Dr. Gabrielle Lyon 0:30

Dr Martin Gibala, welcome to the show. Nice to see you again. Now, one reason out of many I wanted to have you on the show is that high intensity interval training, sprint interval training, all of these modalities. What we’re really after are outcomes, and you are arguably one of the world leading experts in these various types of exercises.

Martin Gibala 1:06

Well, it’s great to be back. You’re too kind with your opening remarks there, but happy to happy to get into it. And I really appreciate the opportunity.

Dr. Gabrielle Lyon 1:13

So we’re going to talk really basics, and then we can get into some of the more controversial aspects. Because, you know, as we think about evolving science, one of the criticisms that we’ve heard over and over again is that they’re just it’s just not a lot of large data sets highly powered studies. But before we get into that, let’s just talk about what it is high intensity interval training.

Martin Gibala 1:36

Yeah, so to me, you know interval training is just alternating periods of higher intensity activity with recovery, so that can be all out rest or lower intensity exercise, high intensity it, it really depends, are you talking in a performance context or in a health context? And so, you know, in a health context, exercise prescription, we talk about light, moderate, vigorous intensity exercise. And so vigorous intensity exercise is that high intensity range. And so we can use different metrics. The WHO World Health Organization would say, on a zero to 10 scale, vigorous exercise is a seven or

Dr. Gabrielle Lyon 2:19

eight out of 10. That’s defined differently for every Correct.

Martin Gibala 2:23

Moderate is a five right. We also have other RPE scales, classic six to 20 scale, they are vigorous is a 1414, to 17. If we’re talking heart rate ranges, you know, in the American College of Sports Medicine would have authoritative guidelines. We’re talking a heart rate of about 77% of your maximum or or above. And there’s also percentages of vO two Max as well. The point being, there’s no single best indicator of what counts as hit. People can use RPE, people can use heart rate, people can use measurements of vO two Max, and so all of those are anchored to some maximum physiological threshold, your VO two Max, your heart rate max. Now if you’re an athlete, you don’t talk like that. Or coaches and athletes will talk about three fundamental domains, moderate, heavy, severe. And so once you get into the severe domain that is high intensity exercise. And in the severe domain, it’s generally not exercise, it’s sustainable, it’s non steady state exercise. And so athletes and coaches talk about, it’s really important, I think, metabolic thresholds. So things like your lactate threshold, your ventilatory threshold. And so, high intensity exercise, if you’re an athlete, is your second lactate threshold, your maximal lactate steady state, your critical power and so, importantly, those are physiological measures, you know, metabolic characteristics that then they will anchor heart rate, RPE, two for them. And so I think this is the real problem. When we start talking about Zone training, that it it’s so variable for for everyone. And so unless you happen to actually know your lactate threshold, your fat Max,

Dr. Gabrielle Lyon 4:19

you’re sort of care about that, and do we care about so from a, you know, I’m a practicing physician, I care about health outcomes. I want to know how much high intensity interval training that I need to do to improve insulin sensitivity for outcomes like better glucose control, yeah, well, you’re fat Max, which I want to talk about, and then a lactate threshold. Do these relate to any kind of health outcome, or is it only performance there?

Martin Gibala 4:46

You know, obviously Zone Two is very popular right now. I’m sure we’re going to talk about that. There’s virtually no studies on zone two per se and health outcomes. Now, depending how you contextualize Zone Two, the. There could be some evidence to support claims about its effectiveness to boost your mitochondria. But back to your point, you’re right. If we look at the WHO guidelines, we have physical activity guidelines that say if you do this amount of physical activity in this general intensity range, that’s associated with robust health outcomes, improving things like your insulin sensitivity, your glucose control, your blood pressure, your brain

Dr. Gabrielle Lyon 5:30

health and metabolic function, correct mitochondrial function,

Martin Gibala 5:34

all of them because they’re all related to fundamentally to health. And so the general guideline is we should all be doing about 150 minutes a week. That’s two and a half hours of moderate to vigorous physical activity intensity,

Dr. Gabrielle Lyon 5:50

30 minutes a day. Do you agree with this recommendation?

Martin Gibala 5:54

Well, absolutely, in the sense that it’s there’s very good evidence to support that if people do this volume of of of exercise like I say, it’s associated with many, many, many health outcomes. I think where we start to quibble, or you start to see debates happening, is around, well, vigorous versus moderate, high intensity versus traditional, moderate and intensity continuous which is better, and those studies are hard to do, but my contention is that, and I think there’s good evidence for this, for a given amount of physical activity, a given dose, there’s good evidence that more vigorous physical activity will promote gains in those markers that we care about, you know, those health related markers, and arguably the most important one is your cardiorespiratory fitness, which we objectively measure with a vo two max test. But you know, if there’s one health metric that people should worry about, I think you could make a really good case that it’s cardiorespiratory fitness, because it’s just so clearly related to your risk of dying from all causes, your risk to develop type two diabetes, cardiovascular disease, metabolic syndrome, certain types of cancers. You know it’s it’s not a guarantee, but we know that if you boost that number, your risk of all these negative things goes down.

Dr. Gabrielle Lyon 7:22

So what I’m hearing you say is that 150 minutes of moderate to vigorous activity, which is defined differently by different populations, that the athletic population is really looking for very specific data points. Is that true? Like a lac Trejo,

Martin Gibala 7:38

so athletic coaches and athletes are worried about performance. They’re not worried about, you know, they they can do. Many athletes can be quite healthy. Many athletes can be unhealthy if they do too much. But you know, fundamentally, athletes are interested in performance, and they use those metrics because they provide very good indicators of specific zones where they think they should spend the majority of their training, right? And so if you’re a high level endurance athlete, importantly, not doing 150 minutes a week, not doing two and a half hours, doing 25 hours a week of training, then there’s good evidence that about an 8020 ratio optimizes performance, so 80% of your time is spent at Low to low, moderate intensity training, and 20% is high intensity training. But again, this is for high level athletes doing 25 hours a week, where I would quibble with the recommendation that that’s optimal for everyone you know. So if you’re if you’re struggling to meet the guidelines I see, or if you’re just meeting the guidelines, I don’t think there’s any evidence to suggest that an 8020 split is optimal there for you. And again, 80% of what these notions of your lactate threshold or your or your fat max intensity, which is really hard, I think, for people to to grasp. And then when we start giving these approximations of it, it just doesn’t, it doesn’t apply.

Dr. Gabrielle Lyon 9:12

Well, I don’t think that people have thought about it in that way. And what I mean by that is that online, there’s a ton of information, and it really there is a line that people are always talking about optimization, optimization for an athlete. Arguably, I don’t think that that exists, because what I see in my own practice is that the better the athlete, the poorer the health outcomes. Because the more they’re training, the less they’re recovering. They’re getting ready to quote, peak for whatever that is. But the general population we are still talking about, people are looking for longevity, buzzwords like longevity, house ban, house ban, muscle span, sexpan optimization. But the information is largely informed, not from, I would say, arguably, the general population. It’s. Is informed the evidence, or I would say the majority of the evidence, at least, that I see, is related to sport and performance, and so the populations are different. And the danger in saying, Well, if we’re doing 150 minutes, and 80% of that time is spent at zone to training, which, if people are arguably not quite conditioned, might not be as meaningful as we want it to be. Then Are they really getting the health outcomes?

Martin Gibala 10:31

Yeah, no, bingo, right. And so I think depending on the person, and depending on the metric, you know, 80% of that 150 minutes a week telling people that they should be doing low intensity training for that, I don’t think is the best prescription for them, but I would just say, Show me the evidence that it is right. So where is the evidence that three hours, four hours a week of Zone Two is optimal for your mitochondrial health, and there isn’t any, you know. Now, I totally appreciate where it’s come from. You know, athletes have very high metabolic capacities, right? If you’re doing 25 hours a week of training, and you’re training at that classic 8020 mix, and there’s definitely good evidence to show that. Yeah, athletes have, you know, elite endurance athletes have very high metabolic capacities, have very high mitochondrial function. But again, I come back to then just saying, well, that’s the optimal ratio for for everyone. I just, I don’t see the evidence forward, and that would be the, let’s talk about the science. What does the science show?

Dr. Gabrielle Lyon 11:44

Let’s talk about it. I’ve got a few great papers here. Talk to me about, I suppose, clarify as to where high intensity interval training could be applied to the regular person who is listening or watching this podcast, yeah.

Martin Gibala 12:01

So first of all, if we accept, and I think there’s good reason to accept that high intensity exercise, when we hear that term hit high intensity intermittent training, that just means vigorous intermittent exercise, right?

Dr. Gabrielle Lyon 12:15

And so non specific. But why I

Martin Gibala 12:18

say that is because vigorous is well established in the public health guidelines, in ACSM guidelines. So let’s accept that it’s vigorous, and then we know the threshold, right? If you’re above this threshold,

Dr. Gabrielle Lyon 12:32

that’d be your example, 85% of your VO two Max. How would we define vigorous?

