Interview: Dr. Mark Tarnopolsky

[MUSIC] Hello and welcome back to the path the podcast from LifestyleRex. Thank you so much for joining us again today. In today's episode, Brendan interviews Dr. Mark Tenopolsky, who is a neuromuscular and neurometabolic clinician and scientist, received an MD and PhD from a Mastering University. He currently holds an endowed chair opposition from a Master's Children's Hospital Foundation in the area of neuromuscular and neurometabolic genetic disorders and follows over 1500 patients with myopathies, mitochondrial disorders and other neurogenetic disorders. He's published over 550 peer-reviewed papers and his research focuses on pharmacological, nutraceutical and exercise therapies for neuromuscular and neurometabolic disorders, mainly mitochondrial diseases, aging, obesity, and other disorders that affect mitochondria and muscle function. He's also the founder, CEO and CSO of ExtraKine Corporation, which is a biotechnology company developing therapies for aging, obesity, muscular, dystrophy, and mitochondrial disorders. Those are a lot of big words there, Dan. Yeah, I know. This is one of the most fascinating interviews that I've done. It's really interesting because I think it's very actionable what Mark has created here. First of all, Mark is a world-class expert around mitochondria. And so you might be wondering in a metabolic health program, what am mitochondria have to do with it? Well, turns out mitochondria have everything to do with metabolic health. That mitochondria, the powerhouses of the cell, mitochondrial dysfunction happens in the context of insulin resistance, chronic inflammation. And there's a lot of people that think that it is actually kind of the mitochondria that are at the center of all of this. It gets quite complex that way. But what I really loved in the conversation with Mark was was really kind of this notion that if mitochondria are at the center of this, what can you do? Right? And we talk a lot about muscle. And we talk about a lot about the fact that you can build up your mitochondrial capacity through exercise. And that exercise is the absolute key here. But Mark deals with a population of patients that are really severely, these are genetic disorders of mitochondria. They're not. The mitochondria really are broken in some way. And so trying to address this, you've got to come out with a bunch of different approaches. Versus somebody who has normal mitochondria, but the mitochondria become dysfunctional over time because of lack of exercise, gain of weight, you know, poor diet, and so on. So that role of exercise, he's been looking at it from the perspective of what else can you do to help with muscle? And we know that with insulin resistance, you get something called anabolic resistance. Right? So you start to lose muscle and it's hard to build muscle. And in our program, we talk about, okay, you've got to get enough protein into the muscle and you've got to exercise in order to overcome this. And the protein that we recommended, the program is higher than the RDA. So the RDA says, you need 0.8 grams per kilogram of body weight in order to maintain muscle balance. In people with insulin resistance and people with, well, frankly, people aging. Any of us are over 50. You need more. And it's because it's harder to get the protein uptake. And so we recommend 1.2 to 1.6 grams. That can be difficult to get. And so you start to get into, well, what about supplementing? And so Mark has, in addition to his research, well, actually as a product of his research, they started looking at protein supplementation. And they started looking at kind of what is going to be the best protein supplementation to offer for somebody to help preserve muscle or potentially increase muscle in people that have already lost muscle. So they've developed a formulation that they've studied. And I think this is the kind of key message for this. Well, there's a few key messages. One of the key messages is very much that the product that he's talking about and the product that we're going to share with our listeners is a product that has very impressive research. And I'll probably do a blog post with this in the links that link the papers so people can read it themselves. These are randomized trials that he's done showing the benefit of this protein formulation. And so versus other protein formulations. So it has that evidence. What I think is fascinating is, okay, stay aside from the product for a second. And just realize that the studies will show benefits for people supplementing with protein. Even when their dietary protein is at kind of the target levels we're talking about. So there's a benefit to people like it. You kind of wonder, well, if you have enough protein, don't you have enough protein? And really kind of what they've been able to show is that no, they could actually get more muscle increase with this. Now, they do all their studies combined with exercise. But you'll see in one of the studies they actually do it without exercise and there's still an antibiotic effect, still a muscle building effect. So it says something in terms of this extra protein can really be helpful for people. And obviously when there's insulin resistance or type 2 diabetes, anything you can do to get more muscles is going to be helpful. So the protein formulation that they have is basically a combination of it has way protein. So from way protein and casein protein from milk, the one thing that they've done that's interesting is they put the proportion of way in casein equivalent to the proportion that it is in mother's milk. Right? So not what it is in cow's milk, but actually what it is in mother's milk. Now, just to be clear, the way protein is coming from cow's milk is not coming from mother's. They do it in the proportion of mother's milk. They've added some creatine. And so we've talked about creatine, I think in previous podcasts, creatine is kind of a well-known muscle supplement that increases muscle mass, increases muscle strength. So some of the benefits you may be seeing from this particular formulation, maybe that creatine comp, on top of the way in casein, they've also added some vitamin D and some calcium. And this kind of goes along with what happens when you lose muscle? Well, you lose bone as well because muscle is the stimulus on bone to make bone stronger, you lose muscle, you lose bone. So they really kind of tackled it from a standpoint of what are the issues for people like this. And then the evidence for it is really quite impressive. They compare it to other protein powders. So they compare it to collagen protein powders. And again, you can kind of look at this and say, well, collagen, if you know a lot about protein, isn't exactly kind of the best comparator because collagen isn't really a very good protein for muscle-lilling. But Mark makes the point, collagen is marketed like crazy. And so a lot of it gets marketed around skin and tendon and so on and so forth. But there is very clear marketing that, hey, if you take this collagen powder, you're also going to build your muscles by that. And I think this is very, very clear here that compared to collagen this formulation really, really is much better. So I think that when you look at this, there's a few ways to view it. First of all, the way I looked at it was, wow, this really gives some very, very powerful evidence of protein supplementation for people who are either older or people with insulin resistance, people with chronic inflammation. There's very solid evidence that protein supplementation above and beyond hitting your protein targets in your diet can be helpful. And so Mark makes the point that while they showed kind of benefits without exercise, that's not what they're recommending. This comes with exercise. So I think that that's kind of the first part of this that I took away was, wow, this is important. And it's something that I've been doing myself, because as I turned 60 this last year, it's hard to maintain muscle. I'm naturally a pretty lean person and I run, so that's probably not helping on muscle mass. So I've added this to my routine. So I think that's the first thing, is that protein supplementation, even if you're eating enough protein, may have benefits for you. I think the quality of protein that you're using is important. And so we've tended to recommend single ingredient protein powders. And I think that, you know, know, we've, we, for people that want plant-based proteins, we've kind of, you know, talk about kind of pumpkin seed proteins or pea proteins. And then for people that that are, you know, comfortable with, with animal waste, we've said, you know, go, go with a way protein. I think here we, we reevaluate that and say, you know, I think this way, KC, and kind of balance probably makes sense. And there's some additional evidence. We didn't talk about this, but there's some additional evidence that there's different kind of half-life in terms of the way or KC and getting into the muscle. And so I think the balance between kind of having both of them, you get the immediate protein uptake and you get a delayed protein uptake. And so I think there's something to that, although we didn't really talk about that. The, and then the second thing kind of, you know, take, take away. So, so, you know, along with the, you know, protein quality, you know, what else if you're taking the supplement, what else should you do? And the creatine has been something that I've been interested in and I've never actually used before. And so one of the