Ketone Supplementation and Performance Optimization with Dr. Peter Hespel 

World-renowned sports scientist Dr. Peter Hespel explains the potential benefits of ketone supplementation for athletes.

Fast Talk Femmes ep 124 with Dr. Peter Hespel

In this week’s episode, we talk with world-renowned sports scientist, Dr. Peter Hespel. We dive into his research on the utilization of ketones to enhance endurance performance. What does the research show – does ketone supplementation adversely affect or optimize an athlete’s performance?

Tune in to hear about Dr. Hespel’s five gold-standard studies on ketone application to both dispel the myths and assess the hype surrounding ketone use. We also consider potential benefits of ketone use in various circumstances across specific populations. Dr. Hespel also shares how he applies his research findings when working with World Tour cycling teams, such as Quickstep.

Catch up on previous episodes of Fast Talk Femmes and subscribe for episodes on Apple Podcasts, Google Podcasts, Overcast, Soundcloud, Spotify, Stitcher, or wherever you listen to your podcasts!

Episode Transcript

Dede Barry  00:05

Hi and welcome to Fast Talk Femmes with Dede Barry and Julie Young. In this episode we’ll be discussing ketone use the hype, the potential performance benefits and the possible drawbacks for endurance athletes.

Dede Barry  00:16

Our guest is Dr. Peter Hespel, a Belgium based researcher and biomedical science professor who has published five scientific studies on ketone use and endurance sports. Peter obtained his PhD degree in Biomedical Sciences at the University of Leuven, Belgium, and since 2001, has been teaching courses and Exercise Physiology and sports nutrition to students and human movement sciences, physiotherapy and sports medicine. His research primarily focuses on the regulation of muscle energy, substrate metabolism during exercise and training and nutritional strategies to enhance Recovery Training, adaptation and performance and endurance athletes.

Dede Barry  00:55

For more than 20 years, Peter has worked with elite athletes and training and competition for the Belgian Quickstep Pro Cycling Team and for the Belgian cycling Association. He also works with a wide range of Belgian Olympic athletes in different sports disciplines, primarily cycling, triathlon and track and field translating science from the lab to the field is his passion.

Dede Barry  01:15

In this episode, we have the opportunity to dissect and discuss five of Peters studies on the various ketone applications. These studies are considered the gold standard in ketone research. In this discussion, we dispel the myths and the hype surrounding ketone use, as well as identify potential benefits of their use and specific situations or specific populations. Peter also shares his knowledge on how World Tour cycling teams such as Quickstep are using ketones to aid recovery. Welcome to Fast Talk Femmes.

Background Noise  01:47

In the future of coaching, which is the last module release of the craft of coaching with Joe Friel, we envision what the future of coaching looks like in the years to come. While artificial intelligence will play a critical role, AI will never completely replace coaching. However, leveraging its attributes to find the right balance of personal connection with automated tasks will be vital to remaining relevant with future generations. Check out the craft of coaching module 14 at fast talk

Julie Young  02:18

Hey, Peter, welcome to Fast Talk Femmes. Our introduction barely scratched the surface, describing your illustrious career as a researcher and scientist and your contribution to sport science. But can you give us a little bit of an overview of what you’ve been up to recently?

Dr. Peter Hespel  02:35

Yeah, sure. First, thank you for inviting me for this podcast. It’s nice to be in and help you out with some questions about ketones to introduce myself, I have been a professor at the University of Leuven for unfortunately, a very long time means I’m getting old since more than 30 years, and my research was mainly directed to looking at how one could improve endurance exercise performance by nutrition and promote training adaptation by using the best possible nutrition. So we have been doing work on creatine, Beta Alanine carbohydrates. And the latest one is the ketones that emerged since I think that first publication by the group of Oxford in 2016, I heard at that time, the nutritionist from Team Sky on a congress hearing, some are giving some hidden information about the use of ketones in the team. And that’s what triggered something in me that I had to do research on that and it never stops in until today.

Julie Young  03:43

Well, as we were chatting offline before hopping on to this recording, there’s been quite a bit of conversation about ketones and has generated a lot of curiosity. And then especially like as we were chatting, you know, you hear these super teams like Jambo visa supposedly using ketones, but you know, we don’t know how they’re implementing ketones into practice. And now it’s becoming more apparent just through your studies that there are nuances to how and when ketones are used. So in this episode, we wanted to go straight to the source to get a better grasp on ketone use and in chat with you, Peter. Since you are one of the foremost researchers on ketone use and endurance sport, and your studies have focused on its various applications, we thought one of the best ways to provide a clearer understanding of what ketones can do and cannot do would be to dissect and discuss in chronological order five of your studies in which you studied different applications of ketones. And for me personally, after reading your series of studies, one of the things that I found interesting was that ketones may improve performance but in more peripheral ways, and perhaps less obvious, direct ways then have been promoted by the ketone industry. I also found it interesting that in some of your studies, you had these unexpected yet significant findings, not necessarily related to ketones, but findings that could potentially improve training methods, which I thought was super exciting. So I’m personally really looking forward to this conversation today,

Dr. Peter Hespel  05:22

same to me, so please launch your questions, and I will be very happy to try to give a straightforward answer that interesting for your public.

Julie Young  05:33

Okay, here we go. So, I think to kick things off and to set the stage and I know this has been covered in other podcasts, but I think it’s important to help our listeners understand the difference between endogenous and exogenous ketosis and the various options available for exogenous ketones.

Dr. Peter Hespel  05:53

The difference is that when they talk about endogenous ketones, it refers to the production of ketones by our own body without the ingestion of any external supplement. And the liver is able to metabolize fatty acids and one of the main fuel sources during exercise, so the liver can convert it into ketone bodies. And these ketone bodies can then serve as an energy substrate in the body. But that only happens in some very specific conditions, to nutritional interventions that can increase the use of ketones, endogenous ketones in the body, the easiest one is just fasting. If you stop eating very rapidly, the carbohydrate stores in your body will get exhausted. But especially your brain needs glucose for energy metabolism. So very early in the fasting period, the brain would get in problem if there were not the ketones produced based on fatty acid conversion in the liver. So when you stop eating, the liver will start producing ketones, and that hydroxy butyrate and acetyl acetate, and the brain can use that really as a perfect primary fuel in replacement of glucose. Second intervention to stimulate endogenous production of ketones is the use of a so called ketogenic diet. And the ketogenic diets also, maybe I have to say, unfortunately, have become very popular in society and also for some time in endurance athletes. And what you do then is just eliminate most of the carbohydrates from the diet and replace them mostly by fat and protein. So the amount of fat you eat is dramatically increased, you increase the availability of fatty acids in the body, and then the liver also starts to convert some of the fatty acids into ketone bodies. And that’s why it’s called the ketogenic diet, because the supply of fatty acids is so high that the leaf starts producing ketones. And also in that condition, probably the brain starts using some of these ketones as an energy substrate. And fortunately, I think there is substantial evidence now that search a ketogenic diet in Perth and urines exercise performance because you eliminate carbohydrates from the diet, you deeply the muscle glycogen stores, and you impair carbohydrate metabolism in the muscles, which is essential for endurance exercise performance, then the next thing is what are exogenous ketones. This refers to raising the ketone body level in the blood, without interference of production of ketones by the leaf. So we just use a supplement that increases the blood ketone levels. And the first supplements that have been used are the so called ketone salts that combine hydroxy butyrate males mostly with sodium, potassium, or calcium. And then at some point, University of Esther has launched the eat on mono esters, which allow us to very rapidly increase the ketone body concentration in the blood. And these ketone supplements which are exogenous have become the most popular because these ketone mono efficacy, in fact, are the only ones that are able to substantially and rapidly increase the ketone body level at rest, but also during exercise.

Julie Young  09:35

What have you found generally about a no with ketone ingestion? There’s like association with gastrointestinal distress and what have you found generally about that and ketone use?