Martin Gibala 12:37

Yeah, it’s 77% of your maximum heart rate or above, and it’s even less of that for vo two Max, it’s that 14 out of 20. It’s that seven out of 10. So if you’re doing that, you know, going back to the talk test, the talk test is, you know, if, if you know, certainly, if you could carry on a conversation, it might be strained a little bit, but you can have a conversation that’s moderate intensity, right? Once you move into the vigorous range, you can’t keep a conversation going, you know. And at the higher ranges, you could spit out a

Dr. Gabrielle Lyon 13:06

couple of words, but that’s about like, don’t usually swear words, yeah,

Martin Gibala 13:09

don’t talk to me, exactly, right? So, you know? So, so that, let’s just say hit is vigorous, intermittent exercise. Then we know. Here’s all the metrics that you can use to determine if you’re doing hit or or not, right? And so I think hit is a very effective way for people to integrate vigorous physical activity into another day. And we know there’s just robust evidence that hit protocols of varying durations, intensities can certainly improve your VO two Max can improve your mitochondrial health and function. Can improve health metrics, like we were talking about insulin sensitivity, things like that,

Dr. Gabrielle Lyon 13:45

if you were to say so, for example, I don’t do any zone two training. I only do high intensity interval training, and I lump that in with my I do it one of two ways. I have a strength training workout, and then I will put a high intensity burner at the end. And I would argue it’s probably closer to sprint interval training. I mean, I’m pretty maxed out. It might be eight, six or eight calories on an air dye, or six or eight calories on a SkiErg, and it might be four, four sets in between something else now and then. On a Saturday, it’s more high intensity. I say that probably 70% I’m not swearing on the floor in a puddle of mush, but I don’t do any zone two. And as people are listening to this, people struggle with time. So where does would that be acceptable versus do? I also now have to add in zone two training again, in the literature, the way that is discussed zone two is, is, I don’t want to say superior, but that’s the foundation, and that’s the base, but is, is that?

Martin Gibala 14:55

Yeah, I don’t think you’re missing out on on anything you. In this given the time that you want to put into it, right? And so I think you can be completely healthy. You can improve your health by a largely interval based approach. I think that’s you know again. What if there’s one thing I’ve learned, there’s no one size fits all approach. And so if someone’s gonna you know you’re you deal with clients all the time. But if someone’s gonna come to you, it’s like, what’s the goal? You know? What is your primary goal? How much time do you have to train? Right? And when we’re suggesting, given what you just mentioned, that so many people are struggling to meet the Physical Activity Guidelines, which are two and a half hours a week of moderate to

Dr. Gabrielle Lyon 15:43

vigorous. How many people meet that,

Martin Gibala 15:45

you know, depending on the survey, less than half. Right? Yeah. And so then suggesting that, well, you have to do actually, three to four hours a week of Zone Two. It’s just raising the bar. It’s such a high barrier to entry that I think you know it, yeah, you’re, you’re losing people

Dr. Gabrielle Lyon 16:03

there talk to me about some of the the new research on Sprint interval training. And before I, before we jump into sprint interval training, is it important to differentiate between high intensity and sprint interval training?

Martin Gibala 16:17

It is. And so to me, and I think many others. Sprint interval training is an intense variant of hit. So basically, once you get above those thresholds that we talked about, there seven out of 10, you know, 77% of your maximum heart rate, anything up to an all out sprint from danger, PACE counts as hit sprint. Sprint interval training is that that that, that real top range of, you know, we typically, it’s typically defined based on power, is once you’re above your maximal aerobic speed, so the speed or work rate that would cause you to reach your VO two Max, you’re even above that, or the pace is truly all out, right? And so typically, those intervals are one minute or less. They can be as short as 10 or 20 seconds. One minute sounds long. It does even, you know, you’re pushing at the end. But you know, 10, 20/32, sprint intervals are sort of the classic, you know, tabatas are 20 seconds, right? And so that’s where so those are those intensity ranges. You know, you’re, if you do repeated sprints, you’re getting up above 95% of your maximal heart rate when you’re doing repeated one. So it’s, it’s pretty intense. But to be clear, it’s a variant of hit.

Dr. Gabrielle Lyon 17:33

It’s a variant of hit. And how important is it to progress into some of these other definitions? Because what I want, my goal for people, when they are finished with this podcast is a few things, number one, to actually have a clear understanding as to what high intensity interval training is and what it’s not, what it’s used for, where its actual benefit is for performance and where its benefit lies for health. And then finally, protocols, what do we actually have to do? And and within that, I want to hear some of the controversies and some of the things that we don’t commonly think about, and then the new emerging research and how we can implement that. Yeah, so this, this low volume. I have low volume sit and this says this generally first to protocols in which training sessions are 15 minutes or less in duration and involve a total of up to five minutes of intense exercise, right? I mean, this isn’t I should ask you, is this important to understand? Because what I don’t want people to do is to just try something and be like, Well, I tried it, it didn’t work, or it didn’t have any metabolic benefit. I didn’t improve. What can we tell them specifically as to when they incorporate these varying definitions, and you can take that wherever you want, what are they going to get?

Martin Gibala 19:01

So at the end of the day, there’s no free lunch, right? And so if, if you want the benefits of brief, very vigorous, intermittent exercise, you have to go very hard. It’s an extremely uncomfortable way to exercise and training, we’re not suggesting that it is for everyone. We’re not suggesting that everyone likes that type of training.

Dr. Gabrielle Lyon 19:27

To be clear, nobody likes that type of training, and I would argue everybody should experience it, because how the only way we grow is is resistance and

Martin Gibala 19:39

but I would say too. You know, the general contention is, well, if exercise is vigorous or intense, if it’s above your lactate threshold, if it’s uncomfortable, it’s aversive, you don’t like it, you’re not going to stick with it. Now there’s, there’s really good evidence to show that it’s well, well, wait a minute, we need to think about total dose here, or total volume. And. Certainly there’s a number of people where they’re more than willing to trade off. Or you give them the option, you can do an hour of traditional continuous or you can do 10 minutes of really vigorous and within that one minute of all out sprint training. Which do you like? They’re like, yeah, I really don’t like that sprint training in the moment, but I certainly like it when I’m done in 10 or 15 minutes, and I would much prefer that to doing an hour or 90 minutes of the traditional approach. Again, that’s not everybody, but the point is to just generally dismiss sprint interval training out of hand. Is, oh, no one will do that. Or how could it possibly provide benefits? Is is unfounded.

Dr. Gabrielle Lyon 20:43

What are some of the new there’s new sprint interval research that’s been published. So the last time you were on

Martin Gibala 20:50

Yeah, and so I a valid criticism of hit in general, and especially the sprint training literature is like a lot of areas of Exercise Science, many of the studies, they’re relatively small, they’re relatively short term, and so, you know, we don’t want to have your listeners and viewers eyes glade over, glaze over and talk about statistics, but you know, there are rigorous ways to design experimental Studies, and there are not, and many proof of concept studies are just that. They’re relatively small. They’re trying to demonstrate a finding, but they’re not large scale randomized control trials. And what you’re seeing, I think, in the hit field generally, and in the sprint training area, is you’re seeing much more robust studies being done, true randomized, controlled trials, where you take a group you, you know, you and you, you know, even, I’ll use us as an example. We’re not working with bio statisticians. We to plan our scientific studies.

Dr. Gabrielle Lyon 21:53

You know, should, should someone be Well, I think

Martin Gibala 21:56

absolutely your your studies should at least be informed by, you know, what’s an appropriate sample size, what is an effect size? And that just means, is this biologically meaningful? You know, again, in medicine, we see examples where, you know, 100,000 people take this pill, and there’s a statistically significant finding, but the effect was a 0.1 change in blood pressure that’s at the other end of the spectrum. You know, often in exercise science, it’s small studies, and so we’re not really able to tease out, well, did this work? Is this better than this? Suffice to say, the evidence around sprint interval training studies is, is markedly improving, and now we have robust evidence to say, if you do six, 812, weeks of Sprint interval training, you will see clinically significant improvements in your VO two Max compared to an untraining control group. No question.

Dr. Gabrielle Lyon 22:55

Talk to me about time frame and give you an example of a sprint interval training plan. Yeah.

Martin Gibala 23:04

So we’ve used a protocol, and where the name of the book, my book, The One Minute Workout came from, was our protocol was 3/22 sprints within a total time commitment of 10 minutes. So start to finish, you come in, you do about a three minute warm up, you do your first 22nd sprint, two minutes recovery. Sprint again, two minutes recovery, and then a two minute cool down. So basically, start to finish there, it’s 10 minutes of it’s a 10 minute exercise session, but within that, there was only one minute of very intensive exercise. And there’s other protocols, one known as rehit, reduced exertion, high intensity training. That’s 10 or 22nd sprints, and only two of them. So we’re really talking less than a minute of really sprint effort in a typical time commitment of 10 minutes or less.

Dr. Gabrielle Lyon 24:01

And how does someone who’s listening to this, they’re like, All right, well, I’m pumped up. Martin’s awesome, and I’m gonna go do 3/22 sprints. Are they running? Are they on a bike? Are they on a rower? Yeah.

Martin Gibala 24:17

So it’s as long as long as there’s no underlying joint issues, all of that. You know those cautions, Hill running would be a classic way to do it, right? So you can, you can really go all out, but you can imagine, as you’re running up a hill, what happens if you’re truly sprinting uphill. You slow down about halfway up the hill. Even after a few seconds, you start to slow down because the load of the hill is is so challenging, and so it’s hard to do. You can there’s examples of sprint, like training that you can do on a bike, but you really you set a workload, you set a workload that’s quite high, and then you. You try to hold that as long as possible. Now there are

Dr. Gabrielle Lyon 25:04

without losing the RPMs. I mean, is that important? So, for example, as I think on Saturday, I’m sure I’ll be doing 10 cows, which I swear, I think the bike is broken because I’m like, these cows aren’t increasing. I cannot hold that the RPM once, you know, I might be 7580 but I can’t hold that. And then mentally, I’m gassed if I can’t hold it for the next set, and say, I’m on just set number two. Is that considered high intensity interval training? Do I need to be very clear on the dose that I’m getting. For example, if I am taking, I don’t know, one unit of insulin, it’s one unit of insulin. Yeah.

