"Muscle Protein Breakdown in Response to Nutrition and Exercise" with Professor Kevin Tipton

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We Do Science Podcast

EPISODE 150

DEC. 03, 2020

"Muscle Protein Breakdown in Response to Nutrition and Exercise"

with Professor Kevin Tipton PhD

[INTRODUCTION]

[00:00:01] LB: Hi and welcome to episode 150 of the We Do Science Podcast, the Institute of Performance Nutrition’s podcast. I am the host, Dr. Laurent Bannock. And in today's episode I had an awesome conversation earlier today with Professor Kevin Tipton, and I’ve just been reflecting on it just now. And I’m excited for you guys to share this conversation I had with Kev Tipton where we talked about muscle protein breakdown, and in particular the relationship – Rather than the relationship, the importance or relevance of muscle protein breakdown as it relates to the influence of exercise and nutrition and what can we do about this and what is relevant and what is not so relevant from the science as we apply this to practice as it relates to sport and exercise nutrition performance, nutrition advice for active and individuals and elite athletes and so on?

We had all sorts of chats about this and related topics, muscle protein synthesis, that whole concept. How does muscle protein breakdown fit into this? The importance of things like protein balance, energy balance, and principally why the exercise stimulus is so much more important for you to be focused on rather than just factors like how much protein you're taking in. But anyway, I will let you enjoy that conversation in just one minute with Professor Kevin Tipton, who of course I’ve had on this podcast many times before on his own and with other experts, namely Professor Stu Phillips. We've done quite a few all about protein in one form or another. So if you're a regular to this podcast, you'll be familiar with Kev. And if you're new, well, this will be a treat and you'll want to go check out all those other episodes that I’ve done which you can find in our back catalogue on the podcast website. All of that information, the transcript, the other recordings, the other episodes and the paper that we discussed today along with some other relevant resources can all be found on the podcast website. All you've got to do is go to www.theiopn.com. Click on podcast and it'll take you to the podcast landing page so to speak which will give you the links to the actual microsite that we hold all of the podcast and related contents to. 

Whilst you're there, please do check out the other things that we do at the Institute of Performance Nutrition. My team and I are working hard all the time to produce educational and practice related resources for sport and exercise nutritionists, our main two sort of outputs, our products. I shall quickly plug, we have our 100% online diploma in performance nutrition. This is not any normal kind of program. It is specifically a practitioner-focused program. Most of our students have degrees in things like sport and exercise science. We have dietitians and we also have people with degrees in sports nutrition. So why do our diploma? Well, because it is an advanced level program with a practice focus. So you can learn more about our diploma at our website, www.theiopn.com. Just click on diploma. 

And also since I’m talking about developing practitioners enabling effective practice, not just practice, but effective practice. We have recently released our SENPRO platform, which is an online software system, if you like, which is a set of tools specifically designed for sport and exercise nutritionist to help you work with your clients, coach, do nutrition coaching and tools to assist you in that process, but specifically active people, athletes, professional athletes, recreational athletes and team settings as well, but also business tools to enable you to run your practice. And that is a very exciting set of tools. Go check that out. Just, again, go back to www.TheIOPN.com and click on the SENPRO button. Right, that's it. That's enough of me plugging what we do at the IOPN. Now you can enjoy this conversation I had earlier today with Professor Kevin Tipton, and I hope you get as much out of it as I did. 

[INTERVIEW]

[00:04:36] LB: Hi and welcome back to the Institute of Performance Nutrition's We Do Science Podcast, the IOPN podcast. And I am mega excited to welcome back Professor Kevin Tipton. Hi, Kev. How you doing?

[00:04:50] KT: I’m fine. Thanks, Laurent. It's grand to be here. I’m really looking forward to this. It's always fun. 

[00:04:54] LB: Well, look, it's strange times. So I’ve made jokes about this before, but it's kind of true. This is actually good excuse for you and I just to have a chat. We're going to talk about some interesting stuff that the rest of my family do not want to have a conversation with me about. So, Kev, I’m pulling you in for this conversation. 

So, look, you've been a guest on this podcast quite a few times. Going to be up there with one of the most frequent re-visitors, visitors to this type of conversation that we're going to have, and there's a reason for that because the area that you're well known for, which has been the topic of previous podcasts, some of which you've done a double act with your good friend, Professor Steve Phillips, is sort of protein and things relating to protein and why we're interested into protein in sport science and sport and exercise nutrition in particular things like muscle protein synthesis. Factors that relate to getting bigger, stronger, faster, all these sorts of things that are pretty critical to anyone remotely close to being an athlete or interested in physical adaptations to training that result in whether it's functional or aesthetic responses. It's always going to involve protein in one form or another. 

But I didn't want to specifically go into that area. I wanted to delve a bit deeper into sort of a sub layer of that topic that we will have referred to before in previous conversations, but I think I felt was worth focusing this whole podcast on when I re-read your review article from a couple years ago on assessing the role of muscle protein breakdown in response to nutrition and exercise in humans. And we're going to have a good chat about that today. But before we do, it is possible that we've got some new listeners who haven't yet listened to previous episodes. So give us an overview as to who you are and what you're up to currently.

[00:06:52] KT: Yeah. Well, thanks for having me on again. As you say, I’ve been on here a number of times and I feel like I need to get some frequent flyer miles or something. 

[00:06:59] LB: Yeah, we'll arrange it. 

[00:07:01] KT: So, as you say, Professor Tipton, Kevin Tipton, and I have been working in protein nutrition and metabolism for close to 35 years now. 

[00:07:12] LB: Long time.

[00:07:13] KT: Yeah, it hurts sometimes to realize that. But most recently I was at Durham University, but I recently resigned from there. And so I’m going to be heading out on my own to see if I can make a go of it. And before that I was at the University of Stirling in Scotland, and before that Birmingham, and before that, as you could tell for those who hadn't heard me before, I’m originally American. And so I did a lot of my training with Professor Bob Wolfe in Galveston, Texas, and that was really what sort of set me up for my career. I was very fortunate to work with him. He's one of not only the sharpest minds in the business, but extremely kind and helpful. And I was just lucky. Better to be lucky than good is what I’ve always heard. And I think my career defines that.