things that I've done over the last kind of one to six weeks is I've started to use this product. And it's been interesting because I've noticed the, I've definitely noticed the benefit in terms of my, my training that I'm a little bit stronger even though I'm not really particularly training all that hard on, on resistance training. And so I think that creatine is actually helpful from that perspective. And so now creatine only works as long as you take it. So when you stop taking it, you, you, you kind of lose a little bit of strength and you lose a little bit of the muscle bulk that you had. But I think, I think if you're going to be taking the extra protein powder, I think there's a pretty good rationale for, for, for doing this. The vitamin D, you know, in Canada, between October and April, we don't get enough sunlight to, to make vitamin D or so. So you do need to have a supplement for that. This, you know, just having it in your protein supplements kind of, you don't have to think about it. And then it comes alongside some, some calcium that's, that they, they, they've studied as, as being kind of a good combination between kind of the exercise protein and calcium. You kind of have all the ingredients, you know, there to, to make stronger bones. So I think that, that makes, makes a lot of sense. So, so I think, so I think, you know, I think there's, there's, there's some pretty good reasons to, to kind of look at this, look at this, this particular formulation is being something that could be, could be helpful for people. And, you know, and, and, and so, you know, Mark has provided the lifestyle or X people with a code to use, they'll give 20% off. Now, I want to be really clear, lifestyle or X doesn't make any money off of this. And, and, you know, I've never recommended a product before. And I think I, you know, I'm recommending this product in the context of, yeah, I think that, you know, extra protein supplementation is going to be helpful. I think that this particular product has some advantages in the way it's been formulated very thoughtfully. And it's the only product I know that, that is, it has the level of research behind it. So, so I'm very comfortable saying that, hey, this is a good product product. I, I can't say that this is better than, than, you know, the other kind of protein powders that we've traditionally recommended. And there is a caveat to, to this, and people will notice it very quickly when they kind of go look at the product. The product is formulated in, in, in flavors and there's a vanilla flavor and a chocolate flavor. And there's a little bit of stevia in there and we've, you know, tended to say, hey, we really don't want these non-nutrugative sweeteners. And I've talked, I talked with Mark about that and, and, you know, I think it's something that they're considering, you know, can, can they do it? What they found is, is that the taste of it is pretty bad with without us. I have to say that, you know, I, the product I've been using is the chocolate version. And, you know, I just basically put that in with some soy milk or oat milk and some ice and, and it makes it's pretty tasty and it, it's not overly sweet. It's so, but I put that caveat out there because you know, anyway, it's kind of a lifestyle or ex-listener is going to be wait a second. You know, there's something else here. I haven't tried the vanilla product and so I'll throw that out. But anyways, we thought it was worthwhile to share this because these protein powders are all very expensive and if there's 20% off, we did want to share that. But lifestyle or ex is not not having it. There's no financial incentive for us to share that. So it's just something that people can use as well, you know, what they said, it's, you know, the, the, the thing here is, you know, it's really a recommendation that, that, you know, supplementing with a protein powder to be helpful. This particular protein powder has a bunch of really good evidence for it. But I can't, I can't definitively say that it's better than, well, I can't say it's better than collagen. So if you're taking collagen and think that's working, then, then definitely, you know, there's evidence to say this is going to be better. But I can't say it's better than, you know, if you're taking kind of a pumpkin seed protein and the right for four things and so on. So all that caveat aside, the, the discount code here, where, where did I put it? Well, make sure we put in the description. Yeah. So Lsr20 is discount discount code and it gives people 20% off this product. But, you know, and it may be just to close. No, you can tell me a little bit uncomfortable giving a discount code for product on the podcast. But maybe what I'll just close by saying, you know, and it's kind of the point that Mark made was, you know, first of all, this, you know, this never replaces exercise. So, yeah, even if they did part of their study where they didn't have people exercise, this never replaces exercise. This supplements exercise, it is going to be helpful in addition. If even if you think you're getting a protein is probably going to be helpful for you, if you're, you know, if you're over 50, if you've got chronic inflammation, you got insulin resistance is probably going to be helpful for you. It's better than collagen. And, and, and then, you know, I can't say it's better than everything else that is out there. But, but I think that it's an incredibly thoughtful approach to, to protein supplementation. And it comes from somebody that just a body of evidence that they put into the literature and the contribution that they've made is really impressive. So I totally enjoyed the conversation. And, and I have to say, I actually like the product. So I continue to use it. So there we go. Perfect. All right. Let's get into the interview then. All right. Good morning, Mark. I'm very excited to have you on the podcast today. I think I'm going to get a lot of satisfaction out of our discussion because you have a both a fascinating background that's intriguing and your researcher on something that is just integral to metabolic health and and not very well understood, I think is, you know, for most people. It's so. So let's jump in a little bit. Maybe tell everybody a little bit about your your your background. I think you've got some unique aspects that bring you here today. Yeah. Well, thanks very much for having me. Having me part of this. It's always a pleasure to talk to someone who's doing such exciting and interesting work that's near and dear to my heart. I spent my life as a child doing sports and exercise and all through high school. I thought that was going to be a phys ed teacher. That was sort of my goal in life. Which is a great goal and I was very excited to go to university and start as I went through university. I became more and more interested in the scientific underpinnings of exercise for nutrition and did a fourth year project with the late Dr. Duncan McDougal who's one of the top exercise physiologist. And I thought, geez, maybe I should go into sports medicine and, you know, really apply this to the general population. Went through university, finished my undergrad, went into medicine to be a sports medicine doctor and then got really excited about neurology. And then got really excited about research. I went back and did a PhD looking at essentially how exercise impacts protein requirements and then I kind of fused everything together. And essentially applied my experience with nutrition and exercise to my clinical practice, which is treating patients who have primary genetic and metabolic muscle diseases and other neurologic disorders. And what we found very early on when I first started is that there's no therapies. There's no cures that really were doing anything for our patients and neurology was a bit of a nihilistic discipline. I had a different approach and a different belief and I felt that exercise nutrition was beneficial and we've spent 30 years showing indeed that really the thing that works best for many of our patients is just manipulation of diet, optimization of different exercise programs. And we've had just dramatic success in different metabolic disorders, which, you know, we're not curing the gene, but people are living a completely healthy normal lifespan and health span by following exercise nutrition interventions. As part of that, we have looked at different types of protein, different supplements to further enhance function in patients with these disorders. But then your group might say, well, what does that mean to me? Essentially, as we'll get into all of us are experiencing atrophy and weakness of muscles as we move from age 35 to age 70. And we're all experiencing what's called mytochondrial dysfunction, which further contributes to muscle weakness. In addition, it contributes to dysbysemia, it contributes to obesity, which, you know, we can talk about later. And so a lot of what we've done, I think really has applicability to pretty much every human as we age. people with obesity, people who are overweight, people who have dysglycemia, all can benefit from some of the stuff that we've worked on. Yeah, I think this is the fascinating point and I think that mitochondria, you know, first of all, I don't think people understand or appreciate exactly what they do and there's a high degree of complexity there. But this link between, you know, just regular aging as you talked about and the mitochondrial dysfunction that comes with aging. And in the spectrum that we see of people in terms of