Exogenous ketones for sleep, cognition and recovery - Chiel Poffé

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

Hey everyone, it's Mikki here. You're listening to Mikkipedia, and this week on the podcast, I speak to Chiel Poffé about his research in exogenous ketones. Now those of you who have been listening for a while know that I have, over the last few years, experimented using ketone salt, also managed to get some ketone esters. So I was super excited to talk to

Yale, who is at the sort of co-face of the research, looking at their application in both health and performance. So Chiel is one of the lead researchers that investigating ketone esters. And we discuss ketones as the fourth macronutrient, what their role is in the body, and what application they have for the athlete. Chiel’s research was one of the first to look at exogenous ketones for recovery, and subsequently,

products such as S fuels, as an example, use ketones as part of their recovery fuel, based on, in part, Chiel’s earlier research. And more recently Heal is involved in assessing their application beyond this, looking at both sleep, performance, and actually just an athlete's ability to adapt to the training load. It appears that appetite effects of

and long days so athletes are more able to meet their energy needs. We also discuss ketones during ultra endurance events and results of their research on cognitive function and just other applications in this space. So I think any athlete who is in endurance sport be it cycling, running, triathlon is really going to be interested in what Heal has to say about these things.

in exercise and muscle physiology at the University of Leuven in Belgium. And his research interests in this field include exogenous ketones, recovery and adaptation and how these can be used to enhance these aspects of an athlete's training cycle. As I'm pretty sure Heal and I talk about, he's not overly active on the social media front but he is most active on Twitter and that's where you'll get up to date information on other podcasts he's been on.

He has just been on Hit Science with my friend Paul Lawson. I think you'll be super keen to check that one out as well. And he also posts updates on research from his lab. I have put a link to Heal's Twitter page in the show notes for you to check out what him and his colleagues are up to.

Before we crack on into the interview though, I'd just like to remind you that the best way to support this podcast is to hit the subscribe button on your favourite podcast listening platform and share with your mates. This increases the visibility of the podcast out there and amongst literally thousands of other podcasts, so more people get the opportunity to learn from guests that I have on the show like Chiel Poffé. Alright team, enjoy this conversation.

Chiel, thank you so much for taking the time to speak to me this morning. Actually, are you watching Tour de France right now? Yes, I'm watching the Tour de France. So the riders just arrived in Belgium. So I'm definitely watching the stages. And we also have like a small study now during the Tour de France with one of the teams. So that's really interesting, but that's not focused on the ketones. It's just in general.

Which team would that be? Are you allowed to divulge that? So that's with the Sulu Quick Steps cycling team. So the Belgian team. Awesome. In fact, we are watching the Netflix documentary on Tour de France right now. And I'm interested because we're here, obviously, to talk about ketones. And in the...

reports that came out last year, which is obviously when the Netflix documentary is focused on, there's a lot of this talk on ketones as a drug for the cyclists. What's your thoughts on that description? So really at the beginning the ketones were really promoted that they can help at all different circumstances, so both during exercise and after recovery and then it really felt like it's something magical that will

push the riders, like also because our first study there we had like a performance improvement at the end of our study with 15% and then it was promoted at least in Belgium, that like when you take ketones your performance would increase with 15%, which is not really the case. So I think it's a lot of overstatement that ketones are really a drug that can help athletes in all cases. But of course there are certain circumstances

can help the athletes. That they just have to be aware that it's not helping acutely and during COVID. Just, it really depends on what type of exercise they are performing or when they are taking the ketones, whether they will help or not. Yeah, no, that's awesome. And that's what I'm excited to chat to you about today. With regards to your research here, your masters was focused on ketones as sort of a recovery tool, is that?

Correct, looking at it rather than performance per se. Can we just sort of kick off with your sort of finding, I know it was quite a number of years ago now, but does that spark your interest in this whole field? Yeah, so I did my masters in 2016, and at that time, the big paper from the University of Oxford came out where they showed that when you take ketones during exercise, you have a performance improvement. But like my PI,

Peter Hespel, he was more interested in the recovery aspect. And that's why we were studying that one. And so in that study we looked at the effect of ketones immediately after resistance exercise. And there we found that there was an upregulation of the markers of protein synthesis after exercise with the ketones. So that was triggered our research.

