Ketones for Ultrarunning with Chiel Poffé PhD | KoopCast Episode #180

trail and ultra runners what is going on what's happening welcome to another episode of the KoopCast as always i'm your humble host coach Jason Koop exogenous ketone esters is the subject of this podcast and it is a supplement that is smack dab in the middle of the current hype cycle you might have seen some elite athletes using this during competition claims that 60 of the pro peloton has been using it in the tour de france you probably saw your favorite influencer using it during a particular workout and if you trust the fine editors over at outside online ketone esters are a cure a cure for overtraining it is also a supplement whose use case has shifted over the last few years you long-time listeners of the podcast can go way back to KoopCast number 10 almost in the single digits one of the first podcasts that i did i recorded with jeff browning and one of the subjects of our conversation was some testing that he did on himself with some of these ketone esters during a graded exercise test to see if they would improve his performance during that test or increase his fat metabolism the use case has morphed over the years from one that is focused on this aq performance to now we're looking at recovery aspects and aspects where that where

ketones could be preventative of cognitive decline particularly during arduous and long ultras now with all this moving and shaking and some of the early stage development that the research is in you can absolutely color me skeptical so to peel the curtain back a bit i have on the podcast today he'll pofe who is a postdoctoral researcher out of belgium he works in a lab that has been at the forefront of ketone research and has examined everything from ketones effect on cognitive function to aq performance effects recovery aspects and how they might actually improve the adaptive response to training i found this conversation with heel very practical unhyped and he presented the research as it is which is in its very early stage but fascinating nonetheless i hope you all find this conversation fascinating as well and and with that as an intro i'm getting right out of the way here's my conversation all about exogenous ketone esters with heel pofe how are you i'm doing fine just the end of the day now so oh man i'm catching you at that new brain fog you can take a ketone shot and apparently alleviate some of that we'll talk about that we'll talk about that for sure man thanks for uh uh thanks for joining me first off thanks for coming on

um i'm always interested to talk to people that are kind of at the forefront at the forefront of things and kind of like watching the research that's come out of your lab it just see it seems like you guys are some of the only not the only people but some of the only people that are actually looking at um that are actually looking at this concept of exogenous ketones and i kind of want to know before we jump into things how did you like personally get involved in all this and like where's the root of your fascination with it because it is a lot of work and it almost seems like you're completely immersed in it now yeah so actually i started with the ketones during my master it was actually the first study that we did it was already in 2016 yeah which we looked at the effect of ketones in post-exercise recovery and then i started my PhD and was purely focused on ketones and yeah we found some really interesting stuff and based on that we just continued our ketone work and now there are three PhD students working on ketones and i'm still as a postdoc still working on the ketones so we have a lot of outputs related to our ketones you know i had this i had the same conversation with uh jamie burr uh who's a physiologist i'm in canada and he's he and his lab have started to get into the the cannabis research and one of the questions i posed to him is is do you want to be that guy do you want to be that guy where like all of your research is kind of like concentrated on this like one

one one little area not that you can't diversify uh eventually but it does seem like you guys have kind of like carved a niche out yeah we just yeah we want to focus also on other aspects and we try to do also studies just focusing on exercise per se not looking at the ketones but there are such interesting things coming out of the studies that we do and that keeps us going we just want to understand how do ketone works and how can we use ketones to improve performance so that's just why we keep working on these ketones okay so uh you know more than anybody else that the kind of the value proposition of this has changed at least in the public at least in the public size because when this first came onto my radar right around 2017 or 2018 the the the the use case for it was to use it in exercise as an ergogenic aid much like we would use like carbohydrate supplementation or even something like sodium bicarbonate or something that was to be used acutely right before or during exercise in order to enhance performance during during that one particular bout but it seems like over the course of the past several years that the that this value proposition has kind of like shaded and shifted and kind of morphed into into different things before we get into that let's set the table on like what ketones are endogenously and in exogenous ketones and then maybe we can use that as a dovetail into

why all of these different use cases have started to emerge over the past few years so ketones they are just simply energy substrates that are produced by our liver and these substances can be used by all different tissues so by the brain but also by skeletal muscle and we can use them just uh to generate atp so to have energy so it's like carbohydrates proteins or fats that are like the fourth uh energy substrate and because they are an energy substrate and there have been previous research showing that ketones might be more energetically efficient that's why the initial idea was ketones will help athletes during performance i was all driven by a seminal study from the university of oxford where this showed that when you ingest ketones during exercise you have a performance improvement and but the problem with endogenous ketones is that they are only produced when you have low intake of carbohydrates for instance when you do a ketogenic diet or you have a couple of days of fasting but that usually is a negative for performance especially high intensity performance so that's why they developed the exogenous ketones where you can just drink the ketones while you still adhere to a high carbohydrate diet and so that's why our research we try to whether if we ingest the ketones together with carbohydrates whether we can still improve performance

