 Quickly explain the importance to our listener of the mitochondria and its function. Sure. So mitochondria are, you know, everybody's heard that mitochondria, the powerhouse of the cell, and that's pretty much where all the knowledge starts. But mitochondria are sort of, you know, think of yourself, think of them as cell organelles that power everything you do from moving to thinking to sort of recovering from exercise. So they produce what is called this ATP, which is sort of the currency, the energy currency in our bodies. And think of mitochondria as the battery inside a Tesla car, for example, that has a certain capacity to keep driving the car. But after a while, you need to sort of, you know, give it more sort of, you know, feedback and you need to nurture it. And so that's how these mitochondria held is so key and mitochondria function is so important to especially metabolic organs such as muscles, skeletal muscle, cardiac muscle in the brain. Yeah. And as I've written about in most of my books, particularly the last two, our mitochondria in general are on death's door. They have taken a beating that is actually unimaginable from our Western diet, from our Western lifestyle, from our environment, environmental toxins, you name it. We have not been good caretakers of our mitochondria. Not at all. And you absolutely spot on right. There are two actually two great ways to boost your mitochondrial health and that's regular exercise and calorie restriction. But as you mentioned, we have not been kind to our own mitochondria by not paying attention to what we eat and how we move around. Now something that's probably not on everybody's radar, even though I think most people remember high school biology and seeing this mitochondria in a cell and it's the powerhouse of the cell. But there's an important relationship between our immune system and mitochondria. Can you elaborate on that? Yes, sure. There's a big, so there's a number of years back, the hallmarks of aging were described and these hallmarks of aging really all are deeply connected by logical pathways. So there's sort of the DNA repair mechanism slowed down. You have the epigenetic alterations. And now, of course, the mitochondria are the central pillar to all these hallmarks and connect them. And now you have this chronic inflammation. So as we age or as we have a more sedentary lifestyle, things like biomarkers like C-reactive protein, which is a marker of inflammation go up. And what we are seeing actually in a number of trials in older adults is that with declining mitochondrial health, there is this sort of both gut dysbiosis and chronic inflammation. And so the immune system, the immune cells have a mitochondria that basically power off and shut off as we age. And that's the link between immune cells and mitochondrial health. And I think one of the things that people particularly during COVID is immune function might be very useful. Plus, particularly in terms of cancer, we know that one of the theories, which is widely accepted that the reason cancer becomes so prevalent at the older we get is because our immune guardians against cancer cells, you're right, are underpowered or are not functioning the way they should be. Sure. And we recently published a fantastic paper in one of the highest ranking immune journals called Immunity. And we showed actually in this that in certain cancer models by improving mitochondrial health via, of course, the compound we'll talk about, urolatin A, you could actually lower the incidence in these models of cancer recurrence. And more importantly, what the thing we are seeing is even once you treat the cancer, so once you do the chemo radio sort of new adjuvant therapy, the immune system is basically zero, you know, in the recovery phase. And so how fast it comes back to sort of receive the immune system is the key determinant is mitochondrial health. Yeah, that, you know, it's interesting as a transplant surgeon. One of the things we learned early on was that the older our patient was who we did a transplant in, the much less immunosuppression we had to use. And in a way it was great, you know, oh, you're, you know, you're 75 years old, this is going to be great because we don't have to give you a lot of immunosuppression because you're so already immunosuppressed. And in a way that's actually very scary. So this function of mitochondria in our immune system clearly needs to be given some attention. All right. So speaking of aging, what, what new pillars of aging have we learned about in the last couple of years? Well, I think if you look at the hallmarks of aging, there is these nine hallmarks of aging that, you know, kind of link all the organelles of cell biology to the epigenetic alterations as I was mentioning. In the last, let's say decade or so, a lot of emphasis has come on this gut microbiome, this biosis, right? With aging, the gut microbiome starts to alter. And that leads to declining production of gut metabolites such as, you know, postbiotics, et cetera. And, and, and what happens is then because of this chronic inflammation, so the immune system we take upon that, and the mitochondrial health and the declining mitophagy. Now