Why Muscle, Our Neglected Organ, Is The Key To Healthy Aging - Transcript

Dr. Stuart Phillips (00:00): No cell really ever "goes to sleep." Even if we go to sleep, the cells are continuously regenerating themselves and renewing themselves, and that's a function of mitochondria. Dr. Mark Hyman (00:14): Welcome to The Doctor's Farmacy. I'm Dr. Mark Hyman. And that's Farmacy with an F-A-R-M-A-C-Y, a place for conversations that matter. And if you care about your muscle mass, if you care about healthy aging, if you care about finding out if you can extend your lifespan and your healthspan, then you should listen to this podcast because it's with two extraordinary scientists who are at the cutting edge of research on aging and muscle and health. Dr. Chris Rinsch, who is the co-founder and CEO at Amazentis, which is a extraordinary new company. It's like a biotech company, but for nutraceuticals. He oversees their operations in Switzerland, and he's been working for two decades innovating in life sciences arena. Dr. Mark Hyman (00:56): He founded Amazentis in 2007, and he's worked in various industries. He's published in Nature Medicine, Gene Therapy, and has really been focusing on an incredible compound that we're going to talk about today called urolithin A, which is all about energy. And if you want more energy, and if you need more energy, you should listen to this podcast because it's all about mitochondrial health, and how we can use various compounds that are found in plants to upregulate our biology. He is really doing some cutting edge research on this incredible product that we're going to talk a little bit about. Dr. Mark Hyman (01:31): Also, we've got Stuart Phillips. We've got a doubleheader today. He's a professor in the Department of Kinesiology and a member of the School of Medicine at McMaster University, where I tried to go to medical school, but they wouldn't let me in. I went to the University of Ottawa instead. He's authored more than 220 original research papers, 90 reviews. He's a five time nominee and three time recipient of the McMaster Student Union's Outstanding Teacher Award, which is a great accolade because I think people really need to learn, and it's hard to get great teachers, and being a great teacher is a great thing. He's also on the scientific advisory board of Amazentis talking about muscle, health and aging. So welcome, gentlemen. Dr. Stuart Phillips (02:12): Pleasure to be here, Mark. Thanks for having us. Dr. Mark Hyman (02:14): Okay, great. So let's talk about aging and longevity, because we have learned a lot about this in the last few decades, especially when it comes to not just living longer but living better. And so the goal as we age is not just to add years to our life, but life to our years, and live as vibrantly and energetically as possible for as long as possible, or as I like to say, to die young as late as possible. So how do we do that? Dr. Stuart Phillips (02:41): I think you hit on it in the introduction. It's not just about longevity, but it's about healthspan, and so it's the quality of the years that you spend. I think when you pull back and look at the main theories of aging, one of the things that Amazentis has really achieved in is being able to influence mitochondrial function. And so the tissue that we're interested in, which is skeletal muscle, we think that's pivotal not only for locomotion but metabolic health as you age. And definitely keeping your mitochondria inside that tissue as active and as long as you can is a key to not only long life but better life as well, better quality of life and better healthspan. Dr. Mark Hyman (03:30): Maybe you said a couple of important things there that I think we should loop back to. One is mitochondria, because I don't know if everybody knows what that is, and why that's so important. How is it related to muscle? And why is muscle related to metabolic health? And to add on an extra question, why is the muscle such a neglected organ? Because it seems to be the key to aging, and we don't really talk about it. Dr. Stuart Phillips (03:54): Yeah, it's interesting. The answer to the first question, mitochondria are the sub portions of a cell that generate energy, and we need to have those operating at their full function. And when they do, our muscle becomes a great big sink, if you like, for controlling blood sugar, blood glucose, so it protects us against things like the development of type 2 diabetes. It also is a major contributor to burning energy. And so I think the main reason why when you talk about, why is skeletal muscle neglected? To come back to your radical school example, there's really not a subspecialty in skeletal muscle. It's a little part of neurology for some people, but it's not like your muscle breaks or fractures like a bone. There are no specific issues until you get into neuromuscular or neurometabolic diseases, and then really, it's a neurologist issue. Dr. Stuart Phillips (04:55): A lot of neurologists focused on the central part of the system, and that's the brain. I Just think there's only a few people that make it their business to study skeletal muscle, to be honest. Dr. Mark Hyman (05:06): It's so important, and I think people don't realize that it's not just muscle for locomotion, but it's a metabolic organ, and it's what degrades as we age. And when your muscle function and your muscle mass declines, not only are you more likely to fall and injure yourself and have trouble with just your daily activities of life as you age, but your