Episode 381: Brendan Egan, PhD - Exogenous Ketone Research

Brendan is an Associate Professor of Sport and Exercise Physiology, and currently Head of School for the School of Health and Human Performance at DCU. His current research investigates skeletal muscle function and adaptation across the life course, with special interest in the synergy between nutrition and exercise interventions ranging from athletes to older adults.

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Episode Transcript:

Brendan, welcome to the show. Thanks for having me, Zach. It's a pleasure to talk about ketones, especially with someone who actually uses them. Yeah, it's been such a fun topic, I think in terms of just I mean, there's been a few fun topics in my kind of endurance long enough now. I guess I've seen some trends come and go and then some trends, like gain a lot of momentum. And I think some of them are more interesting than others. And the exogenous ketone one has been one that I've been following now for a few years. And I probably get pinged on this a little more than the average endurance athlete, just because I followed a lower carbohydrate diet in efforts towards ultramarathon stuff for a little over 12 years now. So any time things that topics of fat metabolism and ketones, whether they be exogenous or endogenous, usually find their way across my table at some point. 1s Um, yeah. No, I've had I've had multiple people tell me that you would be a great guy to talk to about this topic because you are, uh, very much in it in terms of looking at like what we do and do not know when it comes to the usage of exogenous ketones across kind of a variety of different, uh, targets, whether that be kind of performance or recovery. Yeah, yeah. Look, lots to talk about. So let's get on with it. Yeah, yeah. Let's jump in. So I think maybe for the listeners, if they're kind of a little new to this, they're probably aware of Josh's ketones. I would say most people listening to this podcast probably aren't like what is what is what is he even talking about? So where they may kind of be in a position to, to, to get updated on maybe what we're talking about here is just like. When I say exogenous ketones, that's sort of an umbrella term. So if I went into the store or online, I just searched for an exogenous ketone. There would be a variety of different types of that fuel source, if we want to call it that, um, that, that I would potentially be able to purchase or come across. So would you be able to give us kind of like an overview of just like kind of what is out on the market when it comes to exotics, ketones that, uh, an average person just go and buy if they wanted to. Yeah. So I'd like to start just by explaining to people that, uh, ketones are a molecule that are produced within the body anyway. And generally speaking, the kind of rule of thumb is that, if there's a deficit from a carbohydrate availability point of view, whichever way that is produced, that the, the, the production of ketones is then amplified. So this can be overnight fasting. It can be a ketogenic diet. It can be starvation, these types of scenarios. So really what the companies have done is to manufacture ketone bodies in a way that's orally ingestible. So as far back as the 1970s it was possible to infuse ketone bodies. And, um, there were many, many studies published in that area at that time of, you know, the 70s, 80s, 90s, where the really dramatic metabolic effects of ketone bodies were demonstrated, but largely through infusion studies. And, you know, fast forward then, into the kind of, uh, you know, this part of the last part of the. Last decade. So about ten, 15 years ago and you had an increase or kind of more availability of exogenous early availability. So ingestible forms of, of these ketone bodies. So effectively what we have now is a number of different mechanisms by which you can ingest either ketone bodies or what we'd call ketone precursors. And they will increase the concentration of ketone bodies within the bloodstream. So if we're thinking about it, I mentioned fast and overnight fast. They're, you know, typically if we're talking about, you know, after a meal, ketone body concentrations are generally below 0.0. one millimeter. After an overnight fast, they might be 0.20.3 for people on a, you know, 24 hour or 48 hour fast, they may increase to 0.5.7. Um, people on the ketogenic diet, if they've ever done, um, a finger prick sampling, may have noticed a value somewhere between 1 and 3 millimeters. So effectively what we're talking about is different degrees of, of, um, carbohydrate availability, low carbohydrate availability, for that matter, are producing larger concentrations of ketone bodies. And so the comparison as such is, you know, when we ingest these different forms of exogenous ketones, um, to what extent do they increase ketone body concentrations within the blood? And I guess from that comes the question, does the dose matter? Does the concentration in the blood matter? And again, in the context of things like performance and recovery, like you've mentioned already. So that's kind of the background of such. And so I suppose the question you ask is, you know, what is available on the market. Um, so I suppose where do you start? So there's lots of different ways to start. We can start at the bottom or the top. Um, but I, um, let's start with just the concept of the ketone ester, which I think is what most people are familiar with. And really, I break it down into a, into the idea that the ester piece is referring to the fact that you have two molecules that are bound together with an ester bond. So they're terrified. And the ketone esters that were U1 generally talking about is the so-called ketone mono ester. So it's available from delta g. It is one of the versions. Ketone is another haeggman used to sell it. They don't any longer. But this particular molecule is a beta hydroxybutyrate which is the ketone body. When I was referring to concentrations in the bloodstream, beta hydroxybutyrate was really the ketone body. What I was talking about there. Um, that is a starfighter bound to this molecule called butane diol. And butane diol is what we call a ketogenic precursor. Essentially, if you were just to ingest butane diol by itself through a process that uses an enzyme called alcohol dehydrogenase, you actually elevate the concentrations of hydroxybutyrate. So the reason I started with the, uh, the ketone ester as a concept is because it kind of nicely illustrates that. On one hand, you're ingesting, let's call it pure hydroxybutyrate. You're just alongside a ketogenic precursor. So by having the kind of pure BHB, for want of a better word and the precursor, you're kind of getting a double whammy effect where you're providing ketone body directly more or less into the bloodstream, and then you're also generating within the body via the precursor. So because of this, um, double whammy effect, so to speak, and might also say purity which, which we can get into, but that they're the molecules that tend to produce the greatest increase in hydroxybutyrate or ketone body concentrations in terms of per gram value, that they are per milligram value as we use. And so they tend to have the supremacy in terms of what people are interested in, what we use in research and so on and so forth. But ultimately, there are a large number of other, um, molecules that are available on the market that can do, um, that they can have effects on ketone body concentrations within the bloodstream. They're probably not as, um, as efficient or effective as raising hydroxybutyrate concentrations, but they are a lot cheaper. And the question then becomes striking this balance between, um, you know, how high would you like to elevate the ketone body concentrations? For how long would you want to do it? Um, how much are you willing to pay for that? And, you know, other things, considerations like taste and, and, um, transport ability and so on and so forth. So, um, so that's the ketone. Esther. Um, um, explain anything you want to jump in with before I move on to the others? Uh, yeah, maybe just, uh, as long as we kind of have that out on the table. Just a clarifying question. So if I would go with either the ist or the, the, um, um, the dial. Yeah. I'm going to get some form of exogenous or, I'm sorry, some sort of blood ketone response to that. The research would be pretty clear that these things are actually raising the blood ketone levels. Uh, is there specific, is there like a threshold that I need to cross in order to see that, or is that going to be like contact specific from one person to the next? Yeah. This is uh, this is really the crux of the issue because, um, the answer is we don't really know. Um, we know that there are dose response effects. Uh, again, depending on the outcome. And I'll explain some of those in a second, but we don't really know what's optimal. Um, so we wrote a review. Um, I think it was 2017. It was first published. And, um, I say this all the time because I do want, like, we proposed essentially, that there might be a threshold or a sweet spot, uh, between about one and three millimeters. And, uh, the ketone actors are very effective at getting people into that range. The other molecules are less so. Um, but there are a couple of caveats to that that I, that I come back to. But effectively, the way we came up with this, um, 1 to 3 millimeter, uh, concentration was that we were looking at a number of different infusion studies and studies of different fasting durations. Um, and there had been at that time, in 2016, just one study published with the, with the ketone monastir. And we kind of, you know, taking all of this on board and just having a best