Mitochondria and Amplifying Adaptation with Professor David Bishop #193

Trail and Ultra Runners. What is going on? What's happening? Welcome to another episode of the Coupecast. As always, I am your humble host, Coach Jason Koop, and this episode of the podcast is with the renowned Professor David Bishop. Professor Bishop is a world leader in muscle exercise physiology with more than 250 scientific publications to his name. He leads the Skeletal Muscle and Training Research Group at Victoria University in Australia, and the focus of that research group is to examine how diet, exercise and genes interact to regulate skeletal muscle adaptations.

I'm excited to bring Professor Bishop on the podcast today because he has had a tremendous impact in the landscape as we know it. He has held many different and important positions within the exercise science community in Australia. He was the youngest ever president of Exercise and Sports Science Australia. He has been named as one of the top 25 influencers of exercise and sports sciences in Australia. He has twice been on the Excellence in Research Australia panel and he was made a fellow of three different organizations Exercise and Sports Science Australia, the American College of Sports Medicine and the European College of Sports Science. Professor Bishop is now a director of the Victorian Institute of Sport, as well as an assistant editor of medicine and science and sport and exercise.

In this conversation we discuss the mitochondria's role in exercise performance. We discuss how the mitochondria developed differently at different ranges of intensities, which is of supreme interest today, given the current zone 2 training craze. We also discuss how we might be able to amplify improvements using dietary interventions as well as supplements. What I have come to appreciate the most about David's approach is how he recognizes how the minutiae of things like signaling pathways and other phenomenon that he investigates are both important and limiting with respect to how they might impact end performance. Okay, with that, as an extensive but well deserved background, I'm here to present to you today my conversation with David Bishop. I am very much looking forward to this, david.

I think that well, I don't want to speak for you, but your knowledge set has probably come back into high demand recently, since there's been a lot of emphasis on mitochondrial development and function. Whenever I've had guests on previously that their area of expertise has come back into the vote, they always get really excited. People with that domain expertise. They never get to show off what they know To hell. There's a global pandemic and everybody wants their services. I feel like you're in the same boat right now. To give the listeners a little bit of context of what I'm talking about. Can you just go over your areas of interest and research that you've been focusing on over the course of your career?

Yeah, it's been interesting because first thanks Jason, thanks for the invite to be on the podcast. It's interesting getting a little bit older now so I've sort of been reflecting a little bit of that. Sometimes it seemed haphazard, but looking back maybe there was a plan. All along, From my younger days and then also when I was doing my PhD, I've been interested in exercise prescription. I think that's fundamentally like what's the best way to prescribe exercise to get the benefits out of performance, and also increasingly I'm interested in health as well. My PhD was actually more on resistance training and endurance performance. From there we were looking at that.

I started working with team sport athletes and I've worked with a lot of repeated sprint ability and things like that. Maybe leading into this discussion, we got started to look at supplements and different types of ways to improve performance but also improve adaptations to training. We did some really interesting work, I think probably 15, 20 years ago now, using sodium bicarbonate. We used it not as in its probably traditional sense, but as a supplement to train alongside training. It wasn't for an acute, one-off event, but during an eight-week training period we saw some really surprising benefits in terms of endurance adaptations.

We kind of got thinking to what that might be and sort of a long-winded answer, but we sort of settled on the mitochondria might be the role there. I had an opportunity to go to France and work in a lab that's specialized in mitochondria or functional measurements. I guess from there really got interested in the mitochondria. It's a pretty cool organism, obviously when you think of it as the powerhouses of the cell having a really critical role and it's a nice little nexus, I think, between you need energy for performance, but mitochondria also have a really important role in health. It kind of became a nice focal point to be able to look both at my deep interest in endurance, athletic performance, but also an increasing interest in health.

I think the way that the conversation for this particular podcast is going to go, we're going to reverse engineer that because we're going to start at the mitochondria and then probably go to the supplement side of things. As a quick programming note, I'll direct the listeners to previous podcasts that I did with Inigo San Milan on mitochondria as well. That's a great resource for anybody who's going to be more interested in this topic. So development has come back into vogue with the recent Zone 2 craze. I almost actually have them right here. I'll show it to you, David. The people who are watching the YouTube video of this will get a kick out of it.

I didn't plan this. That's why the break right there. But I had these shirts made for some of our coaching staff to remind them that in fact all zones do matter. We support all training zones, not just Zone 2. We had to make this just because of the over infatuation with this particular training activity and it's inevitable tie to mitochondrial development. But let's take a little bit of a step back. We have kind of colloquialized mitochondria's importance as just what you said it's the powerhouse of the cell. But in reality it can be described as a little bit more complex than that, how would you describe the mitochondria's function, not only within exercise, but also within health?

Yeah, I think it's a really good one and there's probably a little it might be. I don't know if it's too academic for some of your listeners, but Martin Picard, who's originally Canadian researcher but he's based in America now, did a nice paper just talking about, I guess, the terminology. Then I don't want to go too down to the rabbit hole, but sometimes mitochondrial function can be like a bit of a catch-all phrase, like you say, oh, someone will say what's my best training to improve mitochondrial function? And it's kind of like saying what's the best training to improve muscle function? And you kind of go okay, what actual function are you talking about?

And, as I think you alluded to nicely there, mitochondria have got lots of functions. They've probably they're most famously and you see this everywhere the powerhouse of the cells and they supply more than 95% of the energy. So when you're sleeping, walking, running, that's where your energy is ultimately coming from. So that's their key function. But they seem to have important roles in cell signaling. They've obviously in also, you know, ros production and also combating ros production. They've also seemed to have important roles in program cell death. So as your cells are getting older and they need to be recycled, that in producing the energy, not only for function, as in like the outward function, like running, cycling or whatever but also all the other energy producing functions that are going on, you know, building new cells, breaking down new cells. So yeah, they're a critical organ now that have more than just energy producing functions.

