studies found in females, they are exposed to 45 kilocalories per kilo of fat-free mass per day during energy balance. So that's an amount of energy availability that allows a person to sort of maintain body weight. And then we brought them down to 10 kilocalories per kilo of fat-free mass per day of energy availability so that's a sort of 78 percent reduction in energy availability. This is aligned with other literature, know, other classic literature in this area that has done or titrated the energy availability exposure from 45 to 10 so it's not the first time that someone does it but it's the first time that it's done it's been done in males in a study of these characteristics for this duration. Wow, yeah, that is a big reduction in calories. So for our listeners do you have like rough idea of what the body weight was in kilos is fine too from like one of the participants or average participants? Yeah, it was around, I can't remember the exact number right now, but it was around 80 kilos. em And the weight loss in that period was of three kilos over that five day period. Yes, yeah. Yeah, so we basically, that's what we were expecting. So we did the intervention that we did, in terms of like energy deficit and the energy deficit, the amount of weight loss was exactly what we were expecting. So. that shows that our control was really good in terms of what we wanted to do. We achieved exactly what we wanted to achieve. Fascinating. And did you do body composition scans before and after this study or were you monitoring that via the doubly labeled water? Was that? No, we did body composition assessment with two different methodologies. We used Dexascan, which you're probably quite familiar with, that allows you to determine body composition in a sort three-pool model, which have like fat mass, fat-free mass, and bone mass. em And we also did bio-electrical impedance analysis. So them two methodologies allow us to see different characteristics in the changes in sort of body composition. And what we saw from the DEXA scan, was the decrease in like three kilos of body weight was around 0.8 kilograms was of fat mass and 2.1 kilograms was of uh fat free mass. But then we can see that the decrease in fat free mass, know, the DEXA scan measures um fat-free mass is a measure muscle. So you see, there's a decrease in fat-free mass. Did they lose muscle? Well, maybe they did a little bit, but the DEXA scanner is picking changes in body water as fat-free mass. So it might not be like actual tissue, but losses of water. And we know that acutely during energy deficit, there's a significant decrease in water. And that's what we saw from the bioelectrical impedance analysis, which allows us to... measure total body water as well. And we saw a decrease of 1.2 kilos of body water. in terms of the decrease in body weight, the majority was, so a good part, a big part of it was body water, but that's completely normal. And you know, the decrease in fat free mass, probably a big, part of that was we have water as I've been saying before, but. When you do a uh calculation of the contribution of energy from different tissues and you look at the energy equivalents from different tissues, each kilo of um fat mass provides around 9,000 calories of energy, whereas it's a lot less for the fat-free mass. When you uh multiply the amount of energy from the amount of... fat that was lost compared to the fat-free mass with its energy equivalent, the majority of energy was derived from fat mass. Oh, interesting. Wow. And so when you were in the deficit to talking about the meals that were being controlled, was protein at all held consistent or was it even able to be held consistent in the deficit phase? that's a great question. that's one of the things that are quite tricky to decide what to do when you run these type of studies, because you could be changing the energy from all the macronutrients the same, or you could be manipulating each macronutrient. So in this case, we decided to do what pretty much all studies in this area using similar methodologies have done. which is clamp the percentage of energy provided by each macronutrient and then basically you reducing in the same proportion each macronutrient. So we have from in the energy balance group, they were eating, for example, 2.2 grams of protein each day. per kilo per day. em The total protein intake was 174 grams. During the energy deficit was 0.8 grams per kilo per day. So typically when you put someone in energy deficit and you want them to maintain their muscle mass, you would increase the protein intake a little bit. In this case, we were not trying to look at how protein could rescue fat-free mass. We've done research already on that. we were trying to see like energy deficit as a whole, what are the effects on muscle. But you know that's a relevant question for future study is what would happen if you change the macronutrient composition for sure. Yeah, yeah. This is very fascinating. The fact that you've broken down the energy from fat versus the energy from muscle tissue broken down. The difference there, I think, is very fascinating. I've never heard that really broken down like that. It's always like, this many kilos of muscle versus this many kilos of fat. And looking at it from that lens versus the amount of energy you're getting from the fat versus the em muscle or other tissues, right? And for our listeners, There's nine calories per gram of fat. that right? Okay. Versus like four in muscle, four per gram of Yeah, it would be a little bit less. it's about, know, the thing is that you have to think that there's four kilocalories per gram of uh protein, but your muscle is around 75 % water. Yeah. Yeah. So the majority of your muscle is water actually, it's not protein. Yeah. think too within that deficit, when the deficit phase and some of the