this is a term your listeners may or may not have heard. One of the new hallmarks of aging is declining mitophagy. What that means is basically is that the mitochondria are working over time as we age to deliver us the energy. But then a lot of them get corrupted and they get faulty. And the system that basically recycles this trash bin of poor mitochondria also slows down. And so how you can rev up and get all these bad faulty mitochondria packaged into garbage bin and then recycled so they can become healthy mitochondria is one of the, the new key pillars that is, is getting a lot of interest and excitement. All right. So as I mentioned before, you know, in the introduction, we've, we've known that pomegranates are pretty cool and that pomegranates have some very interesting polyphenols among eagallic acid. But it was, it was really work on certain gut bacteria can transform these polyphenols into urolithrinate. Tell me all about that compound. Why is this? Sure. Why is this such a miracle? Sure. What's it, what's it do? Yeah. So well, we've spent 15 years studying the pomegranates. So we started with the, with the whole fruit, you know, because much, you know, I was trained in medical school where nutrition was not well taught, but yet we all learned that, okay, nutrition needs to, you need to focus on certain superfoods. And so we started studying the pomegranate because there were all these, in the literature, some exciting studies on cognitive function, vascular health, et cetera. And when we looked, we brought the biotech approach to basically deconstructing the pomegranate. And so we looked around and there were all these great compounds as you were talking about. There were these polyphenols such as penicolagens and the elagic acid. But what we realized one day as we were sort of screening all these hundreds of compounds inside the pomegranate, we gave them to a famous professor just in the university campus we are in here in the Swiss Institute of Technology. And he was running these sort of assays trying to see if certain worms and rodents would basically run faster and live longer. And one compound really attracted our attention and which molecule called urulitin A, which is basically the, the results of gut microbiome digesting these polyphenols and releasing this postbiotic, which is the urulitin A. And so this professor, Professor Averix, came running to our lab and he said, what is this compound? Because it's boosting lifespan in worms by 50%. The older animals are running faster by 60%. And so that's really the whole journey of the last 10 years for us. We got more interested into urulitin A and we started studying in different human populations its producer status. So in terms of what is the percentage of population and people actually making the molecule? We looked in the French, the French were doing better 30 to 40%. And I'm guessing because French are probably eating a lot of fermented food, et cetera. Then we looked in the American population and the Canadian population, it was much lesser 10 to 15, 20%, probably again, a mix of diet and sort of physical activity contributing to it. And that's led to, you know, kind of us synthesizing the molecule and starting to directly supplement in the randomized trials in humans and older adults and overweight adults, and really seeing these remarkable effects on muscle health translate into humans with improved endurance and improved strength. So how exactly does it work? I mean, it's great that I'm going to have stronger muscles and I might live longer. What is it doing at the mitochondrial level? Yeah, sure. Yes, one of the, again, the first studies we did was we were looking in older adults and we took about 70, 75 year olds who have been running half marathons and training for half marathons all their out of life, for example. And we took little chunks of their muscle. So this procedure called as a muscle biopsy where you can take small chunk and look into how the mitochondria are behaving in the muscle tissue. And then we went and we took age mat 70, 75 year olds who were really what we call as frail and they were sedentary. So they didn't have good functionality. They didn't have very good levels of physical activity and they had lower muscle strength for sure. And we looked in the same way into their skeletal muscle tissue. We saw that both mitophagy and mitochondrial health was super compromised in the frail people. And so we took these same people, the sedentary frail people, and we started supplementing them with Urla today as a first randomized trial. And we saw when we took four weeks after, again, these muscle biopsies, we saw a big signature of improved mitochondrial health that was mimicking basically months and years of exercise. So basically it's hitting the same pathways of improved mitochondrial health and enhanced mitophagy that, for example, a six month aerobic exercise regimen would give you. So it's basically biologically hitting the same pathways. Oh my gosh, you mean exercise in a jar? I don't think I can put that claim. But scientifically and biologically speaking, yes, the pathways are pretty much similar to trials done in humans with