on acute performance, but like the most promising findings that we do are related to recovery aspects of the ketones. That's super interesting. And so when you see people talk about then ketones as this massive performance enhancer, do you sort of go, I think you guys have got the wrong end of the stick or like you're not really focusing on the most important thing? Like what? Yeah, like that's because

you see it in a range of areas where ketones are used. So it's definitely not the most important thing. And there are still a lot of uncertainties on the performance enhancing effect, because there are a lot of studies showing no effect, some studies even showing a negative effect. And then there is the big study from University of Oxford, that was the first one, that is actually the only one that's really showed an acute performance enhancing effect. And it seems to really depend

on the type and duration of exercise with like a negative effect on performances when they are like a 20 or 30 minute time trial. But when we go to two to three hours of exercise when you provide carbohydrate during exercise then there is no effect on performance. And then we have now a more long term study in which they do an ultra run of 100 kilometers

on physical performance, but there are some benefits on cognitive function, which is obviously really important for that type of athletes. Yeah, totally. And I really want to have a chat about the range of studies that you've conducted that show these things. But first, Hyl, can we go back to sort of the 101 on ketones? So can you tell us, you know, what is a...

What is a ketone and what's the difference between the exogenous ketones and also endogenous ketones? So when we refer to ketones we actually indicate the ketone bodies and these are just small molecules that are produced by our liver, more specific by the mitochondria, and they are produced from the breakdown of fatty acids. So in these ketone bodies which are beta hydroxybutyrate, acetoacetate

They are produced under conditions when there is a low availability of carbohydrates. So, for instance, when you do a couple days of fasting or when you're following a low carb high fat diet, then there will be an increase in the ketone body production. And that's what we call the endogenous ketosis. While we can also induce an increase in keto levels in the blood by taking specific supplements. And there we have a different range of categories.

So we have the ketone esters, which is what we use. And in that case, there is a ketone body, which is mostly either beta hydroxybutyrate or acetate, and there it's bound to an alcohol, for instance butanediol. And these ketone esters can then be also converted to the pure ketone bodies, and will result in a similar increase of ketone levels in the blood, as when doing a ketogenic diet or when doing a couple days of fasting.

Next to the ketone esters we also have the ketone salts. So in this case the ketone body is bounded to different types of salts which are most likely sodium, potassium or calcium. But there this gives more gastrointestinal distress and it's really difficult to increase your ketone levels to the same extent as with the ketone esters. And then there is like the ketone precursors which are like butanediol.

And that's also a type of an alcohol and that butanediol can be converted by the liver in the ketone bodies, beta hydroxybutyrate and acetoacetate. So that's like the different types of ketoses that exists today. Yeah. And that last one, is that a, would people be able to use the last type of ketone that you just described? Cause I've heard of and have like ketone esters and

the salts and things like that. But that last one, is that a commercially available product? Yeah, that's also commercially available. So you can just buy it. But there is also a bit higher risk for gastrointestinal distress. Yeah, the most accessible ones are still like the ketone esters and the ketone salts. But the butanediol is definitely available. Yeah, yeah. And would you describe a ketone as

a fourth macronutrient. I've heard people talk about that before. Yeah. So ketone bodies are just like carbohydrates, proteins and fats. They have a specific calorie content and they can drive ATP synthesis. So like the ketones, they have an energetic value of like 4.7 kilograms per gram, kilo calorie per gram. And they are indeed like the fourth fuel.

But under normal conditions, they will only contribute to a really small extent to the energy provision. But under conditions of starvation, there the ketones will really come into play, especially as an energy source for the brain. So there is a really interesting study from the 1960s where they had a lot of patients on prolonged starvation, it was like 40 days. And then they saw that...

Almost 50% of the energy of the brain was provided by the ketones and thus replaced glucose as the primary energy source for the brain. That's interesting because depending on where you listen and what you sort of take in, you see it quite often people say that your brain can only run on glucose, whereas studies like that show that actually the brain's quite...

flexible as to what it can use given different circumstances, which I find which is super interesting. Yeah, that's true. But there it's also depends like how challenging the conditions are. So that's also something that we observe and as previously been shown that for instance, when you also go to high altitudes, there also the contribution of ketones to energy provision of the brain increases. So it's really under challenging conditions like starvation, like hypoxia.

that the contribution of ketones increases. And that's why they are often called like an energy source in case of emergency. Yeah, yeah, yeah, for sure. Because even under a ketogenic diet, is it true in my thinking that we become physiologically insulin resistant so glucose is spared for the brain even under that sort of ketogenic diet condition?