And kind of related to the zone this is the zone two craze that I was mentioning earlier. From an endurance standpoint, we've typically divided mitochondrial development into kind of two different pathways right, building more of them or building a greater mass of them and then approving their function I was going to say efficiency, but that's not going to be the right that you'll probably slap my wrist for using that type of terminology. Is that the way that we should be looking at it from endurance athletes is down these two different pathways, and if that is the case, fundamentally what types of training activities would facilitate those two different types of adaptations?

Yeah, I think you spot on and, without sort of complicating things, I'd maybe just add a third one in there. So I think you've got how much mitochondria? So your mitochondrial mass inside the muscle is probably a key development. One is also going to be, I guess, the morphology of the mitochondria, so things just to do with shape and connectedness and also crystal density and those. If we've got some young researchers listening, they're really right for study, because there's very little research on that. So I don't think we'll really talk about that today. And then the third one is actually is exactly like you said, and is the, I guess, the ability of mitochondria to take substrates, use it and, combined with oxygen, to produce the ATP that we need to do, everything that we need to do.

And part of this mitochondrial like we'll just use the term development. One of the questions that a lot of coaches have that there's been an extensive amount of research on is is it site specific Meaning? Can we use one training mode to develop mitochondria that might have an effect in another training mode arms versus legs or cycling versus running? And I think that this has a critical impact for coaches that are using a lot of like cross training modalities and things like that in order in order to train their athletes. For whatever reason, what do we know about that site specificity of mitochondrial development?

Yeah, I'm just trying to stretch my memory where there's no one's exactly looked at mitochondria, but I think what I always say to people is that you know you've only got one heart, so that if you're running, cycling, swimming, rowing or whatever you're going to be challenging your heart, so you will get, you'll get central benefits from any sort of exercise with the mitochondria, I'd expect. Yeah, maybe you know in some ways the same analogy you're using the heart for whatever you do and so you're going to get adaptations whatever you do, but with the muscle you really need to be using the muscle to get, I'd say, significant benefits. So there have been studies where, like I said, I don't think I'm not sure specifically with the muscle, but where you train leg and measure what's happening in the arm and you see very little change in things like the lactate threshold, which I would expect to relate strongly to the mitochondrial adaptation. So my expectation would be that you that would be quite muscle specific, in that you need to be able to stress the muscle to get those adaptations.

Having said that, there is some effort and we've seen it. It's difficult to do this in humans but other organs responding to exercise. So we haven't published this, but I think we did some really cool. This was in a rodent study where you get them running on a treadmill and doing their endurance training and we saw improvements in the mitochondrial respiration. So the ability to take ADP and produce ADP in the kidneys and other organs inside the muscle, inside the in the bodies I think I suspect that's probably something to do with blood flow. But with organs, you know, contracting your muscles and doing exercise does seem to have beneficial effect on other organs. But in terms of the muscles, I'd expect very little carryover from running to arm muscles, for example.

And I think the take home message here for the athletes and the coaches that are programming training for athletes is that there's a large degree of specificity within the movement itself, and we talk in trail running a lot about even hiking versus running right.

Those are two kind of completely different movements that stress to. You know that stress different, stress the muscles differently. I'll kind of like phrase it like that, and I could have implications for some of the developments that are going on at the cellular level and some of the mitochondrial developments that are going on. I want to talk about something, or I want to move to something that is endurance, athletes' favorite topics, and that's volume, because part of mitochondrial development is simply dictated by high volumes at low intensities, and I remember reading a paper that you were a co-author on and postulating that there seems to even be no ceiling. There seems to be, either there seems to be no upper limit to mitochondrial mass improvements with increases in volume, and I wanted you to describe that a little bit in terms of can we get more specific on what the intensity of this low intensity volume needs to be and how is it a linear relationship between volume and mitochondrial adaptation?

Yeah, and stop me if I go too long here, because it's probably a couple of things, that kind of base knowledge, that we need to go through. The first one and this could be a podcast in itself is just the whole intensity conundrum, because when you go through and there's low, moderate, high and different papers will have moderate intensity, but if you look closely the intensity is actually low intensity, another paper and then, as you said, there you've got zone one, two, three, and then you've got zone one, two, three, four, five, six, seven.

So if I would simplistically, I would try and base it a little bit more on physiology. So what I would say is if you think about the two commonly accepted metabolic thresholds, so I'll use lactate because that's what I'm most familiar with.

But if you have runners, if they're doing an incremental test, so starting off at a low speed and gradually increasing the speed, the lactate will stay pretty stable for a while for the first few speeds, so it won't increase. If we measure it in the blood, then we'll come to the first metabolic threshold where there's a slight tick up in the lactate in the blood. Keep increasing the intensity and then you'll get a more rapid increase in the lactate level and there's changes in ventilation and other things going on there. So I would put low intensity as a low, the first metabolic threshold, moderate intensity, as between those two metabolic thresholds, and then high intensity from above the second metabolic threshold to, I guess, the sort of VO2 max intensity, and that's just so that we can be on the same page when we're trying to compare intensities.

And the long-time listeners of this podcast will recognize that we are on the same page. We did a podcast with our lab manager, renee Eastman, who described the zones kind of exactly as you had described them, so everything is running in parallel here.

Okay, that's great to know. In terms of mitochondrial mass, one of the I guess the difficulties with the field is that it's mostly measured indirectly. So you'll see a lot of studies, including ours, that have measured this one enzyme called citrate synthase and used that as a marker of mitochondrial mass, and I think the jury is probably we need a little bit more evidence to. So I just had that caveat, because most studies are talking about and including ours, when we talk about mitochondrial volume and mitochondrial mass and training volume are using an indirect marker of mitochondrial mass. There's been maybe half a dozen studies that have directly measured mitochondrial or more directly measured mitochondrial mass with actual imaging.