Martin Gibala 25:48

So you know, just about the bikes themselves, traditional bikes, it’s, you can still do sprint training on it. But you know, in laboratory studies, the classic bike, or the classic test has always been a Wingate test, right? 30 seconds all out as hard as you can go. And those are done on specialized pieces of equipment that essentially, if you can imagine that the power output adjusts over time and sort of meets you where you are. So you’re giving that example of you start to tire late and exercise in your sprint training, but maybe you could have actually done a little bit more at the start if the power output would have been higher. So, you know, there are now devices on the market. You know, apparel, bike, we’ve we’ve used these in our research studies, where you know that the bike uses a self learning algorithm so that

Dr. Gabrielle Lyon 26:44

it can adjust over time. So um, we are. We just recently partnered with Carol bike, and one of the reasons I love the Carol bike is its ability to, in real time, adjust for a specific outcome. So I want to just make a note of that. And now I would love to chat specifically about what the Carol bike does and how it can be used.

Martin Gibala 27:06

Yeah, no. And, you know, disclaimer, from the outset, I’ve engaged with Carol in terms of providing some scientific advice for them. I’ve never been paid. We have some of their bikes in our lab because we’ve seen the research studies. They work. We’ve tried them in some of our recent studies and applied them successfully in our sprint interval training studies, but yeah, what the bike does is it adjusts workload, and so the classic Wingate test, what you do is you set a load on the bike that’s about seven and a half percent of Your body weight, and why that is for most people, that’s sort of the optimal combination of load and RPMs you’d imagine. You set the load too high, you can’t even turn the pedals right. You set the load too low, and you can only spin so fast, but you’re not getting a workout. That’s right. So that seven and a half kilogram load on the bike was sort of that optimum. Now, if you’re a high level athlete, it might be 9% of body weight, less trained people 5% and so my understanding then is the Carroll bikes have sort of used that initial setting, but then what the self learning algorithm allows you to do is for you, right? It adjusts specifically for, for for you to sort of optimize the workload setting as you move through a period of training. Bottom line for us is, as compared to traditional wingates, we’ve used it down in our studies as it as an intervention, as a sprint training intervention, and shown that it can prove vo two Max after six, 812, weeks of training. And, you

Dr. Gabrielle Lyon 28:46

know, before then, I we’ve seen

Martin Gibala 28:51

changes as early as two weeks. So it, you know, depends on lots of things, but, and

Dr. Gabrielle Lyon 28:56

this is any, and I’m talking about now any sprint interval training, right? Yeah, yes, yes, yes, any sprint interval training? Yes. And do you have to be well trained for? Oh, you have to edit this part. So what I mean to say is, there is this almost novice what do they call it, the newbie training phenomenon, when all of a sudden they gain more muscle than, say, someone who’s been training for years in sprint interval training, is that the same effect? Is it kind of the same architecture?

Martin Gibala 29:31

Yeah, this idea, I don’t know if shocking the system or that, you know, I like to think that that, you know, the physiology is the same. It’s just the inputs can be different, right? And so you can improve your VO two Max with a lot of traditional moderate intensity cardio,

Dr. Gabrielle Lyon 29:49

meaning, like three hours of zone two.

Martin Gibala 29:52

I mean, is that with that, with, with many? Yeah, yes, and again, depending how we define zone two, but yes. Bottom line is, you know, if you do continuous moderate. Exercise for several hours, and you train that way three times a week for 612, weeks, you improve your VO, two Max. Can you though

Dr. Gabrielle Lyon 30:09

you can’t. And the reason I say can you is because, you know, we all know those people that are going on the treadmill, and for the last five years, they’ve done exactly the same kind of training.

Martin Gibala 30:20

You know, I think you always want to have progression in your training, right? And so to be clear, most of these studies are where people are starting out at some level. You know, they’re exposed to this new stress, and then their vo two Max goes up. You know, it’s not necessary that it’s going to continue to increase, unless they then adjust. You know, they have progression in their in their training, but you know, to be clear, you know, people can do moderate intensity physical activity of high volume and improve their vo two Max now, whether they can improve to the same level with less total exercise performed in a more vigorous manner, yes, I think there’s good evidence for that. And this is we, how we get into how do we compare the traditional encroach and high intensity interval training? But you know, the studies also show that more vigorous for a given dose, more vigorous physical activity will lead to greater improvements in vo two Max, and that’s not only in apparently healthy individuals. This is in individuals with many different chronic conditions as well. So these, you know, high intensity interval training has been applied to individuals with type two diabetes, many different types of heart disease, conditions, certain types of cancer.

Dr. Gabrielle Lyon 31:39

So talk to me about that. I want to, I want to double down on that, the dose of high intensity or sprint interval training. Now I’m kind of self conscious. Are we using them interchangeable? Are we saying that it really should be sprint interval training that is going to be the most effective for the outcomes that we care about, is it really sprint

Martin Gibala 32:02

interval training? So when you know this word efficiency again, which gets thrown around a lot, I think sprint interval training is the most time efficient way to improve your VO, two, Max, it doesn’t mean it’s the best. It doesn’t mean really anything more than than that, you know, if there’s different ways to achieve outcomes, and I think there’s exponential benefit to increasing intensity,

Dr. Gabrielle Lyon 32:32

there’s exponential benefit, yes, increasing intensity, right?

Martin Gibala 32:34

Which means the, you know, it goes like this. So the more intense you’re able and willing to go, you can have exponentially less total time commitment to get to the point where you want to be. What about

Dr. Gabrielle Lyon 32:49

from a physiology perspective, there is there a difference between what we know from mitochondria, from you know, various roles of proteins, like, you know, you can,

Martin Gibala 33:07

no, it’s, it’s a great question. And I think you know this, something that keeps me excited as a scientist is, there’s still, we have a lot to learn about the mechanism. So let’s even stick, you know, let’s start with VO two Max. VO two Max, we can see similar improvements in vo two Max with 12 weeks of sprint training, where the total amount of exercise is 90% less than the traditional moderate intensity training person. So basically, you can imagine 90% correct. So you know that’s the idea of the exponential time efficiency. Now, what is VO two Max? It represents the integrated function of a lot of underlying physiological systems, your heart, your lungs, your blood vessels, your mitochondria in your muscles. So is the reason why vo two Max is going up to a similar extent with those two types of training, the same or not? We don’t have a good answer to that question right now. We definitely know that both can improve your your mitochondria, and we know in the same way, yes, and so in the same way in that, how do we measure mitochondria we measure the maximal activity of representative enzymes we you know, there’s different ways that you can measure mitochondrial content, but you can see similar improvements in mitochondrial content, again, with those two very different types of training. So you know, but why do mitochondria go up? Mitochondria get stimulated by things that we produce during exercise. So your muscle responds to a stress. Your ATP levels go down, right? Calcium levels go up. Oxygen levels change. Hydrogen ions. Accumulate. All of those are metabolic signals. You can think of them as like fuel lights on your car that start to turn red. And so what they’re signaling is we need some adaptation here. And so all of those signals stimulate the process of mitochondrial biogenesis, so they stimulate proteins and genes that tell the muscle we need to grow additional mitochondria here. So you know, the point is, those underlying signals are the same. We can turn those signals on

Dr. Gabrielle Lyon 35:35

regardless of weight intensity. So regardless if you’re if you’re thinking about MPK or PGC, one Alpha. Does it matter if it is a slow, steady state input or a high intensity input? If you know if the outcome is the same, I

Martin Gibala 35:55

think we know that the we know that the inputs can vary. In terms of sprint training, you have a very sharp, sudden change. And so I think of it as you know, if it’s you’re dropping the gas pedal really hard, right? And so is it the rate of change, or is it getting to some level? And I think we still have to answer that question, but we definitely know that a sudden drop in or a sudden activation of many of these pathways, seemingly, is at least as good as the traditional long, steady approach, and it might be for different reasons. You know you do prolonged, continuous exercise, takes a long time for your glycogen levels to slowly go down slowly, get the activation of AMPK and these other pathways. Or you can have a really sharp drop in your glycogen 20% in 20 seconds or so, and a really rapid activation of AMPK, you’re sort of at the same point in terms of the AMPK activation. But one way you did it really, really time efficient, and the other one took a prolonged time.

Dr. Gabrielle Lyon 37:01

I mean, that’s that’s fascinating, the fuel utilization. Talk to me about that. Talk to me about, you know, as they we know that the new dietary guidelines came out, there has been arguably, on the surface, potentially, a reduction in carbohydrates. What is the difference in fuel utilization of a sprint interval training session versus a slow, steady state training session. Yeah, well,

Martin Gibala 37:29

sprint interval training, you’re basically churning only through carbohydrate, and a lot of that is, you know, what’s known as anaerobic metabolism. But to be clear. You know, when we do repeated sprints, most of the energy is coming from the aerobic system. So Will people talk about, oh, it’s anaerobic training. No, when you do repeated sprints, most of your energy comes from aerobic metabolism, and virtually all of it is coming from from carbohydrate, right? And so then people say, Well, how can that improve my metabolic flexibility, right? Like, how can this lead to an enhanced capacity to oxidize lipids? But it comes back to that improvement in mitochondria, right? So as long as you’re boosting your mitochondria, that is going to allow an improvement in in metabolic flexibility, so you can use whatever fuel you’re you’re feeding the muscle, sugars or fats.

