[00:00:00] Luke Storey: I'm Luke Storey. For the past 22 years, I've been relentlessly committed to my deepest passion, designing the ultimate lifestyle based on the most powerful principles of spirituality, health, psychology. The Life Stylist podcast is a show dedicated to sharing my discoveries and the experts behind them with you. Alright, Chris, let's talk about mitochondrial function and energy. I'm really excited to discuss this with you.

[00:00:32] Chris Rinsch: Sure. Thanks. So, mitochondria is basically an organelle inside of our cells that acts as the power supply of our cells, and consequently, our body. It produces ATP. It takes the oxygen that you breathe and the foods that you consume, and it transforms that into energy.

[00:00:51] Luke Storey: What happens when people have what's called mitochondrial dysfunction?

[00:00:57] Chris Rinsch: Mitochondrial dysfunction comes from, well, it can be associated with many things, but usually, it's due to, in a non-disease state, if you will, it's due to less activity. If people are sedentary and leading a sedentary life, the mitochondria are less robust, if you will. So, exercise and movement is one way to keep your mitochondria very active, and of course, also a very healthy diet.

[00:01:26] Luke Storey: What are some of the diseases associated with acute mitochondrial dysfunction? What happens if your mitochondria just totally tank as you get older and you don't do anything to fortify them? What are some of the issues with that?

[00:01:40] Chris Rinsch: Well, as we get older, we peak in our 30s in terms of muscle function if we just talk about muscle function for a second. And as we get older beyond our 30s, the muscle function starts to decline, but we can maintain it, and it can be still very, let's say, robust, although not as good as our 30s, as long as we're exercising in a regular basis. But people who aren't exercising very well and very often, you often see that they're not very mobile into the later part of their life, yeah.

[00:02:17] Luke Storey: And what about mitophagy? Could you explain kind of the recycling system? I know some people are familiar with autophagy, where your cells are recycling. How does that work with mitochondria?

[00:02:28] Chris Rinsch: So, inside of our cells, there's a process that's innate to maintain sort of a homeostasis of our mitochondria, and this process is called mitophagy. And essentially, what happens is that as mitochondria are producing energy, the mitochondria can get damaged basically through reactive oxygen species. It's producing energy and reactive oxygen species that are produced, and that causes the damage that then needs to be cleared away, otherwise the mitochondria won't be very functional, yeah, on a continuous basis.

[00:03:04] And so, the cell has this process that's called mitophagy, in which these damaged mitochondria are then sort of sequestered into a recycling pathway. And they're broken down into their component parts, and then these component parts are then sort of used to reconstitute mitochondria essentially and grow mitochondria, which then divide and keep the bioenergetic status of the cell at its optimal place.

[00:03:32] Luke Storey: How old are mitochondria, do we know?

[00:03:37] Chris Rinsch: Well, mitochondria are passed from—the mitochondria in our body come from our mothers, originally. And, yeah, in terms of the mitochondria itself, the cells, all of our cells, with the exception of our red blood cells, contain mitochondria. Yeah. And depending upon the cell type, there may be more or less mitochondria. So, there's not, I would say, a particular age of the mitochondria. It's a very dynamic process of recycling.

[00:04:13] Luke Storey: I think what I was getting at is were they here before us, or you know what I mean? Like because are mitochondria essentially a bacteria? Would that be a valid statement? Like what are they? And I guess how did they show up throughout our evolution as a species, or are they just like in the first human from day one, or what?

[00:04:35] Chris Rinsch: Well, I think that comes with the evolution that it's been believed that the mitochondria are basically other bacteria and that they sort of somehow fuse during evolution with our cells to then allow ourselves to produce ATP.

[00:04:55] Luke Storey: Okay. And so, if we're inheriting mitochondria from our mother, would that mean that if the mother's mitochondrial function is robust, and she has them working functionally and has a lot of mitochondria, would that offspring have a better chance of success, and energy, and mitochondrial function?

[00:05:21] Chris Rinsch: For sure, yeah. I mean, as we receive the mitochondria from our mother, this is a great sign in terms of your longevity, so normally, you would see that people who have mothers with highly functional mitochondria, they're going to be also very fit as well.

[00:05:44] Luke Storey: So, say a woman wants is preparing to give birth and wants to ensure that they have an abundance of mitochondria and that they're well functioning, are there any tests that have developed where one could assess that, like you could test your micronutrient levels, for example? Are there means by which people can test their mitochondria?