And, to your previous point, it looks like and we need it looks like this probably starts to get a plateau at a certain point. So I think when we in the paper I think that you mentioned when we've grafted, you see this linear increase and the last, there's only one or two data points at the end, but it looks like maybe it's starting to plateau. So, in terms of, if I wanted to give a kilometers per week or something like that, I don't have that number for you, but I suspect there is going to be an upper limit and yeah, I don't know what that is, but I think there probably is an upper limit to the exercise volume.

What would potentially be the biochemical or the physiological governor for those improvements? That's what I've always wondered. Whenever there's a ceiling for something, we always talk about the rate limiting step or the rate limiting factor and any sort of physiological process, or we're talking about VO2 max or whatever. And it's always been curious to me, within mitochondrial development, what is actually limiting the total amount that the body can synthesize?

Great question. I think it's probably two things. One is that your body is supremely good at maintaining homeostasis, and so we've seen this with our studies and I think everyone knows this as well is that the first time you do exercise it's going to be quite stressful. And then all of the adaptations that you get from training. The ultimate goal is to make the next exercise session less stressful. But that stresses what's driving the adaptations. And so over time I think and we see that I think that's a large reason why athletes plateau and it's also why I'm really interested in this prescription idea is it's almost like a self-limiting thing is that you get the stress, you adapt, so it's less stressful. And so next time you do that exercise session and this has been repeated over weeks, months and years it's less stressful, so that's going to drive a smaller adaptation, and then you're going to adapt and it's going to get less stressful again. So I think in some ways that's the heart. And the million-billion-dollar question is how do you maintain, how do we best prescribe exercise to keep that stress as high as possible, to continue to get the adaptations. And I think the second part of it is as well.

If you look at the mitochondria. In untrained people the mitochondria might be 2% or 3% of your muscle. That's the mass that it takes up, and you can probably get that to 8% to 10%. But there's lots of other things in your muscle other than mitochondria so you would never get there. But you could never be like 100% mitochondria, because then you're kicking out every. It's like I don't know if you had a car and you made it 100% engine, cool, it might go fast, but you haven't got room for all the other things that you need for the car to work. So I think there's also a. There's always probably like a and there have been some papers that have suggested that there's some. There's almost like a space limitation to how much mitochondria you can actually jam into a skeletal muscle.

Yeah, and that's what I've always wondered Is this spatial limitation the thing that is actually limiting this ultimate ceiling that we could get to, Because the muscle can only get so big and then that four limits the space and you can only jam so much stuff into it, like a room or your car analogy or whatever else it is? Yeah, exactly.

I want to get your take on a prescriptive element of this, because if we know that there's a linear or relatively a linear relationship between volume and mitochondrial development, is there any way that we can manipulate volume to enhance that development? And the main way that we look at doing this from a practitioner's point of view is just through the duration of the session. I can do one two-hour sessions, or I can do one two-hour session, or I can do two one-hour sessions. When we start to manipulate volume that way, do you actually see any differences in mitochondrial biogenesis?

Yeah, another good question, and maybe that's where we kind of need like a little quick breakout as well. So when we talk about exercise volume, I guess I probably we're using it in terms of a bit like, I guess, in a resistant training concept. So not so much time but total amount of exercise. So, like you, in that analogy, if you ran 10 kilometres an hour for four hours or 20 kilometres an hour for two hours, that would basically be the same exercise volume. So it's not just Duration is not the only thing of volume.

So I guess you could normalise it to work right, you could normalise it to work the kilojoules, it's fast to work.

Yeah, exactly, and that's what we do when we do a lot of our studies on this cyclogometer, so we can actually measure the work and we'll match it in terms of external work. So I think there's two things out. I think that there's. I think that it's not just a volume, I think that there's probably, I think there's also an intensity component, and what I mean by that is that, like I think if you walked for six hours at six kilometres an hour, that wouldn't be the same as running for at 12 kilometres an hour for three hours. But I think there's probably I don't know what the best terminology is here An intensity hurdle that you need to pass before the volume becomes the critical factor.

And we haven't published this, but we just did a study where we had people training for 90 to 120 minutes four times a week just below their first metabolic threshold, so the upper end of zone one, and we saw some changes in mitochondrial mass, but they probably weren't as high as what I've expected. And I think that and this is where I'm sort of going a little bit out on a limb but I think probably getting above that first metabolic threshold is an important intensity, where the role of volume becomes more critical, and then back to your other point. So you know we've done a lot of our early studies with high intensity interval training, and what high intensity interval training allows you to do is to get quite a large volume of work. So if you multiply the intensity by the duration, you can get a very high total amount of work done, and we've seen that to be very effective for increasing mitochondrial mass as well.

So to your first point. There seems to be like a minimum viable product, so to speak, where the intensity can be too easy and it's not enough of a trigger, or the alternative conspiracy theory is you would just have to have such a large volume at that very low intensity that it becomes impractical, right, just from a I can't train for 20 hours a day type of perspective, which is always really interesting because, as ultra-marathon athletes are listening to this, they're always wondering when is it too easy, like, when are my workouts too easy? When have I spent too long in the mountains on a training activity to where the work becomes either not productive or unproductive, right, either. Like it detracts from any sort of future sessions that you can do. And there does seem to be a minimum viable proposition. That keeps kind of like cropping up in different people's work, and I'll bring up an interview I did with Steven Seiler in the show notes where we talked a little bit about that minimum intensity viable proposition that he's been exploring.

I want to move to the. I think just to Sorry, can I just add? One thing there I was just going to say that. I think the other thing I've sort of been thinking about when I have these discussions with people is that you know we're talking about mitochondria and yeah, as much as I want to think that mitochondria are the be all and the only thing, that matters is that you know it may be that for argument sake, maybe a four hour run at a really long intensity is important to increase blood volume or some central adaptation, some other capillarization or some central adaptation.

So I think that, yeah, I think that's one of the I don't know about dangers. But one of the caution is that I'm talking specifically about mitochondrial adaptations and that there could be training that maybe isn't optimal for the mitochondria may be really important for for some other parallel adaptations that are critical for ultra-injurance performance.