mitochondrial function from, you know, elite and endurance athletes who, you know, the amount of power that they can generate from their muscles, you know, by the mitochondria is phenomenal. But all the way kind of on the same spectrum back to some of our patients with type 2 diabetes where unlike kind of your other patients, there's still, you know, you know, more normal genetics around the mitochondria, but the mitochondria are in a situation where they're not functioning as well. And I think what to me is so exciting about that spectrum is there's an element, obviously there is underlying capabilities, but there is an element of training capacity and ability to take control by, as you said, from exercise and nutrition to move along that spectrum for all of us. So I like to kind of dig a little bit deeper into that and maybe kind of have you, I guess first of all kind of, you know, explain kind of the mitochondria and kind of really, you know, what mitochondria do. And then what happens with mitochondria over time from an aging perspective, but also in these metabolic diseases like type 2 diabetes and insulin resistance. Yeah, so mitochondria have been with us probably for two billion years, evolutionary perspective. They were thought to be a bacteria that our initial cell, which is called a proto-ukaryotic cell, our cells are part of the eukaryotes. And what was thought to occur two billion years ago is that the bacteria was either engulfed or somehow there was this relationship where we engulfed a bacteria. And why would we do that? The bacteria that we engulfed turns out eventually to become what's called our mitochondria. And what they do essentially is the earth's environment was increasing in terms of the amount of oxygen that can cause what's called oxidative stress. But in addition to offering that oxidative stress, we also could extract more energy from our food. So anaerobic metabolism, meaning without oxygen is very inefficient. With mitochondria, the efficiency rate goes up many fold order magnitude even a bit more. And so that was the advantage. So to become multicellular, you know, eventually from a single cell and then eventually to the trillions of cells that we have as humans, we needed lots of energy to grow. So over that period of time, this bacteria is now what's called our mitochondria. They're present in every cell in our body except for our mature red blood cells. And what's happened is initially it was thought that there was about 1300 genetic products which were needed to make the mitochondria. Now most of that is made from what's called the nucleus of our cell. All of us have around 22,000 genes which are packed into chromosomes. And they make still around 1200 of these different components that make a mitochondria. A mitochondria are interesting. They've got this little circular piece of DNA just like bacteria that makes sort of the core structure. And once we have mitochondria in our cell, what they do is we efficiently extract the oxygen, mix it with the food that we eat from bats, proteins, and carbohydrates to give ourselves energy. Cells have a varying amount of mitochondria, roughly proportionate to their energy requirements. So for example, heart have up to 20% of their volume as mitochondria. Muscles which really can change the most, generally around 2 to 3% of the total volume of muscle is mitochondria. But that can increase. We've done studies where we did muscle biopsies before and after three months of exercise training. And we double this mitochondrial volume in our muscle. And the reason why that's important is that we can better extract energy from fat. We can better extract the energy from carbohydrates. Our overall fitness for that kind of a better term goes up. Now in humans, you pointed out athletes, you know, more mitochondria, which indeed tops more endurance athletes have more for sure, is roughly measured by what's called our VO2 max. So the VO2 max is the maximal oxygen consumption that we can do. Usually it's expressed per kilogram body mass per minute. And when we sit here, we're at around three to four middle of leaders of oxygen consumed per kilogram per minute. When we are the top sport athlete, we can see that that number can be as high as 80 or even 90 milliliters per kilogram per minute. Most of us at maximum exercise are going to be around 30 to 40. And why that's important is there's very good evidence that those who have higher VO2 max have better lifespan and health band. And you know better, but certainly you get about a four year lifespan extension if you're a top sport athlete. But more importantly, I think most of us are interested in that last 10 years of our life. And that's what we call health band. So that's your ability to live without disability. And that is significantly enhanced with fitness as reflected in your VO2. And then one final point about VO2, why it's so important is for daily activities. It's estimated that for independent living, we need a minimum of 12 milliliters per kilogram per day. And that's so important because many people as we get older, we get weakness and also mitochondrial dysfunction. If you drop below that threshold that increases the likelihood that someone is going to be institutionalized because they can't look after themselves. So the mitochondria essentially take our food substances, the breakdown of our food substances, carbohydrate or carbohydrate or fat and turn that into energy. So there's an energy flow that's happening there. Obviously, you know, one of the challenges we see with people with insulin resistance is often not very good fat burns. Right. And so they have excess fat stores and fat kind of in places that shouldn't be a topic fat fat in the liver that's actually driving the insulin resistance process yet can't aren't able to utilize fat as fuel. And that fat, that fat oxidation happens purely in the mitochondria. That's correct. Yeah. Through a process called beta oxidation. It only occurs in the mitochondria. So in many respects, in order to, you know, become a better fat burner in order to kind of, you know, get rid of some of this ectopic fat, we need to actually have our mitochondria become healthy and able to utilize fat as fuel. Absolutely. Yeah. So with this dysfunction that occurs, describe that a little bit in terms of, you know, because you've talked about kind of there is a natural decline in mitochondria function. And I think that correlates with the natural decline in beyond to max that we see. But how does that also, you know, what what what's happening in in metabolic diseases that that creates this inability for the mitochondria to utilize the fuel sources that are available. Yeah. I mean, one of the things that's very clear is the flip side of exercise and that's immobility. We did a study where we put an immobilization solution on otherwise healthy 20 to 25 year olds. And we dropped mitochondrial function by about 25% in two weeks. So the problem is it becomes a vicious cycle if one is overweight you often are doing less steps in the day. You know, there may be more pain in the knees because of excessive weight or it's just more difficult to go upstairs, etc. And then as you do less, then you don't do sort of fuel or turn on your mitochondria and it becomes a bit of a vicious cycle. So that's part of it is decreased activity, which is why step count and increased activity is so important. What we found is that in people who are who had overweight or had obesity that there was a lot more fat in the muscle, but they was just sitting there and not close to a mitochondria. So with training, we were the first to describe that the mitochondria come in contact with the fat. So there was this thing called the athlete paradox where top sport athletes had more fat in their muscle and people say, well, this doesn't make sense with the people who have obesity have high fat. And then athletes have high fat. What's the paradox here? And it is that the mitochondria increase in the athletes and or with exercise training in those who have a grow over weight or obese. And then they come in closer contact so we can utilize that fat for energy instead of it being a storage site, it becomes a sort of like a furnace. And why that's an issue is that there's certain bi products which come from fat storage and the excessive ectopic fat, things like dysoglycerols and others which can then in turn impair insulin sensitivity and it becomes a bit of a vicious cycle. So shulman and others have shown when you look at muscle biopsy samples from people with diabetes or people with obesity that the mitochondria just aren't functioning well. But we and others have clearly shown that you can get this improvement in mitochondrial mass, more mitochondria touch the lipid, we've earned more of them. the exercise, both acutely and chronically, we actually can pull more glucose from the body into the muscle. What I call the glute-4 transporters are both in higher abundance, but they also migrate immediately after exercise to the muscle membrane to pull more glucose in. So there's many ways that physical activities, especially endurance exercise, can reduce dysklycemia, and it's important for metabolic health also from a B-steak perspective. So, really, especially often what we see with insulin resistance, it happens in this context of energy overload. So there's just too much energy available, and it's being stored in places that shouldn't be. But if we can flow that energy through the mitochondria by exercise, basically have a place that that stored energy gets