metabolic health, your hormonal function, your levels of inflammation, your ability to regulate your blood sugar, your testosterone, all are affected by the quality of your muscle. And what happens, for most people who are listening to me and not realize this, you could be 65 and the same weight that you were when you were 25, but your muscle can be completely different. Dr. Mark Hyman (05:50): You can look the same on the outside, but on the inside, your muscle has become marbleized bad, essentially turned into a rib eye from a filet mignon when you were 25. And that is enormous consequences for aging. Every single thing that we think of in terms of aging, heart disease, cancer, diabetes, dementia, in some ways, they start in the muscle and the muscle function because without optimal muscle function, we can't regulate our metabolism, and we can't regulate inflammation, we can't regulate our hormones. And that all leads to these abnormal cholesterol levels, abnormal blood sugar levels, abnormal levels of inflammation, low hormone levels that we associate with aging, but often it really starts with the muscles. Dr. Mark Hyman (06:31): It's one of the most neglected and important organs, and it starts to go downhill pretty quick when we're in our 30s and 40s and it gets older. As we get older, we lose strength and muscle mass. But what I think is a little scary is that while you can improve muscle mass at any age, recent studies have shown that it may not actually be able to be fully restored, so why should we focus on prevention? And what can we do to help improve our muscle mass and function, especially in the mitochondria as we age? Dr. Stuart Phillips (07:08): I think you hit on a key issue about when muscle mass begins to decline, and when the function of our muscles begin to really go sideways. A lot of people debate when that starts. I think as your example goes, we can find individuals that we pluck off the street, who are in their 60s and 70s, who metabolically look like they're in their 30s, and that's pretty much because they're physically active. They keep themselves busy. They probably exercise on a regular basis. But similarly, we can find individuals in their 30s and 40s who look pretty much like they're in their 60s and 70s because they spend a lot of time sitting behind a desk, they don't eat particularly well, they're not that physically active. And really, that's a direct reflection of the quality, and maybe to some degree, the quantity of their muscle. Dr. Stuart Phillips (07:58): I don't know whether your listeners are familiar, but probably if they've heard the term sarcopenia before, that's the age-related loss of muscle mass and muscle function, that I think for a long time geriatrician said that's just a normal part of aging. One of the things that we like to push is that it's not and it doesn't have to be, and that really, you should try and be as physically active, which is probably one of the key things, have a good diet. And then there's Chris's company, as Amazentis has found out, you can probably do a few nutraceutical tricks, if you like, and prop up that mitochondria inside the muscle, which is another just local indicator function of that tissue. Dr. Mark Hyman (08:43): Yeah. It's really key too, that it's not just the muscle that there is mitochondria. There's many, many mitochondria in heart and brain tissue and every single cell of your body, because essentially, it's the engine that runs every cell. Some cells, like the brain cells, have literally tens of thousands of these mitochondria, other cells have less, but heart and brain have the most, and that's when they tend to break down as we age. I think most people don't understand anything about the mitochondria. They don't understand that they can actually measure its function in different ways, that doctors can. Doctors don't know much about mitochondria. Dr. Mark Hyman (09:24): We learned this thing in medical school in first year called the Krebs cycle in biochemistry, and we quickly forgot it as soon as we learned it, which is the only time we really paid much attention to mitochondria. And yet, it is central to every age-related disease and the aging process itself. In fact, it's one of the most underappreciated aspects of our health, which is why we're having this conversation. I think people need to begin to understand how important their mitochondria is. A lot of the healthy aging strategies, low sugar diet, more good fats, quality protein, these are all about ultimately helping our mitochondria, and exercise also and strength training are critical for building muscle and helping mitochondria. Dr. Mark Hyman (10:06): The role of mitochondria is pretty interesting in aging, and there's a lot of age-related phenomena that happen that can be reversed by improving the function, the number of the mitochondria. And this is some of the work that's being done, for example, around NAD which is another healthy aging nutraceutical. But a lot of the intermittent fasting, time restricted eating, the low carbohydrate diets, ketogenic diets, these are things that have been experimented with, all impact the mitochondria and affect their function. And so I think, can you talk about how the mitochondria affects us in terms of the aging process, and why it's so important to focus on them? Dr. Stuart Phillips (10:53): Yes. I think one of the key things, as you said, is that the metabolic processes inside cells require energy non stop, and it doesn't have to be a muscle cell. Your cardiac