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Dr. Steven Gundry – Can you briefly explain Amazentis and the role you guys are playing in developing amazing new supplements like Mitopure? How did you discover urolithin A in the first place? This is a great story.

Chris Rinsch- You know, it all started out in the very beginning of the company. We were really looking at natural products and trying to understand what are the compounds inside of natural products that can really create a meaningful impact on people’s lives and really target specific biological pathways and we’re looking at a number of different foods. And one of those foods was the pomegranate at the time. And so we were very interested, there was talk about antioxidant, abilities of pomegranate. A lot of people were taking pomegranate juice, that was very popular time. And so we took this deep dive and we started doing things like juicing the pomegranate, trying to understand what types of compounds are in different strains of pomegranates actually. And this led us to a greater understanding of the various compounds inside of the pomegranates. And looking particularly at a class of compounds called the ellagitannins. And inside of the pomegranate, there’s a very rich source of ellagitannins. And one of those is the punicalagin, which is a compound that’s very predominant in the pomegranate. And I’ll tell you about how our discovery went from there into urolithin A. In fact, what’s interesting about punicalagin is that while it’s in the fruit of the pomegranate, when you consume it, it’s transformed into other compounds. And this is something that you don’t really think about when you’re consuming different types of foods. You think, “Okay, I’m getting vitamin C from orange juice,” etc., but here you have pun collagen that’s transformed by your gut microflora into urolithin A, which is a prebiotic. And so that’s sort of how it started and that journey from looking at fruits themselves to getting to urolithin A

Dr. Steven Gundry – How did you guys actually, you know, make that connection that there’s an intermediary here that we really didn’t know about that was, you know, you could kind of drink all the pomegranate juice in the world and you might not end up with what you were actually looking for from the benefit of that pomegranate.

Chris Rinsch – It was very interesting, when we started, we were looking at specifically at punicalagin, and we were testing this in various animal models and particularly, we’re looking at animal models of cognition and brain health, and we were feeding punicalagin to mice that had Alzheimer’s disease through a genetic mutation. And we were seeing an improvement in their swimming. As they get older, their swimming and their memory declines. And so we saw this improvement linked to punicalagin. And then, you know, we started to go deeper to take a look at how could that actually, you know, as the punicalagin is consumed by the animals, what transforms afterwards. And so this was where we started looking at the postbiotics and we started making different postbiotics that were derived from punicalagin and then taking those into the lab and studying those in the lab. And we did that together here at the EPFL, with Professor Johan Auwerx, who is a specialist in mitochondrial biology.

Dr. Steven Gundry – Let me back up for a second. You and I are kicking in the term around “postbiotics” like everyday conversation, which it is for you and I, but postbiotics, I’ve written several books about them, but people, I think know probiotics was, let’s just say friendly bacteria and people know prebiotics. They’re beginning to understand that these are, if you will, the compounds that bacteria wanna eat. And postbiotics for our listeners, are the compounds that the bacteria make when they eat these certain compounds like pomegranates. Is that a good simple description?

Chris Rinsch – That’s perfect.

Dr. Steven Gundry – All right. And what we’re finding quite frankly, is that the postbiotics are probably the most important missing link between our gut microbiome and the end effect on our overall health. And that’s why I think this discussion, particularly with Mitopure, but in postbiotics in general, is so important for all of us to understand.

Chris Rinsch – You know, we take for granted that our body is designed to extract all the benefits from the foods we eat, but in fact, it’s really depending upon, you know, the composition of the microflora that we have in our gut. And then its ability to actually make this transformation of the compounds in our foods into postbiotics.

Dr. Steven Gundry – Once you discovered that, you know, these mice were making urolithin A, then you turned it over to your scientists and said, “All right, why is this compound getting these observed effects,” and take it from there?

Chris Rinsch – We were very curious about, you know, how did that compound transform and translate into these effects? And so we started studying the metabolism of the compound punicalagin in the ellagitannin found in the pomegranate. And it was known that it was transformed into compounds like urolithin A and other urolithins in this sort of class of postbiotics. All of your ability to transform into different types of urolithins depending upon the actual gut microflora that each person has. And we asked ourselves, are these compounds more than just the body’s way of clearing the punicalagin from the body? Because most people who had been studying it had been looking at, this is what you know, is excreted, you know, when you take this type of a food. And so less at what is the nutritional value. And so we took a deeper dive to see and explore are there any real health benefits linked to urolithin A?