guess, we thought that there were some scenarios where there was a lack of effect observed below one millimeter, and there were maybe what you might call, um, detrimental effects, or, let's say, the reasons to think that going above three molar molar might not be a good thing. So it was a guess. Uh, it remains a guess. Um, we wrote an updated review in, um, just published late last year. Um, we're sticking to our guns in terms of expecting that there's probably a, you know, a zone, um, where it would be ideal to get into. But we're probably less firm on what and what those concentrations would actually be. So if you look at something like, um, there was a study a while back that, that infused ketone, um, um. Sorry infused ketone bodies to a certain concentration of BHB was kind of step wise. And what you could see is that there were metabolic effects that are as little as 0.5 mineral per liter. So, you know, again, when we're talking about optimal range and performance and, and so on, generally in my domain we're talking about either something to do with, you know, potentially acting as an alternative substrate to an exercise or modifying the kind of respiratory response to exercise or substrate utilization to an exercise. There is the kind of context that we're talking about. Or it could be, you know, how much might you need to take in the post-exercise recovery period. But I would say there are two things there. One is that there's not enough studies done at the moment to know whether there is an optimal range with these exogenous ketones. And number two, there probably aren't enough. What would you say? There aren't enough? If we're talking about performance, there's actually more studies that show a lack of performance effect, and there are studies that show a benefit of performance. So on the whole, I think we're at the moment where the conclusion, as we did in our review, is that, you know, it's very hard to see exactly where we could say there's a performance benefit directly during exercise. There's a little bit more evidence that may be accumulating on the recovery side. I guess we'll probably talk about both of those contexts as we go along here. But um, to summarize, really what you're asking is that like, yes, there probably is an optimal range in terms of what you want to get that concentration to, and that's going to influence. It's going to be influenced by the outcome, let's say that you're interested in it. But then that's also turned on influence, which is the best product for an individual. Yeah. No, it makes sense. And I think if I'm looking at it through the lens of whether I go with a dial or the Astor, my target should presumably be somewhere in that kind of 1 to 3 million range. And that's what my that essentially would be, the target I'd be looking for if I were to say be able to test that and kind of confirm while I'm out there training, racing, whatever happens to be the operating zone, so to speak. Yeah. So I agree. And so I suppose that brings us on to the other types of ketone supplements that are out there. So the reason we often say we emphasize mono ester and ketone monastir is because there is a ketone digester that was tested in one study back in 2017 or thereabouts by the group in Australia, Louise Burke's group. And that ketone digester has been extensively used in animals. But there's only one human study to date on it, and that's a slightly different ester in the sense that instead of it being a molecule, sorry, BHB molecule and butane diol, it's actually an acetal acetate, which is another ketone body and butane. So it's slightly different chemistry, bringing about slightly different effects in terms of ketone body concentrations. And in that particular study, it had a very clear detrimental effect on performance, although as explained by the authors, largely to do with the fact that it caused a lot of gastrointestinal upset. Um, so that's the so-called digester. And it'll be interesting to see whether that does get commercialized. And then there are a number of esters that are being developed, um, by a team at the Book Institute. And um, again, these are different um, ketone body precursors. So essentially they're using different short chain or medium chain fatty acids as, as the, as the ketone precursor. And so they're moving away, um, to, you know, different chemistry again, producing quite nice, uh, changes in blood, uh, BHB concentrations. But at the moment those aren't being used in context, at least as far as I know of sport. They're more being aimed more as, um, um, longevity, um, um, and cognitive function, actually, uh, more to the point. So, so they're the kind of classes of esters. The the BHB, the ketone, um, the ketogenic precursors, I should say, as a, as a whole, their, their own, uh, um, group. So again, going back a few years, although it's kind of gone out of style now, but there used to be a lot of interest, of course, in the in medium chain triglycerides being consumed as, as a ketogenic diet effectively. Um, so you would had, would have had things like, um, um, brain octane and these types of products that were, um, medium chain triglycerides. Again, some of them were um, um C6, C8, C10, so carbon length of the fatty acids or medium chain and of various again various different priorities. And again, some people can tolerate these very well. Others don't tolerate them so well and do get GI upset. But ultimately those medium chain triglycerides were generally even with fairly high doses, probably weren't getting people up to more than 0.7. eight millimeter. Um, in terms of of concentration, again, that varied. If someone was more ketogenic in their diet as opposed to more caribou. So again, there's some nuance there. Uh, butane dial that the dial that you refer to, the, um, ketone IQ, which is the molecule that, that hashem's and sell. So that's, that's butane dial. And that is a ketogenic precursor. And again, a couple of, um, studies that at rest show that the butane diol molecule can produce uh values above one mil molar. Um, the couple of studies that were done during exercise and remembering exercise, you've got, um, you know, when they when it's been ingested, you've got a relative appearance of, of the ketone body within the bloodstream. But during exercise, there's a greater disappearance because there is evidence that the muscle will, uh, will burn some of the ketone body. Um, so in effect, what we see is that at rest, um, sorry. During exercise, the ketone body concentrations that can be. Produced with something like butane diol tends to be rather low. Um, and to try and bump them up any further does tend to have either that kind of, uh uh, what would you say? Euphoric effect? Um, kind of a drunk -like effect. Or they do tend to cause, uh, gastrointestinal. So it's, uh, it's a tricky molecule to work with from, from that point of view. So again, um, the likes of, uh, medium change sides and to, you know, smaller number of studies on, on butane. These have been tested in performance contexts and generally not shown to be beneficial, which again is why people tend to fall back to the Asta as a better molecule. Um, and then lastly then is probably to mention the uh, the ketone salts as a call. So I think when people walk into a store again, I haven't been in the US or Canada in a while, but when was the last time I was there? Um, I'd probably looked in the stores a couple of years ago, and there was a, there was a lot of ketone supplements on the shelf. And I guess there's even more now from lots and lots of different companies. And again, a little bit, uh, unclear as to what exactly what we're in these products, but, uh, the vast majority of them, um, tend to be ketone salts, which effectively means the BHB molecule. And rather than being bound to a butane molecule, it is bound to some form of salts or sodium, potassium, magnesium chloride, and these ketone starters, uh, they're a lot cheaper. Um, and they're reasonably effective at increasing blood ketone body concentrations. But they do come with the downside of, again, as you try to ramp up the intake in order to get those ketone body concentrations a little bit higher, you have a greater salt load. And as a result, you tend to have gastrointestinal issues. We saw that in one of our studies fairly dramatically. So the point I make and I, um, I probably have to go into a little bit of chemistry here just because there is an important, um, development, I guess, that's happening in this field at the moment. So, um, up until relatively recently, the ketone salts that were for sale were generally what we call racemic, uh, ketone salts. And the chemistry piece there is really that, um, again, some of you, some of your listeners and viewers may have heard of these, uh, the idea that you can have, um, uh, left and right handed molecules for, for want of a better description so you can have a ketone in the case of, um, BHP beer that we have and talk about the R form. And there's also the S form of the BHB and effectively what you're talking about there. So s used to be called D and L just to add even more, uh, complexity to it. Um, so these salts, when they were originally, um, a few years ago and even when we first reported on, we would have talked about DNA, but now they're referred to as R and S, but. What I'm basically getting around to saying is that in the case of the what's, let's call it bioactive within the body, it's the AR form. And if you imagine you're buying this ketone salt and it's got R and S in equal measure, effectively what you're getting there is a molecule that's kind of half as, um, effective as it might be. Now the SP molecule is doing something, but that's kind of beyond the scope, I think, of what we