Yeah, that's true. So, but still like for when we talk about the muscles during exercise, there it's also that as long as glucose is available, our muscles will not use the ketones. Yeah, yeah. So I'm keen to talk to you, Heal, first about your overreaching study in the sort of healthy, active people. Can you describe to us, and we will pop a link in the show notes,

as to the study that I'm talking about. Can you describe the sort of premise for that study and what you did and why you chose that population? So that was actually the first study of my PhD. So it was mostly based on anecdotal evidence from the riders in the Tour de France, for instance, where we heard that ketones really helped them to reduce, for instance, the decline in maximal heart rates during the race.

and that they really felt that they could push more at the end of the Tour de France. So therefore in that study, our aim was to mimic a small Tour de France, but obviously not in elite athletes, but just in healthy individuals, which were not used to do a lot of cycling. Because we really want to get them to what we call an overreached state, because it's impossible to do this with elite athletes in a lab.

You'd have to be there all day. Yeah, they had to train twice a day and so many hours. And also it's not beneficial in the long term for their performance. So that's why we choose like just normal individuals. So in that study, so we increased the training load and the training intensity throughout three weeks to really get them to an overreached state. And then half of the individuals received the ketone Aster, 25 grams,

training session and 30 minutes before sleep while the other half received a placebo. And so they did like six training days per week with two training sessions per day. And then we evaluated their sustained training loads and also their performance on a time trial and on sprint and also looked at markers that we know that change during an overload training period.

but also like the catecholamines excretion in the urine. And what was the major outcome from your study, Neil? So when we look at performance, the most interesting thing was that during the final week of the training program, that the ketone astro group was able to tolerate 15% higher training load. And that's why in the media, a lot were saying that ketones will improve your performance with 15%.

But actually when we look at the 30 minute time trial, there was still a performance improvement, but it was smaller than the 15% in training loads. And then also something really interesting was that we saw that the energy intake remained stable in our placebo group throughout the three weeks, despite the fact that we increased the intensity and the volume of the training. So suggesting that they were an energy deficiency. One of the key to an ASTRO group, it was incredible that they

increased their energy intake in accordance with the increase in training load. And also this change in energy intake was purely due to higher carbohydrate intake. So can you just explain to the listener why, because people might think well of course they're going to be eating more because they're training more but we don't always see this match in energy intake and expenditure with athletic populations in this condition do we?

Yeah, indeed. So it's really an important aspect and it's not purely due to the fact that they had a higher training load, that they eat more. It seems like to be the other way, like they are getting in an overreach state which suppresses your appetite and then you will eat less. What in the ketones seems that this state was less evident. So we also looked at all different physiological parameters and they clearly showed...

an improvement with the ketones before that change in energy intake was evident. And this is interesting as well, Hyl, because ketones, a ketogenic diet, for example, when someone is in a ketogenic state and they're producing their own ketones, often there's this appetite suppressing effect that people talk about, whereas in this instance, obviously the opposite is true.

Do we have an idea of what's happening mechanistically? So that's indeed really interesting. And it's also something that we observe with acute ketone ester ingestion. So we had a previous study where we provided ketones acutely during exercise. And then we find a decrease in appetite after exercise. And this is due to a lowering of the hunger hormone ghrelin. And this has also been observed by other researchers happening just at rest.

So when you take ketones at rest, there will be a decrease in your appetite. But what was interesting in our study was that we found that GDF15, which is also an important hormone which is known to regulate your appetite, that this increases throughout the overload training period, but less in the ketone ester. And we know that GDF15 also suppresses your appetite.

So likely GDF15 caused a difference in appetite and energy intake. Yeah. Oh, so interesting. Now, Heal, with these esters, and this is the Delta G one that I have here, which I have, and I've only ever used this, well, I mean, the way that I use ketones is completely opposite to how you've studied and told me I should use them because I've always...

had ketone salts before like a higher intensity run and felt like they've helped, but possibly that's the caffeine and the sodium that's actually helping me probably more so than the ketones. They taste delicious though. Not this. This is terrible. So the amount of ketones that your research participants had was sort of equivalent to what I find in this bottle, which some people have reported that they have.

They feel worse when they take such a high load of ketones. Something changes with that. They feel like their insulin level, not they feel, but they measured the insulin level and it goes super low. Like, what have you seen any of this in your research? So in our research, we never measured insulin. But what we observe is that, and also others, that glucose really drops after taking these ketone supplements. And then also like...