but there we found that there was no beneficial effect on performance and even during real short high intensity exercise there was even a negative effect of these ketones on exercise performance and that's why we went to look at other aspects because we heard from a lot of athletes that the ketones help during intensive training periods and that's why we shifted our research to look at the recovery aspects and that's where the most of the research is going into right now and it's an interesting paradigm shift because once again you have this like what i always call a bio plausible mechanism of performance of of being an ergogenic aid you test that you decide and then through the research it's determined that it's not only not beneficial but in some cases it's detrimental you then go back to the observational side talking to athletes who are saying hey listen this is helping us in some way can we figure out what way that actually is and now you've landed on this i don't even know how to describe it it's not an ergogenic aid or it's it's almost like a recovery tool at that point like a lot of people think of their recovery tools as their their guns and their normatec boots and recovery shakes and things like that is what you're looking at now somewhat analogous to that yeah definitely so it's really like all the what we call the signaling effects of ketones that's all what's emerging right now so we also we and also others have shown that ketones for instance increase uh erotropoietin production and that's something that

goes way beyond the effect of ketones on energy metabolism so these signaling effects they look way more uh yeah they have a lot uh higher potential influences on performance right so i think what you're trying to say is it not only impacts the body's ability to recovery but it also can enhance the body's adaptive response to the training stimulus through certain mechanisms true so that's what we found in our overtraining study that when you challenge your body that their ketones will come into play and will help you to perform better or recover better because so far the only beneficial effect that we saw of ketones was when we really challenge the body and when we cause disturbances and then ketones will help you to return to normal okay so we're going to talk about that study in a little bit but just to set the table a little bit more i'm holding on my hand for the people that are watching the youtube version of this a 25 gram shot of hvmn ketones that i bought with my own money there's no sponsors on this podcast as is always the as is always the case but when we talk about the format and the dosing of the ketones that you're going to be referring to in your research can you explain that a little bit because there's there's different companies and varieties and amounts that are out there i want you to explain that to the audience a little bit so when you just google

for ketones there are so many supplements coming up but actually so far most research focused on what we call the ketone esters and you have in general two different forms of ketones esters so you have the one with the ketone monoester which has uh commercialized by hvmn as well as by ketonate and these are the esters that we use in our research and then there is also another ketone diester and that's also really effective to raise your blood ketone levels but there are also a lot of other products on the market that even that don't raise your ketone levels in the blood so these are just a waste of money and really the ketone esters that will help you to get any benefits i'm glad that you mentioned money because one of the things that i'm sure that you're aware of is the cost of the intervention and it ranges anywhere from about 25 bucks to 100 bucks depending upon the type of intervention can you kind of explain that landscape and then maybe what like why is it so expensive yeah it's probably so expensive because it has been patented the ketone esters and therefore they're only limited companies that can produce it and that's why it's so expensive while all the other products that are on the market that don't raise your ketone bodies yeah their price is much lower but they are not effective so that's why it's another it's another glaring issue with the supplement industry just the fact that there's

very little regulation and people can come in with supplements that have a little bit of you know whatever the supplement might actually contain but it's not in a biologically significant dose or they're just outright lying of what's what's actually in there so needless to say this is a you get what you pay for type of uh type of supplement like you have to be willing to pony up a certain amount and we'll go through how much those interventions are when we start to talk about the the research that uh you did and how we might actually translate it into the field but it's one of those things where it's going to cost you you're not going to be able to get away with a you know 50 cent intervention like we might think of a gel right or a block or or or uh some sort of carbohydrate electrolyte drink where those are you know 50 cents or a dollar a serving or something like that this is you know maybe even tenfold that true so therefore it's also really important that you use it right and just don't spill any ketones correct i remember there's this study going around the pro peloton that they had a whole water bottle full of uh ketones that they were passing around one team and somebody dropped it and it was like well that's like an eight thousand dollar mistake at that point anyway that's neither here nor there okay let's talk about the first paper that you already mentioned which is an over which is an overtraining study and um i was looking at this this morning and the thing that that kind of came away for me because i'm a coach is you really did a good job frying these athletes like just this setup itself i can tell like knowing the setup and knowing who you're actually bringing into the

intervention you did you probably did a pretty good job overtraining them like i don't know what how are they how they were communicating to you after this three-week intervention but i can imagine you had a lot of unhappy and disgruntled uh athletes coming into your lab every day to work out so why don't you set the table on what exactly you were examining and what the research protocol was for this particular study so yeah definitely the participants were really mad at me especially in the final week so the idea of the study was that we want to overreach the athletes or were just uh healthy fit individuals so we had them perform exercise that goes beyond what they could tolerate so they really had to go to exhaustion every single training session and we decided to use like healthy fit individuals rather than real athletes as it's almost impossible to overreach a real athlete within only such a short time frame plus nobody's gonna sign up for that that's i mean that when i saw it i'm like it's hard to get athletes to sign up for a study where you know where they know they're intentionally going to get fried at the end of it yeah because it will cause a lot of uh disturbances that are not beneficial for them so that's indeed we had a lot of difficulties with getting these subjects in but eventually we succeeded and that's why when we start with study so we increase the training load