cells, your heart is working all the time, digestive tissue, brain tissue, it's always metabolically active. There's always something going on, so that means that mitochondria are turning out the currency, the energy that we need to be able to function. So no cell really ever "goes to sleep." Even if we go to sleep, the cells are continuously regenerating themselves and renewing themselves, and that's a function of mitochondria. Once those mitochondria begin to function suboptimally, then you begin to see tissues begin to break down, not just muscle, but as you said, brain tissue, cardiac tissue. It could even be adipose tissue. Dr. Stuart Phillips (11:42): And all of these things really begin to tie together to slow cells down. They don't function as well, and they really can't then talk to each other. So what we call organ crosstalk between muscle and fat and liver and in parts of our brain, it really begins to break down. And so as we've said, it's essential theory of aging, which is to say that once our mitochondria begin to decline in function, then things are really going to go poorly. Exercise is one way to prop it up, but not everybody can exercise, or not everybody exercises to the degree that they want. And so these adjuncts that we're now seeing, you mentioned NAD, urolithin A for example, are all of these, I think, pretty cool compounds that once we just thought, "Not a big deal," but we're now seeing are pretty important. Dr. Mark Hyman (12:37): Absolutely true. I think the phenomena around mitochondria in the research is pretty exciting, and there's all these genes that regulate aging that are in the mitochondria, like FOXO, DAF-2, they're sort of two ends. These are really important regulators, and they're regulated by diet but they're also regulated by these various compounds, these phytochemicals in plants, which we're going to talk about in a minute, because this is the work that Amazentis is doing. This is the work that they're looking at in terms of compounds that come from plant foods that can actually regulate these biological functions in our body. You can't, obviously, just take a nutraceutical and eat crappy and not exercise, it's all a package deal. But it really can accelerate the muscle improvement and function. We're going to talk about that. Dr. Mark Hyman (13:23): But one of the things that's exciting, and Chris, I want to ask you about this, because we have been hearing a lot about this phenomenon called autophagy, which is this idea that we can clean up and recycle old cells and old proteins and clean up the system to repair, rejuvenate and extend life and improve health. And that's why people are doing intermittent fasting or time restricted eating or ketogenic diets, for example. These all improve this phenomenon called autophagy, which literally means eating yourself. But there's another thing that happens in the body called mitophagy, which is an incredible breakthrough in understanding longevity and longevity science, which is understanding this phenomenon of mitophagy. So what is mitophagy? And how does it help to address the phenomenon of aging and improve our overall health and energy production? Dr. Chris Rinsch (14:20): Mark, thanks for having me today. Mitophagy is really a way of renewing our mitochondria, particularly when they're damaged. So as you get older and as you're more sedentary, your mitochondria get damaged as they work, as they're producing energy, and what you have inside of each of your cells is a process of renewing your mitochondria. Under this umbrella of autophagy, as you were mentioning, we have mitophagy and the self eating of mitochondria. So basically, it takes care of recycling mitochondria as they get damaged, so that the mitochondrial pool is maintained very robust, and you have basically cells that are more bio energetically active than they would be otherwise. Dr. Mark Hyman (15:14): That's incredible. One of the things that I find fascinating is this whole idea that I've talked about in some of my books called symbiotic phytoadaptation, and it's a big word I made up myself. But what it means, and this is just my theory, that we've evolved in conjunction with the plant world and the foods we eat to regulate our biological functions. And that there are 25,000 plus different phytochemicals in plant foods that regulate every single biological function, from our hormones to our immune system, to our microbiome, to our mitochondria, to pretty much everything that happens in our body. We really have only begun to appreciate these recently. Dr. Mark Hyman (16:04): In fact, Rockefeller Foundation has funded a study which they're calling the periodic table of phytochemicals, which is mapping these all out, identifying their function as much as we know, and talking about how do we actually use these in the promotion of health. And so in everything, there's protein that we eat, there's protein fat, carbohydrate, fiber, and vitamins, minerals, etc, but there's this other class of compounds that have not been thought to be essential, and I call these the phytochemicals. And that's why I think we actually need these to stay healthy. You're not going to get a deficiency disease, but you might get a chronic disease if you don't have these things. That's my theory, anyway. Dr. Mark Hyman (16:45): I am so excited by the work that Amazentis is doing because it's really rigorous science that has been published in some of the top medical journals in the world. It's looking at some of these compounds in plant