Start Optimizing Your Mitochondria Today

Chris Rinsch joins Dr. Gabrielle Lyon to discuss muscle's vital role in longevity and how the novel nutrient Urolithin A supports muscle health.

Podcast

The Dr. Gabrielle Lyon Show

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Unveiling the newly studied molecule that supercharges your mitochondria, turns back the clock on aging, and battles sleep deprivation from Timeline Nutrition.

Topics covered

  • Why you need to know about Urolithin A.
  • How your mitochondria affect aging and longevity.
  • What’s needed to create healthy muscle.
  • The keys to optimal mitochondrial health.
Transcript
Dr Gabrielle Lyon
Welcome to the Dr Gabrielle Lyon Show, where I believe a healthy world is based on transparent conversations.
Dr Gabrielle Lyon
In this episode, I interview Chris Rinsch. He's co-founder and CEO of Amazentis. Now, it's very unusual for me to bring in a CEO or founder of a company unless I am deeply invested and believe in the work that they are doing; and that's exactly why I brought Chris on.
Dr Gabrielle Lyon
He has, for more than two decades, been an innovator in the life science areas. Before founding Amazentis in 2007, he worked in venture capital, investing in pioneering life science companies in the nutrition space, and in biotechnology developing cell-based therapies at the Swiss Biotech company.
Dr Gabrielle Lyon
Rinsch has authored several original publications and leading scientific journals, including Nature Medicine, Nature Metabolism, JAMA-open, Cell Reports Medicine, and others. What he has researched is this compound called Urolithin A. Urolithin A is being shown to have a significant impact on mitochondrial health, muscle function, and joint health. This is exactly why I had him on. I absolutely believe in the science that he's doing. I wanted to hear it, quite frankly, from the horse's mouth.
Dr Gabrielle Lyon
In this episode, we talk all about Urolithin A. We talk about what it takes to maintain healthy muscle, what are some of the compounds and influences to really impact mitochondria, and what we can learn from Urolithin A and how it has the potential as it relates to health and longevity and overall aging.
Dr Gabrielle Lyon
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Dr Gabrielle Lyon
This is where Eight Sleep comes in. I actually have the Eat Sleep pad cover, and this pad cover, it'll fit on any mattress. We have a king mattress. It allows us to adjust the temperature. He likes it cold, I like it warm. I don't have to kick him in the middle of the night or punch him, and it works out really well.
Dr Gabrielle Lyon
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Dr Gabrielle Lyon
That is incredible, you guys. You know how important that sleep is for your health and well-being. Better sleep is a health habit that you'll love sticking to night after night, I promise. You'll wake up more rested, fully energized, ready to crush the day. Go to eightsleep.com/dr.lyon, that's eightsleep.com/dr.lyon, and save $150 on Eight Sleep pod cover.
Dr Gabrielle Lyon
Thank you to Timeline Nutrition for sponsoring this episode of the show. There is a new product that I'm totally hooked on and it is called Mitopure, which is in fact what this episode is all about. It's really important to understand that the body is an energy-generating machine.
Dr Gabrielle Lyon
Cellular energy is like your personal health speed limit. Every second of the day, even as we sleep, our cells need energy. It keeps our heart beating, it keeps our muscles healthy, it keeps our lungs breathing, and our brain functioning. The challenge is as we age, our energy generators, our mitochondria become damaged, making it harder to produce the energy we need to feel our best.
Dr Gabrielle Lyon
Where does MItopure come in to the picture here? MItopure is an evidence-based product. It has Urolithin A in it, which helps our mitochondria produce energy more efficiently by triggering our body's natural cellular renewal process. Essentially, it replaces damaged mitochondria.
Dr Gabrielle Lyon
This is where Timeline Nutrition has really thought through and thoroughly researched their products. They have over a decade of peer-reviewed published science. For those of you who are following the muscle-centric lifestyle, then you want to improve your muscle function and health. One of the studies show that in adults over the age of 40, Timeline has been shown to increase muscle strength and endurance with no change in activity.
Dr Gabrielle Lyon
Go on over to timeline.com/dr.lyon. Use the code Dr. Lyon to get 10% off your order. I recommend trying their starter pack. I would love to hear what you think. Again, that's timeline.com/dr.lyon.
Dr Gabrielle Lyon
Dr. Chris Rinsch, thank you so much for joining me. I'm really excited to sit down and talk with you. I've spoken to your team, I've read many of your papers, and you've done a fantastic job publishing. But before we dive into the topic of mitochondria, muscle health, aging, mitochondria dysfunction, and then, hopefully, the positive interventions that we can actually help with mitochondria, I'd love to hear a little bit about you. I don't know much about you, actually. You're a PhD, and I'm curious it's your area of specialty.
Chris Rinsch
I did my PhD a long time ago now, and that was in cellular and molecular biology and more in the translational side of things; so looking how do you impact health and… I'm not good at the data.
Dr Gabrielle Lyon
I'm really putting you on the spot. Here's why I'm putting you on the spot, is because I have the privilege to interact with so many people. It's very rare that you find a group of individuals that are so committed to a mission a collaborative team. I feel very privileged because I do work with a group like that, and that's actually a first form, which is a company that I work for.