need to talk about. Um, but the R molecule is the one that is probably doing most when it comes to metabolism, and it's also the one that we measure with any of these ketone meters. So kind of a long winded story here. What I'm getting to say, and is that when people in the past have been and a lot of the companies are selling the, um, racemic, uh, ketone salts, they're selling a molecule, which of which half is probably not, you know, really that useful in a performance context. And over the last number of years, I'm not sure if there is one that is commercially available at the moment. Um, but I've seen some preliminary research data where there's now more pure versions of ketone salts. So there was one. There definitely was one study published out of Jeff Lab, where I think, if I'm not mistaken, it was something like 73% was R and 27% was S instead of a 5050. And I have seen some data from uh, 100%, uh, our form of, of the salt where the change in beta hydroxybutyrate concentration is really impressive. It's well over one millimeter. So my my long winded point there is that, um, when someone walks into a store and they buy a relatively cheap ketone salt, uh, off the shelf if they're ordering online, and it turns out to be a racemic form either designated by DL or R s, they're probably not getting a very good molecule. And I just would keep an eye on this field at the moment, because we've generally concluded in our reviews, in our papers that ketone salts won't do much. But if we move to versions that are pure, um, RB, I think that may change things, and it might need less salt as well, which might solve some of the problems with the GI upset. So I do think that there's something to watch within that space, because you could have effective molecules that are a lot cheaper than the ketone ester. And again, I'd be interested to see how that develops over the next while. Do you know what the salts and the digestive issue that they had was that that was in the context of like an intro workout performance type study, or was that just generally speaking, people were getting digestive issues because I can think of this as like, let's say I decide, okay, the salts are going to get me into range. Maybe I use them as a recovery tool versus an intro workout tool and potentially bypass the digestive issue when I'm not doing it during a session. That's a great point. So, um, by and large, the effects were seen during exercise. Um, okay. The only the only anecdote I would say is that when we were doing some pilot work, but now this is again, this is going back, um, when we published that first paper, 2008 or thereabouts, it's going back a few, five, six years at this stage, uh, we at rest just as part of our pilot work. We're trying to ramp up the amount as much as we can. And we were having those GI issues even, even at risk. So, um, again, as I said, uh, there's probably better products available now, better purity, less salt. And in fact, I definitely think a couple of companies have talked about having reduced salt load in their products. So I think you make a good point. If we thought that at rest, we just needed to get up to 1 million molars and that can be achieved with salt. Um, because again, bear in mind and we'd probably talk about some of these studies, some of these astro studies are using lots and lots of ester for prolonged periods of time during recovery. And you know, we talk about the expense of one. And I don't we haven't actually said that yet. So if you're talking about almost one dose of the ketone ester, you're talking about $30. Um, if you're talking about one dose of the ketone salts, it's maybe somewhere between $3 and $5. So, you know, the, the, um, the cost of, of the ketone esters can be prohibitive to, uh, to some people, just especially if you're targeting relatively high concentrations, um, and doing it over a number of hours, you know, then it becomes really the, the purview of the elite athletes, um, probably elite professional athletes to. Yeah, yeah. You can rack up the price tag pretty quickly just playing around with it for sure. Uh, I want to back up just a little bit and just say like, let's say, for example, I decided as an athlete or, or whomever that I was going to try to do this, but I wanted to make sure that I was hitting some of these ranges and let's go with that 1 to 3 mile range. So I go and I get my blood ketone monitor and I test my blood ketones. I take some of the yester I get up into that range. In theory. Could I start working out and then periodically check that to just kind of see am I getting in range and start piecing together a protocol that I could use for myself, where eventually I would like to get away from having to prick test and but if I know, kind of like, hey, in this context, I'm hitting because my experience is like 1 to 3 is a pretty wide range. So like obviously you need to get up to one. You don't want to exceed three. But I think I could probably pretty accurately come up with a formula with a little bit of testing in certain contexts. Of how much of that Aster I would take to land and that 1 to 3, and then just kind of piece out what the frequency would end up being like that. Is that something that, um, you could see being feasible or is that still a pretty tough, uh, tough scenario to, to be, to, to, to actually put into practice? Uh, no, I think, I think what you're suggesting is, uh, is what people should be doing, to be honest. Um, so, um, I think we can talk about maybe how best on an individual basis to decide if it works in the comments. Um, but I think the first point would be establish the doors that that's right for the individual. And so in the case of the ketone ester, um, many of the studies are done on a milligrams per kg of body mass basis. So although you can buy again depending on the company, something like 2025, 30g of of ketone ester within, within the the shot, so to speak. Um, when we're doing it in a research study, we generally weigh it out, uh, or measured out in milliliters in terms of trying to hit a target per kg of body mass. So effectively what what can be done is, you know, someone could read a few of these studies. And it actually turns out that across studies, um, there's a range of different protocols that are used. Someone's like a single dose and then maybe the person exercise for an hour. Others are that they give multiple doses over the course of, say, 90 minutes or 2 or 3 hours. Um, and so what you end up seeing is that, you know, with a little bit of, of, um, intuition, just by reading these graphs, you can kind of get a sense of, well, I'm going to be out for less than an hour, so I don't need multiple doses. I'm going to be out for three hours, which means I am going to need multiple doses. And like you described there, it's a little bit of trial and error in terms of where the person starts out and thinking about again the duration of the exercise. But doing a finger prick sample. I don't think you need to do it any any more frequently than every half hour, or even maybe every hour. If you're going to be out there for five, six hours, you know? Um, but it would, it would be the longer the duration of exercise too, probably would need to be top up doses. So, um, what I'm seeing at the moment, again, if I just think about the studies that have been done, generally people are using around 500 mg per kg of body mass as an initial dose. Um, so for someone who's a, you know, 70 kilogram, for example, that's going to be roughly one of those shots. And then what tends to happen is that the top up is about half of that, and it's occurring every 45 minutes to an hour. So almost like a half shot every 45 minutes to an hour. And that will generally get people into the 1 to 3 millimeter range again, uh, depending somewhat on whether the person's ketogenic or carb and whether they are consuming food or not. Um, during the exercise session. But anyway, to again, to a long winded answer to your question, is that in short, you can actually titrate with dosing and again measure it and probably not have to keep measuring it every time you exercise. Yeah. No, this is great, I think. Bring on the long winded answers as far as I'm concerned. I think this is important, though, because I'm thinking of just like the people who are going to likely listen to my podcast, and it's going to be a range of people who are on a moderate to high carb diet, to people who are on a strict ketogenic diet. So, like, there'll be people listening to this who'll be like, well, if I went out and did my long run, I'm going to if I test my blood ketones, I'm already in the 1 to 3 million range. And the way I think about that, I was like, so there, if I'm thinking of it through the lens of that person, and then I'm thinking about an exogenous ketone and where that might fit in my toolbox, if I'm going to use it, I would be thinking along the lines of, is this something that I can use that will reopen the carbohydrate toolbox, which I'm more or less likely removing almost altogether? In the case of if I'm already at a 1 to 3 million mole while I'm out there. So I'm thinking like a race setting now all of a sudden, instead of trying to take in some of these like fat sources of fuel during the event, maybe I do go back to some carbohydrates, get the benefit of that, but not lose the 1 to 3 million mole ketone range that I was having by abstaining from those. So if I'm like the strict ketogenic athlete. Is that something worth considering? Or is that something where if they're already in that 1 to 3, they should just leave the carbohydrates alone and keep cruising along? Yeah. This is, uh, this is a brilliant question. And, um, I guess maybe you and I are going to tease this out as we