Dr. Gabrielle Lyon 38:21

How would you think about dosing again, you’ve done this in in research. Do you think about dosing carbohydrates for the participants in the studies, or just in general, I don’t know if you work outside of the academic sphere.

Martin Gibala 38:36

So Well, we’ve been in, you know, we’ve been interested in nutritional manipulations, and it looks like exercise is the big hammer, right? And so maybe you get some very subtle changes with dietary manipulations, but they’ve been really subtle in our studies. And you know, if we’re just talking about, we’re still trying to compare the exercise doses, right? From a you know, study design perspective, the nutrition studies layering that on are very, very challenging to do, and you need huge numbers of participants. I I think there are studies to show that if you have less carbohydrate on board, so you, you you lower your glycogen stores. Yeah, low glycogen training.

Dr. Gabrielle Lyon 39:15

This is I can’t be brought. This is one of my favorite I’m really nerd. This is one of my favorite topics in over the last year, this low glycogen training. Yeah, so can you explain?

Martin Gibala 39:26

So that’s you know, especially if you do vigorous exercise with reduced glycogen stores, the metabolic stress is higher. And so there is evidence to show that those signaling proteins we talked about, AMPK, some of those can be turned on to a greater extent.

Dr. Gabrielle Lyon 39:44

Isn’t that fascinating? So we have to, we have to just talk about this for a second. And this is where the semantics become interesting. Is in the conversation is, should you train fasted or not? I don’t know if that’s really the question. It’s in my mind. Should we. Train in a lower glycogen state or not

Martin Gibala 40:04

again, which What’s your outcome of interest, right? There are some again, I’ll use the caution, sorry, but we have to call the evidence as it is, relatively small, short term studies that show, acutely, if people train with reduced glycogen, you can have greater activation of some of those signaling

Dr. Gabrielle Lyon 40:24

proteins and also myokines, the proteins released from muscle, they seem to be more robust when an individual is training in a lower glycogen state. That doesn’t mean they’re fasted, it just means low carbohydrate within the muscle, yeah,

Martin Gibala 40:40

you know, and there are studies to show that again, over six, eight weeks or so, you can see some measurable increases in mitochondria to a greater extent with reduced glycogen training than when your carbohydrate replete. Now, if you’re an athlete, it didn’t appear that that translated to an improvement in performance. And we got to be careful here, when we’re talking about low glycogen training, what it is is typically selected sessions with reduced glycogen, you know, if to chronically reduce carbohydrate availability, that actually can impair your capacity to do high intensity exercise because of A key enzyme that seemingly is, is is suppressed, but, but periodic training with reduced glycogen availability, I think athletes sort of naturally do this

Dr. Gabrielle Lyon 41:31

so, and the reason I was interested in it is for health outcomes. So I’m thinking about, okay, muscle quality is important. We don’t know enough. From my perspective, how muscle quality relate to long term health outcomes. And when I say muscle quality, I’m not talking about strength. I’m talking about the fat infiltrated the intramuscular adipose tissue. The intramuscular adipose tissue, this idea of the athlete’s paradox and so, and you could perhaps speak to this, because I think from what I’m seeing, the way in which people train affects the fuel utilization and the fuel deposition within muscle. Yeah.

Martin Gibala 42:21

Well, you know, the athletes paradox, of course, is just, it’s sort of that U shaped curve where people who are very unfit will have high muscle triglycerides and and athletes have very high muscle triglycerides as well. And sort of active, recreationally active people are, are have, lower amounts. Obviously, the big difference there is it, the unfit individuals are unable to use that lipid, whereas the high, highly trained athletes are and that’s that whole idea of metabolic flexibility.

Dr. Gabrielle Lyon 42:53

And what about the location of the mitochondria, where the fat are, the triglycerides? From what I understand, the triglycerides are not within a good location to the mitochondria. So the fuel utilization is, yeah,

Martin Gibala 43:07

efficient, you know. This is, you know. And again, these hard studies to do, right? You need to take biopsies. You use electron microscopy to try and look at spatial orientations of things. But, you know, you can see, and there’s some suggestions of where the lipid droplets are located, spatially, if they’re near the mitochondria, that may be better better able to utilize them. So So again, I think there’s evidence to support some of these contentions, but I think for the person in their health, it all comes back down to, do you have metabolic flexibility or not? And probably the best, one of the best ways to improve that is to boost your mitochondrial capacity, right? Boost Your Health.

Dr. Gabrielle Lyon 43:52

Do you think that it would be fair to compare steady state zone two? So we just talk about metabolic flexibility and we can define. I’ll give you my definition of metabolic flexibility, and then you can tell me where I’m wrong, please. I love it in my mind. At rest, a healthy muscle is burning primarily fatty acids as exercise intensity increases, it then switches to being able to use carbohydrates, as opposed to over feeding carbohydrates, and muscle at rest would be forced to utilize carbs.

Martin Gibala 44:29

So I would consider metabolic flexibility to be you know, it’s the ability to have a high rate of oxidation of either fuel. So whatever you feed the muscle, whether it’s carbohydrate or fat, it’s able to utilize that to produce energy. Arguably, one of the best measures of metabolic metabolic flexibility is maximal. Is Fat Max? The maximum

Dr. Gabrielle Lyon 44:55

rate I know very little. I’m starting to hear more and more for health outcomes about. Fat Max. Talk to me about fat max.

Martin Gibala 45:01

So fat Max is basically what it sounds like. What is the maximal rate of fat oxidation by the body? So we’re talking grams per minute, right? And so that’s going to be a combination of two things. What’s your overall metabolic rate? So as we’re sitting here, rest right now, our metabolic rate is low. If we go and do a vigorous mode of exercise, our metabolic rate is going to go up. So fat Max is a combination of what’s the overall metabolic rate, and then of that value, what percent of fats are you? Are you using? Does that make sense, right?

Dr. Gabrielle Lyon 45:40

So what would we want to be using? So what would be considered normal? Yeah, well,

Martin Gibala 45:44

and so for most people, their fat Max occurs around 45 or 50% of their vo two Max, or around 60% or so of their maximum heart rate. But such again, coming back to zone two such huge variability. So fat Max can range from 40% of your maximum to 90% of your maximum, but for most people, it’s going to be around 60% or so. So what you’re doing is ideally to measure that you’re imposing an exercise stress, sort of through that moderate range of intensity, and you’re going to see, you know, as you go from rest to low to moderate intensity exercise, your overall metabolic rate goes up and your utilization of fat goes up, and then at some point it starts to go like this, right? So the overall metabolic rate continues to increase as you go to higher and higher intensity, but you really start to shut down your ability to utilize lipid and so you’re looking for where’s that peak point, right there, in terms of your maximum rate of fat oxidation.

Dr. Gabrielle Lyon 46:52

And would a general person care about fat oxidation? Fat max?

Martin Gibala 46:59

So from a health perspective, fat Max matters, but it’s very challenging to measure. And so unless you go into an exercise laboratory and have this test done, you don’t know. And so it’s difficult to estimate it. And this is where I think, again, that the issues with zone two, I think there’s there multiple but one of the ones is there’s not a good way for people to estimate their fat max. And so, you know, let’s even go back to to what is zone two. The most common here would be the most common definitions that we hear. Zone two is fat max intensity. Zone two is your first lactate threshold, or just around two millimole or below that. So those are metabolic markers, right? Fat Max and your LT one those are not the same in most people. Fat Max tends to be lower, so even right there, they’re not the same in most people, right? And then these estimates of what those might be, well maybe it’s somewhere between 78 80% of your maximal heart rate. But again, that’s where it really depends, and the range is probably 40 to 90% so I think people are hearing about that. They’re starting, okay, I sort of get what zone two is as classically classically defined. It’s this, but as classically defined, it’s really hard for most people to get those measurements, unless they go into an exercise lab. So we’ll use these surrogate markers, but that only introduces huge variability. So unless you know this, and then you start to apply the surrogate measures, that’s why I think in practice, Zone Two, intensity could be way too low for many, slash, most people, it might be moderate for some, and it might even be vigorous for for some, which, again, is the whole problem. Suggests that this is this magic zone where you should be in 80% of your training.

Dr. Gabrielle Lyon 49:13

That’s a hard pill to swallow. You know what? I mean? It’s a hard pill to swallow because we have these large I don’t know, large information highway saying this is we need to be doing zone two because of this, and this is what it looks like. And here is your formula to be able to show you, if you are in Zone Two, are those accurate?

Martin Gibala 49:38

Not for an individual? No, right? So again, Zone Two, it comes you

Dr. Gabrielle Lyon 49:43

just broke in or not zone two training. What he’s saying, so I’m talking to my producer. What he’s saying is that all this discussion around Zone Two is arguably, I don’t want to say irrelevant, because I have a scientist here, but it’s we’re not defining zone two appropriately. See, and even if we were, even if we were, so we are saying zone two is what, what is the traditional definition?

Martin Gibala 50:09

It’s fat Max, or it’s your lactate threshold, one, just below two millimoles.