Dr Gabrielle Lyon
Your company is really amazing. I got that same experience where you guys have really created a culture and behind a great culture and behind a great movement of bringing something that's meaningful forward really is a testament to the person. As a true scientist, it sounds like you don't really like to talk so much about yourself, which is very noble.
Chris Rinsch
Well, why don't I talk about, if you'd like, we could start off by talking a little bit about the origins of the company and how we got to where we are now and then explore and dive into some of the science and, I don't know, any other questions that you have.
Dr Gabrielle Lyon
Sounds great.
Chris Rinsch
Maybe that would be a good way to kick it off.
Dr Gabrielle Lyon
Okay, I'm ready.
Chris Rinsch
That work for you?
Dr Gabrielle Lyon
It sounds great. Tell me about how you got interested in all this, because you're originally from LA, and you're now in Switzerland.
Chris Rinsch
Right. Well, it was back in 2007, actually, that I came together with my co-founder, Patrick Aebischer, and we had decided to create a new company that was focusing on this next generation of science-based, science-backed nutrition. Really the origins are around this the idea that as you get older, there's slow degenerative processes that are taking place. It would make so much sense if we could just incorporate into our diet foods that had the right ingredients in them that could basically slow down that process of aging.
Dr Gabrielle Lyon
That's something that actually everybody is talking about now and really concerned with in terms of aging with this progressive loss of, oftentimes we think about, muscle strength, function, and not even from the muscular side, but also the metabolic implications. I think that that is so important. How did you become interested in specifically—and you're going to have to correct me on this word—the ellagitannins?
Chris Rinsch
Well, actually, when we started out, Gabrielle, we were looking at different foods that were showing that scientists had showed some type of, let's say, preliminary science of benefits; and one of those was the pomegranate. Some scientists had been feeding juice to animals and been seeing some first effects. At that time, it was qualified as more of antioxidant effects.
Chris Rinsch
So we thought, "Well, maybe there was something to the pomegranate." So we started looking at the pomegranate taking a deeper dive to see if there was really anything there that was backed by science. What we began with is making extracts of the pomegranate and looking at the different compounds and then testing the compounds.
Chris Rinsch
We went through this process that is called by scientists, a bio-guided fractionation, where basically you take all the compounds that are inside of the pomegranate and you fractionate them out, and then you test them, and you see which ones have effects and which ones don't have effects. At that time, we saw ellagitannins, which is one of the phytocompounds, one of the polyphenols that are inside of the pomegranate. We saw that this was having some effects in some in-vitro studies.
Chris Rinsch
Then we started looking at the effects when we fed them, fed animals, with various ellagitannins and extracts of the pomegranate. This is when we started thinking more about the ellagitannins and what type of potential benefits that they could bring. Then we started thinking more about the method of their metabolism, of the ellagitannins.
Chris Rinsch
After the animals and after humans consume ellagitannins, what happens to them? One of the things that is happening, following consumption, is basically the transformation into what's called a postbiotic. In this case, it's transformation into a compound that's called Urolithin A.
Chris Rinsch
What happens is that there's bacteria inside of your intestine that transform different foods that you take, in this case, the polyphenols, the ellagitannins, into Urolithin A. It was thought at the beginning when we were looking at this that Urolithin A, this postbiotic, was just a way of the body to cleanse itself and eliminate the ellagitannins. We took a deeper dive and looking at Urolithin A to see what type of biological effects that this postbiotic would have.
Dr Gabrielle Lyon
That's really interesting. Are there multiple different kinds of the ellagitannins? I mean, Urolithin A is one. Did you have to sift through a whole handful of them?
Chris Rinsch
Well, in fact, the ellagitannins is a class of compounds, and the one ellagitannin that's the predominant ellagitannin in the pomegranate is called punicalagin. What happens is it's broken down inside of the body, and then it's transformed into Urolithin A by certain gut microbes, bacteria. As it was so predominant, it became quickly obvious to focus on this one first and then take it from there.
Dr Gabrielle Lyon
How many years ago is this? This is over a decade ago, right?
Chris Rinsch
Yes. When we started out the company that was back in 2007 and really got things going in 2008 and starting to look at the pomegranate then and evaluating its health benefits.
Dr Gabrielle Lyon
When you were looking at pomegranate and these ellagitannins and ultimately Urolithin A, did you have a working hypothesis as to what it was going to impact? Did you think, "Okay, this is going to be something that's really going to impact and restore levels of mitophagy as a way in improving mitochondrial function"? Or were you thinking, "Maybe this is something that's just going to help improve the gut microbiome"? Did you have a working hypothesis?
Chris Rinsch
Well, when we initially started looking at the pomegranate, as I mentioned, there had been some publications where there was a suggestion that there might be some brain health benefits. Obviously, cognition as you get older, there's all kinds of potential issues with decline in cognition, whether that's an age-related memory decline or Alzheimer's, for example. There's even Parkinson's disease that are all linked to the process of aging.
Chris Rinsch
We initially had been thinking about brain health and how do we improve that during the aging process. That was where the origin started. Then as we started testing and drilling down to Urolithin A and examining its benefits in the culture dish first on cells and even on worms, we really started—that was one of the interesting things—in cells, and we saw this impact on mitochondria function.