talk here because, uh, the answer is we don't, we don't know for sure. Um, so let me give you a few different perspectives. Um, when you look at some of the older studies that were done in the, uh, as I said, in the 70s and 80s, the model they often used was, um, different durations of fasting. So, like, you know, an overnight versus two day versus five day type scenario. Um, and that would produce different, um, uh, ketone body concentrations in the bloodstream. They would then have the people exercise. And in one study, they did infuse, uh, ketone bodies and what those studies are in summary, what they simply what they show is that the the deeper the person is in ketosis, in this case, by prolonged fasting, the less ketone bodies they actually use as a substrate. So we kind of, uh, have this idea that if someone is on a strict ketogenic diet and they then take a ketone ester on top of that, there might not be a rationale for why that would be beneficial. Um, so I'll be keen to maybe get your sense of whether you've tried that or not, but the, the other, um, perspective, just to add to it is that there was one study published today and again out of Louise Burke's group in, in Australia, and they, as you know, they do study the um, ketogenic or low carb, high fat type interventions with within, um, elite athletes. And uh, just one of their studies actually was a scenario where they had people who are on a low carb, high fat diet and then provided them with the ketone ester, the monastir, on top of that. And again, the, the, the, uh. Diet with only five days, if I recall correctly, seven days, but certainly it was short. And so it kind of left a bit of an open question, like had the people adapted well enough to be able to use ketone bodies as a fuel as opposed to just fat adapted and etc., etc.. There's lots of unanswered questions, but the, um, the point I'll overall make is that the question you're asking, I used to get asked an awful lot, and I couldn't and still can't really give an answer of yes or no. Like, would it be a good idea for a ketogenic diet, an athlete on a ketogenic diet to then use the ketone ester? Um, and I suppose my thinking is that if you think about the mechanisms by which ketones might work, and again, with the caveat that there's a lot of studies show that it don't work, um, I'm not sure that it would provide additional benefit in terms of performance in a strict keto athlete, but I'd be interested to know whether you've directly kind of assessed that in your own performance. Yeah, it's an awesome question. And I, I probably am not the best case study because I'd be more in the low carbohydrate category versus the strict ketogenic category. And so for some for some details on that, like so if I would test my like if I'm, if I'm out there doing a any sort of exercise and things like that, if I test my blood ketones, they'll be at their highest usually like some at some point post-workout, whereas like prior to the workout or during the workout, I'm usually sitting more at like the 0.4 to maybe 0.7 million range. So for me specifically, my goal then, and this is kind of what my next question is like. Dosing for something like that, because I've got some thoughts just on my own end of one experiment here. My dosing is going to be different from both of those. Let's just assume the strict ketogenic person in a hypothetical decides I'm going to have some more carbohydrates than I normally would. I'm going to mix that with the exogenous ketone. I'm going to maintain my Miller moles and I'm going to have this, you know, extra fuel source essentially available to me that I didn't have before. Then there's me who needs to take one more step up to get to that 1 to 3 million range, but I'm already including some of that carbohydrate. So I'm sort of just coming from the opposite direction as the strict ketogenic person. Uh, so what I've noticed with that is like, I'll take, uh, I'll take like a bottle of that delta G performance and that'll shoot me well up into that 1 to 3 range. Um, and then I'll start, I'll start going and, um, I don't have data beyond three hours. I have done some events where I've done it. I've just basically like, I'll just side note real quick. So when I first got curious about this stuff last year, my big question was, all right, I think I can thread this needle in training, but what does that mean when I'm out for, say, 15 hours? So I actually did a 100 mile race last year around this time where I just kind of ran. I just extrapolated forward essentially my protocol for a three hour long run and just did it. And I just just basically confirmed that nothing crazy was going to happen where I would be like, oh yeah, that was terrible. I had a massive digestive issue. Or like, I just, you know what? You know, anything that I could pin to ingesting that, uh, exogenous ketone that I could say, okay, yeah, that's just not a good idea for durations this long with my current formula. And it worked out. So I don't have data on, like, what my middle moles were doing in those hours beyond three. But my protocol that I was using going in was essentially I'd have one before, and then I would take another full dose of the delta g performance at three hour intervals. So, um, this is something where I just can't. These are actually floating around now. I'm not sure. I don't think you can get them, but I think if you know someone, I think you can. But you have it, you're going to get exogenous blood ketone monitors now. So 1s I don't know where you fall on the, the, uh, the idea of just like the, um, the, the, the, the monitoring of this sort of stuff to begin with. But like, I could imagine if there's a scenario where, all right, I have this exogenous, I have this, this ketone blood monitor that's giving me live data versus I got a finger prick every time. And I can start to see, okay, I'm starting to drift down closer to that 1.0 number. I'm going to do some delta g performance, maybe pop up to ride that and just kind of just stay in that loading zone and be able to respond more, more specifically because in a scenario like that, I would just wear that thing in the race. And, you know, whether I follow my protocol that I'm doing in training strictly or not would just depend on what that monitor was telling me, assuming it's accurate. Yeah. Yeah, that's what might be an issue. But no. Yeah. So yeah look there's a lot of a lot of threads here. So the um, I suppose if we, if we go back to the question of um, in say an ultra performance, um, the use of low carb or keto type diets, you know, what is the benefit of those compared to, you know, I do a lot of work in team sports, for example, and we're all high carb, uh, in terms of performance and my take on it. But again, jump in and correct me if I'm wrong. Is that one of the things that, uh, the lower carbon keto diets will, will kind of guard against in some ways is that you're very unlikely to have an issue of fatigue caused by hypoglycemia or an absence of substrate, because you've got so much fat and ketones floating around in there. Um, the other advantage is that as you go beyond, say, 3 or 4 hours of exercise, you know, the gut does begin to slow down or shut down. Some people might say. And so this idea of constantly having to rely on sports drinks and gels in order to keep those blood glucose concentrations up, that becomes problematic. And so, again, in the case of the low carb or keto scenario, you're not having to rely so much on that as fuel. So the overall approach and whether it's low carb keto in ultra sport is, is kind of like it's, it's staving off, um, hypoglycemia and cause of fatigue related to hypo. Um, so. So it's a little bit different to the idea that it's the diet that is providing, like the optimal substrate for the optimal high intensity performance, which is the kind of way we think about carbohydrates in the context of team sport. So and again, like I say, if there's anything that you want to jump in and correct me, please do. Um, but I guess if I frame it all, my next point becomes, uh, using a ketone or, you know, bumping ketone concentrations higher than, say, one, two, three millimeters. I'm trying to think of a mechanism by which that would benefit performance, um, or, or like, um, mitigate a decline in performance or might, might come along there. And that mitigating of decline is kind of I'm sort of not deliberately, but it reminds me that one of the elements that's been recently reported is this idea that in long duration exercise or in mentally demanding exercise scenarios, the ketone uh, ester supplement can actually mitigate those declines in cognition and cognitive performance that can occur. So now we're actually into a much more holistic picture of performance when we're moving into a very long duration, admittedly kind of low to moderate intensity. Um, but it's not just about the substrate to the working muscle. It's about the gastrointestinal system and its tolerance. It's about cognition and maybe mitigating declines. And so I just think, you know, some people want these very definitive answers. My kind of position at the moment is that there's a lot of reasons why we think there could be some use in different scenarios, but a lot of it is just kind of guesswork and speculation. It's very difficult to nail it down. And that's why I think even your end is an interesting story. Um, in terms of what might be possible there. So it's the fact that there were no negative consequences. That's always a good start, you know. Yeah, yeah. And it is always hard to compare because like even with the cognitive stuff, it's hard to separate like, well, was I just, for whatever reason, more prepared to take on that task on our 12 of this