weight loss, the water's coming off, is that also a result of like glycogen depletion within the tissue also? Because isn't that pulling water? saw, of course, we measured muscle glycogen because muscle glycogen is extremely important. We saw a reduction of around 30 % of muscle glycogen. yeah, because of how the osmotic pressure inside the cell that there is about, we think, between three and five grams of water bound for every gram of muscle glycogen. So the... That is likely a contributor to the decrease in fat-free mass, decrease in water because of the decrease in muscle glycogen. It was not drastic decrease in muscle glycogen because our participants kept eating carbohydrates throughout. They did exercise, but it was not an extremely demanding sort of glycogen depleting type of exercise. But that was for sure one of the contributors. Mm-hmm. Did you notice in the deficit phase when they had to do their cycling sessions, did it take longer than 90 minutes when they're in a deficit? No. didn't. Their RPE, so we measured a lot of things. So think one of the beauties of these studies that we did a lot of different types of assessments, you know, from uh physiology, endocrinology, and so on. But we also asked the participants, how hard is this feeling? You we used what is called like the Borg scale, where people report like their subjective perception of effort. And that was not different either. Wow. Okay, that's great. I feel like if I'm in a deficit, I'm struggling. uh Okay, so talking about the, the you call it deuterium is what is that the short term for heavy water doubly labeled water? Okay. Yes. Yeah. a technique that is called dynamic proteomic profiling. That's a fancy word to say that we measured a lot of proteins in muscle. eh So you see that the muscle cell, the muscle is a group of cells that are like quite long and you have like a lot of different... types of proteins in them and those types of proteins is what gives the functionality to the muscle to any cell really but we were looking specifically to muscle here. So before and after each uh period we took muscle biopsies from the vastus lateralis of the quadriceps which is the muscle that we typically sample in this type of studies and applying this technique we can look at the expression of different types of protein. So we can sort of have an idea in what direction the muscle is going in terms of adaptation. So this technique has two sort of distinct outcomes. We can look at the uh expression of the total amount of protein. So the enrichment is in protein, the abundance. Or we can also look... the turnover of the proteins, how quick these proteins are being added into the muscle. So we have two separate outcomes, have synthesis and abundance. For us to look at the synthesis rates, which is something that not many people in the world can do, we work with an expert in proteomics for this study. you need to put a tracer, so something that can show you how quick those proteins are being added. It's not something you need to do to look at the abundance, we're looking at the speed of uh protein synthesis of individual proteins, which is like the degree of resolution is really, really high, and this is the beauty of this study. And for us to be able to do that, we have to give them what is called deuterated water. So it's basically water with a deuterium atom. you know water is H2O, that's the way you probably refer to water in the sort of more sort of chemical lingo. This one is D2O, so it's the hydrogen atom is heavier than the normal sort of type of hydrogen. It's got the same characteristics, so the body handles it in the same way. Mm-hmm. But we can differentiate it from the other one and we can see then how that deuterium is being added into the proteins and we can see the speed at which these proteins are being synthesized. So that's a really sort of fancy technique that allows us to see how the rates of protein synthesis change and many other studies that have been done in muscle protein synthesis throughout history. typically look at pools of protein. typically you define the protein pool in muscle like myofibrillar protein synthesis or the contracted part of the muscle or sarcoplasmic protein synthesis, which is the other proteins that are sort of floating around in the cell. But here we go to a, you know, we zoom in and we can have a very detailed resolution of individual proteins. So we're not just looking anymore at, you know, this sort of generic myofibrillar protein synthesis or cycloplasmic protein synthesis, we're looking at individual proteins. So for the synthesis rate, we could differentiate 625 different types of proteins. And for the abundance analysis, which is in a way is easier to handle to the equipment, we measured nearly 1,500. proteins that we can look at the abundance. So it's a very high resolution analysis that we have with this methodology. my goodness. Yeah. 625 different proteins. That's wild. Yeah, that's a lot to... And these are different, 625 different types of proteins. Yeah, that's it. this is a very detailed analysis. When you get the output from all the molecular biology, sort of biochemical analysis, you get a long list of proteins, many of which you don't know what they are. So you have to go protein by protein, try to understand what's the role in the cell and why it is changing and so on. So it's a very granular, detailed analysis that entails many, many hours of understanding the biology of the muscle and why something might be changing and making sense out of it. Typically what we tend to do is because the dataset is so big and can be so overwhelming, there's ways in which we analyse it to look at more trends in biochemical pathways that change in the muscle and that's what we did for this study. Yeah. Okay. Well, do you want to share with us kind of what, once you kind of like