Chris Rinsch
Then we went to worms, and that's where we started to see this impact also on mitochondrial function, also in longevity, also in mobility of the worms. The worms is a great model. It's a smaller model, but it's a complete model that allows you to study things in a more compressed time frame.
Chris Rinsch
It was at that time when we saw an extension of the lifespan in worms by about a little bit over 50% that when we administered Urolithin A to their diet. Then looking at also mobility of the worms as they got older and showing a higher mobility. That was a first feeling on the effects.
Dr Gabrielle Lyon
Yeah, that must have been exciting, as exciting as worms can get. But really exciting and promising that you're actually seeing something work because in nutrition and in the… I don't know if it's the nutrigenomic space or these more natural plant compounds, there's a lot of promise initially, and oftentimes it doesn't stand the test of time and it doesn't actually translate over to humans, which is one reason I actually use Urolithin A, and I'm very excited for you to share some of your research because this does translate over to humans.
Dr Gabrielle Lyon
Before we get into some of the studies, I have one… Again, you published in Nature. There's a JAMA article that was in January, a JAMA-open article. We'll link to all those articles which are open access. Urolithin A, just for the listener, it's this natural food metabolite. It's a natural food metabolite of the gut microbiome. I think cognitively people are thinking, "Well, why would I take a compound when I could just eat a pomegranate?" The evidence would suggest that only 40% of individuals actually can generate this compound. Is that true?
Chris Rinsch
Yes. In fact, we ran a study in Chicago where we gave people a glass of juice, and we compared the levels of Urolithin A that they had in their blood 24 hours later with the levels that you would have in your blood after taking Urolithin A directly. What we saw was that over that first period of 24 hours, that there was basically a more than sixfold lower level of Urolithin A following pomegranate juice.
Chris Rinsch
We saw that you're not getting that much Urolithin A on one hand. On the other hand, we saw that there was only about 40% of people that were making measurable levels of Urolithin A following taking the juice. This goes to show the heterogeneity of the gut microbiome that we all have and that it's not as easy as just eating a certain food type and then hoping that the body can extract all of the benefits from it. It's really a combination of foods and having that right gut microflora in order for you to be able to do that.
Dr Gabrielle Lyon
That seems as if that's the wave of the future to really understanding the individual bio-individuality of the gut microbiome. We're so early on in really studying this. As it relates to Urolithin A, and you might not know the answer to this question, do we know why some individuals can make Urolithin A and some can't?
Dr Gabrielle Lyon
I know that you mentioned the gut microbiome. Because pomegranate is in very particular parts of the world, do we know if those individuals that are from those areas where, say, pomegranates are very robust and harvested and available, that those individuals have a greater ability to create Urolithin A?
Chris Rinsch
Yeah, it's interesting. There's nothing that is so direct, and there's no studies that really indicate clearly that specific populations in areas like, for example, Southern Spain, or Saudi Arabia, or even California, where there's a lot of pomegranates grown, have a beneficial or are more prone to convert and produce Urolithin A than others. It seems...
Chris Rinsch
It's not really known what the right bacteria are. There's been a couple of publications that's given some first suggestions on potential candidate bacteria that are responsible for the conversion of the ellagitannins into Urolithin A. But there's no association with where pomegranates are grown or cultures that are consuming pomegranates and the actual ability to do this bio-transformation into Urolithin A.
Dr Gabrielle Lyon
That's really interesting. I bet you guys are going to figure it out. If it exists, you will figure it out. As you know, we think about looking at some of your papers. I'm looking at this JAMA paper here, and you looked at older adults greater than 60. Again, very relevant because it is the fastest growing population, and we know that they do oftentimes have this progressive loss of muscle mass strength.
Dr Gabrielle Lyon
Again, these metabolic dysregulations that end up happening, but they do have reduced physical activity. You did a randomized control trial in adults, and you looked at Urolithin A on muscular endurance and mitochondrial health in older adults.
Dr Gabrielle Lyon
I would love for you to give us a broad overview of what you were looking for, how you were able to identify, say, lower mitochondrial health or mitochondrial dysfunction, and what results that you found.
Chris Rinsch
Well, it's a really interesting study, and it's really a... It's part of a sequence of studies that we've done looking at mitochondrial health and in this particular age group. We started out very... One of the first studies that we've done was more of an observational study where we looked at people who were 65 and older, and we were looking at people who had high mobility versus low mobility and were considered what they call prefrail.
Chris Rinsch
This is without any type of intervention. We were just curious to see what the difference was in the muscle and what was driving those differences. In that in the course of that study, what we saw was those people who were prefrail had a lot lower mitochondrial function than those people who were active and doing sports all the time.
Chris Rinsch
We looked at that by taking muscle biopsies and seeing lower impacts of the gene expression on mitochondria function, lower protein levels of mitochondrial proteins. We also saw by using a specialized technique called magnetic resonance spectroscopy, we saw a lower mitochondrial function. This is a non-invasive way that uses an NMR magnet.
Chris Rinsch
Basically, you put a limb, it's a limb magnet. You put your leg inside of this magnet and you contract until you use up all the ATP, and then you see how quickly it then is restored. That's a good indication of your mitochondria function. It's a direct indication.