When you're performing high-endance exercise, there is also like a higher perceived exertion with the ketones. Oh, interesting. So that's the opposite of what I would have expected. Like instead of feeling better, they would have felt like it was harder. Yeah, so we did this study where it was a 30-minute time trial and then there was a negative effect on performance. And also another study where they did a 20-minute time trial performance, there was also a negative effect.

on their performance. And then also we observed in another study where we did like a three hour cycling bout that when we had high levels of ketones at the beginning that they really felt worse. And that's also something that we hear from the athletes when they take it during a stage for instance the Tour de France at the beginning and that the pace is really hard then they are really getting into trouble. Is it a dosing thing do you think?

With a 25 gram bottle, you might use this over three different exercise sessions. I don't know. Hey, I don't know. But is it anything to do with the dose of the ketones? That's possible because right now all studies that looked at performance really provided like the 25 grams to go into a ketosis of two to three millimolar. But it has never been investigated whether lower doses just what their effect is. So it might be possible, but at least

don't go above like four millimolar because then you will get gastrointestinal issues. But maybe lower dosages might help but we don't know yet. Yeah, yeah, interesting. So the ketone level of the athletes that you were working with in your study, is that where 25 grams sort of got them was up to that sort of two to three millimoles? Yeah, so when you're taking 25 grams you will rise to approximately three millimolar.

but it will rapidly decrease during exercise. So for instance, when we did like a three hour race, there we provided 25 grams and then two extra dosages of 20 grams. So that was able to keep their ketosis during the first part of the race. And then during an ultra run, there we provided 25 grams every hour and that was sufficient to keep them in a stable ketosis. Great, and I definitely wanna get to that ultra running study.

So not only did your study with the overreaching find that they were able to increase their energy intake to sort of match their expenditure, but obviously their sleep was better as well. And so both the energy intake increase and sleep would have helped protect those athletes from that overreaching environment, right? Yeah, that's our idea. So therefore,

we always advise to also take the ketones before sleep because we found that beneficial effects on sleep. But in the overreaching study there, we did not evaluate sleep yet, but now in a more recent study we did. Yeah, that's also based on evidence from the athletes where we heard like with the ketones, we can really sleep better. Yeah, yeah. And Heal, have you, like, do you use ketones at all in this way to sort of see how you respond to the ketones?

To be honest, no, I've only taken ketones to try out the different studies that we did, like the Ultrarun. There, together with a colleague, we did the Ultrarun before with the ketones just to see whether the dosing was all right. But I never took it or never take it myself for my performance. Oh, so you, so did you do the Ultrarun as well? Yeah, so I'm not one of the participants. But before the Ultrarun, we just tried to figure out the dosage.

we only went to like 60k, we didn't do the full 100 because there we know already okay we're fine now. Yeah yeah yeah oh that's interesting and what did you experience taking the ketones through and I know this isn't a scientific study I'm just interested to know how you found taking them. It really helped me cognitively so it also matched with the results from the study but I also felt like when it's really high intensity then I also felt

worse but yeah I've never done such a thing before so it's difficult to compare. Yeah okay so that's interesting because I um let's move and chat about that ultra running um study and then go back to the sleep because I'm a runner and I have a 100k on my schedule in February actually and I've got so many of these bottles because when I buy anything

I don't just buy one, I buy like 20 and then go, what am I going to do with these? So they're sitting in my cupboard. So I'm quite interested to chat to you. These are the, as I said, Delta G, which I hope is as efficacious as the ones that you used in your study. And you can tell me if they are different or similar to the one that you use. But what was your study in Ultrarunners? So first of all, the Delta G, so that's in our first studies. So like the overreaching study, there we used the one from Delta G as well.