race than I was last year at that time or whenever? Um, I will say, like for my own, just kind of perception in terms of kind of how, you know, all the all the normal caveats here of like placebo effect. Obviously, I knew I was taking an exaggerated ketone. I knew of the potential cognitive, uh. 1s The performance issues or scenarios that could be there. The thing that I thought was maybe I'd be interesting if this is anything this has even been seen in the research at any capacity, is one thing that I find really interesting about these long ultramarathons, as it seems to me that there is a a battle of just kind of mental fatigue in the sense that it's some of its decision making fatigue. And one of the preps that I'll do and I'll coach people I'm working with to do is how do we minimize that decision making mental fatigue when we're going to be out there that long? So how we do that is we try to work on focusing on a smaller list of things and having sort of a Rolodex of more intuitive responses when certain things come up, because then you just make the decision, you move on, you make the decision, you move on. I think the more you can do that, the less you're draining that mental battery, so to speak. And I've always found when with the exogenous ketones that it seemed like I had an easier time doing like, like zoning in on what I'm supposed to and not letting whatever background noise was potentially there kind of creep in and distract from that. Um. And I mean, if that ends up playing out in any sort of like proof in the research, I would say that's probably for an ultramarathon. Yeah. Would be one of the bigger potential advantages there outside of, you know, any sort of like energy availability type of thing. Yeah. Cool. Just, you know, 2 to 2 responses to that. So, um, we have a couple of papers and, uh, the kind of points in that direction. Um, so one of the first studies that we published was looking at an intermittent running protocol that was designed to mimic soccer performance. And in that particular protocol, it's run on a 20 meter track. Um, but the person and they've been given instructions all the time by the researcher, but they've been either told to walk, to jog, to cruise or to sprint. And this is going on, you know, over 90 minutes. And we think that it turns out to be relatively cognitive demanding too, to kind of be listening to instruction and changing your pace and all that and so on. So one of the things that we observed in that particular study was not that there was any physical performance benefit, but when we looked at, um, uh, like you said, decision making specifically, um, what we saw was that at the end of the protocol, when we looked at mistakes made in this, in this decision making task, the number of mistakes made was less in the ketone group compared to the carbohydrate alone group. So like ketone plus carbohydrate versus carbohydrate alone. Um, but then when we subsequently did another study of a similar duration, so it was one hour on a treadmill, just running, looking at a wall and then a 30 minute time trial, um, or sorry, ten kilometer time trial, which. Took around 35-40 minutes. Um, but in that particular protocol, we didn't see any decline in decision making. And our thinking again, it's only two, uh, studies, but our thinking is that the, um, the intermittent running protocol was more cognitively demanding. So there was a decline that was observed. And what the ketones did in that scenario was to mitigate the decline. Whereas in the running on the treadmill, we didn't see a decline. So there was no decline to mitigate. So that was kind of the way we were thinking about it. And again, those studies were published a few years ago at this stage, but to the point about ultra. So this is my second part of the response. Um, Peter Haspel's group out of Out of Belgium published a paper last year where it was done in ultra athletes running. If I'm not mistaken, a 100 mile could be 100km. Um, but anyway, it was a long run. And, um, now the slight, um, weakness of this particular study was that it was a parallel group. So it wasn't what we call a crossover design, where the individuals do like, you know, the carbohydrate plus ketone versus carbohydrate alone on two separate occasions. You know, it's a little bit difficult, probably to do a study where you might ask people to run 100km, you know, twice in a couple of weeks or something like that. So effectively what they did was they did a parallel group design. So there's a slight weakness in that. But what they did observe in the, um, in the group that were using the ketones in that particular race was that there was, again, this mitigation of decline. So, you know, you're describing a scenario where they've a lot of decisions to make and mental fatigue kicks in. That's kind of the way that we're thinking of it, that that does happen with prolonged exercise or exercise where there's a lot of cognitive tasks and effectively the ketones aren't, you know, they're not, um, dramatically improving cognition or they're not making people more alert or any of this kind of stuff we sometimes hear said they're effectively just mitigating that decline that is naturally occurring in these types of events. So, you know, to your point of view, saying that would be a big deal, separate to substrate availability. I think you might be right. And you know, the point I always make in the context of the team sport environment is that, you know, a couple of bad decisions in a team sport are the difference between winning and losing. And, you know, I don't know the ultra sport well enough, but maybe a couple of bad decisions are, you know, enough to send you off track or cause you to trip or, you know, do a variety of different things that could occur. So it's I do think it's one of the again, more interesting, um, findings that have come out over the last couple of years is this whole area of, of cognition and what might be, you know, mitigated in the case of ketones. Mhm. Yeah. It will be interesting to kind of see what gets, uh gets done. It's my understanding that the tour de France athletes are already all on this. So that means there'll be money coming here for research. But again, it's an interesting point about the anecdotes because, um, you know, when you look at the history of how the stories began to kind of come in the media, and I was like, you know, I forget which team was using it, were getting a benefit, and then they're denied it. And then, you know, another one of the cyclists would come out with the athlete and say something like, you know, these ketones are legal, they shouldn't be used. And then someone else says, but how, you know, you kind of play that standard. If you look at all these other supplements and you know, this story is kind of rumbling normally. And it was still very hard to get a picture of who was actually using them or how widely they were being used. But what I've seen again, and just knowing 1 or 2 people who are reasonably close to the sport, they are being heavily used by a number of teams for recovery, um, less so in the direct performance context. Again, there may be some that are doing it, but, um, you know, the odd time you will see like someone relatively soon after race, whether it's in a press conference or whether it's, you know, in the mix zone and they're, they're throwing back a ketone shot. So and again, that links to the anecdotes that I'm hearing from different people that have been fairly widely used during recovery, which is an interesting development. Um, let's jump into that, because I think that's been something that I've been maybe a little more interested in from a long term scale, because that was sort of the initial round of research. More or less suggesting that that was where you should be focusing your energies. If you're going to go into this with any sort of protocol. What is it that we're seeing in terms of recovery? Well, is there any sort of data that would suggest, like if I do this other must be like, I do this versus nothing at all, like where are we seeing the benefits from it? Yeah. So the first couple of studies were actually focused on muscle glycogen because that's kind of been in the, in the performance uh, nutrition paradigm, particularly around recovery. It's kind of like focusing on recovery muscle glycogen, focusing on rehydration and focusing on muscle protein synthesis. That kind of anabolic recovery growth response. Um, so the initial couple of studies done around 2017 or so, they focus on muscle glycogen. One show that there was a benefit to ketone supplementation in terms of improving muscle glycogen synthesis after exercise. The other study showed that there was no effect. So this is true of many of the ketone studies. It does seem to contradict itself left, right and center. But um, in the second of those studies, there was a little bit of an indication that there was at least at a molecular signaling, um, level, that there were more, more of an anabolic response in the presence of ketones compared to, to carbohydrate alone. So carbohydrate and protein versus carbohydrate plus protein plus ketones, so that that tri combination seemed to be better. From an anabolic point. You again kind of an indirect um assessment based on muscle signaling molecules. But I think there was enough there to suggest that, you know, something was worth taking, and that that particular study, again, was by Peter Haspel's group in Belgium. And so they followed that up a couple of years later. With the study, which I think did really change the way that people thought about how ketones could be used. And so in that particular study, they buy their own, um. Um, description. They were trying to mimic the demands