Chris Rinsch
In the study that you're referring to, we basically took the learnings of this study, and we started out by screening people who had low mitochondrial function using this magnetic resonance spectroscopy technique. This basically allowed us to set a level of what would be the entry point of people coming into this study.
Chris Rinsch
We wanted people who had a certain level of mitochondrial function that was not at the very high end. And we also combine that with other types of tests, like the 6-Minute Walk to assess people who weren't very fast walkers too. I would call it a slightly lower level of mitochondrial function, and that's how we selected the group of people. But they weren't considered pre-frail, and they didn't have problems getting around and living life.
Dr Gabrielle Lyon
For the listener, the 6-Minute Walk test is something that we use a lot when we're looking at geriatric patients or just assessing capacity for patients. Now, I'm curious, when you were looking at these older individuals as you initially looked at this study, did you take into account their history of training age? For example, if they were whether they were lifelong athletes or just very robust in their exercise versus, say, recently sedentary?
Chris Rinsch
We didn't look at... It's an excellent question. We haven't gone into a long history of people's physical fitness. But in general, all of the individuals were rather sedentary in their life. But we don't have a prior history, for example, when they were in their 30s, 40s, and 50s, whether or not they were more active.
Dr Gabrielle Lyon
It's interesting to think about mitochondrial health because mitochondrial health is very impacted by exercise. What I love about this concept of urolithinase, the pathways that it push. When I think about mitochondrial health, I oftentimes think about what are the ways. The biggest ways to do that from my perspective is exercise. I don't know if in literature there's a bigger driver.
Dr Gabrielle Lyon
When I say mitochondrial health, what does that mean? I think from my perspective, it's the ability to generate energy or ATP and utilization of substrates. Is there another... After exercise, is there another primary driver for mitochondrial health?
Chris Rinsch
Well, certainly exercise is perhaps the biggest one. There's been a lot of work done on intermittent fasting, and it's my understanding that intermittent fasting can also boost mitochondrial health as it stimulates this process, the same process that Urolithin A is involved in, and we'll get into that a little bit. I think but certainly being athletic and practicing regular sports, that's perhaps the biggest and the most impactful way to improve mitochondrial function outside of taking certain supplements.
Dr Gabrielle Lyon
Again, that's one of the reasons that I... My listeners know I really don't have individuals come on and talk about very specific molecules. I will have someone coming on to talk about Omega-3 fatty acids because typically, again, the influence on something that's relative is relative for the listener or relative for the human`, in general, is limited.
Dr Gabrielle Lyon
But in the evidence that I've seen with these very well-designed trials, you've dosed Urolithin A from 250 milligrams up to a daily dose of 1,000 milligrams. Urolithin A, again, is that compound that is made by the gut microbiome, but 40% of people aren't making it. You guys actually make it and you've dosed individuals. Can you talk a little bit about what you've seen with the lower dosing up into the higher dose of 1,000 milligrams of Urolithin A, specifically on its impact on muscle, endurance, strength, function?
Chris Rinsch
Sure. Well, we all started our very first study where we administered Urolithin A to volunteers was one where we, as you mentioned, we looked at different doses of Urolithin A and what they call a single ascending study followed by a multiple ascending study.
Chris Rinsch
What that means is that in a single ascending study, you give just one dose at one time, and then you see the bioavailability. And then in the multiple ascending dose, you choose the doses from the single ascending dose that you think are the most interesting and have the most compelling data, and then you treat and you administer for a longer period. In our case, we did that for four weeks or 28 days.
Chris Rinsch
What we saw over this... We monitored over this 28-day period. We had... As I was mentioning in other studies, we did muscle biopsies at day one, and we did muscle biopsies at day 28. We also took plasma samples at the start and at the end. What we did on the muscle biopsies, we looked at gene expression patterns. The idea there was to understand what impact, and this was the first time we did that for Urolithin A, what impact that Urolithin A would have on the gene expression patterns of the skeletal muscle tissue.
Chris Rinsch
The cells, the muscle cells that are responsible for making our muscles contract and giving us the strength and endurance that we need. What we saw was that we had what they call mitochondria gene set enrichment analysis, where we saw mitochondria gene sets increase in their expression. A mitochondria gene set is basically a collection of different genes that are involved in actually making the mitochondria function well.
Chris Rinsch
When you see these are upregulated, it's a clear sign that there is mitochondrial biogenesis and basically the production of new mitochondria and improving the functioning of the mitochondria in general. That was pretty exciting. We saw that when we were administering a 500-milligram dose and a 1,000-milligram dose each day for a period of 28 days.
Chris Rinsch
We started investigating those doses more in additional clinical studies. The other impact that we saw was on certain biomarkers that are linked to mitochondrial function when looking at the plasma. We did a metabolomics study, what they call, and that's basically we look at all these different metabolites that are in the plasma, and we analyze the collection of metabolites before the intervention and compare that with the profile following the intervention.
Chris Rinsch
What you're seeing is that you have some enrichment and changes in certain metabolites. Those particular to mitochondria were also observed and specifically the acylcarnitine levels. The acylcarnitine levels declined with time after taking Urolithin A, and this is an indication of performing mitochondria.