and training intensity every week and really cost um the overreaching during the last week of the study and that's where all the positive effects of ketones came out because during the first two weeks we only saw some small differences but it was really in the third week that we observed large differences between the groups so the subjects they performed uh cycling almost two times a day and they did six training days a week and yeah they were not used to perform yeah much cycling most of them did like two to three hours a week and we increased it to more than 10 hours so they really got exhausted during the study and then after each training session we gave them ketones or a placebo and also before sleep because a lot of elite athletes that use the ketones they mentioned to us that ketones help them sleep better during intensive training periods and how much ketones were you administering both after the session and then before sleep so both after each session as well as before sleep we gave them 25 grams of the ketone ester which is the recommended dosing depending it's or it's about the recommended dosing depending upon what what uh what company you're going with i want the so i'm gonna i'm gonna take some liberty here and i want the listeners to appreciate the intervention a little bit more some of this is just once again my bias as a coach

but you mentioned that you increased their volume they were training two to three hours a week and you're getting up to 10 hours you increase their intensity from no intensity to some intensity but it wasn't just that you had them doing intensity on pretty much every single day so one day was a rest day then you had them on the next day you had them do a sprint interval day in the morning and then in the evening they did an endurance session and the next day you had them do some sort of like super a threshold intervals like was it five minute intervals or something like that right and then on the day after that it was another sprint day and the day after that it was another super threshold day and the day after that you did a performance test so it's a hard workout every single day for healthy but not competitive or elite individuals and so you're kind of compounding all of the training variables all at once volume intensity and frequency right all at the same time to induce this just ridiculously overreached over trained whatever vocabulary you want to use state and once again i'm deliberately i'm deliberately uh emphasizing this because i think there are kind of uh interpretations that we need to make amongst a competitive audience into how this type of overreaching and the implications of ketone use can actually go into the into the real world you're kind of fictionalizing what somebody would do in order to get a little bit better sensitivity out of the results essentially so do you want to do

you want to expand on the on the intervention a little bit more a little bit more than that yeah so the intervention is definitely not a recommended way of improving people because we really want to get them fully exhausted so that's why we use like all these hard training days which are not really representative for what a normal athlete would do during his uh uh his career but it's more like simulating the grand tours in cycling where we also have each day is a hard day so it was more a bit about the background of why we choose this specific uh paradigm that's not a bad analogy it's the grand tour for people who've not trained on a bike before right because it's volume and intensity every single every single day for three weeks okay so at the end of the day you're evaluating some biochemistry as well as doing a performance test you want to explain a little bit about that so we took uh both muscle biopsies as well as some blood samples and that's hard too by the way to get elite athletes to do to to do a muscle biopsy it's very painful there's some recovery that's associated with it afterwards so you got good guinea pigs across the board yeah it's almost impossible to get elite athletes giving a biopsy so that's why we also choose for these uh less trained individuals uh so we took biopsies as well as blood samples every uh on the morning before and after the training

intervention just to look at uh all markers that have been shown to be impacted by overreaching or overtraining uh this included for instance uh heart rate because we know during a grand tour that maximal heart rate will drop and we also saw in our placebo group that maximal heart rate dropped by almost 20 beats per minute but in the ketone group the decrease in maximal heart rate was only half of the decrease in our placebo condition so it really helped to partially maintain the uh baseline values related to heart rate uh so another thing that we evaluated was their energy intake because we know that that's really gets becomes problematic during an increase in intensity and train load because people are just unable to match their energy intake with their energy output and we also observed that in our control group we found that although they increased their training intensity and training volume they were unable to increase their energy intake so they got to a state of energy imbalance while our ketone group we saw that they proportionally increased their energy intake with their increased energy output so that's really one of the beneficial effects of ketones that can help to explain the beneficial effects that we observed on a functional level because on a functional level we observed that especially during the last week

the ketone group was able to tolerate a 15 percent higher training load compared to our placebo group okay so there are a number of different really interesting aspects that you just mentioned first one is the energy intake difference between your placebo placebo group and the and the uh ketone group and this is something that we've seen in a few other studies as well i kind of want to i kind of want to table that for just one second and come back to this aspect that you're only seeing the differences in the third week right so you've got this really hard heavy and hard training intervention that you're you know just ridiculously overreaching this kind of normal group you're kind of tripling or even five xing their volume you're incorporating intensity you're doing so on every day they're doing double days they're doing a performance test there's very there's very very little rest it's as you mentioned it's completely unrealistic to do this with an athlete if you're doing a training block or even even in the tour right the difference in in in output would not be that dramatic between their day-to-day training and this type of intervention yet you're seeing the kind of the beneficial effects of the ketones not until the third week what can you speculate as to why that is actually the case like why does it take a couple weeks of that load to actually see some effects flow through based on novel data we have right now we believe that just the body needs to be disturbed to a certain amount to see a beneficial effect so it's