[00:06:09] Chris Rinsch: Well, you can certainly evaluate if you have any type of mutations in your mitochondria, in the DNA of your mitochondria, but in terms of just overall health of mitochondria, I don't believe that there's any test, but I'm not aware.

[00:06:29] Luke Storey: So, if you're testing the function of them, what are those tests called? And if someone listening wanted to go, say, again, a mother is preparing to get pregnant, and was like, oh, man, I want to pass off the best and most robust mitochondria, what kind of testing would one do to determine the function? Is there like a blood test or something that easy, or is it more sophisticated?

[00:06:53] Chris Rinsch: I don't think there's a standardized test for that purpose other than if you have a disease, as I was mentioning before.

[00:07:01] Luke Storey: Ah, okay. And so, what are some of the common ways that people, whether they be mothers to be or not, can improve their mitochondrial function?

[00:07:12] Chris Rinsch: Well, certainly, it's, I would say, a combination of just your lifestyle choices. So, one is exercise, of course. So, if you're exercising a lot, the whole process of exercise stimulates mitochondria and improvement in mitochondrial function, mitochondrial biogenesis, and in fact, also mitophagy. So, if you're running on a regular basis, that helps you maintain your mitochondria at its peak.

[00:07:45] Luke Storey: What about fasting? Does that have any value in this?

[00:07:47] Chris Rinsch: Yes. Well, fasting, as well as caloric restriction, is known to also improve mitochondrial function in general. Yeah.

[00:07:57] Luke Storey: And so, if what we're going for by fortifying our mitochondria and being mindful of their health because we want the ATP, the energy that they're producing, how does something like using NAD that improves the production of ATP play into the mitochondria? Are there things other than ATP that we can use as an intervention to ensure the production of ATP?

[00:08:28] Chris Rinsch: Well, in terms of general supplements today that just help your mitochondria function better, there are the Coenzyme Q10 and L-carnitine that people use a lot, but that's more for the general functioning of the mitochondria. Now, our product is Urolithin A, and I guess we'll talk about that a little bit later, and that's targeting this pathway of mitophagy, as I was mentioning before, which is essential for, basically, the turnover and the maintenance of sort of robust bioenergetic pool of mitochondria inside of our cells.

[00:09:07] Luke Storey: Have you looked into, speaking of mitochondria, because I've done a couple of shows on this, have you looked into deuterium and deuterium depletion as it pertains to ATP production by chance?

[00:09:17] Chris Rinsch: No, we haven't.

[00:09:18] Luke Storey: Oh, okay. Yeah, it's an interesting concept and the audience, the older listeners will be familiar with this, but over time, because there's so much of this heavy hydrogen in our atmosphere, water, air, foods, things like that, especially processed foods and industrial foods, that we build up these really high levels of this deuterium, and it gets in the nanomotors of the mitochondria and slows down the production of ATP.

[00:09:46] It's really interesting. So, there are companies now that are making deuterium-depleted water. And so, if you kind of dilute the metabolic water in your system by drinking this water, then ultimately, you start to deplete your deuterium levels and bring them down. And it's an interesting thing. It's probably the most nuanced and kind of out there thing that I've found in terms of the mitochondria and the ATP production.

[00:10:11] And I'll put that in the show notes for people that are like, what are you talking about? But whenever I talk to someone about mitochondria, I'm like, do you know about this thing? Is it legit? There seems to be a lot of science around it. So, I think many people are familiar with the fact that there are foods that we can eat that have constituents that are supportive to various systems in our body.

[00:10:33] And I think when it comes to eating plants, and eating fruits, and vegetables, and things like that, oftentimes, there are benefits, and there are ingredients, molecules in these foods that have the ability to support our health. But oftentimes, they're not in adequate amounts, or there are other not so desirable molecules or tons of sugar and things like that.

[00:11:00] Aside from what we're going to end up talking about, which is pomegranate, which is really fascinating, because I would have never thought of pomegranate as a superfood, are there other foods that we can derive benefit from, but more so if they're concentrated and isolated versus eating vegetables with tons of oxalates or eating fruits that have tons of sugar? If someone thinks of vitamin C, that's great. Well, I'll drink a huge glass of orange juice, and wreck my metabolism and glucose levels. What do you think about, I guess, that in general about some of the foods and things that are good for us, but also kind of have a downside when it comes to consuming mass quantities of them?

[00:11:48] Chris Rinsch: Yeah, I would say that a lot of the juices are very rich in sugar. So, if you're consuming a lot of juice, that's probably not ideal. And I guess in moderation, everything is fine, but in terms of specific foods, food items that you could concentrate, of course, today, there's a big interest in in making supplements, extracts of different foods that normally are where they extract the sugar and remove the sugars from them to allow people to sort of get that mixture of, yeah, nutrients that you might get from that particular food type.