Dr. Steven Gundry – And what’d you find?

Chris Rinsch – The most exciting thing was when we were working together with Professor Auwerx, he put it onto cells in the lab and he put it into worms in the lab, and I’ll talk a little bit more about that, and he saw improvement in mitochondrial function. And so what was exciting about this is first of all, Professor Auwerx is an expert on mitochondria and mitochondria biology and has tested lots of different compounds including resveratrol and others. And so he understands sort of the potency of these compounds in his hands and in his various models. But what struck him was how much more potent urolithin A was than all the other compounds. And one of the ways that he studies fundamental sort of lifespan and health span is using this worm model, it’s a very basic model. It’s the C. elegan model, they don’t live very long. And so when you feed them different types of bioactives, you can follow life extension. You can also follow what we call health span, which is like sort of the quality of life as you get older. And you do that by looking at their movements in the dish with time. And what he saw was that when he had administered urolithin A to these worms, that you got an expansion of lifespan by about 45%. And this compares to caloric restriction, which is sort of the gold standard getting you the highest expansion and extension of lifespan and worms, which is around 50%. And if you compare this to other natural compounds like resveratrol, you know, you’re in the 15 to 20% depending upon that experimental setup. It was really quite a dramatic effect on mitochondria function that he saw and on and in this worm model. These results caused us to really take notice and think that this could be something really special and take it to that next level and start studying it by administering it directly to the various mouse models.

Dr. Steven Gundry – I’ve written about C. elegans in a lot of my books and I think people should know that it is a really, really useful model that really what happens in C. elegans can pretty much be duplicated in higher animal models, whether it’s a mouse, whether it’s a rhesus monkey and as we’ll get to, a human. So you know, what happens in these in these worms luckily, is able to be brought to the clinic. And you know, that’s what’s exciting about this model. And you’re right, calorie restriction is still probably the gold standard, but quite frankly, nobody particularly wants to do that for obvious reasons. And which looks even better than resveratrol. The famous red wine molecule. So now, these Alzheimer’s mice are doing better. Take it from there.

Chris Rinsch – You Know, what we started doing is then feeding it to mice that were getting older. And one of the first studies we did was what they call a high fat diet model. And this is basically feeding mice, sort of the supersized meat type of diet. And so they, well, they get fat as they consume more fat in their diet. And what we did is we fed the mice either urolithin A or we fed with the high fat diet or with the high fat diet alone. And these were mice sort of at the later part of their years. And what we saw was that as the mice were getting older, we started looking at various parameters and one of those was their physical activity and physical function and muscle strength. And we saw that the muscle strength was increasing in those mice that were taking urolithin A by about 10% and their sort of grip strength as you measure in these types of models. But the thing that surprised us the most is we looked at the running distance and sort of the spontaneous running distance you put them in sort of these wheels that they run on and they sort of run until they get tired and they stop. And what we saw was that these mice were running more than 40% more than the mice that weren’t administered urolithin A. So it was a real shock to us. And then we started looking deeper into the benefits of improving mitochondrial function on muscle function and on skeletal muscle function and the general health. And we went that next step and we said, “Well, let’s take a look in older mice.” And in this time, in that first study, it was a long-term administration, we said, “Well, let’s do it for a shorter period of time and look at older mice and let’s give mice the best diet.” So no high fat diet. And so we followed these mice for about eight weeks and what we saw was something very comparable and in fact, we saw an improvement between 40 to 50% in running endurance in these mice. And it was very impressive. And, you know, taking a closer look, we saw all these biomarkers that were linked to improved mitochondria function in the skeletal muscle of these mice that were taking urolithin A. And so it was at this point when we started to see in multiple studies conducted by different groups that we were all seeing sort of the same thing in terms of improvement in muscle function, that this was something worth going that next step and sort of scaling up into humans and seeing if it actually translated into humans. And it was already, you know, getting something to translate from, you know, cells to worms to mice is quite a feat. Translating to humans is another story. And so this is where we took that step of, you know, going from a small, you know, few grams into manufacturing at a much larger scale and then actually developing products that, you know, we could administer to humans supplements and foods. And that’s sort of how it started in our exploration in human biology.