[00:08:01] LB: Yeah. Kevin, Wolfe, actually I heard him speak about – It was all about branch chain amino acids actually a couple of years ago in the – I say a couple of years ago. Even for me things are flying by. But yeah, it was about five years ago. Yeah, I was in awe of him and I’m jealous of that experience that you've had. And that of course is relevant to this conversation that we're going to have all about muscle protein breakdown. 

So listen, let's get you to jump straight in and take us through a little bit of an introduction to this topic. You've mentioned a number of decades of experience in the evolution of this sort of body of knowledge. So you are very much part of the story, the history, and will be with the future of this too, because it's an ongoing area of course and you're still involved in that. But why is this such an interesting area and why does it continue to be such an interesting area? 

[00:08:57] KT: You mean muscle protein breakdown in particular or – 

[00:09:00] LB: Yeah, just the idea of muscle protein breakdown, muscle protein synthesis. Surely, it's like this basic idea of when we talk about energy balances, calories in, calories out. Boom! That's it. Why is this such a more complex area potentially even though that isn't even complex in itself?

[00:09:20] KT: I think, partially, it's because of the techniques that are necessary to actually measure it. So if we go back to the basics, the metabolic basis for changes in muscle and muscle mass is the balance between the rate of muscle protein synthesis and the rate of muscle protein breakdown. That's the very basic simple way to talk about it. But it's much more complex than that, because you have hundreds of different types of proteins in the body. And I’m sure I’ve said it in lectures. I can't remember how many in the human muscle, but there are hundreds. And so you have to think about what each one of those proteins does and the function and then how those proteins react and the metabolism of those proteins reacts to stimuli, nutrition, exercise, stimuli. So that's the bottom line. Now there are techniques coming on board which are allowing us to look at individual proteins. 

But back when I first started in Bob's lab, we did – I was involved luckily, in the very first paper in this field that I was involved with was the first one to actually measure muscle protein breakdown, directly measure muscle protein breakdown following exercise. We used stable isotopic tracers, metabolic tracers to do that. As I say, there are lots of different proteins, but at that time we just took muscle biopsies. And so without going into the details, boring details of the technology, we were measuring the metabolism of all the proteins. So mixed muscle protein synthesis and mixed muscle protein breakdown. So we could get the balance between those and that gave us an idea of how the muscle was responding to exercise and nutrition. 

So that paper, the first one was published in 95. Gianni Biolo was the lead author on that. And the funny part of that story is I was brought in because I was still finishing up my Ph.D. in exercise physiology, exercise nutrition, and there was no exercise specialist in Bob's lab at that time. So a good friend of mine, Arny Ferrando, who I think you've met, was working with Bob and he knew Bob needed somebody to come in. He said, “Hey, come and I'll get you to talk to him and everything.” So we're sitting there and talking and having a chat and Arny goes, “Yeah, and he's got – All his marks are A's and he's a straight A student and he works really hard and all this stuff,” and Bob's like, “Yeah. Yeah. Okay. Okay. Well, well, well.” Everybody that wants to work for Bob is like that, right? So then Arny says, “Oh, yeah.” And Bob was a really good runner he's run two sub 220 marathon and he ran – Arny was, “Yeah, he's a runner too. He runs a sub 16:30 for a 5k.” And then Bob's all of a sudden going, “Ooh!” 

And so two days later he calls me and offers me the job. And I always tell people that the only reason I got that job, and here's the lucky better than good part, is because he needed a running partner. And I said that to Bob one time a few years later. I said Bob, “I tell everybody I know that you only hired me so that you could have a running partner.” And he said, “Well, let's just say that it didn't hurt.”

So anyway, we started those studies and Bob was the leader in the stabie isotopic tracer methodology, and that's how – So I had to learn all that, which is a fantastic opportunity. But we were doing mixed muscle proteins. And as I said, you get more information. For example, now, it's pretty routine that people separate the proteins into sub-fractions of the myofibrillar proteins, the mitochondrial proteins, sarcoplasmic proteins, collagen, etc., and that gives us some more information. But you can't really do that with muscle protein breakdown. It's very difficult. You can do it with muscle protein synthesis. So we can get more information from muscle protein synthesis responses than breakdown even now. 

[00:13:11] LB: So because we're starting to get into some terminology, and in sport and exercise and sports nutrition, particularly in the types of conversation I have on this podcast, which have gone very deep into molecular biology and so on with people, but there is a propensity I think for some people to get confused about what some of these terms are. And in fact I’ve even read papers where I think some people have gotten confused with the terminology they're using. And we'll come back to that. But this idea of plasticity of muscle and the capability to remodel muscle tissue, I find fascinating. And of course that's what we're trying to influence, whether it's through training or through various things that influence that like nutrition and other factors. But maybe you could just take us through just a quick overview as to what this concept of muscle remodeling is and why that's relevant to the listeners be it they say sports nutrition, sports dietitians and/or sports strength conditioning coaches, that sort of thing.

[00:14:15] KT: Sure. So the way that most people talk about it, and I usually do as well, is we talk about the change in muscle mass is due to these changes in protein synthesis and breakdown. And we can get into in more detail later, and that is true to some extent. But the changes in synthesis and breakdown don't just influence muscle mass. They influence the adaptation to the stimuli. Now some of that is, as you say, we can call it remodeling where let's – For example, in those early studies what we found was with resistance exercise you get an increase in protein synthesis following the exercise and an increase in protein breakdown. So they both go up. It's just that synthesis goes up more. And so the interpretation of that, the simple interpretation is that means you're putting on muscle protein. That may not be true necessarily, because without a protein source coming in, the balance between the two doesn't go into a positive range where you're actually adding proteins. 