not really that it needs three weeks but you just need to disturb the body to a specific to a certain extent before you get these benefits so it's not really the three weeks but really the extent of the disturbance that you induce but also like the energy intake could explain part of the results that we observed but like other physiological dysregulations like the decrease in maximal heart rate these already started to develop already to a certain extent during the first two weeks so it's not purely that energy intake can explain all the difference so okay we're going to come back to the energy intake piece but let me let me kind of colloquialize what you're saying initially right where you need a certain level of disturbance in order to see the effects of ketones i kind of view that as is the athlete kind of really needs to be excuse my french fucked before these key before a ketone intervention may have a material impact am i interpreting that correctly or is this just too much speculation that you have to get to a certain point and that certain point is kind of they're almost really screwed at that point right they're so overreached they're going to going to see performance declines anyway that this type of intervention may be of some benefit yeah that's completely what we think and it's also aligned with the natural role of ketone bodies because they are really a substrate that also come into play uh when it really in a case of emergency

yeah so you only produce ketone bodies when you're low for instance on your glucose and your insulin while in the normal conditions endogenous ketones will not do much that's also what we think that happens with the exogenous ketones it's almost so i don't want to i don't want to like downplay the the results of this but i almost view it as an abortive strategy as opposed to an adaptive strategy and what i mean by that is is let's say if we have an athlete in kind of the real world and they go through a period of training intensification irrespective of how that training intensification happens they can go to a training camp they can do a stage race they can do kind of any number of different things that maybe you're not on the level at least proportionally of what you did you're using the ketones to either keep them out of an over-trained state or if they do get into an over-trained state kind of course corrected a little bit more quickly than they normally would be able to course correct it versus or maybe you can add if this is in addition to when they go through that intensified state the ketones allow them to adapt further to the training stimuli so they're literally getting more bang for their training buck do you have any like opinions on on on on the way that i've kind of like laid that out a little bit in terms of this value proposition that we keep coming back to that we keep speculating about yeah we really believe that ketones will also help athletes to adapt

better to a certain amount of training because what we also saw in that paper was that the increase in muscle angiogenesis so increase in capillaries in the muscle was increased by the ketones and that's really a normal response to training and a primary response and we saw that ketones really stimulate this response so we really think that ketones will help athletes to adapt better to training and we have we are now performing another study in which the training load is way more representative of what a real athlete will do and there we still see these beneficial effects of ketones so the there needs to be a certain amount of disturbance which is also in normal athletes when you perform a really intensive training bout but it doesn't need to be that you do this every single day even if you do adjust two or three times a week you will still have potential benefits of ketones okay i i appreciate that uh that that explanation because there are going to be a lot of people out there including myself who kind of look at this through the lens of well are we simply avoiding an overtraining state or are we trying to get out of an overtraining state more quickly or can we use this in a normal circumstances you're you know you're the current data that you're collecting as trying to tease out can we look at this in a normal circumstance as an ergogenic aid for the adaptive

processes which would be quite interesting to be honest with you and we've that's been the holy grail of all of the recovery modalities for you know decades now is not only do we have to get athletes back into the uh back into the training arena as quickly and as uh effectively as possible so their performance capacity is higher so that they hopefully can produce more adaptations but how can we squeeze more adaptations out of the workouts that we've already done using some sort of nutrition or recovery type of uh type of intervention and this would fall into that certainly fall into that latter category potentially um okay so let's move on to the calories piece because all of the nutritionists listening to this podcast are saying well the differences that you're noticing are just due to the fact that the ketone group was able to consume more calories and as you mentioned meet that energy uh meet that increase in energy output more effectively i want you to kind of describe that because i've heard you describe a little bit of a different theory that it might not be just the energy match that the ketone group would uh uh happen to uh happen to achieve so first off just recap the difference in those in the uh in the in the energy consumption between those two groups and then we can kind of go through why that might actually be the case and what the ramifications of it are so just a brief recap so we observed that in the placebo group the energy intake remained stable although the energy output increased one of the ketones that was the increase in energy intake

and what was really striking was that the increase was purely due to an increase in carbohydrates so we didn't tell them anything about ingest carbohydrates will help you to improve your performance but just naturally they increased their carbohydrate intake it's a free living study right you kind of let them do whatever they wanted to do and it just turned out it just happened to be that the ketone group naturally increased their carbohydrate intake yeah because the only thing that we standardized was that we gave them a protein carbohydrate recovery drink after each training session and before the experimental sessions we also gave them a standardized breakfast and dinner but besides that they were free to ingest whatever they want and we just uh tracked their dietary intake by uh yeah they just had to know down uh at what time did they eat what and how much and so it was really surprising to us that these ketones increased their carbohydrates and we know from previous research that when you match your energy intake with your energy output you will improve your performance compared to when you are in an energy imbalance so definitely these changes in energy intake and primarily carbohydrate intake can definitely explain the improved performance with our ketone group but as i mentioned earlier we already saw that some physiological dysregulations were counteracted by these ketones earlier so before