dove into 625 different proteins and I think you said like 1500 proteins for the abundance, like what is, what comes of that now? What did you ended up kind of like finding from all of that once you kind of sifted through everything? Yeah, so first we looked at the trends, what is going up, what is going down, and so on. And from the synthesis rates, we did the traditional analysis of breaking it down into three main pools. We have the sarcoplasmic pool. We have the myofibrillar pool. And then we also looked at the mitochondrial pool of proteins. When we look at the sarcoplasmic and myofibrillar pool, we see there were no changes in protein synthesis in each of the uh sort of different stages of the intervention in the energy balance or the energy deficit period. This was a little bit surprising. I was not quite sure what was gonna happen in the energy deficit period with uh contractile stimulus. We've shown before that if you do resistance type training, that the mass of protein synthesis can be rescued if you're in energy deficit. I've a study on this many years ago and that's what we showed. But with energy deficit we didn't really know. And some studies show that there can be a degree of reduction in protein synthesis with energy deficit. But here we saw no changes in sarcoplasmic or myofibrillar pools. Now, what is really, really interesting is that the mitochondrial pool. So the mitochondrial pool corresponds to all the mitochondrial proteins. The mitochondrial proteins are a very important part of the cell that is, among many other things, responsible for generating energy in the muscle and generating energy oxidatively, which is using uh oxygen. So the muscle has different ways of generating energy without oxygen, with oxygen, and so on. For your audience, your population, which is runners and cyclists, or like distance runners and long distance cyclists and triathletes and so on, they are all mainly interested in oxidative energy generation because that's when you use oxygen to ultimately break down fats and carbohydrates to generate energy. And that's what mitochondria do. So what we saw is that the mitochondrial pool of proteins, the synthesis rates went up. during energy deficit, but not during energy balance, which is quite, this is already quite fascinating. It was sort of aligned with my hypothesis where, you know, energy deficit might have an effect on up-regulating the capacity of muscle to generate energy. So when we look at the abundance of different sort of proteins, the story is the same. So we looked at, you know, we have a type of analysis that we are looking at two separate things, the synthesis rates and the abundance. When we look at the abundance, let's say, well, this should be telling the same story. And, know, broadly speaking, it's showing exactly the same thing. There was an increase in the abundance of proteins related to mitochondria. And, you know, the mitochondria has like different parts, know, the mitochondria is this. uh bacteria like organelle, during evolution it was uh a bacteria that was eaten by another cell and then this bacteria started living with this other cell and generating energy inside this other organism but it's got different parts and these different parts are the electron transport chain, the beta oxidation and the Krebs cycle, they are all interrelated, that kind of work together. And then three parts of the mitochondria went up as well. So we see that it was not just a one-off, like an odd protein in mitochondria that went up. And we say like, yeah, this one protein went up. And this has sort of a positive effect in mitochondria. We saw a lot of things inside mitochondria changing. And not only that, we saw a few proteins that are quite important for mitochondria. quality control also going up. So it was not only proteins of the machinery of mitochondria, but there were proteins of how the quality control of the mitochondria is regulated that went up with the energy deficit. So it appears, you know, that the energy deficit on its own is having some sort of effect in increasing the quantity and quality of these parts of the muscle that generates energy. Yeah, so it... the way that I think about it is energy deficit as an independent stressor, potentially. Because of the experimental design of this study, we cannot truly work out that there's causality between these two things. the data are quite solid and it seems to be pointing in this direction, where when there is an exercise stimulus, the energy deficit stimulus, Might be well the energy deficit might be a stimulus on its own might be like a stressor You know we think about what I like to think about stressors, you know have the stress of exercise You know you exercise and you get tired, but then you get fitter. Yeah, something similar might be Happening with energy deficit, you know, maybe your body is responding to energy deficit as a signal And then some parts of the muscle are being upregulated Amazing. This kind of makes me think of what is it? uh Like sleep low, train low or not from altitude, but like glycogen depletion. And that improves a little bit of that as well, correct? Yeah, that's correct. So that's kind of what we were coming from. So during my PhD, we did a few studies on training with low muscle glycogen. And that's sort of what initially made me interested in this area. We were manipulating muscle glycogen content and seeing that, oh, there are these genes going up when you train with low muscle glycogen. This is interesting. then we saw a lot of... changes in gene expression with low muscle glycogen and stuff. Many of those studies were not quite clear if it was the glycogen or it was some degree of energy deficit that was generating this response. And that's a reason why I wanted to uh investigate what was going on, because the muscle is seeing different