converted into ATP and used for muscular energy, that that energy flow can start to improve the health of the mitochondria. And that process is dynamic. I think what you're saying is, if your sedentary goes backwards very quickly, but on the other hand, as you start to move, as you start to create more energy flow, even just by increasing step count, or doing some exercise, you start to pull some more energy through that process in the mitochondria become healthier. Absolutely. So, not only do the mitochondria increase and become healthier, they then reduce these stored substances, which on their own, when they sit there inertly, contribute to dysklycemia, this topic distribution, both in the liver and muscle, I think, is where we know most of the deleteries effects of ectopic, especially lipid deposition. So, one of the things that fascinates me around this whole energy flow concept is, is Herman Ponsner's work around, kind of, you know, is there a constrained energy model where humans are designed for a certain energy load, and so there's a certain energy flow expected. And if we don't use that energy for, you know, essentially for mechanical work, like muscular work, then that energy can be converted into a higher stress response or higher degree of inflammation. And I think we also see if there's not, if the mitochondria are not being used, there's incomplete oxidation and higher rates of oxidative stress. Can you talk about kind of that concept of, kind of, when the mitochondria start to have higher levels of this oxidative stress, what that is, and also kind of how that impacts this chronic inflammation that lies at the center of so many conditions that we see. Yeah, I'm quite a mitochondrific individual, and I think it's the mitochondrial dysfunction, which then contributes to most of these other processes that you talk about. There's been a really nice paper that came out in a journal called Cell, where they talked about the 10 essential factors, which contribute to aging, now that's up to 12, but pretty much every one of them can trace back to mitochondria. So, if the mitochondria don't work properly, what happens is that there are electrons which are flowing. So, essentially our food is what we call decarboxylated, we sort of pull it apart, almost burning it like burning food, the potential energy from our food then is used to create a flow of electrons through what's called the electron transport chain in the mitochondria. Those electrons, if properly captured by oxygen and reduced water in complex four, allow the process to make energy. If, however, there's dysfunction of the mitochondria, which we see in our patients, for example, if we have a mutation in any one of those four enzyme complexes, there's a backflow of these electrons, and those electrons can form what are called free radicals. So, when people take antioxidants, which most of you are familiar with, they're essentially mopping up these free radicals. Now, what happens is due to the secondary mitochondrial dysfunction in people with obesity or in type diabetes, there's increase in reactive oxygen species or free radicals. The problem with free radicals is that they can damage protein, they can damage lipid, and they can damage DNA. Because they're being produced in close proximity to this little pieces of mitochondrial DNA, it can further damage that which can form this vicious cycle. So, to reverse that, we can do several things. Number one, good healthy diet with lots of color. It sounds simple, but the simplest thing I think most people can do is have a variety of colors in your food. And what I mean by that is the color in food, like carrots, for example, in tomatoes, those color-emparting substances are generally antioxidants. And if we have a repertoire of them in our diet, they can help us to mop up any excessive free radicals. But also, I mean, a back to exercise in one of the first things that we showed years ago, as everyone was worried, oh my goodness, exercise is bad as we get older because we produce free radicals. Yes, we do acutely, but what happens is the body up regulates what are called endogenous antioxidants inside our muscle. And they then, in turn, lower this chronic elevation of reactive oxygen species. And what we showed in older adults after exercise training, we actually lowered oxidative stress or oxidative damage. And we improved mitochondrial DNA, and of course improved mitochondrial function quite dramatically. So oxidative stress is an interesting one. When you're young, there's some body of evidence that certain antioxidants may be bad because the free radicals that are produced when we exercise actually lead to the adaptive upregulation of mitochondria and some of the benefits. And one study years ago showed that vitamin E and vitamin C together blunted the beneficial effects with respect to dysglycemia. And so people have to be careful. They have to know that antioxidants that they might take exogenously, meaning if you're taking a supplement or something, that they're not going to blunt the benefits. And so you really need to know in an individual, are the antioxidants or supplement you're taking going to blunt the benefits of the supplement that you're taking? Right. No, and so we can probably touch on that a little bit more. But I think the concept of eat the rainbow, the colorful foods and vegetables. And that is the way your body's actually designed to get these antioxidants versus taking a supplement where you're taking them at doses that we wouldn't see necessarily normally in nature. Yeah, I think there's no question. I don't know of a study that's ever said that taking antioxidants naturally through food is deleterious, but there are certainly antioxidants that one can take, especially if you take a single antioxidant. And I would caution anyone listening to this, taking a high dose of a single antioxidant. And the reason behind that is any antioxidant can become a pro-oxidant. So you start off sucking up electrons, but then eventually it can give them back. So let's say it can actually go in the opposite direction. And that's why food has many antioxidants. And one of the concepts I've put forth as early as 2001 is that if we are trying to design supplements to be helpful for aging and in our mitochondrial disease patients, they have to be multiple supplements logically put together as what we call redox couples and not just single antioxidants. And most importantly, anything that's going to be studied or evaluated needs to be done in the context of what we know is best for people. And that's exercise because if you blunt the benefits of exercise, you know, you really should not be taking something that would do that. Yeah, so going back to the role of exercise in this, this mopping up afterwards. One of the analogies I sometimes see is it's, you know, what happens after you finish exercise is a bit like the zamboni coming out on the ice and kind of clearing everything. And we make the point kind of in our program that exercise may be our best anti-inflammatory. Can you expand on that a little bit in terms of kind of that? Like what happens post exercise? Yeah, so with exercise, it's a stress. So it's physiology 101. Physiology 101 is that when an organism is stressed, it doesn't want to feel that stress again. And it imparts signals to the cell to increase a variety of responses. So the next time that stress comes, you can better deal with it. And so yes, we get free radicals produced. Yes, your muscles are sore the first time you exercise, but you know, you start coming back. And eventually those muscles are not sore. And that's because the body is imparting a physiologic adaptation to deal with that stress. And that adaptation over time is what really confers the benefits of exercise. And that's why after training, we see lower oxidative stress in our older adults who have higher oxidative stress to begin with. We lower it with exercise training. We also see chronic low grade inflammation, which you've commented on. And that's well described as we age. And we know for sure, people with obesity and cytotide disease also have chronic low rate inflammation. Part of it is likely from the mitochondrial dysfunction, which when they don't work properly, they activate what's called the endoclamazoam through a process. So we'll get into called the NLRP3 and CaspAce1. So any others, there's markers that we see called IL-18 and IL-1 data, which go up chronically in response to the inflammation from mitochondrial dysfunction. But that too improves with exercise. Now acutely, you get inflammation. So the next day when you feel that pain when you first start, the muscles are a little bit tight and sore, some of those free radicals, some of the inflammation markers have gone up. And in fact, some of them are important. and signaling molecules like interlude 6 signals to the liver to start breaking down sugar and using it for energy. So these are good in short pulse and is with exercise but they're bad if they're chronically elevated the inflammation markers. So the exercise obviously improves the mitochondria health and so makes the mitochondria more efficient but also makes more mitochondria. It helps kind of dampen that oxidative stress and it helps blunt kind of systemic inflammation. Is there something special in terms of mitochondria in muscle and versus mitochondria elsewhere in your body? Well we know that mitochondria are present as I mentioned in many cells in our body and one of the things that we've looked at is what happens to other tissues