these differences in energy intake or carbohydrate intake emerged so that's why we believe that not all our differences are due to these differences in energy intake and that's also supported by a more recent study which is still unpublished where we find find that ingesting ketones during a normal training period when there are no disturbances in energy intake we still find beneficial effects of ketones and a little bit of this goes back to the tour de france analogy right i mean a lot of the tour riders were taking this and they just noticed that they had better appetites during the day and also during their evening meals and that's also really interesting because previous research has shown that when you acutely ingest ketones you have a suppressive effect on appetite you will eat less while during these overall training period you see the other way around so that's really fascinating about the ketones here's here's my theory on this i'm sure you've heard this before they just don't taste very good so you take you take something and it tastes like gasoline you don't want to take anything else right then and there but then after your body is kind of like eliminated that taste from your mouth then the the biology can kind of kick in whatever else is going on fair criticism come on fair criticism it's not that appealing to it's not that like palette appealing i guess is what i'm saying yeah there is still i agree that the taste is awful so it's definitely possible that that causes the appetite suppressive effect but it's also we detected in the hormones as

well that they are changing really the appetite hormones ketones okay so let's try to encapsulate the this study as well as the study that you're referencing that hasn't been published yet but it seems like you guys are either at the tail end or you're just or you're kind of like wrapping up the analysis and and kind of writing it you can you can kind of merge the findings together and and synthesize them if we're translating this to a normal training situation with a regular athlete or a competitive athlete that's either doing an intensified training block or just merely increasing their their their their volume if they decide to undertake a ketone intervention and do it in the way that you described in the study where they're taking it after a workout and then at bed is there any sort of reasonable benefit that they're going to see from that and can we try to encapsulate that and how much can they improve are they going to feel better during the recovery process i mean what does this mean in the real world so how i would advise to use the ketones during training is just to use them during intensive training periods and take 25 grams immediately after exercise and before sleep but it will really depend on each individual what they will notice about the benefits a lot of athletes they mentioned that they notice improved sleep which is like the most common thing that we hear from athletes that they experience after the ketones but others also found the x uh aspects related to muscle recovery

and cognitive benefits and that's also what we found in the ultra running study and we're going to talk about in a second but that's going to be if you do it over let's just say a week a two to three hundred dollar intervention right yeah which is which is not unreasonable for a runner i mean we're buying three hundred dollar shoes now so you know kind of like look at these things that go well that's part for the course from a price point perspective but also for the sleep aspects we have now a study that is uh in revision where we found that taking ketone just one single day after a high intensity exercise training in the evening will improve uh your sleep so also acutely we can still get benefits from ketones and what's the mechanism behind that because once again we've heard that from athletes it just helps me sleep better we've heard it you know reports in the field and are you know kind of with the own with our own athletes that we work with what's the mechanism behind that in theory there is still some uncertainty about that but one mechanism might be that ketones that they drive the energy metabolism in your brain so they are used as an energy source by the brain but another aspect that we are seeing right now is that ketones can increase your dopamine levels in the blood but we never mentioned in the brain uh measured it in the brain but if ketones can also increase dopamine in the brain this can also beneficially impact the sleep so that's a potential mechanism but we haven't tested it yet well and

everybody is uh acutely aware of sleep as an ergogenic aid in any way that you can help improve sleep especially when you can do it over the long term if it's sustainable and and kind of chronic um uh so i i think that that's going to be another interesting area that people are going to start to focus on this on much like they do a lot of sleep supplements right now whether it's melatonin or a lot of the uh herbal or natural uh supplements that are out there that help enhance sleep or even the devices that are out there the cooling pads and you know and things like that or even the behavioral cues right breathing meditation and stuff like that yeah there should all it should be stressed that we don't want to say that ketones are just a sleep drug yeah we just found that ketones help when you disturb the sleep we did it by exercise so we don't know whether it will also help just in the normal circumstances should just use it after a high intensity exercise training but not on a daily basis you're preemptively uh disrupting some nutrition manufacturer out there that is going to market it as a sleep aid or some sort or something like that so i i appreciate i definitely appreciate that caveat that will be coming probably in the next four to six months what do you think ketones is a sleep aid yeah we'll see that come out okay let's move to the ultra running study this is a an audience predominantly consistent of ultra marathon runners and ultra marathon coaches and here is a paper that you guys produce and i'm gonna uh i'm gonna go through the entire title of this which is exogenous ketosis increases circulating dopamine concentration and maintains mental alertness