aerobic and resistance exercise and with calorie restriction. So they all sort of point towards improved mitophagy and improved mitochondrial health. Is that the only human trial that's been done or are there multiple? There are multiple. So this is what I described to you as the first one where we only supplemented for a short period of four weeks just to see the biological effects. And then from there we have done multiple randomized trials that are now published in journals like JAMA and Cell Reports, really the top of the top journals. And in these randomized trials, we supplemented all the way for four months, much longer to see improvements in muscle function. And so what we see in older adults, and by the way, the oldest participants we've had is an 89-year-old, very spiky, robust lady who was a blinded trial but she was convinced she was taking the active and she kept coming to me. So like, you have to tell me if I'm right, if I took the right product, it was not a placebo. And when we unblinded, she wasn't the active. So she actually felt more energy, she felt resistance to fatigue. So what we are seeing actually in older adults is improved endurance and more energy. And these people can do exercise longer. In little younger populations like the 50 and the mid-50-year-olds who are also a bit sedentary, we have done another trial where we see improvements in things like VO2max. So this is a marker of, kind of de facto marker of improved mitochondrial health. We also see improvement in a test that a lot of clinicians use called a six-minute walk test, which is basically measures how much of a distance you can walk in six minutes. So we see about a 10% increase there. And then of course, the muscle strength is a standout improvement we see in these trials. So, and you mentioned this, the cancer trial. Again, that's you find is because of the improved mitochondrial function in the immune cells? Yeah. So this is a pre-clinical trial that was published. We are now translating these findings into two trials. So the effect is primarily even in the immune cells is because of improved mitophagy. Now, what happens in the immune system is a very specialized cell called a memory T cell. And this is a cell that basically has an imprint or sort of a memory of how cancer cells look like or how viruses look like, etc. So what we see basically is that mitophagy is compromised in cancer patients and cancer models in this particular memory T cell. And by supplementing with the post biotic era today, we are reactivating mitophagy in this memory T cell. And that contributes to better immune function, that contributes to clearance and better sort of recovery from the cancer and so that comes on the immune system. I want to backtrack for a second because you're using the term post biotic something that I've written about in my last two books extensively. But most people know probiotics, friendly bacteria. They know hopefully prebiotics, what friendly bacteria like to eat. But this concept of post biotics is for most people they've either haven't heard of it or what the heck is that? So you go ahead and define it, I'll add if I want to hear more. How's that? You know I've read your book and your sort of speeches on the three P's, the prebiotics, the probiotics and the post biotics. So the way I see them is that prebiotic is basically food for these healthy gut bacteria that coexist with us in their millions of them and billions probably. And that's sort of by using probiotics you're trying to modulate this gut ecosystem that exists. So it's all good for them and all good for their ecosystem. But then as a sort of benefit to the host which is us as humans, they take our food and nutrients from our food and they process them to release what are called as post biotics that are beneficial to us as humans. And that's a field that is coming up, post biotics. There are a lot of them like short chain fatty acids, typically butrate and acetate. And then they are from polyphenols derived metabolites such as urolithinate which is a post biotic. But I led you out to it. No, I think in my book I'm writing right now it just does an incredibly deep dive into this incredibly complex ecosystem that you know we're just now beginning to understand because it's you know the amount if you actually look at you know at PubMed searches about the gut microbiome in like 2006 there's there's maybe you know a thousand searches and now you know there's 30,000 and it goes on and on. So what I think is fascinating is that these are communication systems that now we now know exist between the gut microbiome and their host us and we are actually dependent on these messages, these post biotic signaling molecules. And what I think exciting particularly for urolithinate is yeah pomegranates got lots of really cool polyphenols and we you know there's history of how important pomegranates are in various you know brain health, heart health. But what you mentioned before is particularly here in the West, America and Canada, we're screwed because we don't have the probiotics that are able to take the prebiotics in pomegranates and make the active post biotic compound that's going to do all