foods that can actually regulate key biological functions, especially the mitochondrial function. There's this compound that you've studied and that you basically figured out how to actually extract and make, which is called urolithin A. And just for those who are listening, this is what's so interesting about biology, you eat a pomegranate, which has these ellagitannins in it, which is one of these phytochemicals. So you eat a pomegranate, and that chemical interacts with your microbiome, and then if you have a healthy microbiome, it might produce a beneficial chemical called urolithin A. But if you don't, it might not. Dr. Mark Hyman (17:40): What you've done is discovered that this molecule is so powerful in regulating mitochondrial function, and you've really done years and years of research to bring it to market, so tell us about urolithin A, how does it work? How does it affect mitochondrial function? And how did you figure this out? Because there's a million plants out there and a million chemicals, so this is like a needle in a haystack, right? Dr. Chris Rinsch (18:07): Good question, Mark. It all started with, for us, with the pomegranate. We were looking at the pomegranate and thinking about what type of health benefits it could bring. We started looking at the compounds inside of the pomegranate, and this led to us understanding more about compounds like ellagitannins, which are a big family of compounds that are quite large inside of the pomegranate. And upon studying them, we understood that they were transformed, as you were mentioning before, into urolithin, in fact, into a range of urolithins which are metabolites through the gut microflora processing. It was originally thought that this is just part of the processing and the digestion of the pomegranate, and so wasn't sure, were these urolithins actually doing anything in the body? Dr. Chris Rinsch (18:57): We started looking at them, and it was at this point when we were looking at urolithin A that we saw lo and behold that it was acting on mitochondria and improving mitochondrial function. It's one of these processes where, as you say, a needle in a haystack, but it was through a very systematic dissection, if you will, of the compounds in the pomegranate and following their journey as we consumed the pomegranate. Dr. Mark Hyman (19:28): You were like, "Oh, let's study the pomegranate, see what's in there." It wasn't like you studied every plant chemical and found out that there was this one that regulated mitochondria? Dr. Chris Rinsch (19:37): No. We were really focused on the pomegranate at the time, because there had been some general research on the pomegranate and its health benefits, and so we thought, "Let's take a deeper dive and try and understand what's there." I think, as you were saying before, what's really emerged from this is the importance of not only the foods you eat but the importance of the microbiome and how they work together synergistically to create compounds and to extract the health benefits from the food that we eat. It was understanding this and understanding also that very few people can actually perform this conversion. In fact, it's been estimated, and we've done some of our own studies that have shown somewhere between 30 and 40% of the population can actually convert these compounds, these precursor compounds found in the pomegranate into urolithin A, and that's even at various levels. Dr. Chris Rinsch (20:40): What it makes sense when we studied all this was we don't need to give more pomegranates to people, but we actually need to give urolithin A to people. And if we do it in the right way, if we dose it right, if we deliver it in a very precise manner, we can then get the health benefits that we are targeting and that we've shown that work. Dr. Mark Hyman (21:01): That's interesting. I've been using pomegranate powder and pomegranate concentrate in smoothies for a long time because of the benefits of pomegranate. And it wasn't around particularly the mitochondrial function, it was around the microbiome effects. One of the things we know, for example, is that there's a microbe in the gut called Akkermansia which is muciniphila, which essentially creates a coating and a biofilm on the gut that protects it. It regulates the immune system. It's necessary to fight cancer. It's necessary to regulate your metabolism. It's related to autoimmune diseases, and it's very low in many people. This bug loves pomegranate, and so if you feed it pomegranate, it grows and it can help cure all kinds of issues. Dr. Mark Hyman (21:44): Hey, everybody, it's Dr. Hyman. Thanks for tuning in to the Doctor's Farmacy. I hope you're loving this podcast. It's one of my favorite things to do, and introduce to you all the experts that I know and I love, and that I've learned so much from. I want to tell you about something else I'm doing which is called Mark's Picks. It's my weekly newsletter, and in it, I share my favorite stuff, from foods to supplements to gadgets to tools, to enhance your health. It's all the cool stuff that I use and that my team uses to optimize and enhance our health. I'd love you to sign up for the weekly newsletter. I'll only send it to you once a week on Fridays, nothing else, I promise. All you have to do is go to drhyman.com/picks to sign up, that's drhyman.com/picks, P-I-C-K-S, and sign up for the newsletter, and I'll share with you my favorite stuff that I use to enhance my health and get healthier and better and live younger longer. Now back to this week's