Dr Gabrielle Lyon
Essentially, you looked at baseline. I used to do those biopsies.
Chris Rinsch
Really?
Dr Gabrielle Lyon
Did you guys have other people do them? I'm telling you, not fun. And those participants are amazing for doing-
Chris Rinsch
Of course. It's very important to find people who are willing to do these types of... Participate in this type of research because this is what helps us understand the benefits of, in this case, of Urolithin A, and how we can focus our research and scale that to other endpoints that go beyond biomarkers and are more physiological endpoints.
Dr Gabrielle Lyon
For sure. To recap it, you looked at the baseline biomarkers of an individual, including their muscle tissue. You looked at the gene expression of indications of mitochondrial health. You gave them Urolithin A. 28 days later, you then rebiopsied the individuals to look for what the results were with gene expression and other biomarkers. Actually, you did see in such... That's a very short period of time, 28 days. It's a very short period of time to see this increase in positive biomarkers. I have a question for you.
Chris Rinsch
Sure.
Dr Gabrielle Lyon
When we talk about aging, I think it's really important that we know what we're looking at. That's why I'd like to thank one of the sponsors of the show, Inside Tracker. Head on over to insidetracker.com/dr.lyon, and you can get 20% off. Now, in this episode, we do talk a lot about the way in which we age and what happens to muscle. This is why I think it's very critical to know what's going on under the hood.
Dr Gabrielle Lyon
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Dr Gabrielle Lyon
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Dr Gabrielle Lyon
For a limited time now, get 20% off the entire Inside Tracker store. Again, go on over to insidetracker.com/dr.lyon, and that is 20% off the entire Inside Tracker store. Thank you so much, First Form, for sponsoring this episode of the show. Today, I'd love to tell you a little bit about one of my favorite products, and that's Megawatt Natural. This fits nicely in this episode because we're talking about energy, mitochondria health, and really what needs to happen for that.
Dr Gabrielle Lyon
One of the most important things is exercise. That's why I love megawatt. This is a pre-workout that I use. I just throw it in my water and drink it on the way all at once on the way to the gym. This has electrolytes. It has caffeine in it. It really tastes great which I love. It also has B vitamins and neutropics that help with mental focus and alertness. It really gets me dialed in to my training session.
Dr Gabrielle Lyon
I use a handful of things, but this has certainly been something I've been using for a very long time. You can go over to firstform.com/dr.lyon and definitely check out their megawatt, they have all different flavors. I really love the Megawatt Natural, again, as a pre-workout. I may or may not take half a scoop in the afternoon to also help me with the rest of the day, which I do. Head on over to firstform.com/dr.lyon.
Dr Gabrielle Lyon
In terms of the fiber types, did you look at type one, type two fiber types as it relates to the impact of Urolithin A?
Chris Rinsch
Yeah, we haven't looked at specific fiber types. It was very difficult considering the amount of tissue to be able to dissect that out. You need a certain amount of tissue just to perform this gene expression analysis. We tried to take the smallest size biopsy possible to be able to run our analysis.
Dr Gabrielle Lyon
Rightly so. If you looked at 28 days, also two months, four months, and then any studies beyond four months?
Chris Rinsch
In the study that you mentioned before that we published in the JAMA Open Journal, we were looking at physiological benefits after as long as four months. We haven't, in a clinical setting, gone beyond four months, although we have a number of customers who have been taking our product for much, much longer. I've been taking the product since it was available.
Dr Gabrielle Lyon
You were hiding before it was even done. You were ready in the back and probably like, Oh, man, this is amazing. I got to be honest. In terms of length of time it takes to work, we know roughly 28 days, so about a month for individuals to feel an impact. Did you see in any of your studies... You obviously saw changes in muscular endurance as it relates to physical performance for the 6-Minute Walk. What about strength?
Chris Rinsch
With strength, we ran another study that was more of a middle-aged group, so 40-65-year-old individuals who were sedentary and overweight and we gave them 500 milligrams or 1,000 milligrams, and we followed them for a period of four months, and they weren't exercising. What we saw was an improvement in leg muscle strength. We measure a number of parameters.
Chris Rinsch
But the one parameter that really stood out was the improvement in leg muscle strength of 10% from the baseline, which is quite impressive because we're not actually doing any exercise to reinforce and build up that strength. That was a very good finding. When we ran the other study in the older individuals, and we looked at muscle endurance, it really corresponds that we're seeing multiple studies impacting muscle function.
Chris Rinsch
In the study there in the 40-65, we looked at other parameters too. One of the other parameters was this Peak VO2. We also saw an improvement in Peak VO2. This was also giving us this more data to support that we're having this general impact on the body's health.
Dr Gabrielle Lyon
It's interesting. It works along the same pathways, essentially, as exercise, which leads me to another thought, and I'm sure the listener is thinking about this. But what about impacts on specific blood markers that perhaps are impacted through physical exercise like triglycerides or HGL or CRP, fasting blood glucose or insulin? Did you see changes in any of those blood markers?
Chris Rinsch
We haven't done a specific study to analyze those blood markers. Normally, when you're looking for changes, you want to choose a population that might have some type of an issue and then you're looking to correct it. And so the criteria that we had for all of those patients or subjects that were coming into the study were that they're healthy, that they didn't have some type of issue with their cholesterol or another type of biomarker.