when we exercise. And there's good data that there's improvement in eye health, lower risk of macular degeneration for example, hearing health, heart health and one of the ones that we first looked at was skin health. So we actually did skin biopsy from talksport athletes versus sedentary individuals and showed that at the cellular level the skin was much healthier in the athletes and we did all sorts of work to show that the muscle and other organs signal to the skin through something called interleukin 15 which is an eight one of these what we call cytokines which can either be pro-inflammatory or anti-inflammatory and it was aisle 15 that went up with exercise that actually increased mitochondria in the skin. So when you exercise you are not only protecting your muscle but you're protecting your heart, your eyes, your hearing and of course your brain as well but we were the first to show that skin also benefits and mitochondrial health is better in the skin which kind of makes sense. So we know that almost every cancer as you have a lower risk of almost every cancer if you're an athlete with the exception of melanoma that's the only one that's a little bit higher in athletes and so people say well that does make sense if you're improving your skin health wide athletes have more melanoma and it's probably that people like me and some of my friends who are world class cyclists are out in the sun for eight hours. Evolutionary perspective if you're out, you know, doing exercise, increasing mitochondria. You want to increase it in the skin to protect because as you're outside you're getting more UV damage and so folks like me who had a bad burn on his leg I've actually had melanoma cut out of my leg because I was out canilling for many hours and you know couldn't put sunscreen on. So but we do know that if we didn't get that protection and we're 10 or 15 or 20 times more exposed to sun you know we'd be riddled with cancer as athletes because right side in the sun so much. So if people learn nothing from this make sure you put it on your sunscreen. For sure. So so yeah very fascinating and we had Jim Johnson from UBC talking about beta cells and some of the myocons are those the chemicals the signals coming from muscle post exercise even improving beta cell function as well. Again probably fairly similar types of mechanisms. So really kind of we have and I think the thing that's so interesting about kind of mitochondrial health and muscle is muscle we have this ability to increase the yeah we can because of our actions because of our behaviors we can kind of increase the load that our muscles take on we can increase that stress and then forget that that that physiologic you'll 101 response of getting getting stronger where where is you know in other cells we can't we can't really do that right like we can't really kind of you know it's as hard as kind of think of how we're going to you know stress the kidney in order to get it to be stronger but the muscles definitely have this kind of flux capacity. So yeah I would say though that we do know that there as you pointed out these we call them exorkind we were the first to coin that term and we actually called her company exorkind because there's so many different chemicals that go up with exercise they're not all coming from muscle but what they do is they you know communicate between tissues I mean there's ones from the liver called hepatocines once from the fat cells called the dipokines and there's infinite number which are exchanged between tissues which confer these benefits but you know muscles problem muscle and hard to probably the most dynamic to respond but you know we do see it in skin and there is even evidence that kidney health is better for example if you cause a schemia to the kidney after exercise training the kidney is is less damaged by by that and the brain of course we know that we can stimulate what we call neurogenesis in various parts of the brain especially what's called the hippocampus which is important in short term memory and you know many people are well aware that just doing cognitive activities in people with mild cognitive impairment is not as effective as doing cognitive activities with exercise so it's we do get some systemic benefits. So yeah so almost almost almost unlimited and so really kind of the the key here is is is having the appropriate stress that the body then can appropriately recover and so yeah which is kind of interesting it's you know an anti fragile property right like where you know we get we get stronger from stress we actually get weaker without stress. Absolutely. So thinking about that a little bit and muscle so this you know we talked about mitochondria dysfunction we talked about kind of the oxidative stress and chronic inflammation that comes from a muscle or mitochondria that's not being active. What happens to muscle health right if you're if you're not active do you get into a bit of a vicious cycle where that oxidative stress and inflammation actually decreases you know muscle mass and decreases muscle over time. Oh yes so clearly over time we lose muscle I think anyone like me who's over the age of 60 is realized that your muscle is shrinking and that's been well described for many many many decades that we do lose both strength we lose VO2 max and we lose muscle mass as well and muscle mass is roughly proportionate to strength you know in a population obviously the bigger the muscles the stronger you are skinnier the muscles the weaker you are and that process as we age is called sarcopenia which is you know posity of flesh defects bone and muscle the two tend to decline in parallel what happens is as partially related to mitochondrial dysfunction in several ways one we need energy to synthesize new proteins so if you're mitochondria don't work you don't have the energy to synthesize protein and we synthesize protein in two main ways one in our skeletal muscle when we exercise doing more resistance training we get hypertrophy or bigger muscles which is the logical response to a load stress so that we can handle that load better our muscles hypertrophy they get larger so that's a classic sort of resistance or training that you can do to counter measure that the other thing that happens is that studies have shown also that in the areas where there is mitochondrial dysfunction you see that the muscle fibers are a little bit smaller probably because you can't synthesize protein as much but also we know that from age 35 or so to about age 70 we lose about 30% of the nerves from our spinal cord to our muscle they do respond to the ones that are remaining send out these little almost you know strawberry runners called collateral re-innovation to grab onto those muscle fibers but it's a bit of an incomplete process which tries to compensate for the loss of the nerves but those nerves also are you know dropping out through a process called apoptosis which happens when the mitochondria don't work so people you know thought mitochondria only important for your bio-tomachs your physical fitness your metabolic health but work by jet-acon is clearly shown that there's a relationship also to this loss of muscle which we all experience as a consequence after 30 years of research I think if I've learned one thing and that is that for both patients with mitochondrial disease muscular dystrophy and all of us who have aging all of those processes lead to varying amounts of mitochondrial dysfunction and muscle atrophy with resultant weakness and therefore endurance exercise is great to target the metabolic effects helps us you know to attenuate the gain of the body fat that occurs but to keep muscle mass on and to improve strength we need more resistance exercise and so you know I'm trying to practice what I preach I used to be an international level endurance athlete still trained seven days a week but I'm trying hard it doesn't work very well but it is my muscle mass by doing some weight training three times a week but certainly without the weight training which I started about a year and a half ago I couldn't believe how much entropy occurred in spite of doing exactly the same nutrition same exercise every week still shrinking away and we've shown that in multiple studies as of others that you really for optimal health should be doing probably three days of more resistance as strength type training and three days a week of more endurance type training. Yeah yeah no I but I'm a lifelong runner and that comes naturally and easily and however getting into the gym and doing my my my tray so it's it's one of our challenges but okay so so this I think is is you know really helpful you know we're we're combating kind of a natural process that's that's occurring and and and and of course you know when you look at type 2 diabetes, they're now considered kind of five subtypes of type 2 diabetes. The largest subtype is aging related. And I think a lot of us think that that aging related phenotype that we're seeing, a lot of it is actually driven by the loss of muscle mass and combined with a pancreatic beta cell that's not readily compensatable. But when, okay, so we look at this and we say, okay, we're kind of set up to lose some muscle and we can combat that with exercise. But in order to maintain muscle, we need to be getting protein into the muscle. And a lot of people are losing muscle because potentially not getting enough protein in their diet or in their timing of protein isn't particularly good. But also there's the concept of antibiotic resistance where older people, so