Yeah, that's a very important caveat to add is sometimes we tend to get too nuanced in the adaptations that we want and not realizing, or failing to realize, that performance is always multifactorial. You're going to have a multitude of physiological and psychological and even environmental factors that come into play when you're determining the ultimate outcome of whatever, whatever performance outcomes we're looking at.

I think it may be. A good example is also yeah, this isn't my field, but yeah, there's some interesting research about resistance training and plyometric training, improving running economy and things like that, whereas those sorts of trainings, I'd argued, had almost no effect on the mitochondria, but they are having positive effects on endurance performance.

Yeah, that's a great analogy. Actually, now that I'm thinking about it, brilliant. Okay, so let's move to the other side of the intensity spectrum. We talked about the fact that there might be a minimum viable intensity that you need to eclipse in order for some of these adaptations to kick in. What do we know about the improving mitochondrial function you can use a different term if you choose to, because I know that it's been discussed in the literature in various contexts but what do we know about those specific types of adaptations and the intensity and the volume of intensity that could potentially elicit an improvement in the function of the mitochondria that you actually have?

Yeah, and I think it's good. Function is great for shorthand and I think what we would in this case, what we're talking about, I guess, is respiratory function, so the ability of the mitochondria to take substrates and use oxygen to produce energy, and so that's what we often measure in our lab. It's really interesting and I think if I was going to and these things sometimes become sort of dichotomous and it's not exactly the case, but with quite low intensity, high volume, we see increases in mitochondrial mass and these increases in mitochondrial mass can sometimes, in terms of a percentage change, will exceed the changes in mitochondrial function. When we get a little bit more in the middle, we kind of see it proportional. So you might get a 40% improvement in mitochondrial mass and you get a 40% improvement in mitochondrial function. So that's kind of in the middle there. And then, as you alluded to, with the really high intensity, so we're talking sprint interval training. So what we've used, I guess, is the classic Wingate type stuff where it's 30 seconds all out, four minutes break, rest and go again. You know really hard training, and then what we see there is improvements in mitochondrial function, exceed the improvements in mitochondrial mass, and we don't. That's, I guess another what's a really we're really interested in my lab is exactly what's driving that. But what we've, what we've seen and I guess this relates a little bit to our previous discussion and what we think is, you know, exercise is a stress, but what we've seen is that this really really high intensity exercise is a really a more intense mitochondrial stress and we think that this greater mitochondrial stress is driving this proportionally greater increase in respiratory function. And this is, I guess, what we'll explore in the next, in our next

research.

But, like all of the proteins and structures in our body, they're continually being built, built up and broken down.

So your mitochondria have a life cycle, depending on where it is of, you know, from a few years to quite a few years, and so the mitochondria are constantly being getting bigger and then, if they get damaged or maybe not functioning as well, they'll be targeted to be broken down and they'll be their little, their bits will be recycled and you know you keep going through this process where, I think, in skeletal muscle, you know, probably every 15 years all of your mitochondria have been replaced and what we think is that the and this is just our hypothesis is that the really intense sprint interval training.

We think it's maybe speeding up this breakdown process. So when you've got mitochondria that's coming towards the end of the lot, end of its life, we think that the sprint interval training might be speeding it up to actually be broken down and replaced by better, better functioning mitochondria, and so we think that's why with sprint interval training we get not much of an increase in the amount of mitochondria we do see small increases but a much greater increase in function, because we think you're getting a slight increase in the pool. But the main adaptation is that you've got better, better functioning mitochondria that are better able to use substrates and oxygen to produce energy.

So it's literally facilitating the out with the old and with the new process.

I love it. I'll have to use that in my talks. Yeah, I think that's what it's. Yeah, that's I think. I mean we haven't actually shown that, but that's just just our hypothesis. What we have shown is that when we've compared moderate and sprint interval excess moderate intensity and sprint interval training there's a much greater increase in mitochondrial stress. We also see, if you look at you know, if you imagine, like I think most people sort of familiar with mitochondria immediately after moderate intensity training, you see these beautiful bean shaped, you know pictures. They look super healthy.

After sprint interval training, we actually see some mitochondria that look like they're damaged and some of them have got missing, chris Day, and I think they've started to be broken down. So it's not just a wild hypothesis. We have seen, we have seen evidence of much greater mitochondrial damage and mitochondrial damage response with sprint interval training. And sometimes when I've given this talk to other scientific meetings and people get like freaked out about, I know, mitochondrial being damaged. Maybe we shouldn't do sprint interval training, but I think you know the analogy I give is you know, with resistance training exactly the same thing happens, like you get muscle fiber damage and that's part of the stress response which promotes a rebuilding of skeletal muscle. So I actually think this mitochondrial damage is probably a good thing, which starts to start this. Like I said, out with the old, in with the new mitochondrial process.

Well, and it also has a tie into your, the space theory that we were discussing earlier, where there's only a limit, there's a limited amount of space within the muscle fibers itself for the mitochondria to exist, and if you're replacing what I'll call poor, poor functioning ones, or if you're getting rid of poor functioning ones, it literally frees up space for the newer model, right, the newer model can kind of come in, function better and provide, you know, more, more ATP for the muscle.

Yeah, I think you always have to be careful, because I think biology doesn't always make sense. Yeah, that does make a lot of sense to, at least to me that you know the idea that you use this process to, yeah, to fill up that limited space with the best quality mitochondria that you can.

I love the fact that you and I'm going to I'm going to put words in your mouth that I don't think. I don't think you mind. You'll mind me doing. You kind of described intensity and mitochondrial development that goes underneath the intensity, on a continuum, as opposed to these very distinct, discrete breaks that we often try to categorize intensity and then whatever physiological development is associated with that intensity, with and you went through this continuum of low, medium, high. This is what happens at low. We're getting, you know, a lot of improvements in mass. This is what happens at medium. It's kind of a mixture of both mass and function. And this is what happens at high. It's a little bit of mass and a whole and a whole lot of function.