But like in the sleep study, there we used the one from ketonate, but it's a similar one. So you will get the same effect using either of them. So you're safe. Good, good, good. So and then for the ultra running study, our primary focus was on cognition, because it's really difficult to evaluate exercise performance because the subjects can only do it once. Or you need to do like...

a long washout period, but it was also outside so then you have to be able to replicate the environmental conditions which is almost impossible. So therefore our sample size was too small to really say anything about performance. So there was also no effect on performance in our study but it's yeah it cannot be excluded that there might have been a performance enhancing effect. But the most in...

important thing in our study was like the cognition part. And there we found that as we might expect that cognitive function declined during the ultra run in our placebo group, but the key to an astro group, they just performed as good after the run as they did before on the cognitive tasks that they had to do. So what you did was you gave them a cognitive test prior to the one, is it 100 kilometers that they did in the race?

they had to perform that test again after the race. Is that correct? Was that the study? Yeah, that's correct. So they did just before and then after, but not all subjects were able to do the 100K. So some stopped after 80 or 60K, but then they also did like the cognitive performance test immediately after. Okay. And how much ketones, so they had 25 grams of ketones an hour, is that right? Yeah, that's correct. So every hour they received, actually they received every half an hour, 12.5 grams.

Okay, and is that a better way to take the ketones, I mean, than taking a full 25 grams? Or was it better, did you decide that to sort of split it up into the smaller dose? Yeah, we decided to split it up to have like a more stable ketosis, because when you just take it 25 grams at once, then you will likely have a more unstable pattern. So that's why we decided to do the 12.5. And also,

Because it's maybe more difficult also to drink like the 25 grams during exercise. Because when you're using smaller alequats, it's more easy for them. Yeah. And because these taste terrible. They do. Yeah. In some of our studies, we tried to improve the taste, but it's really difficult. So therefore, in most of our studies, we just make the placebo.

as bad as the ketones. It's almost like you'd have to get them to have some sort of petrol or something for your, for your placebo to be quite similar. Um, Hyl, what was the, uh, so they had the ketones. Did each of the runner also have a schedule of carbohydrate that they had to adhere to? So how did you deal with the, the other race fuel, if there was any other race fuel? So in that study, we recruited subjects.

that take normally a high amount of carbohydrates during exercise, but we just let them free. We didn't interfere with their carbohydrates. So they were just able to take as many carbohydrates as they want to. And it turned out that they on average took 55 to 60 grams of carbohydrates per hour. Yeah, yeah. Which is probably like, I know there's lots of research looking at carbohydrate load an hour and what people can take in.

In my experience with runners, I mean, it's harder to take those higher loads that are often reported that cyclists can take, for example, because, you know, your gut doesn't come into into play. Yeah, like if we could decide beforehand, we would also like aim for that 60 grams per hour, because with when we would go to 90 or even 120 grams per hour, we would definitely get a lot of gastrointestinal issues. Yeah, yeah. And with did any of the runners report

GI issues with taking the ketones in the carbohydrate heal? I guess over 100k probably going to get some but just interested if there were any differences. Yeah, they reported a lot of gastrointestinal issues but they were not related to the ketones. So the amount of issues was similar between our ketone and our placebo group. Okay, awesome. And so the results of your study showed that cognitive function was...

enhanced or at least not as yeah it was enhanced in the group that took the ketones compared to the group that didn't. Can you just explain why that's important in an ultra-run? So there it's really important so for instance when you have an obstacle that is unforeseen that you can just anticipate as quick as possible because one important task that they did was like reaction time so when there is an unforeseen circumstance that you can really rapidly react.

that. So that's important and also like just your pacing and like following the directions of the race it's really important ultra running. So therefore cognitive function is really one of the primary determinants of performance in that case. And I have to say that as a so as a I'm predominantly a road runner you know by my history is in road running and I've

gotten into trail running over the last few years, much more so, but I'm a clumsy trail runner. So I think something like the ketones will be super helpful for anyone like me who needs any additional support they can to stay on two feet, actually. So here, what about if we can we go back to your sleep study, please. So you noted that

taking the ketones even though it wasn't something that you measured but you've subsequently gone on and studied this more formally. Can you give us a rundown on what happened or what you did there? So indeed we heard from a lot of athletes that their sleep improved and also in our previous studies we always provided it before sleep but we never measured it before. So therefore we designed a study where we wanted to first disturb the sleep and to do that we had the subjects perform

high intensity exercise just before they went to bed. So really to disturb their sleep. And then we had like, they did it once with ketones and once with a placebo. And then there was also a resting conditions where they did not perform exercise just to have an idea of their normal sleep. And then we observed that when they performed the exercise prior to bedtime, that there was a decrease or a tendency for a decrease in their sleep efficiency.

and also their REM sleep dropped and they were more awake during the night. And interestingly, all these changes were counteracted by the ketone ester. So what dosage of the ketone ester did you use in your sleep study? So in the sleep study, we did similar approaches in our earlier study. So we provided 25 grams just immediately after exercise.

and then 25 grams also 30 minutes before sleep. How long was that sort of period of time then? So if they exercise just before bed time, so they got it immediately after exercise and then they got another 25 grams, like in an hour's time or like just before, like they were like, good night, I'm going to bed, take your ester, go to bed, is that how that rolled out? So the exercise stopped like one hour before bedtime?