Dr. Peter Hespel  09:46

I don’t think gastrointestinal problems are a problem with ketone Ester ingestion. What is true with the ketone esters? I don’t know if you have ever tasted them, have you? No, I haven’t. This is absolutely disgusting. thing, okay, it’s extremely bitter and disgusting. And if you don’t like that taste, you may get nausea just by the taste. But in individuals that have no problem by just putting it in the mouth and swallowing, we very seldom have noticed gastrointestinal problems addressed and not even during exercise. So gastrointestinal problems would not prevent from using ketone esters before or during exercise in the vast majority of individuals.

Julie Young  10:32

Maybe it was the ketone salts that I was thinking about ketone salts

Dr. Peter Hespel  10:35

is the problem. And they are the problem is not the ketones. But the salt. If you ingest high amounts of sodium, you will very rapidly get diarrhea. And because most of the ketone salts are bound to sodium, if you ingest the high amount of these ketone salts, you ingest the high amount of sodium, and that Watts is gifts, or what causes the gastrointestinal problems. And probably also reason why it is impossible with the ketone salts that are currently available to ingest sufficient amounts to significantly increase the ketone availability in the blood. And if you are unable to increase that sufficiently, there is no chance to improve in performance.

Julie Young  11:22

I remember reading your studies and it seemed like in every case, like if there was some sort of potential for positive, the blood ketone level had to reach a certain threshold. And I think you had mentioned like there’s certain brands of exogenous ketones on the market that are more reputable, or they have I think, a higher quantity, or I guess they’re higher quality. Can you comment on that? Yeah,

Dr. Peter Hespel  11:47

I sure can maybe first respond to the threshold level. And what we are actually missing in the ketone research is what we would call perfect dose response curves. That means we still need to look what is the optimal dose of ketone esters, for instance, to use to induce the best possible effects during exercise and training. And in all the research we have been doing, we didn’t want to take the risk to use a too low dose, because the studies are extremely expensive and extremely labor intensive. So what you do then is take a dose of which you say, if that doesn’t work, it’s never gonna work to use pretty high doses. And that does mean that it with lower doses, it could not work, but there’s absolutely no evidence and at present, the only ketone supplements that are able to substantially increase the blood ketone concentrations. It’s one type of ketone mono Ester that has been there is discussion on who has invented it. And, and it has been patented, I know some people are fighting around it. But it’s a Keto Moana, so that has been patented by the University of Oxford, and that is being distributed by two companies in the United States, it’s ketone eight. And in the United Kingdom, it’s t delta that sells the delta G. And they sell, in fact, exactly the same product, the same type of ketone motorist. And all the studies with positive results have been done with these products, either from the UK company are from the US company. And from all the other ketone supplements on the market, there is absolutely no evidence that they can ever work in exercise and training. There are no studies, the only thing we know is that we do not have supplements that are available and are are being fastly marketed to anywhere in the world. It’s impossible, probably to raise the blood ketone level to concentration that is needed to have valuable or to say worthwhile effects on exercise performance, or training adaptation. So it’s easy to make a selection. If you ask me which ketones work. We only know about one type of ketones told by these two companies. I have mentioned the other ones, though evidence, I wouldn’t spend my money on it. So

Dede Barry  14:25

Peter, the mono esters used in your studies that you lied, they were all that mono Ester that you’re referencing. Sure. from the University of Oxford. Yes. Okay. Or

Dr. Peter Hespel  14:36

from ketone aid. We have used both. Yeah. And you get exactly the same results with both products. Yeah. And there may be some minor difference in the way of production but in the end in exercise and training, it’s is the same. We also have checked the purity of both products in our toxicology lab at university and we got the green light for Both brands. Yeah,

Dede Barry  15:01

that’s good to know. So Peter, we’d like to dive into dissected and discussing the five studies that you co authored in chronological order. So first, I’d like to dissect the ketone Ester supplementation blondes over reaching symptoms during endurance training overload study. And if you could give us just a brief overview of the study what it entailed, and then your expectations going into it versus the actual findings.

Dr. Peter Hespel  15:29

Okay, maybe I can first just say why we did that specific study at the start of our ketone campaign is because when you’re in a fasting state, or like a hunger strike, it’s in fact, the ketone bodies that make you survive for such a long time. So it’s a kind of alarm substrate that is being produced in the body when there is a lack of energy. And that continues to provide some energy to make the brain and other tissues survive in the absence of nutrition. And in these conditions you get in a catabolic state, this means that your body starts to have a net breakdown of proteins and fats and carbohydrates because no energy is coming in anymore. And because of my involvement in elite cycling, when you see elite cyclists at the start, and at the end of a grand tour, they are also in some sort of catabolism because the exercise load they had to, or they got during the three weeks is so hard that you see catabolic events happening in the body throughout the Tour de France. And the ones that win a Grand Tour are the probably the ones with the best talent and that are have the best potential to recover and avoid that catabolic state. And that’s where come in the ketones. If the ketones can reduce a catabolic state during fasting, maybe we thought they can reduce the catabolic development during a grand tour. But you cannot do such a study in elite cyclists. So we simulated a kind of Tour de France in our lab with much less trained cyclists. But they came to our lab for three weeks. And we made them train on like swift training on well calibrate the ergometers, twice per day, six days per week for three weeks. And at the end of the three weeks, they were completely empty. And half of the participants after each training session, and before going to bed in the evening, they received the ketone mono Ester supplement. And the other half, they got a fake product. And we saw that as the training progressed, the participants in the fake supplement group, they were more and more unable to continue the prescribed training program. Whereas in the Keto group, they could just continue do everything we wanted them to do. And they also perform better in a time trial after three weeks in the long endurance test. And on average, the improvement in endurance performance was about 15%. So to me, that was clear evidence that when you really bring people who participate in very intense and urine straining, and you bring them to the utmost and of exhaustion in training, you recover much better with ketones. So that’s a very specific situation. That also occurs in Grand Tours, because the exercise loads to administer to cyclists in the Grand Tour. It’s just too much. It’s not appropriate training anymore. It’s just competition with too much exercise, which exhausts the riders. So at some point, we started using the ketones as a recovery agent in Grand Tour cyclists. And we could just see similar effects that especially towards the end of Grand Tour in the last week, the cyclists are just better recovered than without ketones, with no discussion about it. Interesting.

Dede Barry  19:09

And what do you think the mechanisms of this positive finding more of a ketone use?

Dr. Peter Hespel  19:16

It’s, of course, the most important question. We do not certainly have all the answers on that, because the only study that has been done on that specific topic on training overload and ketones. It was our study, I think many laps avoid doing these kind of studies because they are so expensive, and they are so labor intensive. And you have to find the participants, but we were successful in doing it. And what we found for instance, is that normally in the Grand Tour, when let’s take the Tour de France, when in the prologue on in the first stage, you still have a maximal heart rate of 195 when And you get to the end of the Tour de France on the shawnzy elisee. And you go in maximal exercise, your maximal heart rate may have decreased to 175. That’s what you what you see in the pro cycling teams in at that very high level. And it’s also the same as during submaximal exercise. At the start of a Tour de France, when you push, let’s say 350 Watts, your heart rate may be 165. And at the end of the Tour de France at 350, once your heart rate has decreased to 150. And in our study, we could see that this drop in heart rate during submaximal and maximal exercise, due to a endurance exercise overload is almost completely inhibited by the administration of ketone bodies. And if we look at the regulation of heart rate, it’s always a balance between the stimulatory activity of the sympathetic nervous system and the inhibitory activity of the parasympathetic nervous system. And if you see heart rate decreasing at a given exercise load, it probably means that the parasympathetic system is winning in relation to the auto or the sympathetic nervous system, which means that you’re unable to bring your energy systems and your heart rate and maybe your Aspiro system in a state of maximal activation. And this may be a mechanism to save energy in the body, because you spent so much energy, and the body is putting on some alarm mechanisms to save the body from overloading. And that’s why the parasympathetic nervous system is up regulated to calm down the body. And that’s not a good situation for performance.