Dr. Steven Gundry – And I’ve written about this and you know this as well, you gotta have the right set of bacteria to take these precursors to make urolithin A in our gut. Correct?

Chris Rinsch – Correct, yes.

Dr. Steven Gundry – And one of the interesting things is that super old people, people who are thriving at a very ripe old age, remarkably these people have, 50% of them, have the right combination of bacteria to produce urolithin A. And yet most of us, 14% of us have the right set of bacteria to make urolithin A approximately?

Chris Rinsch – It’s very interesting. I mean there’s been studies that have come out, I think it was the year before last on looking at people who are taking a Mediterranean diet and they tend to find more urolithin A in their blood than people who aren’t taking a Mediterranean diet. And so that’s, you know, certainly a combination of you know, eating the right foods because these compounds we were talking about that are in pomegranates are also found in different types of berries, sort of raspberry and strawberry and different nuts like walnuts.

Dr. Steven Gundry – Walnuts, yup.

Chris Rinsch – But you have to have that right gut microflora. So I have to believe that if you have that right diet, that helps steer the bacteria and the composition of the bacteria in the right way because they develop to actually transform the foods that they’re eating on a regular basis.

Dr. Steven Gundry – The point I’m trying to make is, unless you are doing these other things, unless you are what you eat, but you are what the things you’re eating ate, you’re kinda screwed if you think you’re gonna make a lot of urolithin A, and probably, we should be making a lot of urolithin A. All right, so what happens when we give it to humans?

Chris Rinsch – Our first study was trying to explore what was the dose you need to give to humans, you know, to actually see that effect? And so we did what normally pharma companies do when they take a first drug into humans. We applied the same sort of methodologies for nutrition and we started giving different doses and we used that to sort of identify what would be an active dose. And what we saw was that after giving people 500 milligrams of urolithin A for a period of 30 days, we saw an impact on the mitochondria function in the skeletal muscle, particularly in the leg skeletal muscle. And we saw that with both 500 milligrams a day as well as one gram a day. And we assessed this in a couple of different ways, but the key way was the direct assessment by taking a muscle biopsy. So we went and took a biopsy before and after, and we looked at the gene expression pattern. And what you really saw was this, and this is a very unbiased approach and meaning that we didn’t, you know, we saw all of the genes that were expressed and then we looked at the ones that were changed after taking urolithin A for a month. And what we saw was that there was an increase in the expression of genes linked to mitochondrial function. Which is very interesting because when you have this enrichment of the genes of mitochondrial function, it’s a clear sign that there’s increased mitochondria biogenesis. And this is something that you want to see and you see this in athletes after they’re that are exercising. And we’ve also seen it in another study where we were looking at people who were sedentary versus active and we were seeing a decline in the expression of these genes and those people who are sedentary in what they call pre-frail. So they’re starting to have mobility problems versus those people who are active and maintaining active when they’re old. So mitochondria function is really a key indicator of overall muscle health. And that’s what’s I thought was very exciting about that first study.

Dr. Steven Gundry – So you didn’t interfere with an active exercise program. You didn’t say, “Okay, you know, you’re gonna take Mitopure but you’re also gonna go on a treadmill 30 minutes a day.”

Chris Rinsch – This is sedentary. These people were older people who were average age of 70, but sort of 65 to maybe 80, something like that. And they were sedentary individuals and so they weren’t exercising, so there was nothing that was sort of turning on the mitochondria, no change in diets, etc. So very exciting to see that in the very beginning. And of course, we then started repeating that in more robust studies, but I let you.