And then they took the ketones, the first after exercise. Then they just took a shower. Then they got another 25 grams 30 minutes before sleep. And then we put it on all the electrodes to measure the sleep. And then we turned off the lights and then they could go to sleep. So they didn't took it like two minutes before sleep, but really 30 minutes before sleep. Why did you decide on two doses of ISTA?

ketonesis and not just see what would occur if you just gave 25 grams? That was just to be in line with our earlier studies where we always provided the ketones immediately after exercise, because we don't know, but like whether there might be an important window early after exercise. If ketones speed up your recovery, the most beneficial effect will likely be if you take it immediately after exercise. So that's why we just wanted to be sure and better overdose than underdose.

Yeah, yeah, okay. I'm just thinking from a cost perspective, like as an athlete, like the prohibitive thing with the Estes, despite them being available to purchase, is actually having the funds to do so. So it would be interesting to know if we could see similar benefits from like half the doses, like just a bottle rather than two bottles, I think as well, maybe. Yeah, that's really interesting, but we have never investigated it. But what

turns out now in our studies is that it only helps after really strenuous exercise. So when you're just doing normal exercise training, like doing a recovery run or so, then I wouldn't advise to take the ketones, but only take it like after your strenuous exercise bouts and before sleep on these days. Yeah, yeah. And Hyl, you mentioned that there was a reduction in...

that the hard exercise reduced REM sleep by about 26%. So what is the importance of REM sleep in relation to our recovery and the impact of exercise? So the precise function of REM sleep and its relation to performance is still a bit unclear, but there is a clear link with the motivation of the athletes. So in this case,

It really plays an important role in the longer term. But when you have like one night of sleep with less REM sleep, there is unlikely to be a direct effect on your performance. Then the sleep disturbance really needs to be much more profound than what we observed in our study. You also mentioned that ketone esters improved sleep efficiency by 3%, which 3% sounds actually like quite a small number, but was this meaningful?

enough for the participants? I mean, yes, it's all part of the package of improving sleep, right? So first, one important thing to note is that in our study, the sleep efficiency, which is the time that a person is asleep relative to the time that he or she has been in bed. So in our study, we had participants with already a good sleep quality, which means that at least 75% of the time that they are in bed.

that they were sleeping and they also all had more than seven hours of sleep. Uh, so it's unlikely that this small difference might have been, might have be having an acute effect on performance. But of course, if you do this for like three weeks in a row, then there might turn out to be an effect on your performance. Yeah, for sure. And I just thinking about the

implications of this for athletes who are headed into like a heavy training sort of block where you are doing like I'm thinking about cyclists and runners and the ultra endurance people when you have like six to eight weeks of hard runs or long runs or sort of long days on the bike. Like if you're able to protect your sleep during that time, then that's only going to be good for your ability to

get up the next day and continue to do the training that you need to get as fit as you need to be. Yeah, definitely. And also like the subjective part is really important. And like in this acute study, we did not found any change on the subjective perception. But interestingly, when we did a longer study, which is not published yet, there we did found changes in the subjective perception. So it seems that when it's continued or prolonged, then

Also the subjective perception improves with the ketones. Yeah. And in the study that is yet to be published, was that also, was that in athletes? Was it under a similar sort of condition, but just a longer studies? Are you able to give us any details on that yet, Jel? So in that study, the subjects were really comparable with the acute sleep study. So they were all cyclists.

who do like at least six hours of training per week. So they're not elite athletes, but well-trained cyclists. And there they performed like an eight week normal training period. Interesting. And you mentioned in your paper that there could be a link between, one of the things that you measured in your study was an increase in dopamine in the blood, is that?