So what's happening is when you do the exercise, the resistance exercise in particular, but also to some extent endurance exercise, you get this increase in synthesis. You get that response to those molecular pathways, the mTOR pathways. They turn on protein synthesis. If you don't eat anything, then you need to increase that breakdown rate to supply the amino acids for that increased synthesis. And so you're not going to get a net gain. But again, I’m talking the overall mixed response, all the mixed proteins, different proteins are responding in different ways to that particular stimulation, whatever that particular stimuli was. 

We know in the long term of course that you do gain muscle if you're lifting weights. And so yes, you will end up doing that, but a lot of what you're doing especially early on is repair, because you're getting that muscle damage responses. Everybody knows, if you haven't lifted weights for a while or if you're never lifting weights, you're going to get muscle damage. You're going to get sore. And so what happens is most of that remodeling in that early phases of resistance exercise is not adding protein, is not adding mass. It's actually just the muscle is adapting and becoming better at this and you're remodeling that muscle. Probably, we don't know this for sure. But intuitively you'd guess that if all you're doing is resistance exercise in that muscle and in any particular muscle, then you're probably going to be adapting some of those particular muscles and their mass is going down, so maybe some mitochondrial proteins or something. And those amino acids are then used to make the myofibular proteins which are involved in the size and strength. So it's repair, it's remodeling, it's adaptation. And the main adaptation we talk about with resistance exercise of course is increased mass and strength. So, again, we don't have the tools to measure all the various single proteins and their responses at this point. Not with this measuring the rates of synthesis and breakdown. You can measure protein quantities and other things, but those aren't necessarily telling you the whole story. Does that make sense?

[00:17:23] LB: Absolutely. I mean it makes sense. It's complicated. And we're going to delve into that, because there's a fair amount of contextualization to this I think that sometimes is required in order to take you down a few more rabbit holes that I’m going to look forward to taking you down just so we can help people understand the relevance of this in different scenarios. But I guess just to throw a slight over simplification into this, if we think of exercise as – Or this situation, is it a chicken or the egg type scenario where the crazy chicken is the exercise and the egg conveniently happens to be the protein in this concept. What’s more important as it relates to the remodeling of tissue or the adaptation of tissue to becoming faster or stronger or repair? That's where people tend to get obsessed, don't they? They maybe over-estimate the importance of their need for a protein shake after a workout relative to their half-hearted workout beforehand. I mean is that a fair comment?

[00:18:27] KT: I think that's absolutely spot on. And I know that if you talk to the other guys that are smarter than me, Stu, Luc van Loon, those guys. I’m sure they've probably said the same thing a hundred times in talks and podcasts, whatever. Yeah, absolutely, the stimulus from the exercise is what's going to determine which proteins are remodeled in which way. And the protein ingestion is there to support that, right? And I think you're absolutely right that too many people get too involved in the intricacies of all these different – Whether you need a whey protein, hydrolysate, and this company is better than that company, and you need 3.651 grams of leucine. Those details are less important than, as you say, putting the proper session in in the gym. And by the way, I’m so glad you said context, because you got to mention in my talk that's going to be recorded. 

[00:19:20] LB: Yes! 

[00:19:22] KT: I think, because I said you got to put it in context. And I know if Laurent listens to this, he's going to be proud of me. 

[00:19:27] LB: Thank you. Yeah, I’m proud of my association with that word. Although my latest version of that is context has evolved to relevant. Is it relevant depending on what you're trying to do? Well, I’m actually going to come back to that. 

All right. So thank you for that. Again, we've used several terms here, and we're going to be focusing on muscle protein breakdown primarily, but we've got muscle protein breakdown and muscle protein synthesis. And again, maybe they're on either side of that chicken and the egg spectrum potentially. But they don't occur independently necessarily. There's a relationship there, isn't there? So maybe you could give us a better idea about what do you mean by this term muscle protein breakdown and what do we mean by muscle protein synthesis and how do they connect. I know you've sort of mentioned this, but – 

[00:20:14] KT: Sure. Okay. Muscle protein synthesis is the rate at which the amino acids are being put into the peptide chain to make a protein. And then you got to count in, when we measure it, what we're measuring is actually also post-translational modification of the protein, because it's the protein, not just the peptide chain. And as you know, and probably most of your listeners know, that a protein isn't complete until it's been activated in various ways or various ways that can happen. Protein breakdown has been taking those amino acids off that peptide chain. And so these stable isotopic tracers allow us to put a rate on that. So different methods use different units, but essentially we can measure it on a per minute basis or a per hour basis or whatever. How fast those muscles are being built up or broken down. 

Now if you're a healthy adult that's not really doing any particular physical activity, then over time those rates are going to balance out and you're not really going to have much change, because you're not doing anything to cause something to switch. But if you do do something, let's say, again, let's use resistance exercise as an example. Well, as I say, both synthesis and breakdown go up in response for the reasons I said. 

Now where protein nutrition comes in is if you eat protein within close proximity of that exercise bout and we can – It's a whole different topic to talk about what close proximity means. But let's just use that term for now. Then those exogenous amino acids from the protein that you've eaten are also used for this protein synthesis. And Luc’s been using that model where he has the actual labeled amino acids in the protein that is eaten and to clearly show that this happens. 

And so then breakdown doesn't have to go up as much to supply the amino acids, but it still goes up even if it's only a little bit. And that probably depends on how much protein you eat. But in any physiological situation, that's not a pathological situation. Whenever you measure synthesis and breakdown together, they go in the same direction. So it isn't a mistake that a lot of people make to talk about, “Yes, we want to increase protein synthesis and decrease protein breakdown.” That rarely ever happens and it certainly doesn't happen in response to exercise. It happens perhaps in some situations like the opposite is true maybe in burns, severe burns, and that's what Bob's lab – Our lab was actually physically located in the Shriners Burns Hospital. So that was one of the original purposes of that lab. And yeah, it goes way up. Protein breakdown goes way up and synthesis actually goes up a little bit too. But there are very few situations where they go in the opposite direction that qualitatively at least they go in the same direction. It's just quantitatively that changes the metabolism or it changes the result. Yeah, is that where we were going?