Dr Gabrielle Lyon
Right, that would make sense. In terms of the impact on Urolithin A and what you've seen, did it make a difference if they were obese or not? Because the reason I ask this is there's evidence to suggest that sometimes in obese muscle, there's this blunted muscle protein synthesis effect. Again, I know that the Urolithin A isn't necessarily working on the pathways of mTOR or muscle protein synthesis, but we do see a blunting of... It's almost like an exercise effect, and I'm really simplifying that.
Dr Gabrielle Lyon
I'm curious, did you find that the mitochondria gene expression was blunted, and maybe you did or didn't look at this, in individuals that struggled with weight or are more on the obese end?
Chris Rinsch
Well, in our study, in the 40-65-year-olds, they were sedentary and overweight, but they weren't obese. We haven't studied the product in a clinical setting in obese individuals. It would be hard to comment on that. But what I can say is in those overweight individuals who are sedentary, that we improve the leg muscle strength. That I thought was quite impressive after only four months of taking the product and without adding any type of exercise regimen.
Dr Gabrielle Lyon
Yeah, I think that that's really, really profound. Do you eventually believe that you'll look at it as it relates to body composition? Do you think that this is something that perhaps... I know that you've really identified its effect on mitophagy, which I would love for you to talk a little bit more-
Chris Rinsch
Sure.
Dr Gabrielle Lyon
-about mitophagy. But do you expect that perhaps it also has other areas of impact?
Chris Rinsch
Sure. I think that when you think of mitochondria, mitochondria are basically in all of our cells except our red blood cells. They're important for producing the energy inside the cells so that all of the cellular reactions can take place that the cell needs to perform to stay healthy and do its job. And so if you're thinking about improving mitochondrial function, it's not only acting on your muscle cells, at least in the case of Urolithin A, it's acting on a whole number of different cell types.
Chris Rinsch
There have been multiple publications by other groups showing its benefits on other cell types. There was a publication by a collaborator who runs a study for quite some time to research the impact on immune health. They came out with a very nice paper in the Journal of Immunity about a month ago showing the positive impact on immune cells and on T-memory cells and the stemness there.
Chris Rinsch
There's been other studies that we've done where we've looked at joint health and cartilage and showing an improvement in models of osteoarthritis and animal models of osteoarthritis. There's been other groups that have looked at it in the context of brain health as well. They've shown positive impact in brain health.
Chris Rinsch
Now the question is, this goes back to translation, which of these might translate into human benefits? It's too early to tell, and a lot more studies need to take place that we're... In terms of new benefits, we are working on the immune side, and that's one area that we're very interested in. I think a lot of your listeners are probably interested in immune health with all of the issues around COVID during these last couple of years and even now. And so we're going to be running some tests, some clinical tests with Urolithin A looking at its impact on general immune health.
Dr Gabrielle Lyon
Yeah, that is also going to be really important. It's interesting to think when we come up for ways of treating some of these diseases of aging, and I say disease of aging, and really, again, my interest is in skeletal muscle, we don't have treatments. The best treatment that we have is exercise that really impacts skeletal muscle, dietary protein. There may be benefit to some hormonal or anabolic intervention.
Dr Gabrielle Lyon
This is the first compound that I've seen, and I'm not talking about omega-3 or creatine, but as a plant-based compound, this is something that I... Again, my training is as a geriatrician, and this is very interesting as a geriatrician perspective as this relates to overall health and specifically this concept of mitophagy, which is this selective autophagy process. I'd love for you to explain to the listener a little bit about that and how that goes awry and ways in which we can counteract that decline.
Chris Rinsch
Sure. Gabrielle, I think it's very... Mitophagy is at the core of maintaining healthy mitochondria inside of your cells. As your mitochondria are producing ATP in that process, there's a lot of reactive oxygen species that are created. What happens with these reactive oxygen species is that they will attack the membrane with the mitochondria. So mitochondria will get damaged over time. As they do their business of producing energy for the cell, they'll get damaged.
Chris Rinsch
But the cell is very clever and has this process inside that basically recycles the damaged mitochondria. It identifies damaged mitochondria, and it puts them in a path where they are basically engulfed and then digested, and then the component parts are released into the cell so that they can be used to then build a new mitochondria or expand existing mitochondria.
Chris Rinsch
This is really important because without this, your mitochondria would be damaged as they're producing ATP, and then you'd have a collection of damaged mitochondria that weren't very healthy. And so, consequently, the cells wouldn't function optimally. As a consequence of that, then you have your tissues that aren't working very well. Then you start to feel the physiological impact of that, that you're not able to... You can't be as active. You don't have that same endurance. The muscle strength goes down.
Chris Rinsch
That's why it's very important to keep the mitochondria always undergoing this process of mitophagy, which is the self-eating and recycling of the mitochondria.
Dr Gabrielle Lyon
Chris, is there a synergistic impact of Urolithin A plus exercise, whether or aerobic exercise?