and ultra endurance exercise so you get to the results right within the title i always appreciate that you kind of like cut to the chase but it's an ultra marathon specific paper and one of the things that we that any ultra runner will recognize is that a key to performance particularly as the duration of the event goes on and on and on is just their ability to focus and maintain some level of alertness for all different kinds of activities decision making on nutrition route finding even being able to visually pick their feet up over rocks and things like that every ultra runner has gone through the fact that they're just more clumsy at the end of a race as compared to the beginning of the race you're going to take more falls you're going to roll your ankle more and things like that you did a really neat study where you studied ketone ingestion and you measured some uh um some biochemical properties as well as you did uh some alertness type of uh alertness type of testing why don't you go through this study and what the aims of it were and how you specifically started to tease these out so this was a our first actually field study which we really wanted to mimic an ultra run so we just went to a partner and we said hey can we join your ultra run event and couple uh do a scientific study within this event and so we asked participants to complete a 100 kilometer ultra run which was uh performed uh off-road and then half of the the subjects received a ketone aster during the race as well as after the race while the other half

received the placebo because we wanted to look at two different aspects the first one was can ketones improve performance as well as counteract the negative impact of the ultra run on your cognitive behavior and the second aspect is that we wanted to look at the recovery after the ultra run because we know that with the ultra run we will cause a lot of muscle damage to see whether ketones can improve the rehabilitation afterwards but due to the field study nature we were not really able to identify whether ketones will improve performance because we took some biopsies before the race and this caused some people to drop out and because of that our sample size decreased a bit making it unable to really draw a conclusion of whether performance could improve with ketones and it's also difficult to like uh pair different individuals and know what their performance would be so to really look at performance you would need to have the participants perform one time with ketones and one time with placebo but that's almost impossible to do so therefore our analysis mainly focused on the cognitive aspect and we had them perform a reaction time test and we found that the placebo group reacted slower after the ultra run which is what we would expect but the ketones they did not show this

decline in cognitive performance they just performed as good after the ultra run as they did before and that's really striking to us so that's the main aspect of this paper and then we looked at some potential mechanisms that might explain these differences and that's where we found that the dopamine levels were higher with the ketones so are you saying that the effect that you're seeing within these field trials of they are reacting the same there's no there's no decrease in the reaction time is due to the increase in dopamine levels or is there some other mechanism at play here we speculate that it is dopamine but we didn't mention dopamine in the brain so we just measured it in the circulation and it doesn't reflect the brain values because dopamine cannot cross the blood brain barrier but there are other previous studies in animals showing that ketones really can increase dopamine levels in the brain as well and we know from earlier research that dopamine is the crucial factor that explains the decrease in cognitive behavior during endurance exercise so that's why we believe dopamine is likely a mechanism but of course we cannot exclude that there are other mechanisms at play such as the fact that ketones are used by the brain as an energy source during exercise so let me ask you this is the lack of decline in the ketone group

with any of the mental alertness tests is the amount of that lack of decline material for performance because that's what we're concerned about concerned about at the end of the day and i completely understand that it's very hard to determine any sort of intervention when you're looking at performance in the field a compared to b because you either either have to have a huge sample size or you have to look at matched pairs which is problematic or you have to look at the same person doing the same thing over and over and over again which is really difficult to design as well but i want the i want to kind of get your opinion and also for the listeners uh uh kind of for the listeners edification as well is is this going to actually be or can it actually be material for performance or is it just something it's like yeah well they're better on this but it doesn't really matter we believe that it will really help people who perform better in the longer term especially in ultra endurance where the cognitive aspect is so important because this was just a single day race which the 100 kilometer but there are much more extreme ultra run races and there it will yeah have really a significant impact on your performance well i can tell you having done a lot of those doing done the tour de gandre which is a 330 kilometer race in italy that you do you're not and you're probably familiar with as well as cocodona i was out there last weekend which is a 250 mile race in arizona here in the states cognitive performance definitely declines the longer the race actually

gets in the more sleep deprivation and things like that that you're going through and it actually is a big performance consideration because uh not only is there uh is there an effect on your the way that you're perceiving your exertion which is a big part of performance as well there are also just real-time decisions and reactions that you're uh that you're making out in the field whether it's negotiating difficult terrain or trying to stay on pace or trying to stay on your effort level or even you know your nutrition plan and things like that uh so much so that as a coach we're we're trying to counsel and to we're trying to come up with training interventions to help athletes overcome this specific cognitive decline and we don't have very good ones to be frank with you we're just kind of guessing at does sleep deprivation training actually work does this type of training work or does this other type of training work so we'd be keenly interested in something that has an actual cognitive benefit that is simple to take that can be proven to be uh that can be proven to be effective because it will if if if in fact it does actually affect cognitive performance i would say it's highly likely to to affect the actual performance as well particularly when the duration gets longer and longer yeah and also when it gets more challenging because in our case it was not the run itself was not as challenging because they had to do five loops of 20 kilometers uh the direction was clearly indicated so they didn't have to figure out where do i have to go so i think really in more challenging environments