Dr. Gabrielle Lyon 50:13

But that is totally different for, I suppose, an athlete, any athlete at any right? So a zone two. So for Matt, for me, for you, our zone twos are totally different, even if it comes out, as you know, on the heart rate monitor that I’m in zone two is that,

Martin Gibala 50:34

yes, no, that’s correct, right? And then, so, you know, let’s let me try and clarify a couple of things or explain myself, if you will. You know, zone two really well established in the athletic training area, right? And so that’s where I talked about those moderate, heavy, severe, three domains. And then, very commonly, those are split into two sub domains each. And so you that’s where we get these six Zone training models, for example, would be a very classic Zone training model. And so Zone Two is down here. It’s that low intensity exercise that many athletes do. So it’s rooted in the training of athletes, right? It’s, it’s a very well established term in the training of athletes. When coaches use these zone classification schemes, there’s very clear surrogate markers for what it is. If you’re a high level endurance athlete, we can reasonably assign heart rate ranges to that, but then to say that’s optimal. And you know, the last point there would be, we’re inferring that, because athletes do 80% of their training in zone two, that that’s optimal for their mitochondrial health. Then we’re taking all of that and saying, let’s apply it to the regular person. And you know what’s the regular person, the typical person who’s either struggling to meet the guidelines, or maybe they’re meeting the guidelines, and they’re saying, where should I divide my time? First of all, there’s no evidence that that 8020, ratio is optimal for everybody, especially if you’re only doing 150 minutes a week. There’s no evidence certainly that that’s optimal for your mitochondrial health, and it largely stems from the idea that for people, we’re really sort of guessing what their intensity is, and it’s probably not zone two as classically defined for a lot of people. It’s, in some ways, it’s analogous to so many people are doing keto, but Well, kinda, yeah, right. And probably a lot more eating, a lot more carbohydrate than they think, than strict keto, you

Dr. Gabrielle Lyon 52:56

know, it presents a a whole new level of challenge, and I, from my perspective, why it’s so important is one of the challenges, I think, as the world grows and as we are exposed to more and more information, is the there’s a level of critical thinking that we’re starting to see that’s a bit reduced for I’ll give you An example. Saturated fat was set at the guidelines 10% or less. There is no reason where or why it’s 10% the data that individuals quote saying saturated fat is bad and has been moved forward for decades. Do you know where it comes from? It comes from hydrogenated whale blubber in a time of war that this was a short term fix to be able to feed a population not to be used for 30 plus years worried about heart disease, and this quote, saturated fat was hydrogenated whale blubber, which then they ran out of, and so they started hydrogenating other fats. And I know this is like the world’s longest story, but all of that is then lumped under the idea that saturated fat causes heart disease. And instead of questioning that and then going back and saying, you know, maybe this isn’t right. Maybe we missed the mark on this 10% another case in point is the Women’s Health Initiative. And so now where I think what you and I are talking about is entering into this conversation of, believe it or not, zone two training.

Martin Gibala 54:36

I just think precision and terminology is critical, right? And so if we’re talking lactate threshold, one fat Max, most people have no idea what that is for themselves, and there’s no good way for them to estimate it. If then we’re going to use a surrogate marker like the talk test, so you could carry out a conversation. It would be strained, but you could still do it. That’s moderate intensity physical activity. If we’re going to talk 70 to 85% heart rate Max as a guideline, that’s moderate to vigorous physical activity per the ACSM guidelines for the

Dr. Gabrielle Lyon 55:15

general population or for athletes, no for

Martin Gibala 55:19

the general population, right? So that’s just if that you know if, if Zone Two is fat max or lactate threshold, okay, but then, as athletes, well, know, because athletes know exactly what that is for them, because they get that testing done. If the average person wants to get that testing done, then they know exactly what their fat max or lactate threshold is, then they could start to utilize these training regimes of athletes. But if we’re just using a surrogate marker to guess what it is, what are we doing right? And it’s if we’re going to use surrogate markers that are already well established within guidelines, then just call it. It’s moderate intensity training, right? And so I think my point is, if Zone Two is classically defined, if we’re suggesting that this is optimal for mitochondria, there’s no evidence for that. There’s no There’s virtually no scientific studies on zone two training.

Unknown 56:18

If we’re saying, big deal,

Martin Gibala 56:21

if we’re seeing moderate intensity exercise well, then there’s robust evidence that it’s good for your mitochondria and good for your overall health. So, you know, I think we people have to decide, is zone two, this euphemism for moderate intensity physical activity in most people, okay, then that’s fine, but then it’s already in the guidelines, and the guidelines are telling us maybe you should do 150 minutes a week of that to optimize your not sorry, not to optimize, to boost your health, to boost your health, but to suggest that 80% of time should be spent in this zone, two range, which is a nebulous concept for most people, there’s no evidence for that. Certainly no evidence to say that this is optimal for your mitochondrial health.

Dr. Gabrielle Lyon 57:10

If you were to design and think about the health of the nation, no no pressure, how would you inform them, if you could write exactly what shouldn’t be done?

Martin Gibala 57:29

Yeah, I mean, you know, who am I to counter? So how’s this physical activity guidelines based on on robust evidence? Clearly, I’m a proponent of vigorous intensity physical activity, and so I would suggest to people that the more vigorous, high intensity you can do, probably the better for you in terms of boosting these physiological markers that then are associated with health outcomes. Also, we know that so many people cite time as a barrier. That’s Yes, it’s an excuse for a lot of people look at social media time, screen time, all of that. But you know, the reality is that the amount of time that people are willing to commit to physical activity is very limited. Many see two and a half hours as a barrier. And so a lot of our work has been okay. Let’s just meet people where we where they are. Let’s investigate what are efficacious doses of low volume, vigorous physical activity. And so could we say to people, you know, and now again, we have evidence, right? And this is some of the large studies. These are now epidemiological evidence that I’ve been involved with, led by Emmanuel stamitakis from Australia, showing that as little as four minutes a day of vigorous, intermittent lifestyle, physical activity is associated with 25 to 30% reductions in all cause mortality, right? And so this is not cause and effect data, but these are in 25,000 individuals followed. These are individuals who self identify as non exercisers, but if they can do some vigorous effort throughout the day, taking the stairs while carrying a heavy backpack, you know, the classic example getting off an airplane, you grab your luggage and you walk up the stairs for 20 seconds or so, if you accumulate four minutes of that through your day, massively beneficial for you. And so, you know, does your

Dr. Gabrielle Lyon 59:43

heart rate have to, could it also be, do we need to define how that’s done? For example, could it be push ups?

Martin Gibala 59:51

Yeah, it could be, right. And so I think this is where body weight style interval training comes into that right? So, you know, right now we could do an exercise snap. Back by getting up from here and do a series of air squats or burpees, right? Starting to do that. And so

Dr. Gabrielle Lyon 1:00:06

does our heart rate need to get up to a certain i The

Martin Gibala 1:00:11

No, I think what we should do is then use that, use these subjective markers, like RPE, right, get into that, push yourself right. And these are, I know these are sounding like wishy washy a little bit, but when these bouts of effort are so short, it’s all so hard to use some of the traditional metrics,

Dr. Gabrielle Lyon 1:00:31

right, nearly, right? It’s nearly impossible to to prove or to program with a specific outcome Exactly.

Martin Gibala 1:00:40

And so you know, we do know that if you’re going to do something for a minute, you’re going to get into those traditional metrics of what vigorous is that we started talking about in this in this interview, right? And so that’s why our when we talk about an exercise snack, we’ve suggested that it’s a minute of a vigorous intensity physical activity based on those traditional markers. So there, yeah, you would want to see your heart rate get up to around 77% or so. You would want to feel this is about at least a seven or 10 on that RPE scale. So, but I also think, like at the end of the day, maybe we don’t need to over complicate it too much. And the message there is challenge yourself, huff and puff regularly, get out of your comfort zone, right? That type of messaging. For people, we hear these messages around all activity counts, and it’s true. But I think in addition to sort of, you know, sit less, move more, that notion of pushing yourself huffing and puffing with a few flights of stairs, that that’s a good thing for you.

Dr. Gabrielle Lyon 1:01:45

And I also believe that we have to hold ourselves accountable in a way that if we don’t, there is this aging trajectory, and the more clear that we can become, in the more unified, I think, with the expectation of, yeah, if we’re talking about zone two, then we’re talking about Zone Two, if we’re talking about athletes, then then we need to put this over here. But if we’re saying you need to do moderate to vigorous intensity training, and you have to have these snacks, the I think the clearer that we can be, the better. So for example, if someone’s like, well, I don’t, I can’t do 1030 push ups, and maybe they go to muscular failure, then it would be our responsibility to say, okay, you can do five now you have to move to squats, because we can’t have you just have a muscular failure and then no cardiac or cardiovascular stimulus.

Martin Gibala 1:02:39

Yeah, bingo. And you know, so going back to the guidelines are based on really good science. We know a lot of people aren’t listening. And so for some people, it’s so daunting the guidelines, or, boy, I can’t do 30 minutes of continuous exercise, they feel like a failure. That the idea with intervals is that’s okay, right? Go hard as little as it needs to be, take a break, then do another one, right? And and we can start tell people or build the evidence around, you know what? If you only do three or four minutes a day of this, but it’s vigorous, that’s going to be beneficial for you, right? And so maybe eventually we can further inform the guidelines by by saying, here’s, here’s the minimum, you know, effective dose.

Dr. Gabrielle Lyon 1:03:26

We don’t do we know what that is for this type of training.

Martin Gibala 1:03:29

I think the best. So two ways to answer that. Epidemiologically, we’re starting to get the answer there. And again, clearly, around four minutes a day of intermittent, vigorous lifestyle physical activity is everybody very beneficial. Exactly right challenge.

Dr. Gabrielle Lyon 1:03:47

Everybody to do that, and we should be doing that too.

Martin Gibala 1:03:51

And the other studies, you know what we were talking about, the sprint training studies, those also give us some clues around what’s the minimum dose now, that’s extreme intensity effort, but it’s a surprisingly small amount. And so for me, I think the sweet spot is this vigorous exercise, but you don’t have to do very much of it. And I think that might be an achievable goal for for many individuals, or at least if they hear they’re like and trying to say, there’s good science around this now, right? This? Just get to this. Right? The more, the better 100% but just try and get to this.