Dede Barry  21:51

And Did you discover anything unexpected during this study? Yeah, we

Dr. Peter Hespel  21:55

discovered many unexpected things, in fact, and one thing was that there was a totally unexpected effect on the nutrition. What we did during the three weeks of training is after each training session, in all the participants, they got a typical recovery shake after each training session, together with a ketone Ester in the ketone group and placebo effect product in the other group. And besides the supplements, the participants were free to use their diet like they want. And still, we noticed that the ketone group, they were able to adjust their energy aid intake, and especially the carbohydrate intake to the increasing energy needs during training, because during the three weeks, we gradually increase the load. And the ketone gray group without any instructions from our side, they increase their carbohydrate and energy intake gradually, to correspond with the increased energy needs in training, while the group not receiving the ketones. They didn’t do that. Which means that in the placebo group, there was an energy deficit throughout the three weeks of training, why the ketone group, they were able to stay in energy balance, which of course is extremely important to maintain endurance performance, when you repeat exercise day after day, like in Grand Tours. So

Dede Barry  23:27

is that because of the effect on appetite? Or because of the muscle uptake of nutrients? We

Dr. Peter Hespel  23:33

have no clear cut answer on that question. We measured all the appetite hormones, and we didn’t see a really significant difference, except for one hormones that gdF 15. And that’s one hormone of which we know that it’s involved in regulation of the of appetite. And in the absence of ketone Ester intake, this hormone that may cut the appetite was gradually increasing throughout the three weeks of training. And that did not happen at all in the ketone group. So it may be a hormonal effect that is mediated through the gdF 15. But we need more studies to give a conclusive answer on that.

Julie Young  24:14

And one other thing, Peter, in this study with the gdF 15, I think you had said that you think that could then be a reliable marker of overtraining, where we hadn’t realized that in the past. Is that true? Do you

Dr. Peter Hespel  24:28

still live with the idea that gdF 15 in the context of very high volume and urine straining, that’s what we are talking about and we are not talking about sprinters and weightlifters. But endurance athletes doing very long hours of training in Marathon triathlon cycling, that as the cycling load becomes too much, you get an increase in gdF 15. Very clearly, and we still think it might be an appropriate market for to distinguish between function No overreaching and non functional, and it’s really getting too much the research to confirm that still needs to be done. And the problem is that it’s not easy to do that, because experimentally, overtraining volunteers, as you will do in a Tour de France, for instance, it’s not something you can easily undertake in controlled research, because it’s so expensive. And it’s very labor intensive. And doing it in the professional context of cycling makes no sense. Because so many things are happening, that you cannot control the situation.

Dede Barry  25:37

So based on the parameters of this study, it seems like it would definitely be applicable to elite athletes. But do you think it would be applicable to amateur endurance athletes as well?

Dr. Peter Hespel  25:48

No, I don’t think so. That’s an obvious and very important question. Because what we did in our study was massive overload in training, we didn’t intend to make our participants bed in endurance. But we wanted to make them worse due to the overload. That’s not what you want to do in an appropriate training process, where you want to have an adequate balance between training and recovery, and eventually ended up in Super compensation that makes you bet. So in the meantime, we did that study, but we did not yet publish it. And we did a study where we had the same type of well trained cyclists but not elite cyclist involved in an eight week training program, that we have a good balance between training and recovery. And the same principle half of the participants with the ketone s, same dose as in the first study, and the other half with a fake supplement. And in that study, actually, we almost see no effect on performance, we see no physiological effects. We don’t see any effect on erythropoietin. Maybe we have to discuss this one a little bit later, because that’s an important one. So what seems to be true in a situation of overtraining with the ketones doesn’t seem to be true in a situation of well balanced training. So that’s one reason for me not to say that recreational athletes, please do it. Because you will get that No, no, I can only say you can only use it when you think you would get worse when you train too much. A second thing is, in our study, we overloaded subjects for three weeks with two training sessions per day, with very high volumes of training. I don’t know any recreational cyclist in my environment who is doing that, because it’s too much. You go training as a recreational cyclists, especially in the weekend, and maybe twice in the week, because you have to work or you study, you don’t have the time to train every day, most of them and certainly not twice per day. So the total training volume in recreation cyclist is much less and in general are very often you have at least a full day of recovery in between the sessions. And that’s probably a situation where the ketones will become much less effective. So I would conclude that today, we have no conclusive evidence to even suggest that recreational cyclists training three four times a week could get any benefit in training from using the ketone test.

Julie Young  28:33

So Peter, this study was really to simulate the extreme demands of a grand tour. Yes,

Dr. Peter Hespel  28:40

not only because we also use the ketone Ester in other sports, for instance, when we apply to marathon running at some point in the preparation of a marathon, when I look to world class marathon runners, and we have one in Belgium Bashir Abdi who had the bronze medal in Tokyo, at some point, they go to training weeks of 200 220 kilometers per week, which is also killing. Also in triathlon, we have the same situation than when athletes are peaking to Ironman Hawaii are another important competition. At some point, they will accumulate extremely high training volume. For me based on our study, that’s probably a potential application to make sure that when endurance athletes at a very high level, applied to extremely high training loads, at the end of search training cycle, they will be much more fit. But that’s the only other situation where I think that the ketone esters could really be helpful in having a significant effect on training adaptation.

Julie Young  29:47

I think with the amateur athletes, it’s really easy and attractive to chase that silver bullet yes and spend a lot of money and but yet just consistently hitting the fundamentals of sleep, nutrition hydration and which will allow them to optimally train and recover as the best way they can make the biggest gains. I absolutely

Dr. Peter Hespel  30:06

agree with that, because you probably know the cost of the ketone supplements, the ketone esters in the doses we have used are the most expensive supplements are you pay about $30, or euros for one single dose. And these companies have started selling lower doses to make it less expensive, and probably stimulate the sales. But we have no evidence at all that these lower doses may ever work. So these higher doses, they cost 30 euros. And if you know that in a three week training cycle, you may need 20 to 30 doses, you end up by paying about $1,000. If I would have to spend $1,000, as a recreational cyclist, or triathlete or marathon runner, I would focus on the primary things that’s carbohydrate intake, rehydration, having optimal materials, and maybe by better tires and better materials, running shoes, and other things to do. But I don’t think that ketones are in the first choice to improve performance in recreation endurance athletes,

Dede Barry  31:15

that seems like really sound advice, focusing on all the fundamentals that you know, have large performance gains. First, before you start experimenting with something that, you know, might accelerate your performance a tiny percent, but it’s not quite proven.

Dr. Peter Hespel  31:32

Yeah. And besides working with elite cyclists, I will very often work with recreational athletes. And if you notice which big mistakes they still make in basic things, I think first thing to do is avoid these kinds of peace mistakes, and get better in the basic things even before you start talking about use of these special things like using keto nest. Yeah,

Dede Barry  31:58

that’s really good advice. Peter, has there been subsequent research to confirm your findings in this study, not

Dr. Peter Hespel  32:05

on the overtraining and not on the well balanced training? And I know some people have been doing studies on ketone use during exercise and training. But none of them I am aware is running a study on long term training at the moment, which is very unfortunate. But he’s experienced by the fact that these studies are very expensive and not easy to do. Yeah.

Dede Barry  32:28

And your studies were done on male participants. But do you think the results would be the same for female participants?