this good stuff. And you're right we're not the French. The Swiss are actually very close. The story I tell and it's my personal experience. I can personally you know I grew up in India where there's rampant use of antibiotics. So for everything when I was probably a kid with the little flu here and there everything was antibiotics right. So my microbiome just never recovered, just never recovered and I can drink six glasses and I've done this challenge with myself. I've had six glasses of pure pomegranate juice and then I've led myself at different times to see if my body would make pomegranate. Guess how much it makes zero because well maybe there is hope if I eat a lot of fiber maybe I figure out and we have spent years trying to figure out what's the right mix of probiotics that will basically do the conversion and the answer is it's very complex. The ecosystem is so complex we have gone in and taken people these lucky 10, 20, 30% people who are producers. We have really taken their stool samples and we have really done a high throughput gut microbiome sequencing. We don't know what we do see is that they have a very rich and diverse microbiome which is rich in things like acromansia which now is also you hear it so much. But you know to get there you need to somehow yeah you need to give your system a each better exercise and then probably third billers would be talking is supplementation for cellular health and postbiotics. All right so that's why timeline and mitopure exists. The work around you guys have synthesized so what is mitopure? How does it work? So mitopure is the trade name for our proprietary urinary which we synthesize with a patent protected methodology and it's 99.9% identical to the natural molecule. So the work around is essentially and we have actually even developed in the works of developing a small health kit where people can actually measure themselves in a lab or in a clinic if their body is actually you know if you can. So what we do is we send you the pangorinid juice you take the challenge you just take a few drops of blood from your fingertip put it on a card and we can tell you if your body is already conducive to making your urinary or not. And then you take the direct supplementation so you take a dose of 500 milligrams of mitopure and then you see the change in bioavailability and I can tell you that the average is about six fold higher in even people who can make it. So for people who don't make anything well we go from zero to 400 kind of levels of urinary pretty fast in about six hours of pips. So that's you know what we have done we've basically short circuited the whole natural process of getting it from a diet or relying on your microbiome to produce it. So everybody's going to want to know is it a pill? Is it a liquid? Is it a powder? How can I take it? Yeah so we started out all our randomized trials at the start were with the pills so you know very calibrated dose of 250 milligram in each pill. So the doses we are seeing that have the best effect in clinical studies are 500 milligram and then the gram gives even a much better response and a much quicker response but most people do take 500 milligrams so it's basically two pills. And since then we have also gone in and because good science and good nutrition should come with good taste as well so we've developed a lot of food products. So there's you know these berry and ginger flavored powders now that come that you can mix in your smoothies and your high protein shakes and there's even a product with 20 grams of weight protein sort of hitting on muscle mass and muscle energy at the same time. So this is the whole breadth of our product portfolio that whatever lends with your lifestyle. Now you mentioned early that obviously mitophagy is a good thing. Basically recycling our damaged mitochondria and I've written about kind of the last thing you really want to do is have these mitochondria simplistically explode and throw their pieces out into the cytosol because the membrane of mitochondria mitochondria are actually in golf bacteria ancient and our immune system actually views mitochondria at least the wall mitochondria as an evil bacteria and it can actually produce inflammation as these mitochondria die inappropriately. So you're right recycling these guys is really beneficial in lots of ways. Now you mentioned that fasting does this and as you know I'm a big fan of time restricted eating intermittent fasting. Is it the same mechanism that might appear hits? Yeah so fasting induces autophagy at the high level. So autophagy is basically recycling of the whole cellular machinery right and a focus autophagy is what is called we call it. It's just focused in the mitochondria recycling that's what we call as mitophagy. So both urolitin A and fasting are known to use autophagy. Now what we see very specifically with urolitin A in different trials and different models is this unique ability to activate mitophagy specifically right. So we have compared different markers in different experimental systems comparing caloric restriction to supplementation with urolitin A and it's pretty much similar in terms of autophagy even. So it's both a