Dr. Gabrielle Lyon 1:04:29

And once someone has gotten to that point, so now we’ve moved into someone like myself, who might isn’t, is averagely athletic. I’m not, you know, I’m not a great athlete, and I’ve been training for a long time, for someone who’s listening to this podcast who, let’s say they’re really into fitness and interested in it, if they wanted to change their body composition again, there’s a lot of discussion. We’ll just add in 30 more minutes of cardiovascular training or. Potentially high intensity interval training, sprint interval training from a body composition standpoint, assuming people are doing resistance training, which would you prefer? And why

Martin Gibala 1:05:12

not to hedge, but it would be, how much time are you going to put in? Right? And so I think exercise is exercise plays the role in terms of supporting weight management, you’re not going to see mass, to my mind, massive changes in body composition with aerobic style training, whether it’s hit or moderate intensity, continuous. And I think right now, that’s what the evidence shows. Right the there’s there’s subtle changes in body composition. There’s not huge changes in body weight, if you’re just adding on a little bit more of that exercise stress, right? And we know in the real world that people, you know, who am I talking to here, but you know, you like, you talk about this a lot, right? Like, people change their behavior, right? Energy comp, you know, energy intake can change. It’s a really, really tough topic to study, right? To say that, okay, if we tweak this exercise, what effect is this going to have again in the real world, right? It’s sorry to hedge on that one, but it’s really hard to

Dr. Gabrielle Lyon 1:06:16

answer that. Well, it’s complicated. It is. I think what we’re getting to is, you know, we’re able to, I think that exercise and is so much more difficult to study than you know, in nutrition, I could say Martin, you know, we’re gonna have 50 grams of carbs and 50 grams of protein. And let’s see what your oral glucose tolerance test does, or let’s give you 90 minutes and let’s study so we’ll fast you the night before. We have clear outcomes and we have pretty immediate feedback. But if we say, well, you know what your dose is going to be, 10 push ups, four air squats, and, you know, three reps of bicep curls. I have no idea if that stimulus is adequate or meaningful. We’re just not there. And that’s the biggest struggle in the way that we’ve been able to get very specific with nutrition. I mean, we’re really specific with nutrition, and we have good evidence as to what those improvements are, and I can test it. You give me three months, and I’m going to measure your hemoglobin. Amaze you. Give me two weeks, and I’m going to see your triglyceride changes. Once we reduce your carbohydrates to 130 grams or less, I’m expecting your triglycerides to be within normal range and exercise muscle as this lever is arguably the most important, but I have no way to say, You know what that helped your muscle quality to this degree?

Martin Gibala 1:07:51

Yeah, that’s, you know, we definitely have evidence around, you know, we’re going to do this exercise dose or this manipulation, and then look at your HBA 1c or your insulin sensitivity, you know? We, we do have evidence around that that, you know, okay, this, this dose is effective to do that, but you’re right. In terms of muscle quality, you sort of got to look inside the muscle, right? What’s the best way to assess that? Little more challenging for sure.

Dr. Gabrielle Lyon 1:08:15

Where do you think this fat? And I know that I’m like harping on this fat Max. I just think it’s, it’s interesting, because if we take, if we think about athletes as the pinnacle, just, you know, my perspective is how that we think about athletes as the pinnacle, and we know what right looks like when I say right, meaning, if I’m looking at this definition here, it’s the determines the intensity, meaning heart rate, power, piece at which your body oxidizes the highest amount of fat as fuel. Like you said, every athlete knows this potentially and their lactic threshold. How can we look at that from this is what, quote, healthy mitochondrial look like. This is what good training adaptation looks like. And then translate this over to, let’s say, some of my patients who have had covid and they’re exhausted and they are gaining weight and their hormone status looks okay, but they are struggling with mitochondrial efficiency. And I use this term loosely because we’re not defining it, but then you see this reflected in their fat Max, right? Yeah.

Martin Gibala 1:09:21

And so it, the problem with mitochondrial health is it’s so we don’t have clear, call them guidelines, VO, two, Max, again, let’s come back to that it’s relatively easy to measure in that it’s non invasive. You know, you can do it really direct measure in a lab, we have some pretty good ways to estimate it based on sub maximal heart rate responses. So you can get a pretty good indicator of your VO two Max with a sub maximal exercise test or a maximal test in a laboratory, and we know then if your VO two Max is this. Your risk of developing type two diabetes cardiovascular disease is this or at least, if you change your VO two Max, your risk will change by this much. So it’s such a good metric, because we have these quantitative characteristics around it. By saying, change it by one met, and your risk for all cause mortality is going to go down by about 15% we just don’t have that for mitochondria, right? So we get going, get mitochondrial health. But this is where you know if, if the zone two discussion have done anything, it’s, it’s at least really put these concepts out there of advancing this idea of the hell is fat Max actually, right? And so people are thinking about it. People are are, you know, and so you could definitely see fat Max being added as a mark or a measure that, again, you need to do an exercise test in a laboratory. Be like getting

Dr. Gabrielle Lyon 1:10:54

a beauty. And get there, I think that event measured, have it

Martin Gibala 1:10:57

measured, and then start to say, This is what a good fat Max looks like. Or this is, you know, fat Max in a very high performance athlete, or in a very deconditioned individual, you know, who’s has type two diabetes or pre diabetes, and maybe start to get those and it’s not going to take a muscle biopsy to look at your mitochondria. We can use fat Max as the marker, as a proxy marker, absolutely right? And that’s where, again, if you’re measuring fat Max, I do think it is highly beneficial. It’s pretty cool, right? But just estimating it on your own, you’re just guessing.

Dr. Gabrielle Lyon 1:11:32

I think, as there’s advancements in this focal point of skeletal muscle, just as this organ of longevity, this is the future of where we’re going from an architecture of healthcare. Talk to me about this idea of rehit and conditions like diabetes and other health conditions.

Martin Gibala 1:11:52

Yeah, so rehit Is it really? It’s a so rehit stands for reduced exertion, high intensity training, a bit of a misnomer in that it’s really a version. It’s a variation of Sprint interval training, because rehit is pretty high intensity. But, you know, class define that now, yeah, but you know, rehit protocols would sort of be 10 to 20 seconds of all out effort, usually on a bike. These, these studies have been done, is

Dr. Gabrielle Lyon 1:12:23

that, because it’s easier to control? Yeah, pretty much

Martin Gibala 1:12:25

it is. And so, you know, those are often, sometimes as little as two, but typically three times a week. So you’re talking there, you know, 20 to 40 seconds of all out exercise, typically within a 10 minute timeframe, a few times a week. But again, there, you know, there’s, there’s some small, randomized, controlled trials of rehit. There’s definitely studies on rehit showing that it’s, can be, it’s going to boost your VO two Max, right, just like the classic sprint training. So it’s, it’s a variation on Sprint interval training that’s certainly a lot more tolerable than classic Wingate style training that’s been done.

Dr. Gabrielle Lyon 1:13:06

And it’s more tolerable because it’s shorter, shorter. So the two and there’s, and we can link to these studies. This is two to 3/22 sprints, and that is able to again. So I’m thinking about these statements to have health and fitness benefits comparable to quote, normal exercise in a fraction of the time, 10% of the time. How do we is that? Would you feel comfortable?

Martin Gibala 1:13:40

So what I can definitely say with confidence is rehit style training, which, again, is 10 to 22nd bursts, two or three of those, our studies, which are classically 3/22 bursts. So there we’re talking two or 310 to 22nd bursts. If, if people do that three times a week, for six, 810, 12 weeks, most people will see an improvement in their VO, two, Max, there’s definitely studies significant improvement. Yes, yes. Signet, and you know, we normally power our studies on a one met change. So frequently you will see a one met change in your VO two Max, with six to 12 weeks of training, one met. What is that? It’s about 10% for the average person. So a met is a very specific term. So there’s, there’s solid evidence to demonstrate that when we start to talk about, how does it compare to the traditional approach? That’s where the evidence is not as good, but that’s where, again, coming back to what we were talking about, the beginning of a conversation, those are the studies that we’re doing now we’re trying to move into this space and say, Okay, there’s good, solid evidence now that rehit Sit works. How does it actually compare when we do these studies the right way? Right? Like, let’s true, randomized, controlled trials in adequate numbers of people to tease out differences if they’re there or or not, right? And just to Geek it up for one second, very exciting. You know, it is so we, we, you, you do these trials called non inferiority, which means I have no, not different, right? And so oftentimes. So let’s, let’s say here’s the well established drug on the market for this condition, right? We want foreman. We want to test this new drug against it. We want to say it’s not worse, right? So the benefit you might see is not worse than the standard. Well, what does not worse mean? You try to identify a margin that doesn’t matter, non inferior, right? And so we it’s basically saying, if we see a change, but it’s within this difference of the gold standard. It doesn’t matter, right? Because this margin of non inferiority is is sort of meaningless in a physiological context. Those are the studies now we’re doing with sprint training, comparing it to the traditional moderate approach, right? If we see a change in vo two max and the margin is within this compared to the traditional approach, then they’re the same. They’re they’re not inferior. The new method is non inferior to the old one. And again, those are, that’s a very specific way of designing experiments. We’re literally running it in our lab right now. So, yeah, can’t wait.

Dr. Gabrielle Lyon 1:16:40

Well, I cannot wait for that to come out. I want to hear a few things, and this is really about aging and muscle and intervals. Do you think high intensity interval? Again, should we agree to call it high intensity sprint interval?