Chris Rinsch
We haven't tested that yet, but we are... I mean we haven't completed tests of that. We're in the process of conducting a study over in Australia looking at athletes who are taking Urolithin A as well. This is something that we think is going to be very exciting. But the jury is out on that, and we're waiting to complete the study to analyze the data. But it makes sense.
Chris Rinsch
We're not suggesting that because the effects of Urolithin A are, and Mitopure, are exercise like, and some scientists who've looked at our data say, "Oh, this looks like an exercise mimetic." I would not encourage people to forego exercise. I do think there's likely to be a synergy between having a very regular exercise regimen and taking Mitopure on top of that because exercise will have a certain impact but Urolithin A, you can take that, and that will have its impact at different times during the day. So you can imagine timing your exercise, for example.
Dr Gabrielle Lyon
Yeah, I agree with you, and I think it's going to be very beneficial. Do you think that there's any role of the compound Urolithin A in, say, bedrest, in preservation of mitochondria in individuals who are fully on bedrest?
Chris Rinsch
Oh, for sure. I mean, this is another area of great interest, and we're working together with our partner to conduct a study with Professor Stuart Phillips.
Dr Gabrielle Lyon
Stu's a friend of mine.
Chris Rinsch
Yeah, Stu's great.
Dr Gabrielle Lyon
Is the best and just an incredible human.
Chris Rinsch
Yeah, no, he's great. He's going to be conducting a study where we look at the effect of Urolithin A in people who have a bedrest type of exposure to see how that can maintain muscle function while you're inactive, because as you allude to it, when you're immobile, your muscle tends to... Yeah, you tend to have less muscle. It wastes away. Then you need to get back on your feet and exercise again to build out that muscle.
Chris Rinsch
I think the one interesting thing about, and we haven't really touched on that yet, is the importance of not only muscle mass, but having all of your cells function optimally, no matter how much muscle mass you have. You could have a lower, I mean, as you get older and you have reduced muscle mass, the key is making that muscle mass, and those muscle cells that you have function at their peak. That can even counterbalance the negative effects of not having enough muscle tissue if you can just take what you have and make it work better.
Dr Gabrielle Lyon
Yeah, that's one of the most important things that we see in aging, and it is like almost this tipping point. There comes a point that I can appreciate in the literature, it talks a lot about how muscle is... You can always build muscle, and you can maintain it. But the reality is it gets more difficult because just the tissue effect is blunted to the efficiency of components of muscle, muscle protein synthesis decline. It's really critical to be able to highlight and maintain healthy mitochondrial function.
Dr Gabrielle Lyon
Clinically, people, as they get older, they often when they lose muscle, and I know that we're not necessarily talking about the loss of muscle in and of itself only, but they complain of things like being tired and fatigued and having reduced exercise capacity. I think that this is where this compound really can push the needle for people. I'm sure that you've probably seen that in reports from the participants.
Chris Rinsch
Yeah, less energy. What you're saying is people feel like they have less energy, and and lots of people feel like they have less energy out there. What's interesting is that when you boost your mitochondrial function and with Urolithin A and the product that we've developed, I mean, what you see is that people are consistently speaking of having more energy. There's even people who have have stopped taking coffee. Because-
Dr Gabrielle Lyon
Are you serious?
Chris Rinsch
I stopped taking coffee a couple of years ago, and I don't see the need for it after taking Urolithin A on a daily basis.
Dr Gabrielle Lyon
It's a really amazing product, and I love it. I actually love the powder. I'm actually designing a meal plan, and I reached out to Ian because I want to put it in one of these... I love yogurt-type stuff, and so I want to actually put the Berry Mitopure in it. Hopefully, we'll get on board. I'm just getting a little plug now here because maybe you know someone.
Dr Gabrielle Lyon
But I think that the way in which you have created and packaged and delivered this, I think is very beneficial for people in the way that it's not a pharmaceutical. This is actually... A lot of pharmaceuticals, actually, or chemotherapy drugs, they actually do come from nature. There's many of them-
Chris Rinsch
Of course.
Dr Gabrielle Lyon
-things come from nature. It's wonderful to see such promising evidence that... This is done in randomized controlled trials in humans.
Chris Rinsch
I think what you're saying is important because it's all about the safety of the product that you're taking. You want to make sure when you're having a food product that is very safe and that the customers don't ask themselves when they purchase it or when they're consuming it, "Could I get sick?"
Chris Rinsch
I mean, here we've gone through this whole process that you're familiar with called the GRAS or Generally Regarded Safe with the FDA. As you were mentioning, we've now run a number of double-blind. I think it's important to say that these are all double-blind, placebo-controlled studies with our product where we analyze not only the beneficial effects, but we take a look and see if there's any types of negative effects. We haven't seen any today.
Dr Gabrielle Lyon
I do think that that's also really critical. In terms of... I know that I'm getting short on time, but I do have a lot of questions. I promise I'm just going to just choose the most salient ones. Do you think there's any benefit in combination of say, something like Urolithin A with creatine or any kind of synergistic compounds that one would ingest with Urolithin A?
Chris Rinsch
I think there is. I mean, when you consider Urolithin A as a supplement, it's basically rebuilding your mitochondria. It's taking a population of mitochondria inside of your cells that may not be optimal and tuning them up to make a population that's more robust. Then once you have that population, if you can give other nutrients that will be beneficial to the mitochondria, it makes sense that the mitochondria will be able to perform even better.