of a really intense three week race. And now the individuals in the study were recreationally active, but they were able to cycle. I mean, they ended up doing two sessions a day, um, six days of, of the week for, for three weeks. And the recovery protocol was to use, uh, ketones after each exercise session and then to have a dose right before bedtime as well. So over the course of the, uh, the three weeks, um, again, there's a lot of data within the, in the paper, but the, the top line summary is that there were a couple of tests that they did where they saw greater work performed, um, in the ketone condition compared to the placebo condition. And this is not to do with, say, a ketone as a fuel. This is to do with, um, essentially the blunting of the overreaching response that would typically take place with such demanding, uh, training. And what becomes a little bit controversial about that particular study is that what's obvious is that the ketone group, um, they end up eating more food, um, over the course of the three weeks. Um, it's not obvious in the first couple of weeks, but by the third week, the ketone group is eating more food. The argument is that they're recovering better and that that's what expands the difference. And, um, you know, I can see the argument there. Again, from a purely scientific point of view, you want to know if the effect is due directly to the ketone or is it indirectly through this alteration in appetite. So if it was happening, instead of appetite being suppressed with this overreaching, it's not being suppressed. It's, you know, because the ketones are there. So you see a lot of debate about that particular study. But when I put on the other hat, which is as a practitioner, it'll be, well, I don't care how it works, it seems to work, you know, and um, and that's, I suppose, where a lot of people have gone with that, and that's maybe where the professional cycling teams would look at it and go, you know, we have the budget to cover something like this. Um, it's very unlikely to have a negative effect. It could possibly have a positive effect over the course of three weeks. And again, I won't go into all the molecular details, but there's a good rationale as to why ketones will be useful, either as an anti catabolic or anabolic agent. And we've written a little bit about that. Um, but the other piece which becomes really interesting is just again in the last year. Um, so that paper again was probably published, um, you know, 2020 or so, it's 3 or 4 years old at this stage. Um, but the, um, just in the last year, there's been a couple of other interesting papers, one effectively showing that, um, EPO concentrations are elevated during recovery when ketones are ingested during exercise compared to when they're not. Again, the effect is relatively modest. The question is over how many sessions and over what duration would EPO need to be elevated in order to actually have a real effect on red blood cell volume? Um, but it's interesting. Uh, so that's the recovery effect. And then the other story that was published was an improvement in sleep, um, when ketones were ingested as part of recovery as well. So, you know, you begin to put all these things together. And again, it's one study on this and one study on that. But at the same time, you know, as you well know, um, as an athlete, you're looking for an edge and as a team who might have a budget to fund something, they're looking for an edge and they will take a risk on things that might just have 1 or 2 studies to, uh, to support them. So I do think that that's where the, um, the direction of the field has gone. It's this idea about recovery. Because again, off the top of my head, it's in the region of 2025. Papers have looked at performance now. And it's, you know, it's a handful of 3 or 4 that have actually seen a benefit. And again, you look into them like it's with bicarbonate and it's kind of, you know, it's very nuanced. Whereas the recovery side of things just seems to be a little bit more concrete and obvious. And I do think that that's where things are going. You mentioned kind of the protocol for the recovery research, which was a shot of the exogenous ketones post-workout and the one before bed. Is there a similar metric that someone can measure to see if they're kind of hitting the targets, like there is with that 1 to 3 million goal during the training session? Or is there just something unique about the total in the recovery side of things? Yeah, that's a really important point here because um, again, if we go back to the cost like these are, I should have said all of these studies now are ketone ester studies. Um, so again, I may have the numbers not exactly right here, but generally speaking it's looking at like a shot every hour or thereabout or maybe a shot on the first hour and then a half a shot, half a shot. You know, it's that type of recovery protocol. Because typically in recovery protocols we're kind of looking at carbs and protein at a ratio of two or 3 to 1 consumed every, you know, 60 or 90 minutes for a number of hours. And the ketone shots are being taken alongside that. Um, so ultimately, like you're looking sometimes at the recovery protocol could look like $100, you know. Um, so it becomes expensive, but it hasn't there hasn't been any, um, let's say drilling down with the details of does the concentration matter? It's more like the convenience of like the 20 or 20 5 or 30 gram shot being taken alongside the carbohydrate and protein, and that's where the effect has been had. So again, with all of these studies, you know, I often make this point that some of the recommendations that we have for things like carbohydrate, we're down to the grams per minute, we're down to the ground for kg. And that's because there's been 30 years of research. Whereas in the ketone situation, we're probably at the moment it's kind of like a scattergun approach. See, is there any bit of, you know, a hint that there might be something worth exploring and then maybe people will drill down more into those questions around dosing and timing and and so on. But I think we've a lot of work to do from that point of view. Yeah, it's one of those things where anytime you answer a question, you probably create three more. Yeah, yeah. So it's a natural resource. Yeah. Yeah. It's interesting stuff though I think like, yeah, I think when you're when you're talking about a practically, you know, I think most people outside of like professional teams and athletes are going to look at it as, uh, you know, where does this fit within my budget too? So like, I think, um, if I were to go about it in a scenario like that, I would probably be thinking like, is there any value in, say, buffering some of my larger training sessions where I stand to have the biggest, uh, training adaptation from or that are the most specific, uh, to what I'm, what I'm trying to do on race day and maybe buffer some of those sessions with it versus it or even, I guess maybe if we're looking at the context of ultramarathon, it could be something where I'm going to do a handful of these races per year. Maybe I buffer those as kind of big training adaptation sessions, because they're going to be very specific to whichever race I'm doing for that duration. Yeah. And like I think it kind of what's in your point is that there are other things to focus on as well, and that they kind of need to be dialed in. And, um, my view would be that, you know, if you're looking at you've just done something, uh, intensive, whether it's glycogen depletion exercise or whether it's a very intensive resistance training session, like the the major blocks that are boulders that say to put in place when it comes to recovery will be the carbohydrate and protein provision. And no amount of ketones is going to rescue this. In my opinion, it's going to rescue the scenario where you don't hit those targets first. And similarly, like, you know, there's a lot of things you could spend money on, you know, $100 of recovery. Um, you know, what would $100 look like in terms of better cash or, you know, an adjustment to a bike or, you know, there's lots of, uh, cost benefit analysis that would need to be done. Um, I would put, you know, supplements, for example, are really at the top of the pyramid when you have all of the other, you know, building blocks in place. And I think that's a message that sometimes gets lost. And again, I work with athletes directly, um, in team sport. And again, many of them are at their first question is, you know, what, can I take this supplement? Should I be taking this supplement? And it's not really oh, you know, how many calories do I actually do here to be a better balance? And, uh, should I do something about my body composition? You know, it's kind of, uh, it is that sometimes people have the pyramid upside down, but, um, so that kind of would be my point when everything else is optimal. Um, and I do mean, like almost optimal. Optimal. Uh, that's probably where someone might eke out another couple of percent with the ketones. But I think the idea of going straight to ketones as a strategy, it's just missing so many other things that could be optimized. Um, yeah, it is worth noting. Like, and it is funny because, I mean, it's literally right in the word supplement, like, but, but it still sometimes finds its way to be like like you said, kind of on lower on the pyramid. But yeah, I mean, the way I usually describe to people is like. Just do everything you can within your lifestyle that you can. You can negotiate to optimize sleep and optimize your training just the way you're training in terms of like order of operations, training, load distribution, just in the volume context, in the workout intensity context, and then the recovery side of it and it's like, uh, which is going to be sleep and nutrition for the most part. And well, and taking your foot off the gas pedal to some degree depending on how type A the person is. But um, yeah, it's like getting those all ordered before you start really drilling down on what can I do on top of this? So, um, yeah, it is good to know that like, yeah, if you're, if you're, if you're sort of just doing half measures on those big rocks, you know. Yeah. Sprinkling, sprinkling a bunch of like things that in the context of someone who's got those things fine tuned like a 2% advantage if you can find that, that's huge. But it's only huge if you've gotten the ones that are going to be sometimes double digit percentage advantages like rest and recovery, proper training and all that other stuff. Yeah, yeah. No, I'd agree 100%. Yeah. 2s It's really interesting stuff. I. I want to dive in a little bit in terms of just, uh, what we would look at in terms of kind of how this behaves. 