episode. Dr. Mark Hyman (22:40): What really is fascinating to me is the story of the microbiome in the food we eat. Could you dive a little bit more into how the microbiome interacts with these compounds that we eat, and then what happens to those compounds? How do they then get in our body and interact with everything that's going on? Because I don't think people really understand that. I think it's a very new science, and I think it's really an important thing. Because when you're eating plant foods, it's not just for the antioxidants and the benefits that you get from the fiber and vitamins and minerals, there's other things that's going on that has to do with how it interacts with your microbiome. And that is the future, so talk to us about that. Dr. Chris Rinsch (23:18): Sure. As I was mentioning before about the ellagitannins that are found in pomegranates, they're also found in a number of other foods that we eat. We find them in raspberries, and we find them in walnuts and blackberries. What happens is these compounds are then transformed after you consume them. In the stomach, they're hydrolyzed into ellagic acid, and ellagic acid is then transformed by various gut microflora. So the actual identity of the bacteria have not yet been found, but what we see is that there's a range of different metabolites, urolithin A being the most predominant one. And these are then taken up into the body, into the bloodstream, and then they go to the cells. In our first clinical study, we found that we could identify urolithin A actually in the muscle tissue itself, and [crosstalk 00:24:23]- Dr. Mark Hyman (24:23): Wow. Dr. Chris Rinsch (24:24): So it actually gets right into the muscle cells. We've shown through biopsies of the muscle tissue that we impact the mitochondria and the gene expression level of mitochondria in the muscle tissue itself. Dr. Mark Hyman (24:41): That's incredible. So how does it work to cause this phenomenon of mitophagy, this sort of self-cleaning service? Almost like a self-cleaning oven, right? How does it work to induce this self-cleaning process of your mitochondria? Dr. Chris Rinsch (24:57): Well, with urolithin A in particular, it's taken into the cells and what it does is we've shown that it can stimulate this process of mitophagy. It's not known exactly at what point it acts to stimulate the mitophagy, but it increases the clearance of the damaged mitochondria. And consequently, we see a renewing of the mitochondrial pool inside of the cells, and so you have a much more bioenergetically favorable environment inside the cells, and the cells consequently function much better. Dr. Mark Hyman (25:39): What you're basically saying is that when you have this pomegranate compound, that it basically should be made by your microbiome, but most of us don't. And you take it as a supplement, that it cleans up the mitochondria and helps to improve the energy production of your cells, why is that important? Why should we care? Dr. Chris Rinsch (25:59): Well, I think particularly, as Stuart was mentioning earlier, as you get older, the activity in our muscle, basically we're ... The ability to clear the damaged mitochondria decreases with age, and so this causes a decline in the energy levels inside of our cells and in our muscle tissue. And so then we slow down as we get older and the muscle stops functioning as optimally, our endurance levels drop. This is part of a process in aging where mobility declines. And so what we're doing by stimulating mitophagy is to increase that energy level inside of our cells and basically making our muscles function at their bioenergetically optimal state no matter how much muscle tissue you have. Dr. Chris Rinsch (26:59): It's really a new approach as opposed to what people have been doing in the past, which has been administering more protein to try and bulk up on muscle tissue. We're all about trying to make our muscle tissue the most functional as possible as you get older. Dr. Mark Hyman (27:18): It accelerates the benefits of exercise, right? Dr. Chris Rinsch (27:22): Yes. And as you were saying before, it's not a substitute for exercise. Basically, you want to keep this in your diet as part of your healthy routine, if you will. So you want your exercise, you want to have your right dietary supplements, and you want to eat a very balanced meal, so it's all part of combining the three. Dr. Mark Hyman (27:48): It's like a way to upgrade your biology a little bit, right? It's so important because as we age, it's not just our muscle that's a big problem, it's the mitochondria in our brain and our heart that decline. And that leads to poor cardiac function and poor brain function. A lot of the therapies that we talk about for Alzheimer's or Parkinson's, these are mitochondrial therapies that have been studied, so pretty exciting. What's really exciting is that you guys have been this biotech, nutraceutical company, which is a little bit of an anomaly and very brave, I would say, because I think it's a very daunting prospect to do a decade plus of research before you even come to market with the product. But you've come to market with this product called Mitopure, which is the concentrated bioactive component with urolithin A. Dr. Mark Hyman (28:41): Tell us about the development of Mitopure and why it's so important for our cellular health and our strength as we age. Dr. Chris Rinsch (28:48): Thanks. Mitopure is our proprietary urolithin A that we've developed. And what we've done with Mitopure is bring it to