if you, you know, take by son who's 19, I'm pretty sure that, you know, a whiff of protein that he has will probably end up in the muscle and he'll get stronger. Whereas, you know, for me, it's not that way, right? It's very, it's more difficult. So talk to us a little bit about this concept of antibiotic resistance and why kind of, you know, you've got to get the protein part, right? Along with the exercise and how that all fits together to successfully, you know, combat this natural muscle loss that we see. Right. So that's a good point in the way in which our muscles become less responsive to the stimulatory effects of both exercise and insulin, meaning the glucose doesn't get taken up as well through the glucose transporters, the root four transporters. The same thing occurs with amino acids. So amino acids are the building blocks of protein. What happens is we have to pull those amino acids from the blood into our muscle. There's nine, 10, depending on how you look at it, essential amino acids that we need to get in our diet. There's 10 that we can definitely synthesize inside our body. So we need to have those 10 essential amino acids come in. They all get put together in various combinations for whatever proteins being built. The main protein that we're interested in here and we're talking about is myosin and actin, which are your two contractile proteins in muscle. But to, they're turning over all the time. There's a slow turnover of breakdown and a synthesis, but to fuel the synthesis we need these amino acids. So normally what happens is the amino acids will come in when we eat and we get an increase in insulin. As the insulin goes up, it stimulates the amino acids to be pulled into muscle. And we stimulate muscle protein synthesis. We need ATP from mitochondria. We need the essential amino acids from the diet. And the ones that are most important obviously is to have good essential amino acids. It's about complement of many, which is probably why we've chosen milk to grow little babies, right? And milk really is way encasing, which is a perfect mix of the essential amino acids, which then come in turn on protein synthesis and actually de-creditation a bit. Now this resistance is probably too full. As you pointed out, the beta cells are not as effective. So we don't get the same drive of insulin. The insulin is defined to the insulin receptor and stimulate this uptake of amino acids. But also downstream there's probably a decreased synthetic capacity, which could be related to the mitochondria, not supplying enough energy. So how do you overcome this? What do older adults do that compromise it? Number one, we know we're behind the A-ball with this antabolic resistance. So the first thing that you can do of course, you know, if I'm plugging a dead horse and that's exercise because that's a major stimulus to pull the amino acids in. But you need good quality protein. And one of the biggest issues that we see is many people are, you know, one meal a day. Many people have only amino acids or good quality protein once a day. Stu Phillips, who's one of my first postdoc and he's done a lot of work in protein. And he and others in the consensus have suggested to help with this resistance. We need 1.2 grams of protein per kilogram per day, which is about 50 percent more than what our government tells us. But more importantly, I think is breakfast, lunch and supper. You need these pulses of amino acids to try and overcome this antibiotic resistance. And you're looking at generally 20 grams of good quality protein, at least breakfast and lunch. Most people would get it with dinner because a lot of people have some meat with dinner. But it's that breakfast and lunch where most people are falling down and not getting 20 grams of high quality protein to try and overcome this resistance. And what we've shown too is the benefits of weight training in terms of putting somewhere on a three month program with protein, it depends on the type of protein. We and Stu Phillips have used collagen protein, which is low biological value versus a humanized milk protein, which is 60 percent weigh and the 40 percent casing. And the improvements in strength, the decrease in body fat, all of them are much, much enhanced when we take proper quality protein versus an inferior product such as collagen. I wanted to go back a little bit around this antibiotic resistance, it's from the standpoint of, so we know with kind of insulin resistance and glucose, essentially that glucose transporter, it just takes more insulin in order to get the glucose transporters. We know that as you alluded to exercise kind of gives you this free pass where the glucose transporters just by movement of muscle will come to the surface. With insulin resistance is, there's a concept of selective insulin resistance. But is the insulin resistance that we see actually underlying the amino acid transporters? Is that part of the picture here as well for somebody who's insulin resistant that just simply it's going to take more insulin to get the amino acids also into the muscle? Yeah, as I was pointing out, perhaps it didn't clarify it well enough. I mean, number one, we have some beta cell dysfunction, less insulin, the insulin advice, the insulin receptor, there is resistance because in the way in which the glut 4 transporters are generally about 50 percent inside the cell, 50 percent on the membrane, they go to the membrane in response to insulin, they go to the membrane response to exercise. We know acid transporters not as well describe, but there's good evidence that they do the same thing. So we have a number of amino acid transporters, large, neutral, basic amino acid transporters, which also have to flux from an endosomal fraction to the membrane to pull it in. So that whole signaling process is part and parcel of the same insulin resistance. And insulin, if you think about it, is synthesis synthesis synthesis. Right. Right. And so if it's not working, you're not only, you know, not synthesizing glycogen, which you do after you meet, you're also not synthesizing the protein as well. Fueled or negatively enhanced, sorry, negatively inhibited, I should say, by the mitochondria not allowing enough energy to do that energy dependent protein synthetic pathway. Yeah, so that's fascinating. That's something I haven't appreciated until this conversation. It was just, yeah, because we talk about insulin being kind of a storage and building heart, right? And involved in fat carbohydrate and protein storage. But I didn't really think about it from the perspective of our patients with insulin resistance and the muscles that part of their antivolic resistance may be also just completely tied back to this insulin resistance. And it makes sense then that since the muscle is responsive to exercise and becomes more insulin sensitive with exercise, that that is also going to be a key factor. So, okay, learn something in all of these conversations, which is fabulous. Going back to kind of the, you know, getting enough protein in the muscle, one of the things that in our program, we try to align with circadian rhythm and have people pass for at least 12 hours, just kind of, you know, recognizing that the body more naturally, while insulin levels go lower at nighttime, more naturally able to utilize fat for fuel at nighttime. And we'll have people extend that up to 16 hours. We never want people to go past 16 hours because you can't get enough protein in that eight hour window. But even within an eight hour window, we find it challenging because a lot of people will find that from an appetite satiation perspective, they're now fat burning, they're actually, you know, they've got stored energy, they're starting to recognize the stored energy, so their left and signals are coming through. So they just don't have the appetite to eat three meals. And so you run into a situation where you can get a breakfast where you can, you know, get a good 20, 30 grams of protein in the breakfast. As you said, usually takes care of it for most people. But they end up in this period in the middle of the day where either kind of they they're more of a snack. But if you're not getting 20 grams of protein, you might not have that signal there. And this is kind of the place that we see a lot of people kind of recognizing that maybe they need to go to a supplement in, you know, a protein supplement in order to kind of fill that gap, especially if they're going as long as 16 hour fast. So your research has led to, you know, looking at protein supplements and really kind of from what I've seen amongst the best actual research in the world in terms of, you know, randomized trials. And you've learned, you've learned a lot there. So maybe walk us through a little bit of what you've learned, what works doesn't work. And then we can talk a little bit about kind of the protein supplement that you are now company is Yeah, I mean my first paper back in 1988 was looking at protein requirements for top sport athletes and you know it was thought to be you know pretty rogue at the time because the government and all the top nutritionists said that exercise didn't impact your protein requirements And I took a lot of heat back then that it's it's been well proven now the top sport endurance athletes need about twice the amount of protein And even when we suggested that older adults needed more we were criticized heavily but a consensus by all the top people in the world Stu Phillips my first postdoc and I worked on this stuff You know he was part of that consensus