But in reality that graph is continuous, right, there aren't kind of like break, there aren't really breaks in it, and I think that that's important for athletes and coaches to remember in the endless amount of training zone quantification debates.

You mentioned that. You know you see seven zone systems. I've seen 12 and 20 zone systems in my you know, in my coaching career and I'm always wondering why, why do we really need to delineate things that granularly? Is there something that is specifically happening across each and every one of those, and I think, the more and more practice that I have, it makes me appreciate more of this continuum strategy, that every intensity has some sort of continuum of physiological benefits that we can associate it with.

Yeah, and I really like the, and I think I've seen Steven Sealer present this in a different way, but I guess you know everyone's familiar with the nutrition pyramid and, yeah, there's not too many people who would say just eat this one type of food. It's generally you need carbohydrates, protein, fats and different vitamins and minerals, but you need the range of foods. And I think it's the same with exercise and I guess, specifically with mitochondria. I think that the yeah, in some ways it's a bit simplistic, the classic moderation and everything, and it's probably not quite moderation and everything, but I think hitting those different intensity zones and different volume types of volume will give you different mitochondrial adaptations and I think if you just did one type of training, it's probably not gonna be optimal for your mitochondrial adaptations 100%.

That's a brilliant take home message In a good segue. We can wrap up with that take home message In a good segue to the next part of your academic career and professional career that we're gonna reverse engineer and that's taking the training that you're doing and having it mean more. That's the way that I like to describe it. We all have 10 hours per week and within those 10 hours per week or whatever it is, we can do any number of different things, but literally taking the work that you're doing and the work that you are going to do and having an enhanced response to it via some mechanism training low, taking a nutrition intervention and there's kind of a whole host of others.

I wanna tackle the training low piece first because we might run out of time here, and I think it's the most important from an ultramarathon's perspective. It's a strategy that a lot of athletes will specifically take on to promote greater rates of fat oxidation. It's a really and I'm not gonna profess for that to be the best way, but it is a common way that a lot of athletes or it's a common thing that a lot of athletes do to try to achieve that specific adaptation. But when we kind of work into the reality of it. There's a lot of caveats that we have to work through. First off, to kind of set the table a little bit, can we get superior training adaptations, specifically from training with low carbohydrate availability, and then we can move into. If that is the case, how would we actually set those sessions up?

We've been looking and I think this is, yeah, lots of people are interested in it and one of the tricky things, I think, is that there's so many variables that are at play. So when you look through the literature what exactly train low means can be, you've got whether it's a sleep low type protocol, so you do some sort of glycogen depletion exercise in the afternoon or evening and don't have carbohydrates during the night. Then do you come in and have breakfast or not have breakfast before you do your training session and then is your training session a moderate intensity or high intensity. And so I think I can understand with people looking at the literature. It's really it can be a little bit difficult to decipher and I think the other thing to say there is that most of the studies have really looked at, I guess, self-signalling responses. There's not many studies that have actually done like a training, like where you train for four or six, eight weeks or longer using a different train, some sort of a train low protocol. So we're really relying on these acute changes. Typically people are measuring increases in genes like PGC1 alpha, which is the master regulator of mitochondrial biogenesis, and trying to extrapolate those changes to whole body adaptations and then ultimately to performance.

But having said that, I'd say there's pretty, I think, pretty solid evidence that the train low, especially if you come in and have either a low carbohydrate or no carbohydrate breakfast before you do your moderate intensity training session. But that can increase self-signalling that's associated with phatoxidation and mitochondrial biogenesis and other adaptations important for endurance performance. I think the evidence for doing a train low with a high intensity exercise session is probably more equivocal. I think there's probably two reasons for that. One is it's really hard to do high intensity training if you don't have carbohydrates and so and I think John Holi's shown this nicely that you just can't. You can't do if you're doing intervals or whatever it might be. You can't do that at the same intensity if you're in a train low condition.

So the workout itself is compromised and that potentially offsets any sort of other response. That you're getting is what you're getting at there.

Yeah, and I think when I think John I can't remember the exact numbers, but he was saying that I think his study showed like they could only get to about 85% of the target intensity when they were, when they were trained, low.

And that's a big miss, by the way. Like let me just put that in context right, you're running six minute pace and all of a sudden you're running what is that gonna be? Seven minute pace, or something like that? Like that's not a trivial miss on the intensity side. Whenever I look at things like that, no, no, exactly.

And I think the other thing is that and I think maybe it relates to our previous discussion but yeah, there's probably you'd expect there's some sort of ceiling to how much you can activate the muscle with an exercise session. And so I think what happens with a moderate intensity is you're getting a moderate activation of yourself signaling and you can augment that by training low. If you're doing a high intensity training session, you're probably already getting quite a large activation of yourself signaling, and so there's I don't think there's much room to top that up, so I think. So, just to summarize there, I think there's enough evidence for people to consider doing that.

That training low, especially if it's like a sleep low and trying to avoid carbohydrates before your training session, combined with moderate intensity, is probably going to be a good approach to augment some of your self-sealing there. I think the most of the recommendations would be that if you're gonna do high intensity, you wanna be having a good having your muscle glycogen stores full before you do that training. And I think the other thing I would say that it's pretty hard doing a train low session is that your high intensity. We don't know exactly how long your high intensity performance might be compromised, but I think you probably need more than 24 hours before you can get do the best quality, high intensity training. After a train low session.

So there's a timeframe associated with how long the negative impact is actually going to last.

I'm gonna kind of speak up for the people that are in the back of the room yelling and screaming to avoid box sessions and low carbohydrate training and things like that, because I think we'd be remiss not to mention that there can be negative consequences that can outstrip any of the training adaptations that you could potentially enhance with low carbohydrate training. There's a lot of good research coming out of Australia having to do with iron metabolism and bone metabolism that would suggest that doing some of these low carbohydrate sessions might negatively impact that. And so it might be. You know you're robbing a physiological Peter to pay another physiological Paul when you're kind of seeking these adaptations.