[00:23:11] LB: Yeah. Yeah. Well, because what I’m trying to do is in many ways – As I said, there's quite a lot of rocket science behind this and it can be very sometimes it's difficult to sort of visualize or envision what this actually means as it relates to affecting performance or recovery from injury or even body composition. And there's this sort of exquisite symphony of things going on that is just it's literally mind-boggling to imagine all of this stuff happening at the same time. And the more you delve into it, the more the more crazy it gets. Yeah, we could throw in a conductor and various other things where what's happening in that regard. But I guess one thing, if you were able to like look under the hood, look under the bonnet, depending on how you use that phrase, is this something that we see simplistically happening whereby, for example, there's an increase in muscle protein breakdown just because you're more active, you're lifting weights. And the sort of the increase in muscle protein synthesis is just simply a case of a response to that. Or what about this concept of protein balance? How does that play a role? Take us for a bit more.

[00:24:26] KT: That is a good question. And the assumption that's made most of the time is that exercise – Again, I’m limiting this to – That you get stimulation from the exercise and that increases the synthesis of particular proteins. And then a breakdown of either those or other proteins has to respond as well. And that again, like I say, it depends on where you are in your training cycle. And that's going to change the muscle in adapting to that stress, that stimulation. As you know, training is specific and the adaptations are specific to the type of training that you do. That’s because of the changes in those muscle proteins. 

So, again, we don't know for sure, but what we think happens is that, and I’ll use resistance exercise, again, that we get a change in after the first few weeks you start seeing increased mass. You can start measuring increase in mass, and that's from increase in these myofibrilllar proteins such as myosin, actin titin, these kind of things. Now, presumably, some of the amino acids that when we see that increase in protein breakdown along with synthesis after an exercise bout, just one bout, that's what we measure. Well then we assume that a lot of those proteins that are being broken down are not the same ones that are being built up, that you're using the amino acids from those other ones, because there's redundancy. And you can actually see sort of different – If you measure the amount of certain proteins following a period of training, you can get a little bit of an insight into that. 

But it is possible, and maybe particularly early on in the training that you're seeing that increase in breakdown because you're damaging these proteins or your muscle is trying to respond to that stimulation. And so maybe early on some of those proteins are myofibrillar proteins or matrix proteins, collagen, etc. And of course you can see it with microscopy. You can see the Z band streaming, and we know that that correlates early on with the rate of protein synthesis. That was from a study that Stu was involved in that Philippe Damas did a few years ago. 

Yeah, there are a lot of different – As you say, it's complex and it depends on what training you're doing, where you are in the cycle. Also what you eat makes a difference of course, but still the stimulation and the response is going to be dependent on the training and the exercise that you're doing, and that's where you're going to get that adaptation to that. If you're running a lot, you're going to get more mitochondria. So you're increasing mitochondrial proteins. And maybe not so much myofibrillar, or the myofibrillar is changing, but not really getting more from the standpoint of mass, right? 

[00:27:09] LB: Because what I find interesting about this, particularly when you read a lot around this, as I do, and talk to a lot of people about this, what happens is as we get into the trendy or the sexy side of this topic, which is what makes things grow? What makes things get bigger and faster? And of course you look at the body of knowledge and there's quite a lot of information out there that relates to muscle protein synthesis. And maybe for reasons that seem somewhat obvious, we're not as interested in how can we make muscles break down at least from a nutritional perspective. We're only interested in making them bigger and so on. But why is that relevant to, I guess, this whole movement of trying to get athletes to become better at what they do and or recover faster from what they do? And is that true? I mean do we know so much more about muscle protein synthesis and so much less about muscle protein breakdown? And if that's the case, why is that anyway?

[00:28:11] KT: That is definitely the case, and there are a couple of reasons for that. The first being that when we can measure both of them. And, again, with what I would call reliable and valid methods, we really can't differentiate what type of proteins are being broken down. And I'd probably get pushback from some people on that, but if you read the – For your audience, if they read this paper that you're referring to that you started with, I walked through that argument. 

So first of all it's very difficult to measure protein breakdown. There are two methods that we've used in the past, again, mostly mixed protein or all mixed protein and using stable isotopic tracers. One of the methods you have to do arterial and venous catheterization so you can get the balance across the limb. And usually it's either the femoral artery and vein for the leg or the brachial to get the lower arm. And those have some assumptions, and I can bore you with the details there. But we can also do what we call precursor-product methods. And so we can measure fractional synthetic rate. And I’m sure if people have read papers from Stu and Luc and me, see that lots. And alongside that we can measure fractional breakdown rate. And you can get a balance that way between the two. But, again, it's all mixed muscle proteins. It's the sum total of all the proteins that you take out of that biopsy. 

Now with synthesis we can actually – As I said before, we can get a little bit more resolution by measuring those fractions. And you do a chemical separation of the proteins through these various steps to get the different fractions. And when this first started out a few – Probably 15, 20 years ago, people started doing this and the technology wasn't good enough to do it regularly, and then people started doing it successfully and getting better and better at it. There have been a handful of papers now doing individual proteins, that is we can actually use proteomics to measure the synthesis rate of individual proteins. So we're now down to that level. That's possible, which is going to add lots of information. But you can't do it with breakdown at this point. So the scale of the resolution is one part of it and the technology that's available.  

So the other part of it is, is that when we do measure the mixed proteins, muscle protein synthesis and breakdown, that the main response – Sort of I’ll just throw out some ballpark numbers 80%, 90% of the response that results in a change in net balance of the two is the change in protein synthesis when we're talking about a response to exercise and nutrition in healthy people. So basically between those two factors, what a lot of us have done over the past sort of 15 years or so is say, “Okay, we're not even going to mess with measuring protein breakdown, because at least qualitatively what we're seeing with synthesis is going to explain the changes in the adaptive response to any particular combination of exercise and nutrition.” Does that get there?