showing that older adults do indeed have insulin or antibiotic resistance Slash ins and resistance and need about 50 percent more But the protein is contextual as I mentioned before we have what's called biological value Which is probably the simplest concept there's a whole bunch of other scores that they have but that's one of the easiest ones Essentially what it is is that if you eat a protein how much of that can be converted into muscle is really the most appropriate way of thinking about it And if you have a protein that's deficient in certain essential amino acids It's more difficult to synthesize muscle for example and Stu Phillips did a project that we were about to do but he and my other first PhD student Johnny Parisi essentially took work that we had done You know using creatine monohydrate back in 2003 2007 They took that research took some of stews in my research on protein to put together What are it's probably the the most effective protein And supplement strategy to try and increase muscle mass? So what they did is they took way protein which as I mentioned before Way as part of milk and it turns on protein synthesis And again, you'll see eventually I think Casey should be in there and we've done that They took creatine monohydrate because we and others have clearly shown that older adults who train with creatine get more muscle gains Versus those that train on a placebo they added calcium vitamin D for obvious reasons good for the bone And in their first study they also add omega-3 fatty acids for reasons we won't get into what they showed is that when older adults were taking that combination we call it muscle five is it has five ingredients and Compared it to people taking collagen so essentially everyone was eating their normal diet Which was mixed biological values and meats and eggs and vegetable proteins etc Then they added Actually in their first paper 60 grams of collagen protein Which is all the rage? I think Jennifer Anderson as a product and everyone their dog is spending tons of money for a little tub of collagen and Every day I see stuff saying how great this is for your muscle And there's a company that is promoting how amazed the collagen is for your muscle Then we had these collagen peptides in the study compared to this combination and the muscle gains were We're quite a bit better in those who took the combined muscle five versus those that took the collagen protein So we started a company as I mentioned we call it extra kind and we were looking for you know more of a pharma play to find these extra kinds and use them for diabetes and for aging but then we got more into nutrition So we actually bought the patent from stew and then I took my evolutionary love To say look how did humans grow we grew with 60% way 40% K-teen so we essentially took his muscle five concept brought the protein amount down to 40 grams from 60 because 60s a lot I think for most people to take and we used the 40 because For many people is 20 at breakfast and 20 at lunch it was with you know stew and others mentioned And then stew and I have done work showing that weight turns on synthesis K-teen attenuase degradation Bottom line is we replicated Data in older adults these were all done in older adult men Which was one of the criticisms as it worked in in women And we showed identical improvement in function better muscle You know stew for also showed lower triglystides and if you look at the area curve of the Who goes tolerance test and fasting blood glucose it was better when they took the muscle five versus collagen We recently have data from K-lid degrees at University Waterloo completely independent third-party study RCT and men and women And they did training both endurance and resistance. So exactly what we've always been promoting and the folks took the muscle five Plus they also took a mitochondrial enhancers called trim seven versus the collagen and as we I'm showing other studies There was a significant production and body fat and an increase in lean body mass It was dramatically better in both directions for those that the combination versus collagen Now what's important many people are interested in ozepic great drug. We think it's got a great role in diabetes and no obesity as well The known side effect of course is people lose lean long mass and the Neat-jerk reaction is just eat more protein and you find but our data now a few like old trials To completely dependent of our company Clearly showing that it more protein is contextual and I think going to mother nature protein plus the creatine Really seems to enhance the benefits versus a lower quality protein such as collagen We didn't go gains different plan proteins and maybe mixing together might work But the creatine we think is very important based on our work and others Yeah, so that's what's also interesting here is You know, we think a lot of food in terms of the food there's there's a matrix in food. There's multiple properties coming together and there's synergy And I think that you can part of part of what you're seeing in in your research Well, how much of a part of that is is the synergy of the five elements and maybe maybe just walk through what the five elements are in muscle five Yeah, so as I mentioned before we put forth a concept in 2001 which again is my love for evolutionary biology And that is that you know, we didn't eat just one food We had a mixture of foods and mixture things together and mother nature's breast milk is very different So human breast milk is very different than cow so through an evolutionary perspective Identifying and mimicking what mother nature does I think is always your best at and so that's what we did with the muscle five So that was the ratio the average women's breast milk we put into this ratio. It's completely lactose free of course And you know, that's very important for people like me who are lactose intolerant then the creatine we and others as I mentioned have done so many studies on creatine And traditionally humans evolve eating more creatine We tended to eat more meat depending on you know evolutionary where you live but most Societies had more meat in their diet and the only real source of creatine in our diet is meat And so if you're a vegan you have zero creatine coming into your body and your liver Just can't make enough to keep up which then leads to deficiencies in the brain muscle and other tissues If we look at breast milk it has creatine in it So that's one of the reasons we put it in and we've studied creatine on a zone and so we added that and of course Many Canadians are vitamin D insufficient 15% of our patients have levels less than 25 nanomoles per liter which is in the rickets range and as a neuromuscular doctor I see patients coming in for weakness and query muscular dystrophy and all they are is in the rickets range for vitamin D You give them vitamin D and they feel great. So vitamin D critically important and also everyone knows it's very important for bone health and calcium There've been studies that just increasing your calcium intake alone can be advantageous a slight reduction in body fat, but also of course helpful for bone But importantly If you just take a calcium supplement there is some concern that it comes into the system too quickly and it can contribute to aphorosclerosis but again with a matrix like muscle five which is very much like like milk It's coming in slowly because the casing sort of clots in your stomach and then you get a slower rise of all of these things So we're really trying to mimic a lot of the benefits of even breast milk And it seems to be certainly dramatically better than collagen and some studies have actually shown collagen superior to weight protein So you know, we think this matrix is probably the ideal combination So protein quality is is obviously important and and and I think to be fair I think a lot of us don't really think collagen is a very good protein. So the comparator against collagen You know You said what what do you think for I'm thinking of her plant or plant-based folks who you know maybe looking at like you know What about pumpkin seed or you know what about you know pea protein or hemp Do you think Do you think there's a difference there between the kind of the the way casey in combination and those Yeah, I mean, I think there's a whole A lot to impact there the collagen was chosen first by stew and so we just continued because a huge company started Claiming this is great for sarco Aging and muscle and collagen peptides when you go to the stores all the rage and it's you know one of the top-selling products And it's extremely expensive So that was part of the reason why we used collagen polypeptides there were there is a randomized trial again It was sponsored by their company again all our stuff has been third party validated And it showed that it was superior to way protein, which you know, I still not sure that I believe that Now yes, you can add different proteins together to To come up with the complementary proteins to sort of match the amino acid composition of Of milk for example A single plant-based protein will never give you the full complement. It just doesn't it doesn't give you the full repertoire of essential amino acids But yes, you know You can combine a variety of different ones together to come up with something that's similar. Has it been shown head to head against our concept of humanized milk ratio? No. Do I believe that it could possibly be as good? No. Because we evolved. Mother Nature is pretty smart for, you know, 220,000 