signals of energy deficit, seeing like, there's hormonal changes. We measured loads of hormones in this study. We measured leptin, IGF-1. T3, testosterone, and a few other hormones. Most of it changed. So leptin went down, as you would expect. IGF went down. T3 went down. Testosterone didn't change. So I don't really think testosterone is that sensitive to an energy deficit. em And so the muscle is receiving potentially the signals of systemically there's low energy but there's also an internal signal of the low muscle glycogen and the muscle is maybe going okay we have signals from outside the muscle and we have seen it from inside the muscle that there's not a lot of energy maybe we have to you know these are like two separate signals that the muscle is integrating and then resulting in a response so I think that's quite interesting. Hey everyone, when's the last time you actually looked under the hood with comprehensive blood work? Most of you are training 10, 15, 20 hours a week, but have no idea if your body has what it needs to perform. Here's what we see constantly. Low ferritin tanking your aerobic capacity, vitamin D deficiency that's increasing your injury risk or keeping you sick, elevated cortisol from over-training, thyroid markers that are normal but not optimal for an athlete. So that's why we created our full athlete blood panel. We test everything, complete metabolic panel, advanced lipids, iron stores, vitamin D, B12, folate, magnesium, testosterone, cortisol, thyroid, insulin, hemoglobin, you name it, it's over 20 markers that directly impact your performance and your recovery as an athlete. It's $371 and includes the lab fee through Quest, and you can get tested as soon as tomorrow morning. Check the show notes for the link to order. Some state restrictions do apply, but it's available in most of the US. Stop guessing and get the data. Wow. for like plain language for some of our listeners, is this improving their oxygen like capacity or their like zone 2 base training? Is it helping there? I know the temptation of wanting to draw conclusions from a really interesting data set, because it is a really fascinating data set. But we have to be careful about how we think about things in terms of negative or positive. Physiology doesn't know negative or positive. But we know that more of certain proteins might be a good thing, depending on what you want to achieve. Mm-hmm. Mm-hmm. we cannot conclude that the muscle is using more oxygen or has a higher, you know, maximal capacity for using oxygen because we didn't measure that so we cannot draw that conclusion but it seems to be pointing towards the muscle having a type of adaptation that it might be better to handle the use of energy and you know when you have athletes training for many many hours as know people do hours and hours of zone two training and they do intervals and so on. Ultimately what they are trying to do is to optimize their capacity to uh use oxygen for high levels of oxygen for high rates of oxygen utilization during prolonged periods of time. people typically have an AVO2 max, you know, that doesn't change, it changes a little bit with training, but doesn't change a lot. But the more you train, the more you're able to maintain a higher percentage of your VO2 max for a longer period of time. And that is thanks to the mitochondrial adaptations that you have in your muscles. So, you know, if you're thinking that will potentially a degree of energy deficit, might have a positive effect if that's what you want to achieve with your muscles when you keep training. I'm sure that this question is coming, but we are not advocating for people to be in energy deficit all the time. This is probably conversation that we're going to have now about the potential negative effects of energy deficit that I'm very well aware of. Yeah. Yeah. I think that is a great point because that was kind of what I was thinking is like people will probably hear this and they'll be like, all right, need to cut those calories out. But I do I know that there's also a training seasonality for building that base and intentional structured nutrition around training to get adaptations to occur. So maybe you could share a little bit more on like when or why or like how long of a deficit is okay or not okay and should an athlete be doing this and if so like at what phase maybe of a season to minimize you know issues. Yeah, I think there's a lot of things to say here. I think there is an extreme vilification of energy deficit in the collective mindset at the minute, possibly fueled by all the fear instilled by the relative energy deficiencies, sports syndrome and so on. And in this study, I wanted to look at things from a bit of a more like... sort of neutral angle and say like, let's look at objectively, you how the body is responding to energy deficit without thinking it's like positive or negative. We know that like some top athletes are exposed to a degree of energy deficit and they're still like performing at the highest level. So let's look at what the body is doing instead of thinking, oh, this is bad. And, you know, this is what we see. Now, Going back to what I said before, I think it's very important that we think about energy as a stressor and you don't want to have too much of a stressor of any. And we have to think that we as sort of integrated systems like, you know, living organisms that we are and our central nervous system, our physiology and our central nervous system integrates different types of stressors. The energy deficit stressor, you know, it seems to be quite potent. You know, some people want to lose weight to perform better even though there's no scientific data to show that losing weight is going to make you perform better. It's very interesting. There's also no clear data that losing weight is going to make you perform