combination of autophagy and mitophagy. And getting back to the kind of the earlier studies particularly in worms. Worms are actually a really good model for lifespan and actually believe it or not gut health. And so worms with this compound were literally living 50% longer. Yeah one of the reasons why a lot of aging research is done in worms is they live about 20 to 25 days mac tops. And so one of the most potent compounds that are known to extend lifespan do it about 20-25% things like Resveratrol and NAD boosters. One of the reasons we got so excited was urolitin A in these initial experiments that we published in Nature Medicine was doing it by like 45% and that's kind of yeah unheard of and that's what got us excited. And obviously you can't make any qualifications that my taking this product now for a year and a half has already extended my lifespan by 20 years. Well that's not where we are about I think the goal is health span right we hear you know exactly today the whole longevity space has been split into two. One says oh we want to live to 120-130 years which is really increasing lifespan and I think you can achieve that realistically if you focus on health span extension so moving around you know crossing the road in the 15-20 seconds they give you you know older people to cross the road not get hit by a moving car I think that's the functionality is so key. Yeah back to urolitin A. Is there a time to take it if I'm a 20-year-old athlete is that going to improve my performance or I'm a 50-year-old and noticing that I'm losing muscle mass every year no matter what I do when should I start this stuff. Yeah so well most of our early studies focus on older adults and overweight middle-aged adults because that's where we knew the mitochondria were impaired and mitochondria would be compromised and we could see it we could detect signals to show the efficacy but when we launched it to our surprise we thought this would be mostly advanced nutritional product that a lot of older adults would be taking but to our surprise now a lot of our consumers are very active they are these weakened warriors sort of profile that wants to focus on health wants to preventively address their health issues in their 40s and early 50s rather than wait for you know the symptoms to happen like more medicine would wait for frailty and sarcophenia to manifest before starting to think about it and a lot of athletes a lot of two of the front cycling teams are on it and a lot of top NBA players are taking it and that actually made us think why are these players so much to believe in in EuroLatin A when the sort of the science is still emerging on that aspect and so we actually that motivated us to launch a big study in Australia with one of the most revered sports nutrition researchers lady called Professor Luis Burke in the Australian Catholic University and she's been studying elite athletes for a good part of three decades and she said well a lot a lot of times overtraining in Paris, mitochondria and that's what I think where your compound is actually acting is that some of these players are playing five NBA games or or riding a bike for 50 kilometers to 60 kilometers uphill downhill for you know months and and the body just doesn't have the time to recover and so now we have just finished this study and the results hopefully will come out mid-year it is that we think that by using the post biotic and even elite athletes we can blunt the muscle damage and accelerate the muscle recovery so that's one stream of research that is happening the other is in sort of the hospitalized patient settings now each day you spend in the hospital that and you put it very well you start losing muscle mass at a very accelerated phase and so we think by supplementing in that kind of hospitalized immobilized setting we can also accelerate the recovery of these people so you know the research is just building up and many more people are starting to study this going back a second fasting is one way to produce autophagy so can you have you looked at can you combine fasting or exercise and might appear and get an even additional effect yes so we've done it we've looked in different models where we've added exercise regimens and show that endurance improvements and strength improvements aren't even sort of add-ons with the supplementation with urolithinate the study that I was just describing with elite athletes well these guys are basically yeah the exercise gurus right so that's all they do so if we can improve somebody with a view to max of 70 and make their view to max better gosh that's really the holy grail of our clinical research but you're right the timing is very key as well so fasting overnight fasting induces autophagy and so we use a similar approach in our in our trials is that we supplement early in the morning in the fasted state so we get the best induction of mitophagy and that's what we even recommend consumers today that take this the pill or the powder first thing in the morning that good good point so and this all kind of started because you guys were interested in pomegranate juice it all started with the pomegranate the fruit and and its magical healing powers