Martin Gibala 1:16:56

Yeah, let’s so again, I think the general catch all term is high intensity interval training and sprint is that very intense variant of it

Dr. Gabrielle Lyon 1:17:05

does high intensity interval training prevent sarcopenia,

Martin Gibala 1:17:14

as classically practiced on a bike Running? No, I think, though these body weight style approaches, so we’re talking now high intensity functional training.

Dr. Gabrielle Lyon 1:17:27

Now you have to define it and give me an example. So

Martin Gibala 1:17:29

high intensity functional training is really just the classic example would be body weight style training would be simple equipment style training, kettle bells. You know, air squats with dumbbells. You know, classic functional movements, almost calisthenics, in a way, push ups, pull ups, that type of training. So that is basically resistance based, high intensity interval training, right? And so this is where, again, it sounds bit complicated, but what we’re often doing is, let’s pull it back to the fundamentals. Big picture we talks about, we talk about two styles of exercise, or two types, two broad types, aerobic and resistance, right? And so traditional aerobic style, training, cycling, running, rowing, swimming, that’s traditional hit, resistance style hit is body weight style training, calisthenics, high intensity functional training. But the key difference there is the resistance is higher than with the traditional approach, right? And so that type of training, I think, can be beneficial,

Dr. Gabrielle Lyon 1:18:40

even if it’s body weight. So for Yes, when I think about running, you’re still moving your right. You know, single leg body weight, and that’s different. Is then, okay,

Martin Gibala 1:18:52

then, then, when? Then, then. So it’s the the load on the muscles has to be sufficient enough to stimulate muscle protein synthesis, or at least to prevent declines in in in muscle protein and there, I think you need a more resistance, like stimulus, as classically, you know, done, than an aerobic style stimulus. So Trejo, when, if I when I say traditional hit. What I mean by that is traditional aerobic style hit, cycling, running, swimming, rowing, cardio style. Hit, we don’t see much change at all in muscle fiber size, and so applying that through a sarcopenia lens, then if we’re losing muscle size as we age, you know, probably the stimulus is is not enough, generally speaking. Now, if you’ve never done anything, maybe a cycling stimulus, because you’re so your capacity there is so low, or your starting number is so low, then cycling, yes, could, and there’s definitely some. Cycling studies that have reported an improvement in muscle cross sectional area. So it then it’s like, well, what’s the starting number? But to answer your question, I don’t think traditional aerobic style hit is going to be hugely beneficial in terms of attenuating the decline in sarcopenia. I think that’s where you need a resistance stress, but it could be high intensity, functional training or interval based using body weight style exercises.

Dr. Gabrielle Lyon 1:20:26

And body weight style exercises, even for a person who’s active, would you think would be enough, or is

Martin Gibala 1:20:34

well, so you’re not now you’re changing the question, no, no, but no, it’s a fair point, right? And I think what we’re not dancing around, or what we’re talking about is those two situations are different, right? And so I think, generally speaking, you know, to promote our health span, we want strength slash muscle quality to be high as possible. We want aerobic capacity to be as high as possible. And it’s like insurance, right? And then over time, as we decline, you want to start higher off right now we can still intervene here, after you’ve started to decline, it’s still going to be beneficial.

Dr. Gabrielle Lyon 1:21:11

So we’ll say high intensity interval training does not help prevent sarcopenia, but high intensity interval training with resistance training could, and potentially resistance training, I don’t know if we can ever prevent sarcopenia. I don’t think we know enough about it,

Martin Gibala 1:21:29

but definitely attenuate. We can attend Absolutely, and you’ve

Dr. Gabrielle Lyon 1:21:34

already answered this question, older adults are capable of doing sprint interval training safely. Yes.

Martin Gibala 1:21:41

So yes, to answer the question, we would still advocate, of course, that, you know, the older you get, as you start to develop, you know, some conditions in that increasingly important right to get medical clearance, but you know, there’s, there’s studies being done on octogenarians in Sweden with very intense sprint interval type training and group style classes showing high levels of enjoyment, high levels of benefit. So definitely older individuals can do this as a, you know, as a blanket all older adults should do sprint training. No, that’s not what I’m saying.

Dr. Gabrielle Lyon 1:22:23

What about this is, I don’t know if you’re gonna like this question, sex differences in response. Yeah.

Martin Gibala 1:22:31

So there’s definitely evidence of subtle sex based differences in certain responses, all the usual caveats around small studies and things like that. My own opinion is, I think inter individual differences are much greater than a biological sex specific difference per se. But you know, if you take groups of biological males and females? Yeah, you can see a few subtle differences. You know, coming back to fat Max, women females tend to have a higher fat max by a few percentage points than than males on

Dr. Gabrielle Lyon 1:23:16

average, meaning they will burn more fat during do we say it’s a particular, yeah, no training.

Martin Gibala 1:23:25

So generally, during exercise, you can imagine, if, you know, if, if, if this is so over, you know, over the course of exercise intensity, you’re gonna look like this, right? And this is that point of fat Max women, it happens at a higher percentage of their maximum. It again, I’m generally speaking in there, I’m mixing up sex and gender. But biological females, some of the studies have compared men and women, on average, have a little bit higher fat Max than so they oxidize that. Yeah, have a little higher Yes, exactly. A bit better. Yes.

Dr. Gabrielle Lyon 1:24:01

Is that clinically significant?

Martin Gibala 1:24:06

I think that’s where it really depends on what’s

Dr. Gabrielle Lyon 1:24:13

what we would define as clinically The reason I ask these questions again, this is, I think we’re entering a new era where people are very interested in female specific answers? Yeah, I’m with you. I think it’s from the evidence that I’ve seen. It’s really interpersonal variability. But potentially, are there some differences, albeit they might not even be meaningful. For example, a fiber tips, right? We might have a higher, I don’t know, type one fiber or mixed fiber type, but that difference might be what, 1% or 2% so yeah, we could say that. But is that meaningful at any capacity? I don’t know.

Martin Gibala 1:24:53

You’re right, and I think there, you know. And again, we’re talking these. We can talk about percentages of where your fat Max is. Again, it comes back to, I think, what’s the actual fat max value? And again, we’re just not there in terms of, here’s the numbers. You know, this is a clinically healthy fat Max, right? Or we have those numbers. Well, we know that. You know, you can look at Fat max values in very untrained, deconditioned people, and it’s much lower than in a high level endurance athlete. You know, we can say in this clinical condition, it tends to be lower than this, but I don’t know. I don’t think we have, certainly, the level of evidence like we do for vo two Max, where this number is really good, this is where you want to be, right? We know the higher the fat Max, generally speaking, the better in terms of your metabolic health. But I don’t think we have, you know, certainly clinical cut offs to inform practice or something like that.

Dr. Gabrielle Lyon 1:25:47

What other sex differences male, biological, male or female?

Martin Gibala 1:25:52

Yeah, in getting back to the reason why your VO two Max goes up when you do exercise training. The for most people, the limiting factor is the pumping capacity of your heart, so your stroke volume. So if we took 100 people, measured their VO, two, Max, the main reason to explain the differences between those individuals would be their stroke volume. And so, so it’s not, it’s not a mitochondria thing.

Dr. Gabrielle Lyon 1:26:26

Okay, so it’s not a mitochondria thing. And I do my mind is blown for the second time to Is it a size? So if you have the same size female and the same size male, do we anticipate one having a higher vo two Max than the other, yeah,

Martin Gibala 1:26:44

generally the male will have a higher, slightly higher vo two Max. Part of that is, you know, females tend to have higher obligatory body fat, right? So the, you know, the leanest male will be about 5% body fat. You know, four or 5% the leanest female will be about nine, 10% right because of reproductive reasons, fat is a less metabolically active tissue than muscle, as you well know, and so that explains, in part, the differences in VO, two, Max, but there, you know, so the specific question was about training induced changes, and there, there may be differences in what explains the improvement in vo two Max with training, where the cardiovascular changes in the females may be a little bit less, but the muscle changes, including the mitochondria, may be a little bit better. So there’s hints of that in the literature. You can pick your studies right now. But again, coming back to we just need better quality science.

Dr. Gabrielle Lyon 1:27:45

Think what do you think you’ve been doing this quite some time again.

Martin Gibala 1:27:48

I come back to you some of there might be some subtle differences there, but overwhelmingly, it’s innate biological differences between humans and not a specific sex based difference per se, writ large. Now the last point I’d like to make there is our current randomized controlled trial that’s looking at Sprint versus modern Sensi training. It’s an entirely female cohort that we’re studying. Well done and and that’s for two reasons, partly the the the number of participants. That we need was was lower when we did the statistical calculations, but also we’re trying to do our part to help address the underrepresentation of females in science. And so it was a it was a dual consideration there.

Dr. Gabrielle Lyon 1:28:38

And do you think that you will find meaningful differences.

Martin Gibala 1:28:44

So our hypothesis is no that there won’t be that sprint. So 12 weeks of Sprint interval training in a true randomized design will yield the same improvement in vo two, Max as traditional, modern intensity, continuous training like that, difference will be non inferior. It won’t it won’t matter. So that’s our hypothesis, and that’s informed by our previous studies that we’re not, you know, state of the art in terms of the grade A evidence. So we’re hoping that we’re going to have much better evidence to definitively make that statement,

Dr. Gabrielle Lyon 1:29:24

if you were going to design a week of training for someone who is moderately active or how about yourself, you? I mean, if you tell me you don’t do any high intensity, this interview is totally over. But just from a practical standpoint when we think about designing the ideal week for a busy 45 year old person, yeah, so,

Martin Gibala 1:29:56

you know, if you can even give a half

Dr. Gabrielle Lyon 1:29:58

hour, let’s. Many times. Okay, they’re willing, yeah, what are they willing

Martin Gibala 1:30:02

to give me? Because I was going to be the first question, right? Yeah, yeah.