[00:31:13] LB: Absolutely. Yeah. Look, the reason why I’m taking the risk of delving into such complex area, particularly when you know so much and I’m just trying to keep up with you, but the point is, is as a practitioner, which is my perspective, I have a lot of things I can do. And I always refer to these as tools in the toolbox. So whether we're talking about ways of influencing muscle mass through various types of training and how we might want to support that or influence that through various nutritional strategies, which we've explored throughout many episodes on this podcast to include an area I'd love to get into shortly where it's not even a case of trying to ensure things like protein adequacy or the relevance of protein quality, which you've already inferred is relevant, but not as relevant as the training stimulus. But also given people trained throughout the year at different phases of their training cycle, sometimes they're in a strategic energy deficit. How do these other environmental factors do include other nutritional influences on this process of muscle protein and muscle breakdown? And I guess part of what's interesting about this is how closely are they associated to those day-to-day influences? Or is this something that's highly trainable or highly dependent on how we we’re originally designed so to speak? Does that make any sense?

[00:32:40] KT: Yeah. I mean I think ultimately, as trainable as these are, is probably going to be at the end of the day genetically determined to some extent, at least. Obviously everybody knows some guys that walk into the gym and they put on 15 pounds of muscle and others that spend three hours a day in the gym can barely gain any muscle mass. And saying there are people who run faster than others too, and no matter what – As I said earlier I ran around in the low 16s for a 5k, but I could never get any faster than that. And I was training 60 miles a week and I did everything possible, but that's as good as I got. Or when I was playing rugby, I lifted all the time and I couldn't get up much above 150 pounds. So I don't know what that is in stones, sorry. 

[00:33:31] LB: Oh, don't make me work it out. I’ve managed to – 

[00:33:34] KT: It's probably about 11 stone, right? Because 14 pounds per stone? Anyway. So you can't do it. So at the end of the day there's some limits, right? But everybody can change depending on the training they are doing. So that's clear. There's going to be a response to that training. It's just a matter of to what degree. The balance between those two, the synthesis and breakdown, is always there. I mean, again, the terminology we like to use is those two rates are concurrent and constant. And whenever people try to tell me they want to stop protein breakdown after exercise or something, I say, “Well, there is one way to do that. Die.” Because otherwise the only time you don't have any protein breakdown or any proteins aren't being broken down is because you're dead. And so it's constantly going on. So it's a fallacy to think about trying to stop protein breakdown. What you're trying to do is change the balance between the two to adapt better to whatever is the training stimulus that you're interested in. 

[00:34:38] LB: So the reason why I’m interested in this is not because it is genuinely interesting to delve into the rocket science. For me, because my obsession is, “Well, what actually is –” Not just what is quality evidence to help us with our decision making, but how much of this is actually relevant? And as I sort of joked before, there's a lot of work that's gone in these areas that maybe have made some assumptions about the reliability of their testing methods. They've made conclusions as a result of their studies, which down the line ends up influencing what people like me will recommend to my athletes. And what I feel is an evidence-based perspective on the various recommendations I might make for protein in terms of quality and quantity and so on is based on where that information came from. And I guess my question to you is, yes, one could argue that, say, sport and exercise nutritionists or practitioners don't necessarily need to understand in full detail and fully comprehend the rocket science. But maybe we do need to understand that this is far from a finish story. There're still many questions. And maybe – Or do you think maybe we've taken maybe this too far in terms of what people feel they think they actually know. How much clarity is there, I guess?

[00:36:08] KT: I think you're probably right, and people over interpret this information, these studies, quite often. So just to start with protein breakdown, I would ignore any person who's writing or saying that we need to modify our nutrition to alter protein breakdown. 

[00:36:29] KT: I think that, first of all, we don't have enough information to say that. Second of all, I would argue, and I did make that point in this paper, but also a recent paper from Stu with Tanner Stokes was the first author. He did a really nice job of explaining why protein breakdown, why probably it's a mistake to nutritionally modify or try to nutritionally modify protein breakdown. A, it's not as big a player. But, B, there're arguments that – I mean if you go to the extreme in knockout rodent models, if you knock out some of the genes responsible for the molecular pathways that lead to protein breakdown, the rats or mice don't grow. Their muscles don't get as big and the muscles are – Sort of, if you want to call it, the quality of the muscles isn't as good. So you're actually hurting things. 

We also know that there's study, I want to say L-E-G-E-R is the first author on this study. And then Micah Drummond did one in older people, muscle sarcopenia, and that was associated with less breakdown or markers of protein breakdown. So protein breakdown is an important part of this whole response to the training. But with synthesis, the way I like to sum it up is if you try to say that you do intervention A. Let's say it's protein with – I mean exercise, resistance exercise with protein A compared to resistance exercise with protein B and you get a 50% greater response of muscle protein synthesis to A than B. That does not by any means mean that you're going to get a 50% greater muscle mass, right? It means that qualitatively it looks like something's going on there. 

Now what I would argue, and I think others mostly agree, is that this is sort of – It's a good indicator that you can do in a relatively short period of time and then you go and do training in longer term studies where you can actually look at changes in the endpoint that you are interested in, in muscle mass or whatever or how fast you run or something. And you start by looking at this acute response. And of course now we've got techniques to measure MPS over a day or two or three days or a couple of weeks even. So I think it's a mistake to try to put a quantitative value if you're talking about protein synthesis in response to any particular intervention, but that it does offer information that's valuable. And then you have to also think about what population you're studying. 

Like I say in the training cycle, because if you get a 50% bigger increase in A versus B in untrained people, well it's not clear what that's reflecting, because you're talking more about remodeling and changing the protein rather than later on when you're adapting better after the damage issue. So like you know we keep going back to that it's complex in different situations. Those are the types of questions that need to be asked when people are delving into these areas. And I think it's up to us as scientists to do a good job or trying to make sure that those sorts of things are out there whether we're giving them in presentations like this on a podcast or live in an audience, if that ever happens again, or in papers. We need to do a better job of translating that and making sure that people understand that when I say that we need to eat this much protein based on the changes in protein synthesis or the response of protein synthesis, that there are caveats to that in context, or what's the relevance of it, whichever new word you want to go to? 