the ketones the ketones will help uh endurance athletes ultra endurance athletes i mean it's almost parallel to the overtraining study right you have to get to a certain level before or at least theoretically you have to get to a certain level of distress or cognitive or cognitive decline right before the effect is really uh marked enough to make to make a difference i don't think that that's a reasonable all right i don't think that that's an unreasonable way to look at the intervention yeah that's true because also earlier studies showed that ketones don't improve your cognition in normal color program stances it's just when you challenge your cognitive function then we will see an improvement so there was one earlier study showing that after a high intensity exercise their ketones counteract the decline in cognitive function and also in older adults we also found that there were improvements with ketones but it's more like ketones can indeed inhibit the decline in cognitive function rather than improving cognition per se i mean it's almost going back to the original ketosis research at that point right where you see severe declines in function and you put people on a ketogenic diet and they have some some level of improvement whether it's a physical level improvement or a cognitive level of improvement it's it's really analogous to that if you go back you know 20 or 30 years ago to that to some of that original research okay i agree on that okay so we've gone through a few a few recent

studies and you've mentioned some tangential research right that's kind of that that is emerging suffice it to say that this is still nascent right this is still like early stage and i really want to get your opinion as somebody who has kind of been in the weeds but then you've also seen more of the public perception of this of these types of interventions change over time where are we in this whole state of understanding i i mentioned from the onset of this podcast that the value proposition is kind of changed and my skeptical antennas go up whenever that's the case whenever we think it's something and it's like no no it's not that but we're going to try to you know tease out some sort of improvement or some sort of meaning from it in this case and maybe it's not that case but maybe it's this case over here i wonder if you can give the listeners a little bit more of a lay of the land because this is going to continue to evolve and it's going to continue to pop up in more of the lay literatures and the magazines and online articles and even in the influencer market space as well can you give the listeners a little bit of an appreciation for where you think we're at and maybe where that's going to go in the next several years so it's true indeed it changed a lot so in beginning it was purely take heat and doing exercise you will improve your performance but then a lot of studies showed that it does not and then not only we but also others shifted really to these effects as a recovery aid and that's where we found a lot of beneficial effects so it's not only on sleep it's also like on energy

intake on physiological dysregulations and that's also where the research is now going to and also what has not really started yet is the clinical implications of this research because we know that ketogenic diets will help in the certain diseases like in children with epilepsy ketogenic diet has been used but like the ketone asteris they have not already been used a lot in clinical conditions and that's where i believe that the research will go into well and usually usually once you get it into the clinical populations then there's a resurgence within the sport populations that's typically the cycle right we tend to we tend to poach things that are used on very specific clinical either healthy or unhealthy type of populations or disease state it kind of doesn't matter but things that are used in that setting and say okay well if we know that this is the mechanism here in this specific group how can we exploit that for a healthy an elite or a competitive group in order to enhance their that performance that cycle has been repeated ad nauseum particularly in nutrition and besides the effects that we observe we're also looking at other conditions like in hypoxic conditions so at high altitude there are also a lot of remarkable effects of ketones and that's where a lot of research will go into during the next years in my opinion here's the issue that you're going to run into

though once you start to spread all of those things out if you have the panacea effect right it improves across all of these different things hypoxia uh intensified training sessions recovery you kind of like name it and then people get really skeptical because it can't be everything to everybody and then eventually the use cases get narrowed out that's the that's the run of show with most of these things but that's why we are also yeah like the acute study there was yeah like one first showing other so much beneficial effects but then was unable to replicate this study and all other studies didn't found any beneficial effects but so far on the recovery aspects the things that have been shown have been shown more than once like for instance the cognitive effect that we see during ultra running has also been previously shown doing high intensity exercise so that's why we really think that this recovery aspect is is real and we also found it like the effect during overload training now during more normal training so these effects are real or at least our opinion so far so will you come back on the podcast when that study comes out and it's more practical and then we can kind of drill it down is it with cyclists or with runners uh cyclists cyclists yeah it's just easier in the lab to have more cyclists 100 okay last piece man i've found that you've been very pragmatic about this and i i really appreciate your your your perspective it would be easy to you know be completely overblowing some of

the results from this especially since it's relatively early or uh early stage so i i appreciate that a lot i want to give you the floor a little bit because because of the hype cycle that has been out there with these and you're very well aware of this those of you that are watching the youtube videos is a strong knock from heel right now he he's very much aware of some of this and it ranges anything from ketones or a cure and i'm emphasizing that word particularly it's a cure for overtraining not it's going to help you not be overtrained it's a cure it's a cure for it to 60 of the pro peloton was using it in the tour de france to there's it's an eight thousand dollar water bottle like i kind of mentioned like i mentioned earlier you i want to ask you to take your science hat off because scientists tend to try to like stay in the lane and just put your everyday athlete hat on what's real and what's not out there and what's more material to the athletes that are just training for to finish the western states 100 or to you know finish the next their next grand fondo or something like that what does this mean from a from a practical perspective and can you kind of like help everybody out there like cut through a little bit of the hype and a little bit of the clutter to some of the practical use cases so like you mentioned ketones will definitely not cure overtraining it will just help people to adapt better to exercise but in this aspect it's also crucial for an athlete to really consider is it worth to me and have already done all the other aspects that can help me to improve performance