market in a product actually. It's through a brand called Timeline Nutrition. The idea is that we put it into powders format that you can add into various types of foods that you want to eat, particularly at breakfast. We think breakfast is a great time for everybody who's trying to optimize their health with different types of supplements, so putting it into yogurt, mixing it in smoothies, even in your breakfast cereal, and- Dr. Mark Hyman (29:30): I put it in my smoothie every morning. Dr. Chris Rinsch (29:33): Tastes great, doesn't it? Dr. Mark Hyman (29:35): Yeah. I put a lot of stuff in there. It doesn't have a strong flavor or taste. It's a little pomegranaty, but it mixes with everything. Dr. Chris Rinsch (29:42): Yeah. We're excited about bringing this to market. We just launched over the summer, and now as we continue, we're going to be developing other types of products that contain the Mitopure ingredient inside of it. So it's a very exciting time for us. Dr. Mark Hyman (30:04): I don't know if this is public knowledge, but there's big food companies that are interested in this because they see it as a way of enhancing and upregulating the quality of their food products, right? Dr. Chris Rinsch (30:13): Yes, of course. And in fact, we formed a strategic alliance with Nestle Health Science here. They're a great partner and they're putting Mitopure into a number of their products. They've even launched one product recently, in fact, with that. Dr. Mark Hyman (30:32): That's amazing. So how does it revitalize mitochondria in the sense of the [inaudible 00:30:36], because this isn't just basically, "Oh, this is a cool thing, let's stick it in a pill or a powder." You've actually done the hard science on this. What do the scientific studies shown about how it affects mitochondria? Dr. Chris Rinsch (30:50): Well, it all started with, first, a very strong collaboration with the scientists here at the University of the EPFL, in particular, Professor Johan Auwerx, who's a guru when it comes to mitochondrial function. It was in his lab that they really started doing the deep dive on studying the effects on mitochondria, and we worked together on that. They started out by looking at the effect on worms, on these C. elegans, and they started to show that they were living 40% longer. It was after looking at these worms living longer, moving more, that we started to explore further and understand the mechanism of action. And that's how we learned that we were stimulating mitophagy, and we went through the whole process of showing that this mechanism of action was conserved not only in worms, but also in mammals. Dr. Chris Rinsch (31:56): We moved into mice, and then we moved into humans. And so we've conducted a couple of clinical studies here, and we published one of our clinical studies in the journal, Nature Metabolism. In that study, we showed that administering urolithin A in Mitopure for a period of four weeks, we were able to see an impact on key biomarkers linked to improved mitochondrial function. As I was speaking about earlier, biopsies in the leg muscle, we were able to show that we were increasing the gene expression of mitochondria genes. And then when looking at the plasma, we were able to show that there was a decrease in certain biomarkers linked to mitochondrial function, acylcarnitines. And so as the acylcarnitine level drops, this is an indicator of improved mitochondrial function. Dr. Chris Rinsch (32:57): And also, if you're looking at the plasma, to your point earlier about mitochondria being everywhere, this is also a sign that you're having an effect on mitochondria not only at the level of the muscle but something that's more systemic in general. Dr. Mark Hyman (33:14): That's incredible. That was a study with four weeks, but you also did clinical trials, a double blind randomized placebo controlled trial for healthy adults who are middle-aged. And in four months just consuming the Mitopure every day, they had a real improvement in muscle strength in their legs. Can you talk about that study and what you guys found? Dr. Chris Rinsch (33:35): Yeah. This is a very exciting study, and this was the follow-up study, which we haven't published yet. And in this study, we took a group of people who were middle-aged and overweight, as you mentioned, sedentary in lifestyle, and we provided them with Mitopure where it was taken daily for a period of four months. And there at the end, we looked at the evolution of the muscle strength, and we saw that we were able to improve leg muscle strength after a four month intervention, so that was very encouraging. And running parallels to the type of improvements that we saw in muscle strength in preclinical models as well. Dr. Mark Hyman (34:29): That's exciting. So how do they measure muscle strength? By how much weight they can lift? Or whether you can get up out of a chair sitting up? How do they measure that? Dr. Chris Rinsch (34:37): Well, they use a very specialized instrument that isolates one muscle in the leg, and so you contract your leg and you can measure the specific strength of a single muscle. And that way, you can be very precise in the way you assess the improvement of muscle strength. Dr. Mark Hyman (35:00): That's amazing. Will it improve athletic performance, do you think? Dr. Chris Rinsch (35:05): Well, we plan to run additional studies in athletes and to assess the impact on athletic performance, and this is something that we are getting ready to do this next year, so let's see, and we'll