Dr Gabrielle Lyon
So that would be something like, sorry, go ahead.
Chris Rinsch
No, go ahead.
Dr Gabrielle Lyon
Would that be something like CoQ10?
Chris Rinsch
What - Well, one could imagine CoQ10, for example, that could be one. We haven't studied any type of combinations specifically at this point that we've published, but I think that there are a number of potential actives that could be synergistic with Urolithin A, particularly for the muscle, for energy. Then as we start thinking about other types of health benefits that I was alluding to before, whether that's immune health or gut health or other areas.
Dr Gabrielle Lyon
Yeah, that is really important because when you were talking about mitochondria, just like you said, it's in nearly everything except for red blood cells. You're talking about skeletal muscle health, you're talking about neurodegenerative... Neural health in an effort to avoid neurodegenerative kinds of issues and then joint health, inflammatory-
Chris Rinsch
Heart health.
Dr Gabrielle Lyon
-heart health, all of the things and metabolic dysfunction, which I think is really critical. Just to wrap up an individual number one, you could eat a ton of pomegranates, but it's actually not in the red part. It's in the that bitter white, yellow part, right?
Chris Rinsch
It is. All of these Ellagitannins and punicalagin... That Ellagitannin I was mentioning is really found in that white membraneous part of the pomegranate. The part that's really bitter. When you drink a pomegranate juice and it's really bitter, you know you're getting lots of punicalagin, but you're also getting a lot of sugar because it's one of those juices that has the highest content of sugar. It's probably not too healthy on a metabolic perspective to take that level of sugar.
Dr Gabrielle Lyon
Yeah. Or you're going to choose the most bitter juice that you can find, which no one really wants that. That's gross. You would need about six cups of juice to equal, is it 500 milligrams of a single to get a-
Chris Rinsch
Yes. You would need at least six... You would need, one, to have the right gut microflora, and two, you would need to have about six glass, six eight-ounce glasses of pomegranate juice to equal one dose of 500 milligrams of Mitopure, which is Urolithin A that we manufacture and we are commercializing under this Timeline brand.
Dr Gabrielle Lyon
Yeah, I will be a hard pass on that 6-9 cups of pomegranate juice. I don't know about you. If you could see any massive change, what would be a dream for you? Because you've put in, I don't think people realize the amount of work that has likely gone into this company, your efforts. You've really pioneered something special. What does success look like for you and for the company and the impact that you're trying to make?
Chris Rinsch
Thank you. I think success is really... I think we're really at the early stages on this, Gabrielle. The idea is now to spread the word and educate more people about the health benefits of Urolithin A and Mitopure, and get people taking this on a regular basis. It should be I think most people, when they think of dietary supplementation, they think of omega-3, they think of vitamin C.
Chris Rinsch
I think people should be really mindful that in order for their cells and their body to function, one of the key aspects to first address is energy and an ATP and their mitochondria. That this should be something that should be on everybody's minds that they should first start trying to optimize the cellular health from a mitochondria perspective and then add other nutrients on top that they think would be beneficial in their specific cases.
Chris Rinsch
And so for me, the dream would be that as many people as possible can benefit from the health benefits that Urolithin A is providing and that we are continuing to have benefits in different health areas, whether it's muscle health, immune health, et cetera.
Dr Gabrielle Lyon
Well, I'm really excited. I'm excited to help spread the word. Again, I really appreciate that you've really taken an evidence-based approach to this. That lends a lot of credibility to the movement and the impact that this potentially can make because it has taken so much time and been done so diligently. So thank you.
Dr Gabrielle Lyon
I'm going to link for the audience where to find everything. I think that if they're open to it, should really give it a try. I know that we're taking it over here, which is one of the reasons why I wanted to have you on. I'm so grateful for your team for making this possible.
Chris Rinsch
Well, thank you so much, Gabrielle, for having me here today. It's been fun chatting and discussing about mitochondria and Urolithin A.
Dr Gabrielle Lyon
Yeah. Thank you so much, Chris.
Chris Rinsch
Thank you.
Segment 3: Speaker 3
The Dr Gabrielle Lyon podcast and YouTube are for general information purposes only, and do not constitute the practice of medicine, nursing or other professional healthcare services including the giving of medical advice. And no patient-doctor relationship is formed.
Segment 3: Speaker 3
The use of information on this podcast, YouTube, or materials linked from a podcast or YouTube is at the user's own risk. The content of this podcast is not intended to substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition. They may have and should seek the assistance of their healthcare professional for any such conditions. This is purely for entertainment and educational purposes only.

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These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. References: *Nutrition studies: 500mg Mitopure® have been shown to (1) induce gene expression related to mitochondria function and metabolism and (2) increase the strength of the hamstring leg muscle in measures of knee extension and flexion in overweight 40-65 year olds. Data from two randomized double-blind placebo-controlled human clinical trials. **Nutrition NOURISH Study: 500mg Mitopure® have been shown to deliver at least 6 times higher Urolithin A plasma levels over 24 hours (area under the curve) than 8 ounces (240ml) of pomegranate juice in a randomized human clinical trial.

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