[00:40:01] LB: I use them both. I indulge in both words. But look, since we're talking about context and relevance, which is the perfect segue there, my angle here is primarily from that of a performance nutrition, sport and exercise nutritionist. What can I do about this? What role do I play in in helping my athletes, my clients or my students do that for their athletes, their clients and so on? And let's just start looking at diet or nutrition. And when you get into nutrition and you study nutrition, one area that we're always getting into is this whole thing about energy balance, whether it's just about weight management or body composition. One way or the other, energy balance is going to come into that conversation. And of course we talk about muscle, you guys also start talking about things like having an appropriate balance of protein, various terminology. You have different terminologies for that, or whether we're talking globally from the diet or whether it's within the muscle or whatever. But because there's a lot of reductionism that happens in science, a lot of people tend to focus heavily on one area. So when people talk about weight loss, which itself is a reductionist statement, then they talk about, “Well, you've got to get into an energy deficit and eat less calories. But again, that's an oversimplification, because that might be at the expense of your muscle mass, of course, because you've cut so much energy, you're also not eating enough protein. So when we talk about the role that nutritional diet has in this concept of muscle protein breakdown, what is the role of things like energy balance and protein balance to that bigger picture if you like? 

[00:41:55] KT: Okay. Yeah. I mean energy balance is a good example to try to illustrate the point that, as you say, someone who just decides to lose weight and cuts down their calories, if you're not doing something focused, you're going to lose muscle along with the fat. Now most the time that's not what people want from an athletic perspective, from a health perspective. You probably don't want that. There are some situations I’m sure that people won't care. I mean if you're a lightweight rower and you're a kilo too heavy, well, it doesn't matter whether it's muscle or fat that you lost. If you don't lose any muscle and you're still a kilo too heavy, then you need to get down. Or I know a mountain biker once, he was a professional mountain biker and he said, “Yeah, if I could get away with it, all I would have is enough muscle in my arms so that I could squeeze the brakes and nothing else, because I don't want any extra weight when I’m climbing.” So those are the exceptions. 

As you say you're going to lose muscle if you're not trying. Now you can lift weights, and that's certainly what you need to do if you want to keep the muscle. And there have been several studies showing this. However, a study that we published in 2010, we showed very clearly that in these guys, they kept lifting weights for two weeks. This is Sam Mettler’s study. I’m sure you're familiar with it. And they lifted hard. They were training – And Sam, he was a hard taskmaster man. He made sure that they didn't slack off. And then one group ate their normal diet composition, but 60% of their calorie intake, but normal composition, and they lost muscle. Whereas the other group that ate a high protein diet, they switched to – They ate higher protein when they dropped the calories. They maintained their muscle mass. And there have been several studies that have shown this as well since then. And Stu's done a few of those in different populations. These were trained guys in Sam’s study. 

So first you’ve got to lift weights, then you got to eat enough protein to support that. We just had a paper accepted showing something in women that has a roughly similar pattern. So some of the results were slightly different and partially that's based on the study design that… we can get into that some other time. But anyway, we know that this works if they eat protein. Now, what is that doing to the protein synthesis and protein breakdown? Well, protein synthesis goes down in an energy deficit if you don't do anything in particular to fix that, right? Now there's not good evidence that I would be willing to support. But you would guess that protein breakdown goes down along with it, just not as much. And that's why you lose muscle. 

Now we do know if we go to, say, an immobility model or a bed rest model, well, protein synthesis goes down and so does protein breakdown. A lot of people think the protein breakdown goes up when you immobilize a muscle, but it doesn't. So if you say that that situation is analogous to energy deficit. And, again, anytime we've ever measured the two, they go in the same direction. And I’m sitting here laughing at myself because I’m using my hands for things. And of course your listeners can't see that. 

[00:45:02] LB: He's juggling, folks. 

[00:45:04] KT: Yeah. Now you'd hear a lot of balls dropping if I was trying to juggle. 

[00:45:09] LB: Let's not go down this path. 

[00:45:12] KT: Yeah. Again, directionally the rates go in the same direction. It's just a matter of quantitatively which one goes down or up more. So in an energy balance situation or energy deficit situation, then you want to – If you don't want to lose muscle, then you want to do some exercise, some resistance exercise, and you want to eat enough protein to support that. There have even been some studies where people are gaining muscle in that situation, which if you'd asked me this 15 years ago, I'd have said it's impossible. Whatever I tell students about why it's okay to change your mind and look at the evidence and be wrong and accept it, that's the one I use, because that Sam Mettler’s study came off the back of me having an argument with Nigel Mitchell who at the time he was – I think he was with cycling, British Cycling. 

[00:46:03] LB: No. Not team’s guy. You’re right, British Cycling. Yeah. 

[00:46:07] KT: Yeah. And Nigel is a great guy, but he was saying, “Yeah, I’m doing all this with these wrestlers and boxers or whatever and they're losing weight but gaining muscle.” And I said, “Nigel. No. Something's wrong. They're cheating, or whatever.” And we argued about it and he said, “Well, let's do the study.” I said, “Okay, let's do it.” So he went and got some money from UK Sport to do it, and that's where that study came from. And then there are the results, and I was wrong. And, I said “Okay.” And so it's pretty clear that that's the case. Of course we didn't measure synthesis or breakdown in that particular study. Now Stu has done that subsequently. And synthesis this doesn't go down as much when you exercise and have protein, and that's why you don't lose muscle. 