Dr. Steven Gundry – Mitogenesis, you and I know what that means. For our listeners, mitogenesis means make more mitochondria. And quite frankly, the more mitochondria you have packed in your cells, the better. We also toss around the term mitophagy, and some people have heard of autophagy as probably a really good way to extend lifespan, improve health span, just a basic science here. Mitochondria have their own DNA apart from the cellular DNA and mitochondria can reproduce without the cell dividing and make more of themselves in mitogenesis. But they can repair themselves from damage which is part of mitophagy. Or God forbid, they can explode and have apoptosis, which is a bad thing that I’ve written about, and you and I know about. So you’re finding not only mitogenesis with urolithin A but also mitophagy, repair of mitochondria. Yes?

Chris Rinsch – Yes. Well I think that kind of goes back to the lab experiments that were done and trying to understand how was urolithin A impacting the mitochondria. And we were talking about mitochondrial biogenesis. And what’s fascinating is that, you know, inside of your cells, you have all of these mitochondrias, not just you have one mitochondria in your cell, you have hundreds and thousands depending upon, you know, what cell type. And these mitochondria are working nonstop to you creating energy for all the different biological reactions that are taking place inside of your cell. And in the consequence of doing that, these mitochondria get damaged because of these reactive oxygen species that are produced and the cell is in the body. And the cell has come up with a very clever way of dealing with that. They have sort of a its own recycling mechanism and that recycling mechanism is called mitophagy. And so basically, those damaged parts of the mitochondria are separated from the healthy parts and sequestered and brought into a basically a little cellular garbage bag. And they’re digested by cellular enzymes that allows the damaged part of the mitochondria can be broken down and then recycled by the cell and to make healthier mitochondria. And this is a normal process that’s always going on inside of our cells that we need to maintain. Now, the problem happens when that mitophagy slows down and there’s a lot of things that can link to that. One is simply, you know, poor diet. That can link to a lot of metabolic disturbances. The other one is simply being not very active. We were talking before about older people who were active versus sedentary. Being active actually stimulates this process. You were talking about autophagy, but also mitophagy so that this activity is stimulating that. And then it’s maybe not be evident, but as you get older, this rate of mitophagy declines. And this has been shown to be recently, one of those hallmarks of aging that people talk so much about is the decline in mitochondria function as you get older. And this decline is largely due to a decrease in the level of mitophagy. This is what’s very interesting about, you know, how do you maintain proper cellular health from an energetic standpoint as you get older and just at every stage of your life. And the way to do this is to maintain your mitochondria health. And we were talking about mitochondria biogenesis before and the production of healthy mitochondria. But getting rid of the damaged mitochondria is equally important because you don’t want to have a bunch of damaged mitochondria inside of your cells and not a lot of energy and then the cells sort of being starved for that energy. And so this is what makes mitophagy so interesting. And then going back to what we were talking about urolithin A, the discovery that was made in Johan Auwerx’s lab around urolithin A and the mitochondria function. It also went to that next stage and showed that the mechanism of action was by stimulating autophagy. And what was so exciting is that this is the first compound that was a non-toxic compound, that was a safe natural compound that was shown to stimulate autophagy, not only in worms and in cells, but also in mice. And then we see these very nice effects on mitochondria function in humans.

Dr. Steven Gundry – And you subsequently publish papers about improvement in humans in muscle function in a fairly short period of time? Can you elaborate on that?

Chris Rinsch – We ran a number of studies now looking at muscle function. I think one of the more interesting ones is a study that we did in people that were middle age overweight, sedentary. And what they saw was that after four months of taking urolithin A at 500 milligrams a day, they showed an an improvement in leg muscle strength by about 10%. So this was something that was notably physiological impact on the health and that you don’t see, you know, just sitting around taking a supplement, right? This is a big conversion from just taking a biopsy to actually seeing a functional benefit. We’ve since done other studies looking at people who are older and having a lower mitochondrial function. And what we saw was that after two months, we improved muscle endurance, both in the first interosseous muscle, which is the basically your hand muscle and this the kind that you used to sort of grip jars that you open and also your leg muscle. So that was really exciting to see that transformation there. So we started to see, we’ve now started to see the impact of urolithin A and a number of different human studies all linked to mitochondria function.