keep you informed. Dr. Mark Hyman (35:22): Okay. It also improves mitochondrial muscle function, but does it also help with muscle mass? If you're weightlifting, does it, for example, help you improve your muscle strength even more? Dr. Chris Rinsch (35:37): Well, I would say that it's not improving muscle mass, but the idea here is really to improve the cellular function, the bioenergetics of the cell. And so no matter how much mass you have, it will basically amplify the effect of the cell and the functioning of that cell. So if you do have more muscle mass, it should have an additive effect, if you will. More muscle mass, more cells will be impacted, and so they should function better. Dr. Mark Hyman (36:11): That's amazing. People will say, "Why can't I just drink some pomegranate juice? Why do I need to take this as an additional supplement, as an additional cost?" But you actually studied the comparison of Mitopure and drinking a glass of pomegranate juice every day, so what did that show? Dr. Chris Rinsch (36:28): Well, that was a very interesting study where we basically did a crossover study where we provided people either with an eight ounce glass of pomegranate juice or our 500 milligrams of Mitopure, and then we followed the evolution of the urolithin A levels in the blood of participants in this study. And what we saw over the first 24 hours, under the time points that we analyzed, was essentially a six fold higher level of urolithin A in the blood after taking Mitopure when compared to pomegranate juice. So essentially meaning that you would have to take six times more or- Dr. Mark Hyman (37:17): 48 ounces of pomegranate juice, you should have diabetes at the end of it. Dr. Chris Rinsch (37:22): Yes. At that rate, it is probably not the optimal approach, I would say. Dr. Mark Hyman (37:27): No. Is there anything else you want to share about the research you're doing, what's coming up, what you've seen clinically, maybe just some anecdotes of patients where people have used it, and what they noticed? What's the benefit and payoff of doing this? Dr. Chris Rinsch (37:42): Well, I would say this, one thing that's important to mention is this is not some type of miracle product, if you will, where you take it once and you see a sudden change and the effects on your muscles and on your cells. It's something that you'll need to take for a prolonged period of time, and that's why we're selling it for a period of four months to start with. We think that if you take it for a prolonged period of time, that you get more benefit from the actual product. When you go to the gym for a week, you don't improve your muscle function, although we all would like to. By doing it regularly and having an impact on your cells in a regular manner, you can slowly, basically, change the composition inside of your cells and improve the functioning in general at the organ level, at the whole skeletal muscle level. Dr. Mark Hyman (38:46): Have you had friends or people taking it or patients? And what do they report after taking it for four months? Dr. Chris Rinsch (38:53): Well, we have had people who we know are taking it, and they swear that their performance is improving, and they attribute it to that. We've had different people report different types of activities, but I would say, in general, for those people we know who are athletes, they've mentioned that they've had some improvement in performance, and other people have felt a general improvement in walking. Everyone has their own, let's say, antidote ... not antidote- Dr. Mark Hyman (39:36): Anecdote. Dr. Chris Rinsch (39:39): Anecdote or a story to tell about the improvement that they see. I mean, in particular, I think it's the energy that we need to think about because it's the fatigue that people have, and when they take the product, there has been a general feeling of an improvement in energy levels from a number of people that have been taking it. Dr. Mark Hyman (40:07): That's fantastic. I think energy is all we need more of. We're all overworked, overtired, and anything that's going to improve our energy is going to be helpful. Stuart, I'd love you to talk about the research you're doing around muscle health and function, and how we can boost mitochondrial function and muscle function as we age, because it is probably the single biggest ignored thing in medicine that I see is this phenomenon of sarcopenia, which is muscle loss. And every single age-related disease is a consequence of progressive metabolic poor health, which is really driven by this progressive muscle loss. And it's why at 59, I started weightlifting after resisting it for years. I do biking. I play tennis. I do some yoga. I felt okay, but I really doubled down on the strength training even though it's uncomfortable for me. I don't like it. Dr. Mark Hyman (41:02): Well, I'm learning to like it a bit more. I've been riding my bike through the fall in the colors and the wind, and just the feeling of being free, I could do that all day. Muscle work is harder, but it's so important. Why do we need to be so focused on this? And tell us about what we can do to optimize our muscle function and health as we age. Dr. Stuart Phillips (41:25): I think one of the important points towards Chris's urolithin story is that we don't have a drug right now that does anything for skeletal muscle in terms of it's broadly available both to men and women. I could say testosterone for men, but a large side effect profile. So things like urolithin really tell. They address