[00:12:30] Luke Storey: And what's your field of study? How did you get into this game anyway? I wanted to ask you that in the beginning, it slipped my mind. I just jumped right in. What's mitochondria? What's your, I guess, expertise in your field?

[00:12:46] Chris Rinsch: Well, in the very beginning when we started the company, I had been in the space of investing into nutrition companies, and we thought, this would be, at the time, I was seeing a lot of science going on in the laboratories of, in phytochemist laboratories and biology laboratories, but there was very little sort of crosstalk and crosspollination between the two, and I thought that this was an area that was ripe for disruption. And so, at the time, I thought, let's examine this and see how we can explore the benefits of foods by applying the right science to it. And that was sort of the starting thoughts.

[00:13:39] Luke Storey: And so, how did you stumble upon this Urolithin A. That took me all morning to memorize how to say it, Urolithin A. There are things out there like quercetin, right? So, you have capers are really high in quercetin, but again, like you're not going to eat four jars of capers probably for breakfast. And this, as I understand, is derived from part of the pomegranate. When did you first hear about Urolithin A and start to delve into the research around it?

[00:14:06] Chris Rinsch: Well, we initially started looking at the pomegranate, because at the time, there was some initial studies on the pomegranate and the pomegranate juice. There was talk about antioxidants. So, we started to learn more about the pomegranate. We thought maybe this is an attractive fruit in terms of its molecular constituents. And so, we went and we got pomegranates from different sources.

[00:14:33] We started choosing the pomegranates and learning about what was inside, at what concentration levels, and then making extracts, and studying the different compounds inside. And at one point, after studying some of the compounds, we came to the thought that there might be something to the metabolites, which is a class of compounds called Urolithins, one of which is Urolithin A, and these metabolites are produced when you consume the compounds inside of the pomegranates, the class that are called the ellagitannins. In that class, you have punicalagin, which is very rich in the pomegranate.

[00:15:14] So, when you consume that, what happens is that your gut microflora then will transform that into metabolites. And one of those metabolites is your Urolithin A. And a lot of the work at the time had been showing how this was basically a way to eliminate some of the compounds that are coming from the pomegranate. What we thought was perhaps that this is something that actually has a biological importance. And so, we started studying that as well.

[00:15:44] Luke Storey: Are there other foods besides pomegranate that are high in this Urolithin A?

[00:15:50] Chris Rinsch: Well, so there's a number of foods that have these precursor compounds, these ellagitannins, and they tend to be these small fruits and berries, such as, let's say, raspberry, blackberry. And then, there are some nuts like walnuts and pecans that have these precursor compounds. And so, if you consume them as well, you'll also get exposed to Urolithin A, but only if you have the right gut microbes.

[00:16:21] Luke Storey: Ah, right. So, there are foods, pomegranate and these others that contain the metabolites, but then it's still up to your body to produce the compound, Urolithin A, which is what we're going for, for the mitochondrial function, and autophagy, and such.

[00:16:34] Chris Rinsch: Right. So, there are several foods that will have those starting compounds as ellagitannins, yeah.

[00:16:42] Luke Storey: Got it. Ellagitans.

[00:16:43] Chris Rinsch: Ellagitannins.

[00:16:44] Luke Storey: Elagitannins. Okay. So, I know the word tannins, makes sense, antioxidant-rich foods often are accompanied by tannins. So, if somebody's gut is wrecked, and they just have dysbiosis and things like that, is it more difficult for them to produce that, or is it a genetic thing, where some people's guts are just kind of built to create that process and others aren't?

[00:17:14] Chris Rinsch: I don't think it's really understood why some people's gut microflora are able to make this conversion of the ellagitannins to the Urolithin A, and some aren't. We've conducted a study that we recently published in the European Journal of Nutrition that basically shows that there's around 40% of the population, at least in our study in the US, that are able to make this conversion into Urolithin A when drinking pomegranate juice.

[00:17:44] Luke Storey: So, with the stuff that you guys make, I'll show the camera, it's called Timeline, comes in a little pouch. By the way, it's actually pretty delicious. Oftentimes, I go to conferences and stuff, and I try everything, and some things don't taste that great. I was like, this actually kind of tastes like pomegranate. It's not like a fake sweet thing. So, with Timeline, for example, would some people take a product like this and not be able to actually have that conversion take place? And how would they know if it's going to work for them, whether they eat 40 pomegranates in a sitting or they get a concentrate like this?