Dr. Steven Gundry – I know you guys are very interested in nutrition 2.0. If we’re listening, okay, if I am, if I’m 70 years old, my mitochondria aren’t doing very well and it would be really smart for me to take urolithin A but my 35-year-old listener is now saying, “Well, I’m not 70 years old, I am at my prime.” When should I start you know, considering something like urolithin A like Mitopure?

Chris Rinsch – It’s an interesting point that a lot of people have asked us, you know, “Well, I’m not old enough for it yet.” And quite the contrary, you’re never too young. We have a lot of athletes that are taking our product and really enjoy it. In fact, we’ve recently run a study in an elite and subelite athletes for a period of a month and they experienced better muscle recovery after less received exertion after a month of taking our product. And these are athletes at the highest level who are training or at a training camp. And you’ll see the impact differently depending upon what your lifestyle is like. You know, if you’re an athlete, you’re probably thinking about muscle recovery. As you get older, you’re looking to maintain that muscle strength, maintain that endurance. And so it’s a trade-off. And of course, there’s things that you don’t feel but you’re having an impact on the mitochondria function. You may not feel it in terms of muscle, but you may feel it in a different way, like general energy for example.

Dr. Steven Gundry – And just to be clear, this is perfectly legal for athletes to take? The Olympic committee will not ban this substance/

Chris Rinsch – No, no, for sure. You know, the nice thing about urolithin A is, you know, we’ve been consuming urolithin A for thousands and thousands of years. This is what you get when you consume pomegranate juice, when you consume walnuts or raspberries, there’s nothing at all harmful with urolithin A. The safety has stood the test of time of, you know, of millions of people consuming it.

Dr. Steven Gundry – So you’ve talked about muscle recovery, muscle strength. I think getting back to one of your original points about these mice who weren’t very smart and memory and everything, we tend to forget that our brain is a rather a big consumer of ATP in our brain. Our neurons are packed with mitochondria. We wanna flex our brain muscle well into late adulthood. What you find you know, in muscular mitochondria is that now happening in mitochondria, in neurons as well?

Chris Rinsch Well, there’ve been a number of preclinical studies in mice basically administering urolithin A to them and not by us, by other scientists. And they have seen an improvement in memory in various animal models. And it’s logical that you would see that simply because that there’s a demonstration that in a lot of disease models and a lot of progressive degenerative diseases of cognition, there’s a strong link to mitochondrial function. And not only for just memory but also mood disorders too. It’s a whole sort of spectrum of cognitive deficits. Have a mitochondrial link.

Dr. Steven Gundry – And I know you and I have talked, you know, offline that our immune system is also very important part of us in fighting disease and infighting cancer. And you’ve recently done some studies looking at Mitopure’s ability to improve the immune system surveillance as well.

Chris Rinsch – That’s for sure. I mean, there’s been now a couple of studies that have been published on Mitopure and the effect on immune cells and the benefits are quite remarkable. You basically are seeing that it’s helping the immune cells retain their stemness, which basically means it’s preventing this immune aging. And that’s something that’s really exciting. We have a clinical study underway now over in Germany where we’re doing a full spectrum analysis on all the different immune cells and individuals taking urolithin A. And so this is something that, you know, we hope to have some more knowledge and share with the public next year when the study is completed and all analysis has been made. This observation that administering urolithin A, the mice was able to boost immune systems and I think you’re referring to this paper where it was a boosting immune systems and mice and helping the mice immune system fight cancer better, which I thought was very interesting.

Dr. Steven Gundry – Correct.

Chris Rinsch – Of course, that type of thing, you can’t talk about for humans because we’re talking about a supplement, but I think that the fact that you see the impact on the immune system is just so exciting. I mean, because the immune cells have mitochondria too, right? And so you’re having this broad spectrum effect on the body by improving mitochondria function. And this is where I think that, you know, the power of urolithin A and Mitopure have for general health. This is not just something that’s targeting muscle. We were talking about brain before. We have plans to run a study looking at the effects in brain. You know, there’s this broad impact on mitochondria function in cells and those cells are basically everywhere in your body. So that’s the exciting future.