years with 60% way, 40% casing. Probably there was a reason why we did that and why reptiles and birds chose egg whites. And they do seem to have the highest biological value. Now I would say, you know, and we're likely going to come out with a combination of different plant proteins for those who would prefer not to have a milk isolate. But I think the other components are pretty important and that is to have the creatine in there, the calcium and vitamin D. Now, we are doing some other research to try and look at the different combinations because I do feel that a properly designed plant protein plus the creatine vitamin D. So muscle five with that combination. But the way in which mother's milk is not just one protein, it's not way it's not capable. I think the same thing is true of plants. And we don't usually just eat one plant as we're grazing. And that's the beauty of evolutionary biology is that it tells us what is likely to be the thing to work. And every time we follow Mother Nature in our research, it usually turns out to work. Yeah, and it is the pit, you know, so one of the pitfalls of kind of the reductionist scientific method is sometimes we lose the forest for the trees, right? And so what I love about your work is the scientific underpinning of it and the rigor behind it. And just even kind of the way you describe how you think about this. One of the things that was intriguing kind of what I was going through this was just the the the antibiotic improvements that we're seeing with people. It actually quite like it blew me away. And then even kind of antibiotic improvements without training. So I almost don't want to say that speak because you know, as we said kind of all the way through this, you know, we want to get people to exercise. And it seems to be that this, you know, this combination has an effect even even in the absence of training. Yeah, you know, I think in those who are compromised like muscular dystrophy or an older adult, you know, there is some benefit. I mean, it's small compared to the benefit that we see when you add exercise on top of it. And but, you know, there is some benefit there. I think what blew me away more is I'm such a fan of exercise. I thought, look, the body is going to always respond to exercise. And you'll get these amazing benefits and nutrition is maybe an extra 20% on top of it. But you know, the work that stood in the work that we did. And again, our stuff was all data locked. Third party held the code still. The study was done. Anyone who wants to get a copy of our Excel sheets from an and a third party and Michaela DeBries's work more recently and then and women completely, you know, without us involved. So a third party validated. It was striking. The improvements in muscle strength and muscle mass that we're seeing in those you took the muscle five versus the collagen. So the collagen, they're still exercising. They're still eating mixed protein up to one gram per kilo per day. Which is just on top of it. So it's not just pure collagen is right. Right. Right. It's diet plus collagen and almost no improvement in function, no improvement strength. So essentially people are training their face up and completely wasting their time in terms of functional benefit. And there was essentially no fat loss whatsoever. But in Michaela's data, the fat loss is quite dramatic. Now of course, they also had our mitochondrial enhancer, the trim seven as part of it. But in the anabolic resistance paper that we just put out where we had older adult end to adopathy or were overweight when they trained on the muscle five and the omega three versus placebo, they had increases in function. They had increases in muscle mass, decreases in body fat, but importantly, their functional capacity went up. So going up a flight of stairs, getting out of a chair was all better. And actually in spite of training for three months on top of a mixed diet with the 40 extra grams of the collagen, there was no improvement in function. In fact, they actually gained a little bit of body fat. We've went up a tiny bit, but not nearly as much as with the muscle five and the omega three product. But the stair climb got worse. So what a waste of time. And yet you go to the mall, a tiny little thing of collagen will cost as much or more than the large tub of the muscle five. And it's being promoted as this incredible thing for sarcopenia. It's called gelatine. If people go on the website, you can take a look at how it's being marketed for aging. Yet these folks trained, beautiful training, they even trained a little bit more when they were on the collagen and still had fast. Still a good effect. Yeah. Well, I think this conversation has been absolutely fabulous. And I think there is a fall-up conversation because I'd love to talk to you about your term seven product. Have that idea of can you enhance mitochondrial function? I think it deserves kind of its own conversation. But I think in this conversation, we certainly learned a lot around mitochondria. We learned a ton around it, you know, antibiotic resistance and how to combat antibiotic resistance. And kind of the intriguing research around your product, muscle five product. And we will be sharing kind of with the LifestyleRx patients a discount code for that. So LifestyleRx doesn't make any money off of this. But it is something that your company is offering to the LifestyleRx patients, mainly as kind of a good will gesture to have them try this and see if this is something that they start to see the results of combining their exercise plus this type of muscle support. Well, thanks. We appreciate the opportunity to talk. It's always lovely to talk science. And just for the audience, I just would point out there's so much misinformation out there when people say that something is clinically proven. Take a look at a site called PubMed. That's where all of the pure reviewed research is published. Number one, make sure that what they're saying, the product actually has published research and look for randomized clinical trials. And we get deep into the weeds, we call third party blinding so that nobody knows what they're on. The data is locks and nobody can cook the books for lack of a better term. And then finally in Canada, look for what's called an NPN number on the bottom. That gives you some degree of credibility. It doesn't mean that what's in there has been proven in a clinical trial, but at least that's one step that you know that what's on the label is, in fact, in the product that you're buying. Certainly, we have to get our stuff tested, our expiry date has to prove that we outflow within 10% of the label claim on it. So those are important things for Canadians to be aware of. Yeah, and I think it's really important to emphasize that the category of research that goes has gone into this is world-cloth, right? And so not only, you know, from the basis of being published, but actually the credentials of you and your colleagues around this really, you know, this is world-class. And I think that, you know, the other thing I think it's so important to understand is how you came about this. It's not just, you know, you're not somebody who just said, "Hey, I want to sell supplements tomorrow." And you know, it comes from the background of research. It comes from kind of your work with patients with mitochondrial dysfunction from a genetic perspective. And then it's been proven in the laboratory, you know, and then finally in these randomized control trials. So I have to say, you know, when I, you know, dove down into this research, it frankly blew me away. And I thought I knew a lot about this. And I think that the synergistic combination that you have is really, really interesting. And I also kind of look forward to seeing kind of where you go kind of with other product formulations and so on and so forth. We definitely see a role for it as I said kind of in our group. It's hard to get that protein. And you know, I'll sometimes joke, there's not a single 90-year-old I've met that ever wishes they had less muscle. And I certainly would say kind of in our program, it's, you know, muscle is this phenomenal buffer in terms of metabolic effects on your liver and on your pancreas. And so anything we can do to, you know, have better muscle function is going to, you know, benefit from a type 2 diabetes standpoint from a metabolic health standpoint. But I think probably even most importantly, just from how you feel and the energy that you have during the day. So Mark, this was a really good conversation. This might be our longest podcast. We generally keep some of it shorter. And I was intrigued and I'm going to book you from all of the fuel and dullage me on that. My pleasure. It's been in delight. I always like talking about metabolic health, patients and optimal nutrition. Thanks so much. Thanks Mark. Thanks. Bye bye. All right. Thanks so much for listening to the path the podcast from my style, Rex. We do hope you enjoyed today's episode. If you know if anyone you think would benefit. to fit from this episode, please share the link with them from wherever you're watching. And if you have a question, you'd like to answer on a future question and answer episode. You can use the link in the description to record a video question, or you can always leave a comment in the community or anywhere else you're watching this podcast. And we look at all those and try and answer them. So thank you so much for watching, and we'll see you again next week. Thanks, Dan. (upbeat music) (upbeat music) (upbeat music)