But personally and the listeners of this podcast will kind of will recognize this it's usually a training strategy that I leave on the table, like I don't typically use that type of intervention because I know that there are other low hanging fruit, if you'll excuse that pun. There are other low hanging fruit to kind of gather within the whole training paradigm and it's just something, because of that equivocal nature of it that you mentioned earlier, that exists in a lot of other fashions. I just tend to leave it alone.

I think it's a really good comment and I think the couple of things is that I haven't seen really anything on a lead athlete. So when these studies are moderate amounts of training, it's not people doing 10, 20 hours of training a week. So they're already accumulating all that stress from the other training. And I agree with you. I think whenever we've done these studies, at the end of it the participants have never come back and said is it, can we extend this study? We've had so much fun doing this training. We did it for three weeks where it was like a twice a day training study and, yeah, they're absolutely cooked by the end of it. So it's really stressful physiologically and psychologically and I agree in 100% in that.

And I think it relates to the whole, you know, in general, probably at the whole supplement field, in that you know, whenever people sort of talk to me about supplements, my first question is what's your training look like? I'm pretty confident that your training is not perfect at the moment. You know I would be trying to optimize your training first. When you think, okay, this is spot on, I can't really get this any better, that's when you can maybe think of supplements. That's when you can maybe think of you know train low approaches and things like that if you're reaching a plateau. But I think you know getting the training prescription and your programming and periodization right.

That would be my starting point 100% and we talk about that a lot when we start. That supplement should supplement right. They shouldn't be the cornerstone or the foundation of a training program. Training should be the cornerstone and the foundation of a training program.

And I think you know, back to the you know also with the carbohydrates stuff is I think if there's anything that that's that there is really good evidence is that you don't want to be an energy deficit when you're training. So I think you know that's. You know, if I I'm not a nutritionist, but I think you know most nutritionists, like that's the first, that's your starting point, like, are you getting the enough sufficient calories to support the training process? And if you know, if that you know some sort of different sort of carbon train low strategy is going to get you into a calorie deficit, I'd be, I think, exactly what you said there. I think the negative effects of that are going to probably outweigh any potential benefits of this increased cell signaling during those sessions.

Well, and the energy availability piece is hard enough to do, just especially when you have really high training volumes. You talk about athletes that are doing 15, 20, maybe even 25 hours a week, which is pretty common in iron distance triathlon and then ultra marathon running and things like that. Just simply getting that basic equation correct over many months is is is difficult in and of itself, and then if you wanted to add the nuance of having some sort of even a periodized carbohydrate approach not you know, not to mention having low carbohydrate sessions it just throws another degree of complexity in. Where, really, where I take it from as a coach is I first and foremost try not to screw it up, and I always feel that if I do this, I'm going to screw it up, and so I kind of like leave it on the table. That's literally where I'm coming at it from. Is that I want to screw it up for first and foremost?

Okay, you mentioned sodium bicarbonate. We're going to take a hard pivot here. You mentioned sodium bicarbonate at the very beginning. This is kind of come back into vogue from one perspective, that you can use carbohydrate or sodium bicarbonate and that's to improve endurance performance. There's another aspect of it where you can actually use it, potentially use it too, as we were just talking about, take the training or amplify the training adaptations that you are getting out of a particular session. But since the first is a little bit more topical, we'll tackle that. And the reason that it's topical for the uninformed is that there's a new sodium bicarbonate product out in the marketplace that purports to get around some of the traditional issues with sodium bicarbonate supplementation in order to improve performance, and that's in the main issue with that.

David, as you're aware, it's just GI distress. I use sodium bicarbonate when I was a very mediocre athlete in college. Running the 800 and the 1500 meters is a very good use application for that. We put some in a little, you know, in a glass or in our water bottles, we chug it right before the race, 30 minutes before the race or whatever, and we go out there and probably had some sort of a Q performance improvement because of that and Martin's new product, where they encapsulate the sodium bicarbonate within their hydro gel apparently, or allegedly, can reduce the amount of GI distress coming into the system. We probably won't talk about that a lot, but what is theso the listeners can kind of understand what's the fundamental proposition of using sodium bicarbonate to improve either workout or specific race performance, and then we can kind of backtrack that into is this even applicable in an ultramarathon situation?

Yes. So I think you know fundamentally thesoand this is another great sort of terminology one. But let's just for simplicity say lactic acid. So what we're talking about there is the lactate plus the hydrogen ion, which is the acidic part of that. The lactate and the hydrogen ions. I'll say lactic acid just to keep it simple there.

But like most things in the body, they move down concentration gradients. So you think about if it's cold outside and we're in winter here in Australia, you know, open the door, the hot air moves from a hot place to a cold place. And same in your body. Things move from where there's a high concentration to a low concentration. So what you're doing with sodium bicarbonate is you eventually, after it will get into your bloodstream and it's going to lower the acidity of your blood and what that does is that creates a stronger concentration gradient. So think of it almost like a I guess a sink for one of a better word. But that will help to pull the hydrogen ions out of the muscle and into the bloodstream and then they combine with the bicarbonate and then you'll breathe it off as carbon dioxide and then that'll keep going.

So fundamentally, I guess the sodium bicarbonate is trying toit should speed up the removal of the acid that you're producing during high intensity exercise, speed up the removal into the blood and trying to reduce the decrease in muscle pH. That's going to happen with high intensity exercise, like you said, especially with sort of middle. You know a few minutes of exercise of the 80, if people running 800, 1500 meters I worked with kyker's over the same like a couple of minutes, two or three minutes of really hard exercise. It's pretty good evidence that if you do that you can increase the anaerobic contribution to exercise and improve that sort of high intensity performance. And you know, with 800 or 1500 meter maybe reduce it by a second or two the actual performance time.