Dr. Peter Hespel  32:35

Yeah, it’s a most relevant question, of course, because one of the big issues with exercise physiology research is that 90% of the studies are done on male participants. If you look at ketone esters, or the potential of ketone supplements, and the potential difference between males and females, we know that females are better in fat metabolism than males, which could mean that they could more easily response to elevated ketone bodies circulating in the blood because they have more high concentration of circulating fatty acids. But as long as the studies have not been done, I don’t think we can give a conclusive answer. But for ketones, I don’t think there’s any specific reason to believe at present, that women would have a less of a smaller response to ketone Ester ingestion than males have, which is not true for all supplements. Because I don’t know if you have seen very recent research showing that you notice all the studies with beetroot

Dede Barry  33:41

juice and nitrate, I haven’t actually I’m not familiar with us, beetroot juice,

Dr. Peter Hespel  33:46

and nitrate has been shown to improve endurance performance in males. And now there have been some further studies in females. And they show that this kind of intervention is not working in females. So that shows that it’s very important to look at the differential response, but unfortunately, with ketones we don’t know yet. Yeah,

Julie Young  34:08

interesting. So Peter, next on our list of your studies, is exogenous ketosis impacts neither performance nor muscle glycogen breakdown. Yes, and prolonged endurance exercise. And it seems that the study seems to address the most prevalent misnomer about ketones that they are a super fuel. Yes, yes. So we’ll kind of stick with the same formula and dissecting your study. So going in what were your expectations? And then what were the actual findings,

Dr. Peter Hespel  34:39

when we did that study, in fact, to have a double check of the data published in the seminal publication by the group of Oxford, by Cox at all in 2016, where they published that ingestion of ketone esters was enhancing Time Trial performance. I think maybe To 3%. And the ingestion of ketone esters was also glycogen sparing. And these two things, glycogen sparing. and improvement of Time Trial performance are, of course, sufficient to trigger hype in endurance athletes. And that’s what happened. That’s exactly what happened because everybody wanted to have the ketone s. But if you dissect that study, you’ll see that the study methods used are not what endurance athletes do, or are supposed to do when they want to perform in an endurance event. And as we have been discussing five minutes before, first thing to do to enhance endurance exercise performance, is follow the recommendations with regard to carbohydrate intake, you need to carbohydrate meal, and you need to recommend that rate of carbohydrate intake. During exercise. Of course, if you keep that, and in the place of instead of applying the right amount of carbohydrates, you forget about it. And you give the ketone esters, you get in an unreal situation, because you don’t do the basics. And you gave another potential fuel that in that specific condition might indeed help to improve performance. And it was not really a fasting state in that study. But getting close, it could be that administration of ketone esters during prolonged exercise in the fasted state could enhance and urines excess performance. But that’s not what you want to do in a competition. In competition, you want to see whether on top of ingesting the recommended amount of carbohydrates on top of that, ingestion of ketones could result in an additional beneficial effect. And that’s why we did our study. And there we found out that the performance improvement was completely absent. And also the glycogen sparing effect that was proposed by the publication by Oxford did not exist. So I think that the results of our study were much more close to real life situation than the conditions that were used by the Oxford group. So to translate that to the field, after study, we have immediately recommended to the cycling team we are working with not to use the ketone esters during exercise in this

Julie Young  37:31

study, can you tell us how the ketone Ester ingestion affected blood pH and the bicarbonate, calcium and sodium and why this was important? Yeah,

Dr. Peter Hespel  37:43

that’s very important because the ketone esters, when you just ingest them, they are very acid. And when you use them in high amounts, they cause blood acidosis. To translate in pH, your pH would decrease by about from 7.4 to seven point 35. Which could correspond like with saying that you already start your exercise with a too high blood lactate concentration that goes to some degree of acidosis. Everybody involved in endurance sports knows that you do not want to make an undue performance, and are started in the state of acidosis, because it may impair performance. So our idea was that maybe we should give the ketones only during the first half of a cycling race. And then by the end of the race, the ketones are out of the body. And in the final hour of the race, when you decide about success or non success, you don’t win the race in the first 100k. But in the last 50. So by the end of the race, you have no more ketone bodies in the blood, your acidosis has disappeared. But maybe by using the ketones in the first half of the race, you have saved some glycogen, glycogen sparing, which makes you probably to be a better cyclist in the final half an hour of the competition that we didn’t find. So

Julie Young  39:15

basically, you’re saying ingest the ketones during like that sub MAX type effort. And how long will those ketones stay in the body after ingestion, or

Dr. Peter Hespel  39:24

if you take one to one dose of 30 grams, it would increase your blood ketone concentration for time window of about three to four hours maximum, but during exercise it short. If you ingest it at rest, it will increase within half an hour and then stay high for at least two or three hours. During exercise because you metabolize the ketones more rapidly. You will have a decrease in within one one and a half an hour to almost baseline levels. So you would have to ingest a second dose to keep it high for two three hours during the day. He’s

Julie Young  40:00

got it. And in this study, Did you discover anything unexpected? Well,

Dr. Peter Hespel  40:04

at some point, we thought maybe the effect will be more beneficial if we can avoid the acidosis. So in the first study, we gave the ketones in the first two hours of the race simulated race in a laboratory. But still, you see that the participants they get in acidosis, the pH is decreasing. And maybe this is something to avoid, because also, from cyclists in the field, we could hear that when they were using ketones at the start of a race. And in the early phase of the race, there was a sharp appeal and the race was accelerating. They didn’t feel very well. So we thought maybe we should just perfect the acidosis by CO ingestion of bicarbonate. So cyclists would not start feeling bad during the initial initial phase of the race. In case the race starts earlier than would be typical for a cyclist race were the first one two hours it’s revealing or both being in the peloton and chatting. But it’s not always the case. Sometimes something happens early, and you have to be ready to save you got to go administer bicarbonate to avoid the acidosis. And look whether there is a performance enhancing effect at the end of the race. And that’s indeed what we found. And that although that was our hypothesis, we were surprised to see that at the end of the race, where there were no more ketone bodies in the blood, when there was no more extra bicarbonate in the blood and no acidosis in a 30 minute time trial. After three hours of simulated racing, the performance was better in the ketone group. And to be honest, we still do not understand.

Julie Young  41:51

So it was the ketone plus bicarbonate? Yes, that was the only condition

Dr. Peter Hespel  41:55

that really worked, and that we could also experience in cyclists in the field that cyclists benefited from going ingestion of ketone esters and bicarbonate during the first half of the race, then stop that they were feeling better in the final one hour of the race. It gets complicated, it is very complicated. And for sure, too complicated for recreational cyclists citing

Dede Barry  42:20

I suppose there is also like an individual response, right, that you have to experiment with each individual. I think

Dr. Peter Hespel  42:27

that’s a general rule that whatever you use to enhance performance during exercise, be it a higher carbohydrate dose, or another nutritional supplement than ketones. You always have to you try it out in training, or in simulated competition, or in competition that is not really important to experience whether it really works in you as an individual. And it may be that it works in one of your friends, but not in you because you get gastrointestinal upset and your friend. Does Italy individual thing always since

Julie Young  43:04

you did see a glimpse of some positive results from the combination of bicarbonate and ketone and you had mentioned not certain of the mechanism of why that’s happening. Will you continue to do some more research on that aspect?

Dr. Peter Hespel  43:19

Oh, we did. Because in the first study, we simulated the full cycling race of three and a half hours with the last 30 minutes being all out, like would be typical for the cycling race. But then we thought maybe it will also work in a time trial, because in the time trial you produce, if it’s time trial of 2030 minutes, you produce a lot of lactate, because quite some part of the energy production is anaerobic, because you want to go a little bit higher than your anaerobic threshold, especially at the end. So we believe that maybe if during a time trial, you would use the ketone ester and combine it with bicarbonate, you might still have a beneficial effect of ketone Ester ingest. And the only thing we found is that it didn’t help. It was even worse, that when you were using only the ketone test, the performance in the time trial was worse. And this finding in the meantime have been confirmed by the research group of Gibala. In Canada at Guelph university, they found exactly the same. So very early after that study, we have recommended cyclists and generous athletes in other disciplines when you do a high intensity exercise taking, let’s say 15 minutes to one hour. Please don’t use the ketone esters because the chance is high that it’s going to impair your performance rather than improve and the addition of bicarbonate didn’t help at all. So the message is easy. The ketone esters don’t help with or without bicarbonate, so simply don’t use it.

Julie Young  44:55

Is it due to the higher acidosis or do you also feel like the ketones are suppressing glycolysis is both, okay? You

Dr. Peter Hespel  45:04

see lower lactate levels when you use the ketone esters, due to partially inhibition of glycolysis. And at the same time you have the acidosis. That may partly inhibit the energy metabolism and contractile activity in the muscle. So it’s two different mechanisms when doing a maximal exercise or 1530 minutes. You do not want to enhance acidosis. You’d never want it so you do not want to use the ketone just sounds

Julie Young  45:31

like a double whammy. Yes. So to kind of conclude this study, same question Didi had asked, I believe your participants were male in this study, do you feel the results would be the same for female athletes?