There is one study that they did protein breakdown, and the main response again was synthesis, and that there wasn't this situation where a breakdown is going up and synthesis is going down. Physiologically, it's very, very rarely does that happen, that's been measured anyway. I mean in various situations that athletes find themselves in and various goals that they set, then the response of protein synthesis is the main player in changes in the response of the muscle to either training and or energy deficit, etc. And so those are the types of things that people need to think about. 

Now you started off by saying what do practitioners, how do we deal with this? Well, the first thing to try to do is I think is to be skeptical. As you know, I’ve said this many times. Be skeptical but open-minded. Don't accept every new shiny toy that gets published, new shiny paper that gets published. Wait until there are at least a few papers that come up with roughly the same type of result in any particular question that's being asked. You need support. And also I would argue that a good way for practitioners to try to handle this is to read papers, review papers especially, written by Stu and his gang and Luke and his gang and let us translate some of that heavy-duty rocket scientist as you like to put it. But don't believe everything we say. Read two or three different labs worth of papers and see how they talk about things. And that would be what I would advise a practitioner to do. And what I see the mistake is any new trend that comes along, people jump all over it. And it may or may not hold up over time. Some trends age better than others. 

[00:48:44] LB: Yeah. Yeah, you remind me actually. I did a podcast long time ago. So I did two different podcasts on similar topics. One was with Keith Baar and the other one was with Lee Hamilton who actually co-authored this paper we're talking about with. I cast my mind back, but it's in that realms of mTOR. And they actually both had slightly different perspectives, which I found very interesting, because of course Lee I think was one of Keith’s Ph.D. students. But the point is is they were both right. They're not wrong. And that's why I like having these conversations with people like yourself, because it's not just, “Oh, let's geek out on the science.” It's because if there's one thing a listener will take from this conversation is it's way more complicated than we originally thought. But also we're nowhere near. Well, we're not yet at that point of being able to be able to write down a definitive perspective on this, because you're still learning.

[00:49:40] KT: Yeah. And I think it's also important for people to look at the source. And look at not necessarily the credentials of that source, but how much experience that source has in a particular field. And so if you have someone with a master's degree and a CSCS and they're writing about the response of muscle protein synthesis, I'd be skeptical of that. I would go and say, “Well, what does Stu Phillips say? Or what does Keith Baar say about this?” or that kind of thing. 

[00:50:15] LB: Unless of course they're referencing all of their work and saying, “This is –”

[00:50:17] KT: Right. But even then I’d still be cautious because they may – People always used to say how many citations they've got? And I said, “Yeah, well that's because you've got one paper that was completely wrong and everybody when they're talking about this, they have to point out that Fred Schwartz had said all this and it's just not true,” right? And so if somebody is citing those people, they're interpreting things. Now if they're citing a review or as an opinion that Keith Baar has based on his experience and data, that's different just from someone who has a very peripheral knowledge of that field and techniques and stuff interpreting the results. 

So I think that's where some research, if you will, into the people who are writing these things if they're writing blogs and papers online. Again, when I do a presentation based on this paper, I put up a headline of nutrition is critical for altering protein breakdown in athletes. And it was probably a 2,000-word blog online that someone wrote. And you look and see who this person is and – 

[00:51:32] LB: Yeah. That's why I don't write the articles. I get you to do all the hard work in these podcasts.

[00:51:38] KT: That's a smart way to do it. That's what – 

[00:51:40] LB: It is. Yeah. 

[00:51:43] KT: You played rugby. I was a scrum half. Coach never put me in the front row. So you have different people with different roles on the team. And so hopefully, between us, we can improve, continually improve the delivery of nutrition for athletes and other people. And I’m not out there working with athletes. I don't even know if I – I used to do it when I was younger, but I don't know if I was any good at it. What I was good at was doing these studies and writing the papers that people can read. 

[00:52:19] LB: Well, Kev, since we're on this topic, because you know we're having this conversation at an interesting time. It's a pandemic you. Full well yourself that that's really hit the research community. There're a lot of issues in that regard. Do you worry at this point that we've got this body of knowledge, there are still pressures on academics to go publish papers and do whatnot. There's going to be even more of these like review papers and all this stuff, but it's not based on novel research. It's just people recycling information much of which is being misinterpreted or based on the wrong testing assays. What do think about that? Would you lose sleep on that as far as the quality of this information potentially getting drowned out?

[00:53:05] KT: I think, yes, I’ve seen examples of that, for sure. For example, I recently reviewed a systematic review. Now systematic reviews have a certain methodology and they're supposedly higher quality than, say, a narrative review like the one we've been talking about on the role protein breakdown. That's a narrative review that the three of us were saying our opinion of what this field is like, whereas a systematic review is supposed to take a bunch of studies and quantify various aspects of those to come up with an answer.

Well, I did this. I reviewed a paper. It was a systematic review based on like seven papers in the end, once they went through the criteria. And those papers had all different study designs and different populations and then they tried to come up with this answer and it was just hocus-pocus basically. So I think you know there need to be enough papers, studies published, in a particular area to have a good systematic review and they need to not have all these various variables that are different. And you're seeing a lot more of that, as you say, because while we're all sitting around and not doing research, we can go and pull out the papers and promise these systematic reviews. So I think there's a danger of that for sure. I’m not saying it would happen all the time by any means, but yeah – 

[00:54:23] LB: Well, no. I’m right with you. I mean that’s basically the entire focus of my research for my doctorate was all about evidence-based practice. And like I said at the beginning, and what even constitutes is evidence that's relevant to practice. And the thing that drives me really nuts is when I – And I’m sorry for folks who do this that are listening, but I constantly see people pushing out that hierarchy of evidence, pyramid that we see and say, “Yeah, that's relevant maybe to science, but not necessarily to practice,” because that may or may not be – Well, firstly, just because it's published doesn't mean it's good. But more importantly, just because even if it is good science, it doesn't mean it's relevant to practice. At least depending on your ability to translate the information determine its relevance, which in itself requires you, the practitioner, to have a fair bit of skill in filtering that information. So it gets complicated.