Dr. Steven Gundry – As a former transplant surgeon, heart transplant surgeon, nothing made us happier than getting to do a heart transplant in a 75-year-old person. Why? Because their immune systems were so lousy that we didn’t have to give them a lot of immunosuppressant drugs to allow them to accept that heart as opposed to doing it in a 10-year-old child. We really have to, you know, whack the immune system ’cause it’s so vigorous. And your point is well taken that anything that we can do to improve our immune system’s functions, surveillance ability as we get older is well worth it in so many ways. I started taking Mitopure actually I think when it first came out. I’m in my mid-70s now. And my wife and I are avid hikers and hike a lot over in Europe and Italy and France. And we happened to notice through the years, that a great number of people from Germany and Switzerland were hiking, trekking with trekking poles and we’d say, oh we can spot the Germans and the Swiss ’cause they all got their trekking poles. And as time went on, particularly on challenging, particularly downhill slopes, I found that I’m going, “You know, I can see why these guys are using trekking poles ’cause my, you know, ability to head down these rather treacherous slopes is not as good as it used to be.” And I was talking to my wife and I’m going, “You know, maybe it’s time for me to consider these polls for a balance ability.” And I was really kicking it around and then I started taking Mitopure. And quite frankly, within a couple of months, my balance and my ability was back to, you know, what it was 15 years ago. And my wife and I laughed about it. She said, “Well, I guess you won’t be needing the trekking poles like all the Swiss and Germans we see.” I said, “Well, not yet.” And that was all I changed. You know, I didn’t change my exercise routine. I didn’t change, you know, my diet. That’s the only thing I added and I tell my patients, “Look, you know, I can tell you, this was the effect at least in me, so good for you.” I don’t want trekking poles yet, sorry.

Chris Rinsch – Well, that’s a great story. No, I mean, we’ve had so many people write in and tell, you know, their own stories about how it’s improved their energy or their muscle function. People who have had, you know, leg cramps who don’t have leg cramps on a personal level, you know, energy. I found a lot of energy. It is been now more than 2 1/2 years that I stopped drinking coffee. You know, I just don’t feel the need for it. And it’s very fascinating just to see that level of energy you get on a daily basis.

Dr. Steven Gundry – You know, there a lot of this, at least for me is my neurofeedback from my legs to my brain was definitely improved. And, you know, I could feel it and I could see it in my balance. So, good for you. What’s the future hold for timeline and where are you going from here?

Chris Rinsch – Well, we were talking about the all the difference of health benefits that you might be able to achieve by acting on mitochondria. I know you’ve been talking about the nutritional aspects. You know, we think now that there’s this potential to have this very holistic approach to aging with mitochondria going across all the different health benefits, including topical, and you were mentioning earlier the topical creams to me, and this is something that we’re very excited about because you have something, you have a molecule here, you know, that’s working on your skin and we’ve recently published an article on this. And you can actually see the benefit. So it’s not like taking a pill and you feel it, you look in the mirror and you see it. It’s not just sort of your physical look, but it’s the biology of your cells that it’s important. The skin is the largest organ of your body. If you put product on that can activate your mitochondria, this is something that we think is very potent by taking something and applying it locally to your skin. We’ve run studies, we’ve seen the impact on inflammation. Sort of post-UV exposure, we see the anti-inflammatory properties that we’ve seen taking orally that it also applies topically. And we’ve also seen benefits on gene pathways and proteins around collagen expression. And this is something very exciting because we know that as you get older, the lack of collagen in your skin is what starts to cause that sort of change in that structure of your skin and that change in physical appearance.

Dr. Steven Gundry – So you can swallow it and you can put it on your skin?

Chris Rinsch – Yeah, I think that’s what is ideal, right? And that’s what people want, that’s a holistic solution.

Dr. Steven Gundry – Yeah, no, absolutely. And good for you, guys. As you know, I’m very impressed with you and your company, so keep up the good work. Thanks for watching, but don’t go anywhere. The next episode of The Dr. Gundry Podcast is waiting for you now. Now, this one’s a no-brainer. Anyone who actually thinks that cereal is good for you and is a health food, please think again. But let’s make sure, let’s read the label.