1s When I'm taking this, I had some questions that I didn't really have the answer to, and one of them was that if I take something like an exogenous ketone prior to a workout, is that going to suppress my natural fat oxidation? And if so, does that give some sort of indication that I should either a not do it altogether, or b not do it before, but wait until I'm in the workout and I've already sort of upregulated a lot of the processes to start introducing that. Is there anything to suggest that, like you should be going one way or the other or neither at all? Yeah, that's another uh, important question. So, um, 2s again, I don't know the full context of the question, but there's two angles I think this could be referring to. One could just be the fact that, um, it is well known that, um, an elevation of ketone body concentrations will suppress. Adipose tissue hypothesis. So fat breakdown in the periphery and in so in one context the person might be asking, well, you know, I'm trying to lose weight, I'm trying to burn fat or exercise if I take ketones, is going to suppress that. My answer to that is that it probably will, but it's probably not a meaningful difference when it comes to the overall, um, approach to fat loss or to weight loss. You know, there's lots of other things that matter over the course of 24 hours up to, you know, 24 weeks in terms of how someone would lose body fat. So I probably wouldn't be worried about it from that point of view. But there is another point where the question might be related to which is that there is some evidence around, uh, studies that have suppressed, um, adipose tissue lipolysis with uh, there's a number of other mechanisms you can do by nicotinic acid is one method. But when you do that during prolonged exercise, it can actually have a detrimental effect, uh, in terms of time trial performance. So the, um, the, the, the issue there is that, um, if someone was, say, only consuming, um, a ketone, um, uh, supplement during exercise, suppressing adipose tissue lipolysis, which ultimately means that free fatty acid concentrations would decline, there would probably come a point at which there would be a detrimental effect on, um, performance. And that was one of the, um, when our most recent review, we kind of tried to break down, uh, the review into, uh, speculating on mechanisms why performance could be beneficial or benefit by ketones, but then also why they might be impaired by ketones. And that's one of the mechanisms, um, this adipose tissue, uh, lipolysis, the inhibition of that. So um, again, the answer I think to the question is it really depends on what the issue is of the concern is about weight loss or fat loss. I wouldn't really worry about it. Um, if it's prolonged exercise consuming only ketones, uh, I think the jury is out. I think there's a theoretical basis for why it might be detrimental. Um, but it hasn't actually been demonstrated directly with ketones themselves. Okay. Interesting. No, it's fun to go down the different, uh, the different questions. Like I said before, it's like one of those things where I'm sure this episode will probably generate a bunch of questions, too. Oh, that's cool, I wish, I would wish I would have asked that. Or maybe I'll have to think about that now too. Uh, yeah. It's been, uh, been really fun to, uh, to chat with you about some of this stuff, so, um. Yeah. Do you, uh, do you want to talk just a little bit about. I think we should probably just touch on before I let you go. Different intensities. We've been, I guess, maybe skewing a little more towards endurance. But then in my context, towards ultra endurance, which, you know, is a unique in the endurance sphere in that you're when you're getting up to distances of 100 miles, you're operating below your aerobic threshold, which is going to be a fair bit different than, say, if I went out to do something that is going to be like maybe in the 20 30 minute duration, which would still be endurance, but would be likely above my lactate threshold. Yeah, yeah. What do we know about the use of exogenous ketones and the variance there? If my intensity on race day is going to be different? Yeah. So this, I guess, parallels in some respects the, uh, the debates that have been had around ketogenic diet and its potential application and, uh, ultra versus, say, intermittent sports. Um, so what's often used is the same analogy, which is that, um, the case that's made against the ketogenic diet, say, for high intensity or for intermittent type sports, is that, um, with the ketogenic diet, you more than likely guess inhibition of this enzyme, pyruvate dehydrogenase. Um, and ultimately, what happens again in speculation is that maybe actually, maybe a couple of studies that would back this up is that you kind of lose the ability to really ramp up carbohydrate utilization when it's needed. So you kind of reduce your top end performance, for want of a better word. So, um, that mechanism, um, in theory it's not it's not identical with the use of exogenous ketones, but it is it is somewhat similar in that, um, the presence of ketones as a fuel source within the cell could potentially impair the utilization of carbohydrate. Um, that's the thinking behind it. Um, one of the indirect mechanisms by which that is shown, or people speculate, is that, um, in a number of different studies, but but again, not all studies, um, you see that lactate concentrations in the blood tend to be less, um, when ketones have been ingested. And the thinking there is that, um, there's a, you know, a slight inhibition of carbohydrate utilization. So the rate of appearance of lactate is reduced. Again, there's a lot of assumptions being made there. And it's uh, it's and again, it's not consistently seen. But if we kind of look at the overall picture, that's kind of the thinking here, is that, um, if you were to consume an exogenous ketone supplement, get those concentrations up in the one two three millimeter range, um, there's a there's a likelihood that to again, some, um, reasonably well established mechanisms that you could impair carbohydrate utilization. And if you were doing so in an effort that requires high intensity and reliance on carbohydrates, then you might get an impairment in performance. And ultimately, it looks like there's at least a handful of studies that do show that. Um, so we initially observed a trend within the um. Then the story that I talked about with the, um, with the, uh, intermittent running the soccer protocol, uh, when we did a short run test at the end of that, uh, that protocol, we saw a fairly obvious difference. But the study wasn't powered, but it did look like there was an impairment of performance. And that subsequently there's been, again, a study out of Peter Haspel's group. Um, it was around, uh, if I'm not mistaken, it was a half hour time trial. And then our American balance group as well. In Canada, there was another study that showed an impairment in performance. Overall, I think it was around, again, a 20 minute type, uh, protocol. So the, the, um, the thinking has become more that during very high intensity, uh, efforts that exogenous ketones would not be useful as a substrate. And I say all of that. And yet at the end of, um, last year, a study appeared where it was done in a pro cycling team, and they showed a benefit to performance, um, in the context of a seven minute type, uh, time trial. So like a prologue, um, and the again, the only, I suppose, caveat to put to that is in that particular study, they did congest uh, by carabiners. Um, but the control condition in that was bicarbonate. So, you know, the difference between the conditions was, was the ketones. Um, but again, it's, it's one of those things where there's a lot of mechanistic kind of thinking. And then there's a number of different studies that show this performance decrement. But then there does seem to be this outlier where there's a benefit during high intensity performance. So I would say that that is that that particular last study I mentioned is a little bit of an outlier, and maybe the bike cabin had something to do with it. But um, I think certainly in the context of, of the other studies, I wouldn't be advising anyone who does kind of, you know, less than 30 minutes high intensity or intermittent type activities. I think there's not really any evidence to suggest a benefit. And in fact, it looks like there could be a decrement in those kinds of contexts. Mhm. Yeah I think it sort of makes sense intuitively for me, I, I kind of compare it to like if I, when I'm working with coaching clients or myself for that matter, like if I'm going out for a hundred mile race, I may abstain from carbohydrates the