Dr. Peter Hespel  45:46

I think for this part, I am absolutely convinced that it would be the same for female athletes. Because there’s no evidence at all that the role of glycolysis during high intensity and during exercise, or the role of acidosis would be different between males and females. So I think you can just translate the results from the male studies to female athletes.

Trevor Connor  46:13

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Dede Barry  46:39

So Peter, we’d like to move on now to your study on exogenous ketosis increases blood and muscle oxygenation, but not performance during exercise and hypoxia. What were your expectations going into this study versus the actual findings

Dr. Peter Hespel  46:56

will be expected that the use of ketone esters, in contrast to normoxia, sea level exercise, that there the ketone esters might have a positive effect on performance, because one of the biochemical things known about the oxidation of ketones in the human body, and especially in skeletal muscle, is that when you use ketones as an energy substrate, the utilization of the available oxygen is more efficient than when when you use carbohydrates to with your oxygen to produce ATP, or energy, and certainly much better than using fatty acids. So by pushing the use of ketones as an energy substrate into the metabolism, you might save some oxygen, which might be beneficial at altitude, where you get in a state of oxygen deficiency. So I think the irrationality was logic. So what we found is that you when you ingest the ketone Ester during exit, again, during a simulated cycling race, in hypoxia, at simulated altitude, we saw that the arterial oxygen content was higher by using the ketone s. But in the end, we didn’t see an improvement of performance. And that’s at first glance contradiction, because athletes of course, are primarily interested in the performance and having a higher ideal oxygen with no improvement of performance, no reason to go for it. And in fact, the reason why you have a higher arterial oxygen content is again related to the acidosis. By using the ketone Ester, you create acidosis. And acidosis stimulates hyperventilation. So your lung function, your respiratory rate, and your minute volume of ventilation, when you use the ketone ester is high when you use the ketone, so that’s when you don’t use it. And by causing hyperventilation, you automatically slightly increase the arterial oxygen content. That’s normal effect of hyperventilation. But of course, the hyperventilation also costs energy because your respiratory muscles have to work hard, and it doesn’t yield any real benefit in the muscle. Because in the meantime, we know that what was told in the beginning that ketones are so called super fuel and yield more energy during exercise on carbohydrates that this is not true. And the first idea is launched by the Oxford study that ketones esters would replace carbohydrate in the muscle that has been investigated by other groups and by the same group again, and they have not confirmed that finding, so we should stop considering ketones as a super fuel. It’s not we have only one super fuel and that’s the carbohydrates and in no way we should to inhibit the use of carbohydrates by muscle during high intensity exercise by using the ketone esters, because carbohydrates are a better fuel. And

Dede Barry  50:08

so just to clarify, you don’t think that doing this study, changing the timing or the dose of the ketones would yield any different results.

Dr. Peter Hespel  50:19

Any recommendations on the use of ketone esters based on studies we have not been doing so I don’t dare to say it could be that the Lord does good work, but the studies still need to be done.

Dede Barry  50:32

So moving on, has there been any subsequent research to confirm your findings in this study? Yeah, especially

Dr. Peter Hespel  50:38

the group from Guelph University, from Martin Gibala, there have also done similar studies, and also the group from Dublin University, Brendan Egan, they have also done studies in hypoxia. And what they also see is that when you use the ketone Ester in hypoxia, you stimulate your ventilation, you have a higher heart rate, but your exercise performance doesn’t benefit, you just spend more energy in increasing your heart rate and your lung work, actually due to the acidosis created by the ketone Ester

Julie Young  51:10

intake. So those two things cancel each other out basically,

Dr. Peter Hespel  51:14

probably yes.

Dede Barry  51:15

Was there anything unexpected that you found during this study? Yeah,

Dr. Peter Hespel  51:19

well, it was so unexpected that we our hypothesis was that the ketone Ester would improve performance. Because it lit throughout literature, it said that the ketone esters are more efficient to use as an energy substrate when oxygen availability is limited, because ketone esters are more efficient. So it was logic to expect that ketone esters would help. And we were quite disappointed that it didn’t help. But at that time, we still believed that the ketone esters were used by skeletal muscle as an alternative super fuel, which we know at present is not true. Yeah,

Dede Barry  51:54

this study was done on male participants, do you think that the results would be the same for female athletes in this case? Yes,

Dr. Peter Hespel  52:02

I think so. Because in general, the responses of females and males to hypoxia during exercise are quite similar. Hypoxia is very often used in training these days, in endurance athletes and males and females is to do the same training things. So I think that you can extrapolate from the males to the females.

Julie Young  52:22

So Peter, next up is one of your most recent studies, I think, a very interesting study. It’s exogenous ketosis increases circulating dopamine concentration, and maintains mental alertness and ultra endurance athletes. Yes. Can you tell us your aims going into the study and what you actually found?

Dr. Peter Hespel  52:42

Yeah, I think to explain that we have to move a little bit away from cycling and triathlon, but maybe go more to the very extreme, ultra endurance sports. Like you have the Barclay marathon in the United States, and one of my countrymen, Gyaltsab actually finished the Barkly.

Julie Young  53:05

This year, that is insane. That’s insane.

Dr. Peter Hespel  53:07

But they’re also the trans American cycling race. And you have the Tour de Jr. with the six seven day trial in the mountains in Switzerland and thinking about these kind of events. And these typically are events where you always want to work on sub maximal rate. Well, dosing not to spend too much energy, because it’s just a matter of surviving. And typically this to this type of races is that carbohydrates become much less important as an energy source for the muscle, because many if most of these athletes, they in fact move to a low carb, high fat diet, because during low to moderate intensity exercise, but is the most important fuel. So it’s probably a good thing to train the body to work primarily on fat during ilta, and urine defense. So that’s why a fat rich diet can help to improve performance. So you are less dependent on carbohydrate intake during the race, that during these races that are so exhaustive, typically you get into a state of mental fatigue. Very often they have to do a caffeine nap, stop and weakly sleep for 1520 minutes along the street or in the bushes in the Barclay marathon and then wake up after 15 minutes because your mental alertness is decreasing, which becomes very dangerous. That’s where the ketone bodies could become interesting because in contrast to skeletal muscle, the brain can use ketone bodies as a fantastic fuel. And when in injurious defense, your blood glucose concentration would start to decrease because of the long duration of the event. and you’re on a ketogenic diet, I think it’s realistic to think that ketone bodies may replace the glucose to fuel the brain, which might increase or improve mental alertness. And that’s exactly what we found. We investigated the use of ketone esters during an ultra in 100 kilometer race event that in the woods trail race, and that lasted on average, about 10 hours. And the conditions were very bad. And all these athletes at the end are mentally very exhausted. And we found one thing to one thing was that at the end of the race, the reaction times and the mental alertness in these athletes was definitely better with the ketone test. And probably one of the reasons might be that the dopamine release in the central nervous system was stimulate. And that’s a totally other role for ketone esters during exercise, that improving mental alertness in exercise conditions that are so strenuous that your mental health is decreasing, decreasing reaction time mental alertness. And if our studies are confirmed, I think this is a future application of ketone esters in the future.

Julie Young  56:19

What was the dosage and timing of the dosage during that 10 hours, those

Dr. Peter Hespel  56:23

which was very high, we started with a bolus of 30 grams, and then we gave an additional 10 grams every half an hour during 10 hours. So this was the highest dose ever given of ketone supplements to participants during exercise. And the reason we did it was that we wanted to maintain ketone concentration in the blood of about two, three millimoles. From the start to the end of the race with the intention to supply ketone fuel for the brain, throughout the entire race, in that race, it would not help to just give it at the start. And when at the end of the race, you get in problems mentally, the ketones have disappeared from the blood. No, no, just at that time you need to ketones. So we gave it continuously. And we had no gastrointestinal problems, it was well tolerated. And we found that the mental alertness was improved.

Julie Young  57:22

Does the brain prefer ketones or glucose? If given the choice? Absolutely.

Dr. Peter Hespel  57:26

There are experiments showing that when you give the brain in animal experiments, the choice to use either ketones or glucose, the brain uses the ketones.