and everything inside and that's how it started now there's obviously lots of other historic compounds that have purported history of health benefits and I would assume there are other compounds that you're also interested in can you can you share any of your other research yeah I mean for example a lot of fruits and nuts also have a legit tannins and and and so the body makes the the majority of the urolithin is urolithin A but there are other urolithins that the body could make as well there's urolithin B C and D and we have looked at them it's just that urolithin A is just so much more potent than the others that which is why you know as a small research company you can only put so many research dollars into one area but we are we're now getting excited we talked about something adding on with high protein because I think for the whole muscle space and I've done trials and looking at muscle function improvement for good part two decades adding 20 grams of A protein or alternative P protein for example was supposed to be the only way to build muscle mass right and those studies wouldn't work without adding exercise regimens because you needed to start the whole muscle protein synthesis via mitochondria I'm assuming and so we think that's sort of where a lot of known ingredients in the space whether it's immune with vitamin D for example there's a lot of synergy with mitopyr so that's how we are approaching it but mitopyr is sort of the base in bioactive that can boost cellular health and then we add on well studied well clinical research ingredients that add further benefits and these will be products we'll be launching in the the duration of it so have you looked at the effect of mitopyr on say the gut microbiome or probably more importantly at least to me on the gut wall integrity I happen to think that the the gut wall is the holy grail of health span among other things yeah so we have started translating it most of the research there's a lot of research emerging now with excitement as you mentioned around this molecule there's there's a group out of us that has just basically published and again a very top journal showing that the gut barrier junction was improved following uralitin A intake and and this is was again done in preclinical models of inflammatory bowel disease and and colitis and Crohn's disease where they basically showed that supplementing with uralitin A was improving gut barrier junction and a lot of it was hitting on on all these sort of leaky gut sort of barrier you know that gets compromised with aging again and so this is now this leading to human translation where we're starting to think of how to translate this in people who have irritable bowel syndrome or even irritable bowel inflammatory bowel disease so that's the one area we are actively looking at as you mentioned and the other that excites us just because the science is coming from the national institute of aging and the Buck Institute of Aging is the potential uralitin A as a molecule has on on improving brain health and really counteracting neurodegeneration and they've screened thousands of compounds and they'll found that basically uralitin A is the top that prevents bi-activating mitophagy again it's going to work from top to bottom is what you're going to it's what it's going to work wherever there is an organ and links to high metabolic demand which is either a skeletal muscle B could be the cardiac muscle or the gut as you've been talking about but the brain has the brain cells have they have thousands of mitochondria and they get compromised all right so what makes mitopure well what makes it different is my answer is is a twofold answer one that makes a difference is that probably there are very few compounds that people have studied and put the efforts to study it with the biotech approach for 15 years and only then they believed that this molecule had health benefits have we brought it from the bench scale to you know the human research to the breakfast table as I say of people now that people can you know take it in their daily routine and the second is that it's such a safe molecule it's a natural molecule it has been evolutionary been present in through a diet and of course we've a lot of us have lost the ability to make it and and it's very unique mitophagy activator which is such a well-conserved anti-aging pathway that there are other mitochondrial nutrients that are known to let's say improve energy production like CoQ10 and L-carnitin for example then there is the the biogenesis side of mitochondrial improvement where you can take respiratory or certain NAD boosters like nicotinamide riboside but those will in my opinion will only work if you take out your trash bin right you can't keep putting more trash and suddenly expect that you know that it will clean away and you know be empty space for to have healthy mitochondria so that's where I think this is so unique is that it takes out your trash basically and that allows your healthy mitochondria to come in make sure to check out the next one here the FDA finally employed new criteria for foods to meet and the following of these so-called healthy cereals are not making the cut