worse. So this is something that still needs to be investigated. But as with any stressor, you don't want to do too much of it. Too much or for a very prolonged period of time without having the adequate rest. Same thing will happen if you train too hard. You train too hard, you're going to have a negative effect on your performance and you're to potentially burn out and so on. in terms of energy deficit, we don't have a specific dose. If you say with an athlete, you can look at, what is the right training dose for an athlete? Well, it depends. It depends on an athlete. It depends on their training history. It depends on how well they respond to training. We know that not everyone responds the same. Mm-hmm. to different amounts of training and so on. So I think that something similar might happen with energy deficit, you know, where some people might be a bit more sensitive to it and some people might be less sensitive to it and so on. So I wouldn't feel comfortable saying like, you look, you need to do this amount of energy deficit for this period of time and so on. But I think it is definitely a bad idea. Mm. to target a specific amount of weight you want to lose or make that the target on its own. When you stop thinking about your performance and you start thinking about how much weight you need to lose, I think that's when things start to go south. First and foremost, you have to keep focused on your training plan, on your capacity. to achieve the goals that you want to achieve and see if you're getting fitter and faster. And consider energy deficit as potentially one tool in the toolbox, but something, it's basically, it's a double-edged sword and you've got to be really, really careful. But I think that we need to be aware that that might be the case in terms of like, it might have a positive effect and it might have a negative effect as well. So I think we need to be smart and not vilify it from the outset. And also we need to understand exactly what energy deficit does with quality research because the things that are attributed to energy deficit in the relative energy efficiency in sports syndrome don't have data that show causality between the things they said is because of energy deficit and what it... and the actual evidence. there's a lot of correlation. There's a lot of studies that show that people who have certain symptoms also have some other symptoms. But because energy deficit is so hard to measure in the field, em we cannot really show causality between what they say that energy deficit is producing the symptoms that it's producing. em and the evidence that supports that. Yeah, yeah, it is a fascinating, like I think it's a good like way you're framing that, right? It's like it's potential tool to utilize not for the weight loss implications, but for a performance adaptation effect, potentially like you would use, I don't know, beta-alanine or, you know, or sodium bicarb. Like you don't maybe utilize it all year around, but there could be certain times where someone might want to use it. I'd be so fascinated. to see if you did this exact study in women. I'd like be so curious how it would turn out. Cause when I was like running through, think there's a good em meta analysis that like summarized all the, I think it was like a uh fat oxidation and improvements in performance. when I was going through it, don't think a single study was looking at women. And so I'd be so curious to see what Yeah. happens in those circumstances as well. uh for sure. We have a line of work that is all... around supporting the research in female athletes. And so when we have lines of research in different topics like exogenous ketones and energy deficit and carbohydrate manipulation and so on, we try to do as much as we can in both sexes. And very much, ideally we would do this in males and females, but we have to pick our fights. It's very hard to do a study Yeah. a research paper that you see and you read in an hour and then how long did this take to do? Well, was quite a few years and it cost a lot of money and so on. I would definitely like to do the same thing in women. We think that... males and females respond differently to energy deficit. So from the muscle perspective, I don't really know what might be happening, but honestly, we didn't really know what was happening until we did this. So this is all quite like novel data and it would be even more novel if we had females as well. So this is something to be investigated for sure. What we see that is sort of fascinating and I think it would be the same regardless of the sex and this is maybe to highlight something I explained before but didn't really... Yeah, I'll just highlight and say why this is new and interesting is because we see many hormones that signal that the body is going into some sort of energy preservation mode, I explained before, like leptin and TE3 and IGF-1 and so on, changing in one direction. But then muscles keep adapting to the exercise stimulus. So the muscle is not shutting down. And I try to understand this from an evolutionary standpoint. are originally as a species, uh hunter-gatherers. We have to think that for us to be able to hunt and gather food, we have to be able to move. And if you didn't have that capacity to move, if your body shut down, the capacity to move. when you didn't have enough energy that's probably not the best for survival because it's the only way we can procure ourselves from food. Now I think that that's why if you put someone in energy deficit for a prolonged period of time and energy deficit is eventually going to have a negative effect on different areas of your physiology. quite strong data that it might affect like bone metabolism and you know people are more prone to like stress fractures and so on so uh I think that you know in this framework uh it's very important to notice