Julie Young  57:37

And would you say these athletes were operating? And I realized everyone refers to training zones differently. But I think Zone Two is pretty universal. So that long endurance, were they squarely in that zone?

Dr. Peter Hespel  57:48

Yes, that’s typically what you’ll turn urines athletes do. They’re always submaximal training easily, because it doesn’t make sense to do accelerations in such races and Sprint’s because you just empty your glucose stores in the body. So you just try to maintain the pace of which you think you may be able to maintain it until the finish.

Julie Young  58:11

I live in Truckee, California, which is the Sierra Nevada and it’s the near the start of the Western States trail run, if you’ve heard of that. And I also used to live in Auburn, which is the finish. But sometimes I wonder Are these gals and guys are doing those that race so fast? I’m just like, geez, are they really operating in long endurance? Because it just, it’s amazing to me?

Dr. Peter Hespel  58:34

Yeah, if you see what the Achillea Jr is doing, you know, this one, some athletes are really superhuman, and Killian, Jr. has even been running up the Mount Everest, at an incredibly high speed to I think this proves that humans if they specifically train on something, and at the same time, they’re highly talented, they can do things we believe humans could never do. And that’s probably the thing you’re referring to that the speeds are developing. It’s also in cycling, it’s also in marathon running, if you see that now the marathon runners are running at 21 kilometers per hour approaching the two hour limit. It’s insane. It is that they’re just able to do it.

Julie Young  59:15

I was just kind of curious. So if you think some of these athletes, and maybe they’re not maybe that’s just becomes their long endurance, that pace is just there, they become so efficient, but is wondering, in some of these races, these top level racers, if they are kind of tipping into maybe say that sub threshold at points if this would work for them with those kind of adverse effects of ketones and like the acidosis

Dr. Peter Hespel  59:39

alright, I don’t really there to answer that question. It depends on on the duration of the race. I think it there is a difference between a 48 hour race and the six seven day race. Like the Barclay marathon is just surviving. It’s a combination of walking, jogging, it’s do it day and night. No A they call them a runner’s high pace because they know that they kind of die prematurely. If it’s a 24 hour race, you can still train at some point towards the end of the race, increasing the intake of carbohydrates until stimulate your carbohydrate oxidation in the muscle to suppress fat oxidation, and go fast to think it’s a different type of training depending on how long the event lasts, and whether it’s yes or no useful. Still to put some accent on the utilisation of carbohydrate,

Julie Young  1:00:35

that one important distinction you made in this paper was that the ketone esters prevent exercise induced deterioration of mental reaction time but do not upgrade normal level of cognitive functioning.

Dr. Peter Hespel  1:00:49

This has been confirmed in a series of recent studies by Brendan Egan at Dublin university that in fact, with the ketone esters, we can only expect that you improve cognitive function in a state where there is deterioration of cognitive function by some reason can be a disease, or it can, in our case be exercise. So in our study, we could clearly see that the build endurance race, decreased cognitive function by about 20%. So what the ketone ester is doing, it’s bringing you level back to normal, but not upgrading above normal. That’s not something one can expect. Otherwise, all my students at university would probably already be using the Keto test.

Julie Young  1:01:39

Peter, you touched on the mechanisms when you alluded to dopamine, but were there some other mechanisms you felt that were responsible for this positive result?

Dr. Peter Hespel  1:01:49

At present, we have no indications for other mechanisms that might be useful. It’s certainly true that Dopamine is a neurotransmitter that is important in mental alertness. Still, the problem with our study is that we measure dopamine in blood, which may be different from dopamine in the central nervous system. So the studies that need to be done is measure the impact of ketone esters on dopamine production in the central nervous system. And of course, in humans, it’s a very difficult thing to do. But given that ketones are a priority fuel for the brain, we might even expect that the effect of dopamine metabolism in the brain greater than what we have seen in the blood, explaining the effects on reaction time, but it’s speculation.

Julie Young  1:02:35

And did you have any unexpected discoveries in the study? No, not

Dr. Peter Hespel  1:02:40

really, we had expected that it would also improve performance. And they are there’s a difference between statistics and ecological relevance, we could definitely see that with the keys on st intake, there was not only an improvement in the reaction time, but looking at the means and the variation in performances, there was a very clear trend for a better performance indicator group. But being a scientist, as long as something is not statistically significant, you cannot say that it works that there is a difference between statistical significance and biological significance. In elite sports, you can never prove in a study that intake of caffeine would improve 100 meter sprint performance in Olympic sprint, because the effect is too small, but three hundredths of a second can make a difference between a medal and no medal in 100 meter sprint, you can have to prove sometimes it’s the same with scientific evidence related to elite sports. We cannot do the study in elite athletes because they are not available. So you have to do the studies in less trained individuals. And you have to see a substantial effect in order to find the statistical significance. But even a minor effect in elite athletes is important. If the marathon runner keeps him runs his next marathon 35 seconds fast. He’s earning 159 99. And it makes a million dollar difference on his bank account and many more billions in the years off. So minor differences can make a big difference in elite sports. Yeah.

Julie Young  1:04:25

In this study, if I understood correctly, I think similar to what you’ve done, in the overtraining study, you allowed for free feeding. Yes. And I think you saw that the ketone Ester group increased their energy intake by 30%, which had obviously a positive effect on their energy status.

Dr. Peter Hespel  1:04:46

It’s a potential mechanism, though I’m not sure how important that is in just 100k marathon. It would definitely be important in a two or a multiple Day event where energy deficiency would negatively impact performance. It could play a role also in a 10 hour event, in order to be sure we should have a new study where we control the energy intake. And that’s a problem with that kind of study. Because the only correct way to have a countermeasure for the ketone as the energy intake, we would like to be administer extra fat or medium chain triglycerides in the same energy equivalent, but then this administration by itself might have an effect on performance. It might be that ingestion of medium chain triglycerides could impair performance, if we ingest it for 10 hours by causing gastrointestinal distress. So we have been thinking of administering placebo or a controlled drink, giving the same amount of energy, but we didn’t find an appropriate solution, because either you give more carbohydrates that impact performance, or you give more fat. And in the end, you don’t know what’s happening.

Julie Young  1:06:05

And I think you also felt that the ketone Ester intake improved muscle soreness in this situation. Yeah,

Dr. Peter Hespel  1:06:12

but not muscle soreness. We had some indication that there was a small degree of post exercise, muscular inflammation, okay, which might enhance recovery. But then again, the question is that in these type of events, running a marathon running, you don’t run a marathon every day, after such an event, you have, in general have at least a week of rest. And I’m not sure that the minor improvements in terms of muscular inflammation would have any beneficial effect. After a week of rest after a marathon or another running event. It remains to be established.

Julie Young  1:06:52

It’s all about context. Yes. Yeah. So same question. I think these were mostly male participants, would you first see the same results with female athletes?

Dr. Peter Hespel  1:07:02

If you look at endurance exercise events, it’s very clear from research that the more important the contribution of fat metabolism in energy provision, the more close females get to males. The difference in world records, if you look at the 5000 meter in track and field 10,000 meter, or a 20 kilometer run, or a marathon, the relative difference is small in marathon running between males and females than in the higher intensity events where carbohydrates are the primary fuel. So then the question if, if you have females running an ultra endurance event, and they are more specialized in fat oxidation, one might expect that the potential positive effect of ketone bodies might be smaller, because the females are better able to use the fatty acids and oxidation is possible. So I don’t they’re just to extrapolate from the males to the females. Further studies need to be done once again. And it once again shows that this research with regard to the ketone hype is still in its infancy. And we still need many more studies to be done to really know the exact windows are in we want to use it and when we do not want to use it.