a piece of the metabolic machinery that's hard to fix otherwise. Exercise, of course, is a key part of aging well and improving your healthspan. I agree that everybody can stand to be fit as they get older. Peak exercise capacity has been called by some people, and exercise physiologist are not alone in this, as saying it's a fifth vital sign. It crosses brain, heart, lung, muscle, some multiple physiological systems, and it's probably quite reflective of general overall health. Dr. Stuart Phillips (42:27): I don't know when it starts, but I would urge people to think about creating the image of their future selves. And at some point in your aging trajectory, whenever that is ... People say, "When does aging start?" I'm like, "Well, this year, it's about 56." That's a personal observation. But my point would be that as you get older, some of the things that you're going to have to do on a regular daily basis are going to involve strength, and you're going to want to be able to have the strength to do, hopefully, some things that you didn't really recognize. One of which, ultimately, the fully functional lift is getting off of a chair, so once we can't do that, we're in trouble. But it progresses gradually and it creeps up, so I applaud your effort at trying to stay stronger as you age. Dr. Stuart Phillips (43:20): Not that being fit isn't a bad goal, I think the combination of the two is best. Boil it all down, and it's all still about good mitochondrial function, funny enough. Dr. Mark Hyman (43:32): That's so true. What other things are people exploring around mitochondrial health? Because urolithin A is important, but it's only one component. What other things should people be thinking about? Dr. Stuart Phillips (43:42): Well, you mentioned NAD as a substrate, I think a lot of people have probably moved around in the antioxidant space. It was interesting to hear you talk about the plant and vegetable phytochemical matrix. I think that this is an area where you're going to begin to see a lot of action, and a lot of the things that we attributed as the benefit of consuming diets that are high in fruits and vegetables, if you would have said urolithin A a decade ago, people wouldn't have known what you were talking about, or nitrates for enhancing mitochondrial function, for example, that are attributable to something in the matrix and phytochemicals that we just don't understand. Put in the microbiome, and then you've got another layer of complexity on top of that, that again, I think we're beginning to peel back some of that, and how that interacts with our overall health. Dr. Stuart Phillips (44:43): It's going to become interesting. I think in the next five or 10 years, you're going to see an explosion of these types of compounds and how they affect cellular processes, to be honest. Dr. Mark Hyman (44:52): Yeah, absolutely. Well, thank you guys so much. This is an incredible conversation because it underscores something I've been talking about forever, which is metabolic health. And when I say metabolic health, I mean your ability to manage your basic biological functions in a healthful way. When you have poor metabolic health, you have high cholesterol, you have high blood pressure, you have high blood sugar, you have belly fat, you lose muscle, you get marbled muscle, which is not great. And that all has all these adverse consequences that we think of as aging, but they're actually abnormal aging. What you guys are saying is that we haven't had the science to understand how that happens, and what to do to intervene from what we eat, to how we exercise, to some of these nutraceutical compounds and phytochemicals that we can take advantage of to actually accelerate our repair and healing and function so that we can actually live better, healthier lives and have our healthspan equal our lifespan. Dr. Mark Hyman (45:48): Meaning we will live fully and healthy until the day we die, and then we'll drop dead, which is what we would all like. You don't want to be 60 and have 30 years of disability and dysfunction and live to 90, that's no fun. I think this is an exciting area of research. I applaud both of you for the work you're doing. I encourage people to check it out. Amazentis has launched this product line, which is pretty cool, Mitopure, which is scientifically validated. You can get it through Timeline Nutrition, and there's an exclusive offer for those listeners of the Doctor's Farmacy Podcast for a two-month plan for $200 for subscribers. It's, I think, probably half off, right? Isn't it almost half off? But it's a good deal. I encourage people to check it out and learn more about this company, because I think mitochondrial health is really important. Dr. Mark Hyman (46:34): I think it's important for us to stay focused on our muscle as we age, as well as our bellies. We don't want those to grow. As our bellies grow, our muscles shrink, so they're correlated. Thank you both for being on the podcast. It's been great to have you from Switzerland and Canada. It's great. With COVID, now we can have podcasts from all over the world. It's really awesome. It's one of the silver linings among very few, unfortunately. Dr. Mark Hyman (46:58): Thank you for listening to the Doctor's Farmacy Podcast. If you love this conversation, please share with your friends and family on social media, or leave a comment. We'd love to know about how you're taking care of your mitochondria. Subscribe wherever you get your podcasts. We'll see you next week on the Doctor's Farmacy.