I needed much more than that, by the way. I needed way more than a second or two. So if the application here is in high intensity exercise, where there has the potential for the muscle to be in a very acidic environment, is there a potential performance application for sodium bicarbonate in a lower intensity exercise? Because this is the zillion dollar question with the endurance community as a whole is if we're competing at moderate or lower intensities. Is this a worthwhile supplement to potentially improve performance? For those of you not watching, the YouTube version of the David's forehead just started wrinkling up when I asked that question.

So apparently there's a great deal of consternation going on in the back of your head right now.

Yeah, I think that, like a lot of these things, I think the evidence is pretty, is solid for the high intensity, because I would, to be honest, I haven't looked at this literature for a while but when I was looking at it the bulk of the literature wasn't really supporting endurance performance, and that's not even getting into to ultra endurance performance.

If I was going to clutch at straws, I guess the only benefit would be sometimes, with these different, I'm thinking more like cycling, like we kind of like a long tour where you think and I'm not that familiar with ultra endurance running, to be honest but we kind of think of it as you know, low to moderate intensity but you do have some like breakaways and things like that we need to do to do a sprint, and so I'm not really sure if that happens in in ultra endurance, where every now and again there's a you do have to do like a high intensity effort, but I would say for low intensity exercise of a few hours, I haven't seen any good evidence that sodium bicarbonate would benefit that type of performance.

Can I increase your consternation a little bit with my theory? Yeah, yes, you'll go for it. You can entertain this. So we do see athletes that use these protocols in low intensity situations and they have the sensation that their performance is being improved by that, and whether that's a placebo effect or a real biological effect or a combination of those two, who knows and we've observed this we, meaning me and my coaching staff we've observed this.

Even going back to the transdermal delivery systems for sodium bicarbonate. I've had this sneaking suspicion that in those cases it has something to do with the amount of sodium that's actually being ingested and not the bicarbonate piece of it, because in many of these applications it is a lot of sodium, like on the equivalent of when you're doing a sodium loading protocol and a hyperhydration protocol. It would be the equivalent of that. That's my conspiracy theory on why we're observing some of these performance improvements at lower intensities. This is not necessarily the buffering capacity or the sink effect, as you termed it, that it has more to do with something to do with the copious amounts of sodium that's being adjusted.

It's a really good point to be on, and I've never thought about that and maybe that's why I think again. I haven't looked at the literature for a while, but most of the endurance performance was probably you know, was more that mid-range. So where the sodium is less likely to have effects, there may be something out there. So I haven't seen a scientific study where you're looking at three I don't know exactly how long all of these, let's say four plus hours of exercise where the sodium could be a limiting factor. I think that's interesting and I think that's where different supplements could have a beneficial effect, but for a completely different reason.

We see that a lot within the supplement industry. It's originally intended for this but then years down the line we see that it also has an effect on some other process and then it gets you know there's either another permutation of it or a bastardization depending upon what side of the fence you look at it on of that supplement into another use case.

I think it's interesting as well in that, yeah, sometimes one of the criticism has been of the sodium bicarbonate literature for high intensity exercise, where people go well, how do you know, it's not the sodium that's having the beneficial effect and so people have also used other. You can change the blood buffering with substances that don't contain sodium and still seeing the same effects. I think the sodium has been, I think, largely ruled out as explaining the benefits of sodium bicarbonate on high intensity exercise. But yeah, I think it'd be interesting for some researchers to look at that, whether there is a beneficial effect of supplying sodium on these ultra endurance performances.

Yeah, like I said, that's been my sneaking suspicion because it somehow changes the plasma volume and that's so important in these long duration types of activities where there's an even in hot weather types of conditions. But I digress, we'll move away from that because we're getting to way too much speculation. One of the things that we can at least reduce the amount of speculation on related to sodium bicarbonate as well is its potential to enhance adaptations from a particular training session. This is another area that you've got a great degree of familiarity with. I want you to walk the listeners through how that actually happens, because it's an interesting biochemical cascade that we're looking at in terms of the signaling mechanisms and how sodium bicarbonate can actually take the work that you're doing and make it more impactful.

Yeah, I think I won't digress too much, but I think this is one of those, I guess, kind of happy accidents that we were looking at sodium bicarbonate during training and for summary, I can't even remember the I think we just wanted to do something a little bit different and so we did measure. We've done a lot of studies looking at repeated sprint training and just for this particular study we decided, okay, we've done enough repeated sprint, let's have a look at, let's have an endurance performance test. And it ended up being probably the most interesting result from the study

. But fundamentally, what we did is and these were, you know, you took your athletes and maybe some of these listeners are lead athletes, but so these are university students, they were females, but we had them doing exactly the same amount of training and the same intensity, well, training side by side. But what we did is we gave one half of them sodium bicarbonate, so your classics would dose 60 to 90 minutes before they did the training session. So we didn't say, you know, we've just been talking about the acute effects. We didn't say, okay, if you can train, maybe the sodium bicarbonate will allow you to train harder. We kept them training at exactly the same intensity, volume, duration etc. And what we saw is that both groups improved their endurance performance, but the group that took sodium bicarbonate had a greater improvement in their endurance performance. They both had the same improvement in VO2 max, but the group that took sodium bicarbonate had a greater improvement in their lactate threshold. So that got us thinking that it must have been a sort of a muscular adaptation.

I think I said at the beginning, I went to France and so we had an opportunity to do the same kind of experiment with. We did an annual experiment so with rats and same cool thing, like the rats are on the treadmill at exactly the same time, exactly same speed. But we gave one group of rats and we put the sodium bicarbonate directly into their stomach with a gavage before their training sessions and we saw that the rats that took sodium bicarbonate had a greater improvement in their mitochondrial respiration as well. So that kind of linked the muscle adaptations. We also done some other studies, like just a single exercise session where actually Marty Gabala did this nice study where they gave sodium bicarbonate and they saw greater increase in a marker of mitochondrial biogenesis. And we did the opposite where we gave people an acid and made their blood a little bit more acidic before they did exercise and we saw a dampening of the markers of mitochondrial biogenesis.