[00:55:19] KT: It was a couple weeks ago I think on Twitter, I think it was Kirsty Sale who put it out there an opinion, which do you think is more valuable systematic review or narrative reviews. And personally I have very little faith in systematic reviews because there are so few of them that have enough literature behind them to actually come up with the solid conclusions that they claim to make. That at least with the narrative review you know it's the opinion of that person and you can take that for what it's worth. 

So when people read this paper on protein breakdown that I wrote, it's our opinion, Lee, and Ian, and me. It's our opinion on these things. And a reader should be able to look in there and see how we should be able to try to back up our opinion. But I’ve seen plenty narrative reviews and I would like to think that I don't do this. I try not to. But I’ve seen plenty of narrative reviews that ignore information that doesn't agree with their opinion. What you want to look for is someone writing a narrative view where they say, “Well, here's what we think and here's why, and these studies seem to disagree with it, but here's why we don't think that's applicable.” So you need – A good narrative review is going to have both sides presented and then try to convince you why this argument works and that one doesn't. 

[00:56:36] LB: Absolutely. Yeah. Look, this is directly relevant to not just this conversation, but I think everybody there who's reading a paper or listening to a podcast, they do need to ask themselves, “Is this information – What is the quality of this information and is it relevant?” And I think we've armed them through our conversation not just for muscle protein breakdown, but generally speaking is – It's like you've always said, that what you taught me was to be skeptical but also open-minded. And that's difficult 

[00:57:10] KT: So I’ll just put in a plug now, because as we started out, I’m resigned from academia, but what I do want to try to do is translate the science for people. So that is going to be my job moving forward. So if any of your listeners out there want something written or if they've got an opportunity, then that's what I’m going to be trying to do, is translate some of this high science into different levels for people. So practitioners or even just lay language, that's what I’m going to try to do. I want to try to help people understand the science better. 

[00:57:47] LB: Well, it's just evident. It's a strength. And I say you've influenced me in my journey to where I am as well. So I can provide a reference, so to speak, for your skillsets. 

[00:57:59] KT: Thank you. 

[00:58:00] LB: Look, let's just quickly zip this conversation up then maybe with just a quick summary that's relevant to both practitioners and consumers as it relates to nutrition and exercise and its role in positively impacting muscle protein breakdown.

[00:58:19] KT: I mean, again, if I was a practitioner and knowing what I know now, I would not base any of my recommendations to my athlete or any other person who I’m trying to help based on changing nutrition in order to change protein breakdown. Right now, I just don't see how the evidence supports it. And typically when these things are written about, when I see them online written or whatever, people are saying we want to stop it or lower it. And usually I think that's a bad idea. If you're trying to adapt to a new situation, you're going to need that protein breakdown to help you adapt, because you're remodeling those proteins and protein breakdown is a critical part of that process. 

Now, I think, again, in the future we might understand more about that. One of the main pieces of evidence, to go back to your energy deficit or your immobility kind of situation, there are molecular markers that people use to try to see what’s happening with protein breakdown. Now for various reasons those markers aren't very reliable. And since we're wrapping it up, I won't go into the details. But again, it's in this paper. But those markers in rodents go up when a limb is immobilized. But protein breakdown whenever we've measured it in humans, it doesn't go up. But that's where a lot of that interpretation is coming in and saying that you need to change protein breakdown in these situations. So if we’re talking about protein breakdown, I wouldn't mess with it. I would focus on what we know about changes in muscle protein synthesis, and more importantly you know studies that have actually measured changes in muscle mass or muscle loss during energy deficits and things like that where the synthesis can be the basis of it and then you see does that then translate into some sort of changes. So that's what I would do if I were a practitioner or working with athletes or other exercisers.

[01:00:23] LB: Thank you, Kev. I think we could keep going on this, but I think we have to draw a line in the sand on this one. I’m going to put in the show notes for this podcast episode. I’ll link to that paper and some other resources I know will be of value including how to contact you of course and also some of the other podcasts we've done. I mean we've done a lot with you and with you and Stu, for example. I’ll link to all of those. And just as a reminder, to the listeners, the other reason to come back to the podcast website for this is we now have transcripts. And the editor who does the transcripts is going to have a hell of a time with this podcast. So we'll see how good they get with that. 

[01:01:03] KT: I’m happy to try to – 

[01:01:04] LB: Yeah. Don't worry. I’ll ping it over to you. We’ll got to – Me and Kev, quick edit on that because this is a more complex conversation. But anyway that transcript will be on the website once it's been reviewed by us. So you just have to go to www.theiopn.com, just click on the podcast link at the top of the page there and it'll take you to the podcast page where you get all this cool stuff where you can also download this conversation and access all the other podcasts. So although I’m going to put all the links in there, just quickly for the listeners, the main way to follow you currently is what? Sort of social media? Twitter? 

[01:01:39] KT: Yeah, Twitter is @ProfTipper I think it is.

[01:01:42] KT: Yeah, I’ll tweet it anyways. And then if listeners have questions, my email right now is pretty much the same, proftipper61@gmail.com. So proftipper61@gmail.com. So I’m happy if there are any questions, because as you say, this is kind of complex. I’m happy to try to straighten anything out to somebody that I didn't say well enough for people to understand. 

[01:02:09] LB: Yeah. Well, please read the paper and listen through all that stuff. And I’m sure, Kev, I’ve really benefited from today's conversation. I’m immensely grateful for your time once again. It's always a pleasure. And I look forward to bringing you back on this podcast again. 

[01:02:26] KT: My pleasure, any time.

[01:02:26] LB: Kind of pick up those points. It’s not a frequent flyer miles, but we'll have a – 

[01:02:32] KT: Flyer – Yeah. Well, air miles in Britain, right? 

[01:02:35] LB: Yeah. We’ll call these pod miles or pod hours or something. But anyway, thank you, Kev. It's been wonderful. I of course am Laurent Bannock. I look forward to bringing another episode of We Do Science back to you all very soon. Take care everyone. Stay safe.

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