that performance is probably not the first thing that is going to suffer if you are exposed to energy deficit keeping in mind that you know your muscles keep adapting to exercise and you might be getting fitter but if it's going to have a negative effect on your capacity to adapt or perform or anything like that is probably going to have, it's going to be down the line when some systems that might be more prone to being negatively affected by energy deficit might already be quite affected. It's important to keep an eye on bones and bone metabolism and so on. Yeah, yeah, certainly. So I want to be mindful of your time too since we're getting close on time. So I will ask you one last question before we get into your two truths and a lie before we close things out. But are there any supplements that you suspect could be meaningful in the influence of the balance between the beneficial mitochondrial adaptations and the harmful tissue loss during the deficit, like essential amino acids or protein content, that kind of stuff? To be honest, no. I think that most, I mean, the evidence uh shows that most of supplements don't really do much. There's only a handful of supplements that might have a positive effect on someone's performance, know, like caffeine, creatine. beta-alanine know, them are like something you can typically like trust that it might have a positive effect on performance. And so when it comes to overcoming the sort of potential drawbacks of being in an energy deficit, we've shown and there's some good evidence out there that, know, higher protein intake is able to em allow you to retain some more of your skeletal muscle. Mm. Mm-hmm. we're going back to talking about muscle size and you know we're trying to shift the narrative towards talking about muscle function and muscle quality. So it seems that higher protein intake is good to maintain or to fight the loss of muscle mass if there is any. Now is that going to have a clear effect on the function of your muscles particularly for an endurance athlete? I'm not so sure. Okay. Yeah, I think this is all so interesting. Briefly here, what is coming up next for you research-wise? Anything coming down the pipeline? so we have em a lot of things going on at the minute. So we have some research on exogenous ketones and adaptation to training. We have a study dedicated to only females. So I think it's going to be the first study on exogenous ketone supplementation in recovery, at a range of parameters like performance and skeletal muscle adaptation and metabolomics and so on. quite cool study that we have most of the data set ready now. It's not been sent for publication yet. We have more work on this area looking at training studies across over design, looking at skeletal muscle adaptation in a low carbohydrate, high fat diet versus a high carbohydrate sort of low-fat diet, but both of them in energy deficit. So trying to answer the question that you were asking before, is it the muscle glycogen that is having this effect on the proteomic sort of responses in muscle? we have that one's a little bit delayed, but you know, that's that hopefully will be coming down the line as well. We have more work on exogenous ketones and you know, what are the sort of the metabolic and performance effects of it in sort of the... mixed population of both males and females. It's more a mechanistic study, but it's going to be really, cool uh as well. yeah, we've got quite some work on muscle glycogen and performance. So there's no energy deficit there, but there's more uh muscle glycogen loading and a whole really interesting conversation around muscle glycogen loading and performance. uh And yeah, there's a few studies on the pipeline there. my collaborators on that. yeah, a few other things happening there. So I'm not going to bore you with a list of things that we're working on now, quite a few things. Yeah, the ketone one sounds fascinating. That is an area that I get a lot of questions about from my athletes and from a post-utilization and recovery lens. I'd be very curious. uh Okay. So I'll jump back to your two truths. anda lie. So you had said that you were a black belt in Taekwondo. You competed at a national level in road cycling in Norway and that you fought a bear in the mountains of Colorado. I thought the fighting a bear was a lie. Which one was your lie? So yeah, I've been walking in the mountains of Colorado and I knew there were bears around so I went like, it would be scary to fight a bear here. I actually saw a bear but we didn't fight with it. Yeah. didn't fight a bear. And you did compete at national level in cycling in Norway. That's awesome. did. Yeah. Actually, I was the other day, like a friend of mine messages me and he was like, oh, did you see who's like leading the I think it was the Giro d'Italia and I'm like, oh, who is it? Oh, it's this guy from Uno X team that you ended in the podium with in one of the races. And I was like, all right. Yeah. So I was I was competing against professionals, but my profession was to be a both doctorate researcher. So yeah, it was cool. was cool being part of that. Yeah, that's amazing. And then you have a black belt in Tae Kwon Do. That's so cool. Yeah, I did many, many years in Taekwondo since I was very young. So I got to a black belt quite young. I got many years of training there. Good for you. That's amazing. Okay. Well, I've already took too much of your time here. So uh I want to say thank you so much for joining us. This has been so fascinating. I definitely want to have you back when your, those other papers come out on ketones and all that stuff. I really enjoyed the conversation. Yeah, this has been great. Thank you so much, José. Alright, have a nice day.

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Kyla Channell, MS

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