so i really think that ketones should be like a last a final addition to help an athlete so first you need to just have your tenor sports nutrition and your training being appropriate so just ingest your carbohydrates and then just use these ketones and when you really want to use these ketones they will not yeah they will just help you a little bit but they will not change your performance completely so the amount of performance increase will yeah not be dramatic but it will definitely help you during intensive training periods or during an ultramarathon that's where the ketones can help you if you use them right so don't use them during exercise but just after exercise to recover better that's a really practical look at it because i've always looked at any of these interventions from this to the protein shakes to putting on norma tech boots where i'm kind of like limiting in in the recovery space is that if you really do it right maybe you get an extra one or three percent out of things it's not turning you from you know a national level competitor to a gold medalist without the rest of the training and years of experience and you know correct nutrition across the board not just these one things and that's if if there is a real effect for that particular individual and we can kind of go back to a different world right

the altitude interventions where we thought at one point that that was going to be the separator between the national level competitors and the gold medalist and it turns out that it's probably not that big of a separator and it's only a small separator for a certain for like a certain group of individuals for a small kind of like cohort that can adapt they're like more uh hyper responders to that to that type of intervention that may or may not be the case with that with with ketones but my point with that is is that to your to to re-emphasize your kind of final point is that it's going to help it's probably a little bit and you should have everything else in line that's going to matter a whole lot more yeah definitely true so yeah the results that we see they look like impressive which should always be put in a perspective of an athlete so also when elite athletes would use it this would can help them a little bit we would not change a lot but obviously in elite athletes just the smallest difference is already really important can be the difference between a golden medal and a fourth place so ketones can really help them but not in all cases yeah i mean it's it's that it's the most interesting paradigm with elite athletes as you get further and further down the developmental curve the difference in in your performance or the difference in the amount that you can improve might it might actually improve your performance dramatically because the competition gets narrower and

narrower narrower but the interventions that you use are less sensitive to improvement and irrespective of the intervention that you use whether it's a nutrition intervention or a training intervention or whatever when you're that good usually there's way more noise than there is signal and not that you're guessing that your training's correct or your nutrition intervention is correct or whatever but you might get one percent here or half a percent there and there's far more noise than there is signal when you're talking about those types of of of propositions so if anything like i said with the elite with the elite athletes it's even harder to kind of like tease these things out if things are actually making a difference or not and we kind of got to go back to you know we really don't know we can make our best guesses but we really don't know at the end of the day yeah with athletes you just rely on their subjective perception and there is also the placebo effect that we don't know whether it really works so it's almost impossible to prove whether it works or not with the elite athletes hundred percent okay i appreciate you coming on uh this was a fascinating uh podcast to me it definitely cleared up a lot of uh cleared up a lot of questions that i had about you your research and how this uh can how this type of intervention can potentially be used where can people come to find a little bit more about your work in the lab that you're working in and really you know the work on ketones in general so yeah our work is always published in the scientific literature but i'm also on twitter just under my name and there i also post all our

novel research so there you can just keep track of our publications around ketones that will come out in the next uh couple of weeks and months perfect well i have to bring you back on and we can talk about a little bit more of a normal study i'll leave links in the show notes to your twitter profile as well as the published research that uh you've done keep kicking it out we will uh have you back on the podcast at some point and we got through this whole podcast without having to take a ketone shot so maybe we'll have to rectify that next time thank you very much all right he'll appreciate it yeah bye bye all right folks there you have it there you go much thanks to heal for coming on the podcast today and discussing some of this early stage research on exogenous ketone esters as i mentioned from the onset of the podcast color me skeptical on a little bit of this but i am willing to look at this through the lens of what has actually been produced and i do think that's something that we need to continually look at one of the things that he and i pointed out during the course of this podcast is that if there's a use case for exogenous ketone esters the strongest of which might be when the situation is ridiculously arduous either in an intensified training uh intensified training block or during an ultra that is particularly long and you are trying and you're trying to attenuate any sort of cognitive decline i will open the door up for that to be a potential use case for these but i'd like to see more research

come across the wire ketone esters are certainly not a cure for overtraining and if you want my humble opinion which you know you're listening to this podcast so you're going to get it anyway if you really want to prevent overtraining why don't we just use solid training tactics and load management to stay out of an overtraining state how novel would that actually be but i digress i appreciate the heck out of all the listeners out there if you have a ketone user in your training group please feel free to pass this podcast along to them i hope that they learn something i hope that the entire audience learn something throughout this podcast i cannot express my appreciation for you guys enough as always this podcast is brought to you without any sponsors or endorsements of any kind and you guys know that ketones have gotten a lot of hype recently because of the influencer marketplace you will not see that pop out on this podcast and that is one of the reasons that i can bring researchers like heal on the podcast and we can talk about this in a very practical way because i am not financially beholden to anybody in any way shape or form particularly with the nutrition supplement companies and it's something that i'm very proud of and i hope you guys in the audience can appreciate that approach that i am as unbiased and unfiltered and unadulterated as possible when you hear any opinions expressed on this

particular podcast that is it for today folks and as always we will see you out on the trails