So we've kind of formed this hypothesis that when you're doing high intensity exercise, if you can reduce the build up of acid in, so the decrease in pH in the muscle, that maybe we can augment the adaptations to training, and so I think we've got a reasonably consistent story. There has been a couple of others. There's a study out of Australia where they did a short term study with well trained rowers and they didn't see a beneficial effect of the sodium bicarbonate. I think it may be to do with the training status they also did. There was a short term, there was only a few weeks, and they did a lower intensity of high intensity, like we did quite a high intensity interval training. So I think there's we're talking about how confident we can be in some of these things, but I think it's something that it's definitely worth considering and only with high intensity interval training sessions I think it's something that is worth considering whether that might be a way to try and improve the mitochondrial adaptations to a high intensity training.

Here's how I really look at this. I look at training interventions partially through the lens of hedging bets, and what I mean by that is if you can use a very specific intervention that has multiple advantages, it's better than using a training intervention that's focused on one narrow thing. Here you have a supplement intervention that you would use that has two potential advantages. First and you ruled this out in the first study that you mentioned, where there's an iso work study and I really appreciated that design the first advantage is you can just improve the performance during the workout.

Take sodium bicarbonate during a workout it's a particular high intensity workout you could potentially have a higher quality workout. That, therefore, would hopefully cascade into a more robust adaptation. Now you add on to it the fact that the sodium bicarbonate itself, even in an iso work situation so even if the workout is the same or the quality isn't improved for whatever reason, that supplement might augment or enhance the adaptations that you're naturally going to get out of that workout or series of workouts. I kind of view that, as you're hedging your bets, you're going to get the improvement or enhanced improvement one way or the other either facilitate it through a higher quality workout and or facilitate it through just the ingestion of the supplement itself. That's when I start to get interested, when I start to see the multiple effects, this kind of like multiple effects that could even potentially compound on each other. That's really kind of my threshold, so to speak, as to whether as to look at something as an interesting intervention to actually partake in, and this is one that actually does have that.

I think the flip side, too, is that I haven't seen anything to say that there'll be a negative effect of this type of training, even, like I said, the study in ROWAS that was published a few years ago. I think there's a slight trend, but they definitely didn't see the worst effect on the training. I think it's not particularly expensive sodium bicarbonate, and the worst case scenario, I think, is that you're getting your regular benefits from the high intensity training and you're not getting any additional benefits from the sodium bicarbonate.

Yeah, it's cheap if you go buy baking soda, but if you buy the Marten product you're looking at like I think it's like five or seven bucks US bucks per dose per time that you're going to use this. That makes an expensive workout session, which is fine for some people. You're an Olympic level athlete. That's what you want to pay for. They're great. But if not, you can go buy baking soda off the shelf or pretty cheap.

I think of the other option and I don't know what the options are in the US and I'm not 100% sure what the purpose is. But when we did these studies we didn't do the spoonful of baking soda in water, because it's like drinking chalky water.

It's bad, it's pretty nasty.

But we would get, even before this company that you mentioned, we would buy sodium bicarbonate tablets from a pharmacy so that pharmaceutical grade and there maybe not exactly what special slow release formula they've got here. So we would give and there's quite a lot. You'd have to take 20 or 30 tablets depending on how much you weighed. But that my memory, and it's got inflation going around the world. I'm thinking of the good old days and I'm getting my prices wrong, but my memory was like a few dollars for an actual container with a couple of hundred tablets in it. So I think there are probably cheaper options out there.

Yeah, I totally agree. That was more making fun of the dichotomy of putting sodium bicarbonate in a glass or in a bottle, which is once again what we used to do before all of this, versus having more high tech interventions. Dave, this is really fun. We're going to let you go. I really appreciate the conversation. We hit on a lot of different things. I can just say, from a coaching standpoint, you've contributed so greatly to our understanding of a lot of these biological processes, so by thanks goes out to you and the teams that you've worked with over the years and improving our knowledge in terms of how we can use training interventions and what's going on underneath the athlete hood, so to speak, from a biochemical standpoint, with our mitochondria, and also how we can enhance those adaptations. I'm going to link up any specific studies that we discussed in the show notes, but where can listeners find out more about you and some of the research and the work that you're doing?

Yeah, I think I was going to say Twitter. I think it's X now, isn't it?

Everybody's making that transition and it's hard.

I haven't been as active as lately as I used to be, and I probably do need to, so my Twitter handle is at Blue Spot Science and so I normally put my latest studies not just my research, but other research that I come across. That's interesting, why in large it will be exercise prescription and or sort of mitochondrial type stuff, so they can link on there. I think there's probably a link to my publications there as well, so they can track down the publications.

Awesome. I will put links to that in the show notes

as well. I appreciate you coming on the podcast today.

I've really enjoyed it. Thanks to you, jason, thanks, mate All right, folks.

There you have it. There you go. Much thanks to Professor David Bishop for coming on the podcast today. I've always appreciated his approach and the knowledge that he brings to the table to inform us on how mitochondrial adaptations actually occur, when they occur, to what extent the different nuances of, specifically, how different intensities improve mitochondrial function and mass differently this whole thing. It was something that I originally started my coaching journey with. It was a big part of what I focused on early in my coaching career. It's always nice to bring a full circle with an expert such as David to help enlighten me and the audience even further.

If you like this podcast, please share it with your friends, your training partners, your coach anybody that you might think has an interest in this stuff. Links will be in the show notes to all the research papers that we discussed. If you want a deeper dive, please go check out those show notes. They are great and tremendous resources. If you want to expand your knowledge base even further, all right, folks. That is it for today and, as always, we will see you out on the trails.