Dede Barry  1:08:19

Peter would like to move on now to your most recent study. Exogenous ketosis elevates circulating erythropoietin and stimulates muscular angiogenesis during endurance training, overload. What were your expectations going into this study versus the actual findings? Well, in

Dr. Peter Hespel  1:08:37

fact, that study was one of the unexpected findings. In our first study, that he found out that at the end of the three week overtraining period, the ketone group had really substantially more muscle capillaries, that we didn’t understand why. And so we started to look or we wanted to look at the mechanisms and you start to look into mechanism of muscular angiogenesis. And one of the hormones that really is important in stimulating muscular angiogenesis is erythropoietin. By creative thinking, I would say. We thought that if erythropoietin in endurance sports has been so effective in enhancing performance, and probably the primary reason for blood doping, and erythropoietin administration to enhance performance in endurance sports, and forgive me, I do not only refer to cycling, because it’s also has been used in all the different sports. But my observations in cycling, and I think many people who have been involved long term in cycling will agree that at the times where unfortunately, the vast majority of professional cyclists were using, but doping they did many more races per year. They did 100 races per year. So if More. And in between the races, they were still doing quite serious training. My observations now say that elite cycling, at least in the team I am working with, and I can see what’s happening. We are in the post post blood doping episode. And in general, you see in cycling that the riders do many less races, they don’t do 100 race days per year anymore. They do 6070. And in between, they have many more rest days. So from the field, I think there is an indication that probably the primary action of erythropoietin used in the form of doping was to enhance recovery, which proves its efficacy in the Grand Tours in earlier days. Because the riders that have been very successful have some of them have been admitting that were consistently using blood doping. So from that experience, we thought, maybe just theory, Trump erythropoietin that is doing the job in our study, because we see much better recovery, and we see more capillaries. And erythropoietin is one primary stimulant of angiogenesis in muscles. So the personal was almost perfect. And while we were looking at the effect of overtraining surgery on Erythropoietin, the lab of Javier Gonzalez from a lab in the United Kingdom published the data, showing that acute intake of ketone esters stimulated the release of erythropoietin. So they did an exercise. And after that they ingested ketones in recovery. And erythropoietin was significantly high. So I said, Yeah, we know the answer. We also measure the critical point in in our study. And indeed, we found that in the condition of overtraining, in conjunction with ketone intake, erythropoietin was significantly high. So still today, I think that is probably one of the primary mechanisms of action of ketone ester and intake to improve recovery during very high volumes of training. Because one of the effects of volume overtraining, is to suppress erythropoietin release, and probably by the administration of ketone esters, you correct for this depression, likely the dopamine and the reaction time in il 10, urines. And I say that, because I told you earlier in this talk, that we did a new study with training, that with well balanced training, with a good balance between training and recovery, and there, we don’t see the effect on erythropoietin. So that’s an additional reason for me to say that, I probably have indications to say that in well balanced, appropriate adherence training, it’s not going to help. It’s only when you put your body into trouble by overload, and you suppress your normal physiological activity like secretion of 82 point in dopamine, that you can avoid the damage or reduce the damage by using the ketone test.

Dede Barry  1:13:03

So based on that, do you think that this effect would be applicable really only for the most elite athletes that are writing or exercising to exhaustion day after day, and not really applicable to amateur endurance athletes?

Dr. Peter Hespel  1:13:18

I think I can only fully agree with that statement. I think if you exercise two, four times a week, and it can even be hard to exercise that you recover well, in between, I don’t think that surplus administration of ketone ester is going to help you to get better.

Dede Barry  1:13:36

And was there anything unexpected that you discovered during the study? Not

Dr. Peter Hespel  1:13:41

really, because this was just a follow up of your initial study on overtraining, based on the experience in cycling and publication by another lap on erythropoietin? So we just checked that specific point. And we found exactly what we’ve what we want to find. Still I was I did not expect that we did the normal training with Well, a good balance between training and recovery. I had still expected that we would find higher erythropoietin levels, which we did not and in the fact that I’m not unhappy with that, because it narrows the window for use of ketones in sporting populations. And it’s an extra argument to say to the general population, people don’t jump into the ketone supplements because this is something for the top level athletes that are involved in training loads that you will probably never experience in your life.

Dede Barry  1:14:37

So looking at specifically at elite World Tour cyclists, would it make sense to supplement with ketones on a one week race or really only in the Grand Tours, three week races?

Dr. Peter Hespel  1:14:49

The only thing I can say is that in our study, we could see that the effect was becoming great. The longer the training overload was long lasting and also in practice. We have seen that the Memory benefit was in the Grand Tours towards the end in the last week. But of course, when athletes are in competitive season, you have a rapid sequence of races. And after having participated in one week stage race, you may have three days rest or one week rest, and then you participate in another one. And then you have an one day race or maybe to one day races and another short stage race. Before you go in the grand tour to I cannot exclude that every every even short stage race, you would use the ketone s in the end it after two or three months of preparation, you’d get in a more fit state at the start of Grand Tour. I have no evidence, but neither have I evidence to exclude that as a possibility.

Dede Barry  1:15:49

And has there been subsequent research to confirm your findings in this study

Dr. Peter Hespel  1:15:54

on the erythropoietin? No, I think there is only the 30 by Javier Gonzalez group in the United Kingdom and by our group, but I’m quite sure that because these areas are piloted finding is so important. And so eye catching, I think for everybody involved in endurance training that it will not last long before you results will be published. But I’m not aware of any studies going on. But I’m sure they will come. Yeah,

Julie Young  1:16:23

so if like a world tour rider was using this during a grand tour, they would essentially be using it at the end of like after the stage each day.

Dr. Peter Hespel  1:16:33

If you look at the Grand Tours, one of the teams and by accident is a team I am working with for many years, the Quickstep team with Remco Evenepoel. This team is sponsored by an American manufacturer of the Keto motorist. And even though that’s the reason why I can just say it on television, when even the pool has won another race or just not one another race, the first thing he is doing is taking the ketone test. And he’s repeating that in the evening before going to bed. And not only him the team, and what’s the dosage is the 30 gram dose, the high dose, because again, there is no evidence that five or 10 grams may help. So I would never recommend people to use the load supplements because I don’t think they may help.

Dede Barry  1:17:21

So you’re not adjusting it for the weight of the athlete, it would not be

Dr. Peter Hespel  1:17:25

an logic to do it. But in practice when you’re in competition, and you have the small buffers of 30 grams, which we have also been using in some of our studies, just 30 grams for everybody. We have done other studies where we have rate adjusted, but we see the same effects. So in practice, we just give one bottle with a 30 grams and they drink it. But I agree that in the 60 or a 50 kilogram female cyclist, a 20 gram may probably have exactly the same effect as in an 80 gram, male cyclist. And again,

Dede Barry  1:17:58

this study was done on male participants, do you think the results would be the same for female athletes?

Dr. Peter Hespel  1:18:05

The result on the secretion of Erythropoietin, the regulation of erythropoietin secretion in males and females follows exactly the same mechanisms. So I would think yes, that the same findings would apply for males and females.

Julie Young  1:18:21

Moving on, we’ve now that we’ve had the opportunity to dissect and discuss your five studies, which again, to me have clearly shown like what ketones can do and can potentially do. I’d love to ask you a few follow up questions. So again, we started this conversation like the hype around ketones, and then the conversation about these World Tour teams, and it’s created this intrigue and curiosity. So I mean, do you think some of these superhuman performances we’re seeing at the World Tour level can be in part attributed to ketone use?

Dr. Peter Hespel  1:18:58

I don’t like the word superhuman performances, okay, because in the word superhuman, it seems to suggest somewhere that some illegal things might be happening. You probably consider Remco Evenepoel as one of the superhuman performing guys. Yes. And we have Pugacheva. And who else would you be referring to

Dede Barry  1:19:25

finger banner Vanderpool?