Dr. Gabrielle Lyon 1:30:05

Let’s say they’re going to meet the 150 minutes. So you have, they want to exercise, give you 150 minutes, that’s the baseline recommendation. And yeah, they’re willing to do

Martin Gibala 1:30:16

that, yeah. And so I think in and I more, they’ll give you more. Yeah. And so I think in an ideal world, you’d like to do something continuously for an hour at the highest possible pace, right? So do that continuous exercise and then two sessions, so, you know, a one hour ride at the highest possible intensity,

Dr. Gabrielle Lyon 1:30:39

darn it, right? I need to reevaluate my training. No, but how’s this? I don’t

Martin Gibala 1:30:42

train that way, right? So, you know, I I like high intensity intervals, and so all of my cardio is interval based. Right now, in the winter, when I have to ride inside, I rarely ride on the bike for more than half an hour, and it’s entirely interval based, and I typically do that three times a week, and then on the days in between three other days, I’m doing whole body resistance exercise, whole body functional style training. So myself, I’m meeting the guidelines, but rarely Am I exercising for more than half hour a day. Now, in the summer, late spring, early fall, I like to cycle outside, and so my cycling changes one two hour rides outside. It ends up being all interval based, even though I’m doing a continuous ride, because the altitude changes and things like that. What you asked me was if I was going to give a program to someone, not over here. I like interval training, right? But not everyone does. And so I think doing that continuous, but importantly, not zone two, go, go with the highest intensity you could sustain for that hour. I think that’s going to give you more benefit.

Dr. Gabrielle Lyon 1:31:55

That’s tough for people to Yeah, you know, as I think about because I do that, I mean, I don’t, I haven’t lately, but I love to do a peloton, listen to country music, don’t. It’s kind of embarrassing, but it’s so fun. I like to push myself, but I’m not sustaining. I’m not jamming out, you know, sustained at a certain exertion pattern, and maybe again,

Martin Gibala 1:32:22

when I think what you asked me. And again, I’m really not meaning to hedge, but like, Nuance is so important. Here was the question, you know, what would be optimal for their health versus what generally should they do?

Dr. Gabrielle Lyon 1:32:33

Right? So in my mind, and I am not a training expert, people should be lifting weights three days a week, if I was going to pick a number, and it could be four. I mean, listen, I go wave a magic wand, but I want them to get full body resistance training, because it’s only downhill from here. And from your perspective, for the busy 45 year old, how often should they be training?

Martin Gibala 1:32:57

Yeah, I mean, you know, I I think at least at least two days a week of whole body functional style training. And again, what is that? Well, again, so I’m talking their foundational movements. So push ups, pull ups, cleans, deadlifts, you know, it could be wall sits. You know that are engaging large muscle groups, and, again, ideally, in a functional style, way that you know, translate to improvements in activities of daily living. It allows you to extend, you know, it to climb the stairs better, right? It’s that, again, that challenge of you get off the airplane, you’ve just been on a five hour flight, and the escalator is not working, right? Is it a big deal for you to just grab your carry ons and walk up the stairs, and it’s three flights of stairs. You can do that, no problem. So when you’re challenged to engage and go at that, you have reserve capacity, right? And so I think that’s where those functional style resistance training really comes in.

Dr. Gabrielle Lyon 1:34:08

How many times a week do they do that? So

Martin Gibala 1:34:11

you know, as I said to you, I try to do it at least three, but if I’m going to give a general guideline, get two in, right? For sure.

Dr. Gabrielle Lyon 1:34:18

What about rest intervals? And I asked you this very early on, when I was working on my first book. And I said, maybe it was the second I feel like I call on you for every book The you know. I said, Well, could I just do a I think so we I remember exactly. I was in Encinitas, and there’s this hill. There’s this hill on the beach, so right behind the beach, there’s this hill. The parking is terrible. And so we decided that we were going to use this sprint, this hill for sprints. And after the second sprint, I’m like, I’m done. I need to rest for five minutes, just I’m going to chill for five minutes. And what I remember you saying is. That you really don’t want these long periods in between. It’s not a full recovery. If I’m not going at 100% my my max effort is that, is that accurate to say or if things change

Martin Gibala 1:35:14

so my thinking has changed a little bit. And again, the advice I would give to you, you know, thinking, knowing what you’re most interested in, from optimizing your health to, you know, the average person who just wants to boost their fitness a little bit like I stand by, rest interval matters in that, you know, generally, the longer the rest interval before you go again, the overall quality of the workout is going to diminish a little bit, right, both from a time efficiency, certainly, but also in terms of that, that period of time in in between. But, you know, I think I would say, Take as much rest as you need to come back and do another hard interval, right? If, you’re going to really compromise the rest, and then the interval isn’t very good, like the effort level just isn’t there because you’re so tired, then probably you need more rest, right? But where I’ve come around is our whole exercise snacking approach is based on it’s really prolonged recoveries in between. So people might do three or four one minute vigorous bouts in a day. So they do one in the morning, there’s several hours in between. They do it at lunch, one more in the evening, right? So you’ve accumulated three or four of those there. The recovery is really, really large, and yet we can still see some benefits with that approach. Now, ideally, would they put all those together with short recovery period? Yeah, probably that would be better for them in terms of boosting their health. But we know that other one, which is a way that or a strategy, it offers a strategy that people might be able to build into their lives. It’s still beneficial, the last benefit of the second approach with a prolonged recovery is it also breaks up prolonged sedentary behavior, which we also know so perhaps vigorous, intermittent lifestyle. Physical activity, exercise snacks offer a dual benefit. You do the vigorous physical activity to get that stimulus, but you’re simultaneously breaking up prolonged sitting, prolonged sedentary behavior, which we also know independently can help with your health.

Dr. Gabrielle Lyon 1:37:27

How long have you been studying high intensity interval training?

Martin Gibala 1:37:31

20 years? Have

Dr. Gabrielle Lyon 1:37:33

you found new evidence that has been just has been very surprising, like mood, like sleep, or just something that you hadn’t anticipated and you weren’t even looking for.

Martin Gibala 1:37:51

I’m a physiologist, and so I’m primarily interested in the basic mechanisms of how the body responds to these challenges and the health related outcomes. So probably one of the things that’s surprised me the most is, and I’m most proud to be a part of as a collaborator, is these, these small vilpa doses, this vigorous, intermittent lifestyle physical activity like four minutes a day, 25 to 30% reductions in all cause mortality. It’s that that’s probably been most stunning in terms of what could have impact. You know, I we’re doing some BDNF stuff now, but, you know, I’m not, I’m not a brain researcher. I don’t do brain health research, and so some of that research is fascinating to me, but it’s not what I primarily do. So in terms of what I’ve helped to contribute to, it’s, you know, these just how little you need to really see a benefit, right? And we’re talking mortality. There is the outcome. There’s nothing more important,

Dr. Gabrielle Lyon 1:38:57

absolutely, and we don’t even have a pill that does that absolutely the last question, and then you’re off the hook. How often should people really be? And again, we’re talking about people that are really going for something that they don’t want to be, just not worse than yesterday, but they want to make improvements for that sprint interval training, that that really hard effort that you cringe, that you have to do is that an every two week thing. We’re talking about four minutes. This is the worst idea of my entire life. Type of exercise,

Martin Gibala 1:39:37

ideally do it once a week.

Dr. Gabrielle Lyon 1:39:41

Yeah, yeah. And would you would that be the only training that they would do that day, aside from walking around? Or would you say, go ahead and do your resistance training, and then we’re gonna do at

Martin Gibala 1:39:53

least four minutes? Yeah? No, I would say, save those sessions for ideally. So. Save those sessions that that’s the only thing you do that day.

Dr. Gabrielle Lyon 1:40:06

Martin Gabala, you are one of my favorite scientists as i i just have so much respect for you and your dedication to this field. You also have a new podcast coming out.

Martin Gibala 1:40:18

I do thanks for the opportunity to give a plug. It’s with my friend and colleague, Dr Stuart Phillips, who I know, you know,

Dr. Gabrielle Lyon 1:40:25

he’s actually been on the show. He has trying to get him on the show now for the last, easily, four years, to come back.

Martin Gibala 1:40:32

It’s, it’s going to be called the Exercise Science Podcast.

Dr. Gabrielle Lyon 1:40:36

What is it going to be about? So, totally kidding.

Martin Gibala 1:40:42

Hard facts, no hype. That’s what it’s going to be about, and it’s with our friends at ghost Bureau, Chris Shogun and Chantal Gurdon, who are partners. Chris co authored my book with me, so we have a good working relationship. We’re starting to record episodes, and we hope that those will drop in the spring, so hopefully some of your listeners might find the content that we’re going to talk about to be informative, informative and useful.

Dr. Gabrielle Lyon 1:41:08

What we’ll do is we’ll link it, and when that comes out, we’ll send it out to everybody, and again, just thank you so much for your time and your work. And I’m excited. I’m actually excited to know what’s going to be next for you. Amazing.

Martin Gibala 1:41:21

It’s great to talk to you again, and thanks for the opportunity to talk about stuff we do.

Dr. Gabrielle Lyon 1:41:27

You’re off the hook. I could keep going for another another hour.

Martin Gibala 1:41:31

Thanks. Thanks. I hope that is Ivy.