Is that right? And that is potentially the mechanism by which ketone ester is working. Are you able to give us a bit more detail on that, Hyl? So in this study, we measured dopamine in the urine. So we measured the excretion during the night. And there it was higher. But in the ultra-run study, there we measured dopamine in the blood and was also higher. So this really shows that there is an impact of ketones on the dopamine. But obviously, the dopamine in the urine or the blood is definitely not.

identical to the one in the brain. But we know that dopamine plays a crucial role in the transition from the non-REM sleep to the REM sleep. So if there is an increase in dopamine, it's likely that there is more REM sleep. While in our placebo group where the dopamine was lower, that there is less REM sleep. But we still need to measure dopamine in the brain to really know whether this is the mechanism.

And how would you measure dopamine in the brain? So then you need to put them under a scanner, but that's more difficult. And also way more expensive. Yeah, for sure. So in your mind then, Hel, if I've got these ketone esters, I'm an endurance runner, what is, and despite the fact, see, because I would also use this as a fuel source, because even though...

it's not showing to enhance sort of performance. It's almost like my, I perceive that my performance is better when I use them, which is interesting because you can't, that's not what you see when you look at the studies. You certainly see almost the opposite with ketone esters. What is the best use or best use case example then for an athlete like me?

who is an ultra runner who has the ketones, where would you suggest that I use them in my training? So for an ultra runner, I would really advise them to take them after exercise and before sleep, both like during the ultra run as well, because we saw in our study that where we provided the ketones during the first 36 hours after exercise, that also your recovery improves.

So normally you have like a disturbance in your energy system in the muscle after exercise, but that's restored more rapidly with the ketones. And then providing enduring exercise, I would also advise that for an ultra run because it has that effect on cognition. But then that I would only do for ultra endurance exercise, but not for like a two hour run or even for a marathon. So really the ultra marathon. Yeah.

Yeah, well that's exciting because that's exactly what I'll be doing. So having the, the, trying this out will be super interesting. Um, he also, you mentioned your study that is yet to be published. That is a longer term study on the sleep side of things. What else have you got going on in the lab that we can look forward to hearing about over the next couple of years?

So we have one big PhD project focusing on hypoxia. Because we know that when you're at high altitude, that ketones are becoming a more important energy source. So they're really looking at the effect on both the adaptations to training at high altitude, as well as on hypoxic tolerance at extreme altitudes. So that's one important research line. Then we have another research line.

more focusing on ultra endurance performance. And then we have like a third research line more focusing on what happens in the skeletal muscle when you take the ketones. So that's what's going on these days. That sounds great. And it's just all using the ketone esters as well. Like you're not bothering with assaults because they just don't lift your ketone bodies high enough. Yeah, we're just playing save

keep using the ketone esters as we know what effects we have observed already and then we just want to continue elaborating these effects more and more. So that's why we decide to keep using these ketone esters. Awesome, Heal. Thank you so much for your time this morning, your afternoon. I really appreciate that. Can you just tell the listener where they can find more information about these studies as they...

are published and is your lab is able to share the results? So the results of our studies can be found online at the publications with most of them are open access. So just when you go for instance to Google Schooler and you enter my name with keytones then they will pop up and also on my Twitter account which is just my name there you can also find when a new study is published.

That is great, Hill. Thank you so much and I really look forward to seeing these next steps with your research. It sounds super exciting. Thank you very much for the opportunity. Bye bye.

Alrighty, hopefully you enjoyed that conversation and for what it's worth, after listening to Heal and chatting to him about their application, I'm certainly all on board using these ketone esters and I've got the Delta G. I've got their tactical ketone esters. This was on the recommendation of my friend Dan Plews. And if anyone's gonna know, it's gonna be Dan. And took this out for a spin this weekend on my run. Both Hubster and I definitely experienced.

an enhanced sort of performance after taking it. We were just much better able to continue to engage at that latter part of our run. So we were both pretty happy with it. Gotta say it's not easy getting it down though, because these do taste a little bit like I would expect rocket fuel to taste, but I think all worth it in the end, right? And this is just another tool in the toolbox for us endurance athletes.

So yeah, it was super great to chat to Chiel and I'm really keen to see over the next few years the research in and around this space. All right team, next week on the show, I speak to Jonathan Wakely out of Australia and his research looking at benefits of resistance training, sleep and circadian biology, and overtraining in the athlete. Just a lot of really great stuff in that interview as well.

Until then though, you can catch me over on Twitter, Instagram and threads @mikkiwilliden, Facebook @mikkiwillidennutrition or head to my website mikkiwilliden.com, book a one on one call or sign up to one of my plans. Alright guys, you have a great week. Talk soon.