Dr. Peter Hespel  1:19:27

Yeah, the first thing to say about that is that all the cyclists you’re mentioning are supported by a team that has excellent scientific consultants, not only in terms of nutrition and nutritional supplements, but also for aerodynamics, heat, acclamation, altitude training and materials, aerodynamics, name whatever you want. In all these important determinants of performance. They are Well, then the question still is, is there something happening that makes a pool to be better than most of the others, except the ones we have mentioned, I know Remco, since he was a football player, and in fact, he came to do His first exercise test as a football player in my lap, and I was there. And I was surprised of his physical condition, because the field to max and endures in football place at high level is good, but not at the level of epco. Even so, and he’s training because he was on the point of getting a professional football player or not. But it didn’t just work out. And he said, Why don’t we try as a cyclist? His trainer said, because your endurance is so good. Why don’t you try just for a few months to train on the bike. That’s what he did. And just after three months of training, some scouts from the top teams, set cheeses, what’s happening there. So this guy is just extremely talented. And you may remember remember the World Championship under 23, four years ago, when in the beginning of the race, even the bull, he had a crush, and he was five minutes behind, and he was in the world championships. He was just riding to the front. And he finished with 10 minutes ahead, as the winner of the race, and there’s number 210 minutes behind, I can only say, this guy’s extremely talent. I see what he’s doing, how professional he is. I know his values in exercise test field to Max, I think we are at present just hitting some extremely talented young cyclists that are supported by fantastic teams. That’s the Quickstep team. I’m working with us to Jimbo Wizner team and the Emirates team by Pugacheva. And you have a combination of super talents, young, combined with excellent training, follow up with all determinants of performance. And because cyclists has become a much more pure sports than it has been in the past. I think the chance for these super talents at young age to appear in front of the race at young age have increased.

Julie Young  1:22:19

Yeah. I mean, I just think, you know, the great champions, they have that genetic talent, but they have extreme work ethic. And then they also have that mental determination. I think when you get those three pieces put together, you know, it’s that Remco

Dede Barry  1:22:35

and that community around the athlete, the support the team, the family, that’s

Dr. Peter Hespel  1:22:39

absolutely true. And you know, that’s why I absolutely do not want to use the word superhuman, because we have all to admit you’re never 500% sure about what an athlete is doing. Yeah, they’ve every even if you’re married, and your husband is a top cyclist, you may not even know everything is doing. You’re never 200% Sure. But I have seen the evolution of one of these young top cyclists from the age of 17. Until today, and I have not one single argument to believe that what he is doing is superhuman.

Dede Barry  1:23:19

I mean, the other thing to keep in perspective here is we’re talking about one supplement today ketones and like we all said a couple minutes ago, there’s just so many different factors that affect overall performance. Yes, including what tires you choose the psi, the arrow skinsuit. There’s just so many different factors. And this is a potential factor that can affect performance positively or negatively. But it is a small piece of a very large puzzle that you have to put together to create a top performance.

Dr. Peter Hespel  1:23:51

So absolutely true. And another point is that we are involved in pro cycling with the teams of Patrick Lucero from the time the big Mapei team disappeared, and we immediately to Cove so we have known many of the top cyclists from the teams of Patrick l’affaire from Johan Missy batini Virag trombone in the whole series. Now it’s even the pool and Julia Allah Philippe, I must say that when we were doing exercise tests, in the early days, sometimes we had the cyclists were after the tests, I said, I don’t understand this guy is doing a test with these results. And then he’s racing two weeks after, I don’t understand what he’s doing in the race is not compatible with the values I see in the lab that has happened today. It never happens anymore. What I see the writers of our team doing is entirely compatible with what we see in the lab. And of course you have intelligent riders and riders that are extremely good in their behavior in the race and they smell when they have will be there, and others who cannot do it that makes a difference. But in terms of physiology, I think the performances I am seeing with the writers I’m working are human.

Julie Young  1:25:11

Well, I think you pointed out something really interesting, Peter in terms of the evolution and how it’s changed since that, you know, what we would consider like the dark period of cycling and you pointing out that the riders are doing far less races. And they do have those a lot of times during the year to do their altitude camps and to kind of mentally and physically reset.

Dr. Peter Hespel  1:25:31

Yeah. And sometimes it makes me even angry when you hear journalists judging the performances of the superhumans to jesting, that probably something is happening. I think it’s unfair.

Dede Barry  1:25:44

Peter, are you currently conducting research on other potential applications for ketone use?

Dr. Peter Hespel  1:25:49

No, not at the moment, because my opinion is a little bit that the most interesting findings very often are the original findings that are seminal for further research and newsfeed the findings with erythropoietin and overtraining and bicarbonate and dopamine and mental alertness. And of course, we will do some follow up research, but I don’t expect that in the years to come, there will be new major breakthroughs, the research that will be coming will be more like fine tuning. And because and that’s a bad thing. None of the companies making big money with the sales of the Keto motorist is investing big money in research. And I am not going to invest research money from taxpayers to make these companies even more rich.

Trevor Connor  1:26:45

To be heard that your gut is the gateway to good health. You’re an endurance athlete, gut health is even more important as the GI system directly impacts athletic performance. Did you know that the weather stress levels and the size of your small intestine can affect your unique fuelling requirements. Dr. Alan Lim sports scientist and founder of sports nutrition company Skratch Labs joins the fast talk BIM podcast to discuss the vital role that gut plays in performance. This is a muscle as an episode, check out the fast top BIM podcast with guest Dr. Alan Lim at fast talk

Dede Barry  1:27:21

Peter, based on the research that you’ve done your experience with the teams and athletes that you’ve worked with, if you could give three pieces of advice to an endurance athlete who wants to experiment with ketone supplementation, what would they be? It’s

Dr. Peter Hespel  1:27:36

a difficult question because in this, throughout this talk, we have really been narrowing the window for use during extremely high training volumes, which most recreational athletes don’t do. So I would recommend that most recreational cyclists who are serious recreational cyclists who are training quite a lot, they also go on the type of training camps or cycling holidays where they go for two weeks riding in the Alps or in Colorado and doing a lot of hard work on the bike. I think that’s the right moment to try it. But then you will need to invest quite a lot of money. Because it makes no sense when you go on a two week training camp or cycling holiday where you will bike, maybe not every day, but 12 days, or 14 or 11 days of the 14 to use it on day one, day five, and day eight is not going to help. So you have to use it after each ride. And before going to sleep through will need 2025 Those which will cost you a lot of money. But this may be the only meaningful way to try it out. If you are an ultra endurance athlete, and you have experienced mental fatigue at the end of races and decrease of mental alertness and reaction times that are very important, especially in trail running. I would recommend that at the time when you anticipate in a race that the mental decrease will start to develop to start using the ketone asked to if you are used to do 24 hour races. And you know, after 16 hours, I feel my mental alertness is starting to drop. I’m getting less efficient to try start using the ketone Ester data. That’s really good advice. Thank you.

Julie Young  1:29:24

You know, Peter, I was just thinking as you’re talking about that I trained a team for Race Across America in that hallucination is such a tough or challenging part of that race.

Dr. Peter Hespel  1:29:35

Based on what the observations we have. I think ingestion of ketone Ester might be an intervention to at least reduce the hallucinations because the hallucinations occur due to energy deficiency in the brain. And the ketone ester is the ideal supplements to maybe counteract this type of handicapping events during these races. Oh

Julie Young  1:29:59

Peter It’s been an absolute pleasure and honor. Thank you so much for taking time to join us today.

Dede Barry  1:30:04

Yeah, thank you, Peter.

Dr. Peter Hespel  1:30:05

My pleasure. I hope you and your audience have got some messages that may be useful in your application of maybe ketones, but even more training and if improvement of endurance performance at the recreational level and in the sake of obtaining a better help.

Julie Young  1:30:25

Well, I think you really helped us, as you said, clear up the jungle.

Dr. Peter Hespel  1:30:28

Thank you. It was my pleasure.

Julie Young  1:30:30

Yeah. Thank you very much. Bye, bye.

Dede Barry  1:30:33

That was another episode of Fast Talk Femmes. Subscribe to Fast Talk Femes wherever you prefer to find your favorite podcasts. Be sure to leave us a rating and a review. The thoughts and opinions expressed on Fast Talk Fam are those of the individual. As always, we’d love your feedback, and any thoughts you have on topics or guests that may be of interest for you get in touch via social. You can find Fast Talk Labs on Twitter and Instagram @fasttalklabs, where you’ll also find all of our episodes. You can also check them out on the web at For Dr. Peter Hespel and Julie Young, I’m Dede Barry. Thank you for listening!