morning of that, uh, to promote fat metabolism going into that low duration. But if I'm going to go do A5K, ten k if one of my coaching clients or if I should say if they do, they say, hey, should I if I have this carbohydrate before my race, is that going to suppress my fat oxidation rates? I'm like, I'm not sure I care. Like if you're racing a five kilometer, then I think you may benefit from suppressing it. You might want to go in that scenario. Yeah. Yeah. No, I think you're right. And uh, and that again is a thing that often gets talked about sometimes is like, are you looking for optimal adaptation or optimal performance? And so there are times when it might be beneficial to train on a low carb diet. And even in the context of, of team sports, when I work in, you know, we often almost I would actually say almost never provide carbohydrate based drinks. Uh, during training. Yet we will use them during performance or if, you know, if we're doing more of a skills based session, we definitely won't use them. But if we're doing a more of a well in the US and how do you call a scrimmage if we're playing 11 v 11 or 15 v 15 and it's an ER versus V type game, then we will use like optimal kind of fueling. So uh, in the context of what you described it, you know, if someone's doing an interval workout and they want to get the most out of that workout in terms of pushing themselves really hard, they're probably going to benefit from from carbohydrate. But if they're doing, you know, something where they're accumulating some volume and it's in and around threshold or below threshold, they're probably not going to need carbohydrate. I think some of those same principles we will ultimately start thinking about in the context of, of ketones as well. Um, yeah. It is really interesting when you get into the world of just looking at fats and carbohydrates as both being tools that you can use, and you step away from the online arguments of strict ketogenic diets versus high carbohydrates. Train your gut 120g per hour protocols. And it's like, it's like it could be that there are times where you might not want carbs, and there are times where you would. And kind of looking at it as, as that is, is useful. Yeah, it's good to hold the center ground on this because, um, you know, if you skew one way or the other to fire, um, you will get stuck on 1 or 1 or the other camp, and then you have to move out of there. So yeah, like I say, I mean, as you say, tools is a good word. Tools. And the toolbox is often used in performance nutrition circles. I think that's really what we're talking about, you know. Um, are you seeing with the teams you're working with more like seasonal nutritional approaches to where they're looking at it through the lens of, uh, like in this particular part of the season, I'm going to rely more on fat versus carbohydrates to some margin. Doesn't necessarily have to be like a low carbohydrate diet versus like when I'm in a speed work development phase, I'm just going to lean a little more heavily towards that. Yeah, I guess in the, in the team sport, uh, domain, the, uh, the season looks a little bit different than it would in sort of endurance sport. So um, and say pro sports, they're playing often they're playing two matches a week. And, you know, effectively it's just this repeated cycle of compete, recover, fuel up again compete. You know, and a kind of there's, there's very little, um, switching between, uh, different macronutrient ratios in that context. Um, in the disability domain where there's less frequent games and there's longer recovery periods. And maybe the ratio of training to games is different. Uh, you do get scenarios where you might be working on body composition for, for one of the periodization blocks, um, and particularly that happens in the, um, in either the off season or in the kind of pre-season period. There does tend to be more manipulation of macros, really, to the effect of changing the overall calorie content, because ultimately there's a lot of people who are trying to drop body mass or drop body fat when they come back from the off season. So there's um, yeah, it does depend on, on the, on the phase of the season. But I don't think we've got the same level of, um, we're not kind of manipulating a week to week or kind of, you know, micro cycle or a cycle like you would do in endurance sports. It's a little bit different from that point of view. Mhm. Yeah. Yeah. Endurance is interesting because you have such a polarizing day to day sometimes when, like I always describe myself, if I go and do like a long, long run training session, I might be taking the day off the following day. So that could be like the difference between 2 or 3 weeks of my resting metabolic rate. It's a very different world within a few hours of one another. That that's actually one of the challenges I actually have in, particularly in a team sport where, um, the, you know, we rarely train on consecutive days in, in, in team sports, it's because, you know, the demands of the, the turning, the twisting, the physical contact and so on. Um, it means that generally speaking, it's kind of like day on, day off, day on, day off, you know, in some ways. And, um, what an awful lot of athletes who haven't been educated on the nutrition side, they fail to kind of appreciate that there's different demands and different days. That's probably where, you know, if you're asking me, do we manipulate things? That's probably the message we're often trying to get across is that, as you say, you've got a demand. You've got a lot of different demands on one day compared to the other. You've probably seen it called fuel for the work required is often the way it's described in the in the scientific literature now, but just trying to impress upon people that there's different calorie needs as an initial starting point from a training day to a non training day, but then within training days, if it's a gym day versus a, you know, a a pitch day or a field day, again, the calorie needs and maybe the protein needs are quite different as well again, depending on recovery and so on. So those are the types of, of um, of education pieces that we're often trying to do. And it's yeah, that's where I think a lot of the um, you know, we talked earlier about the big rocks. That's sometimes the stuff we need to be doing better as opposed to recommending supplements. Yeah. The nutritionist jobs are safe. Yeah. 2s You'll have to learn a lot to be taught. Awesome. Well Brendan, it's been awesome to chat with you. I love diving into this topic and I would love to have you back on down the road if you're interested. If you have something that's new and interesting, innovative that's coming out, that changes what we talked about today or just in general. Uh, I'd love to, uh, chat with you again. And I look, it's been a great conversation, great questions, which is always a help. And yeah, certainly if we have stuff, uh, coming out or if, uh, I, as you say, if we generate a lot of questions from this, uh, background sooner rather than later, but, yeah, I'd happily, happily do that. Awesome. I should ask you, uh, before I let you go, is there any studies kind of in the works right now that are looking at any of these questions that we are just kind of in a holding pattern for? Yeah. In our lab, um, we are not focusing on recovery. We're still doing a couple of other studies on, um, on, uh, in fact, we're looking at the running economy specifically. Um, so we're kind of interested in this question as to whether there's differences between carbs plus ketones versus carbs alone versus ketones alone, which isn't often studied. So we have actually done a three hour treadmill type study at the moment that we've six participants completed. Uh, as I was saying some of the other day, I think we're stuck at six. There's just not enough people in Ireland who are willing to run for three hours on a treadmill. So now we've had that actually on the go, and we do need to to complete that. But the idea there was just more looking at the metabolic and, um, kind of respiratory and then also the gastrointestinal response, uh, in that type of duration because it's not often been done and certainly hasn't been done in running. So yeah, we have a couple of studies related to that ongoing. But um, nothing at the moment in the recovery. And I think the one other there was a study actually, I think it might have came out today or yesterday maybe. Uh, but it was looking at this idea of ketones and their ability to promote an anabolic response similar to that, um, provided by, by way of protein. But again, the caveat there is it does seem to do something from what we call the muscle protein synthesis response. Um, but in comparison to where it was only ten grams away and optimal is typically 20 to 30g. So, um, there's a lot more work to be on that demand. So bottom line is there's plenty of studies, I think, uh, coming out and, uh, there's definitely a bit more legs in this particular area of research for the next few years anyway. 1s Awesome. Well, I'm definitely looking forward to the stuff you're working on right now. And then what you'll get down the road. But thanks again for being generous with some of your time. My pleasure. Um, where can listeners find you? Are you online anywhere, or are you just got your head in the lab? I got my head in the lab. I. I deliberately stay off social media, but, uh. Yeah, people. People can grab me if they search my name, they'll find my contact details, like there are papers around ResearchGate or Google Scholar or. Um, yeah, they'll find my email address if they want to reach out. And certainly happy to answer any questions. Perfect. Well, thanks a bunch, Brendan. Cheers.