[00:18:22] Chris Rinsch: Well, so what's important to understand is that Timeline takes all of the issue of the gut microbiota out of the equation, because we're giving Urolithin A directly into the product.

[00:18:38] Luke Storey: Oh, so it's already like pre-converted, for lack of a better term?

[00:18:42] Chris Rinsch: Well, yeah. So, you're getting the actual end product that you would normally get if you were converting the ellagitannins into the Urolithin A, you're just receiving the Urolithin A.

[00:18:53] Luke Storey: Oh, cool.

[00:18:54] Chris Rinsch: Yeah.

[00:18:54] Luke Storey: Damn, that's a pretty badass discovery.

[00:18:56] Chris Rinsch: And so, the nice thing about it is we give a very precise dose that we've studied in clinical studies. And so, you know exactly how much you're getting as opposed to a normal diet, where you don't really know what you're getting, because, one, you'll have to eat the same type of foods every day, yeah, and then you have the whole issue of the conversion. In the latest study that I was referring to, we compared the amount of Urolithin A that you get from drinking a glass of pomegranate juice to taking 500 milligrams of Mitopure, which is our Urolithin A. And we see that over a period of 24 hours, you have six times more Urolithin Aexposure. So, essentially, if you want to take juice and you are a converter, you would need to take six large glasses of pomegranate juice.

[00:19:51] Luke Storey: I wonder how much sugar is in six glasses of pomegranate.

[00:19:55] Chris Rinsch: More than you probably want to consume.

[00:19:57] Luke Storey: I mean, not to vilify sugar, to be honest, last night, I snuck down to the market here, and bought all kinds of things full of sugar, and felt it this morning. But for me, like I don't vilify sugar, but if I'm going to eat sugar, I'm going to eat something that probably tastes more rich and satisfying than six classes of pomegranate juice. So, are you deriving this Urolithin A from the juicy, fruity part of the pomegranate, or is it coming in kind of the rind and those bitter yellow bits that we try to avoid when we pull one apart and eat it?

[00:20:33] Chris Rinsch: Yeah. So, these ellagitannins that I was referring to are really found into the white part of the flesh inside the pomegranate, the bitter part. So, these ellagitannins are very bitter-tasting. So, the more bitter your juice is, the more ellagitannins you'll have in your juice.

[00:20:50] Luke Storey: And typically, that part of the pomegranate is the part that people avoid eating, right? That's kind of the fun of opening a pomegranate, is picking out the little seeds, and you have the reward of that, and you kind of discard the yellow, bitter bits. It's similar maybe to oranges. I remember when I was a kid, and my mom would cut up an orange, she would always recommend that I eat, I guess, the rind, is that what it's called?

[00:21:12] Chris Rinsch: Yeah.

[00:21:12] Luke Storey: The soft, fluffy part. Oh, you got to eat that for whatever, she was kind of a health nut like me. So, it's unlikely somebody's going to eat that part of the pomegranate, honestly.

[00:21:22] Chris Rinsch: Yeah, it's not your preferred part of the fruit.

[00:21:26] Luke Storey: Okay. So, when we get this Urolithin A directly like this, how is that impacting the mitochondria positively?

[00:21:35] Chris Rinsch: Well, so back to the first part of our discussion, we were talking about mitophagy. So, we studied the Urolithin A for a while, and we saw that when we were testing it in the lab, in vitro and cell culture, we saw that it was improving mitochondrial function. And we took a deeper dive to look into the mechanisms, and then we understood after a lot of studies that it was stimulating this whole process of mitophagy.

[00:22:04] And it was very exciting because it was the first compound that's been shown to induce mitophagy in cells. Yeah, natural compound that was safe. Of course, there are compounds that can do that, but that are toxic. And so, it was very exciting and we started sort of translating that to see what its impact would be on not only mitochondrial function, but also sort of physiological function. And we did this through extensive preclinical testing, and looking at muscle function in mice and, yeah, in rodents.

[00:22:42] Luke Storey: When you're doing a test like that and you're using mice, how do you titrate the dosage to get the equivalent of what a human would eat? So, I think these packets were like 500 milligrams?

[00:22:55] Chris Rinsch: So, essentially, the main ways is basically to feed the animals with it and you can balance out how much you want to administer in that way.

[00:23:08] Luke Storey: So, you come up with like the human equivalent dose for a tiny little animal, essentially, to determine if there's going to be a similar response in a human, is that how it works?

[00:23:17] Chris Rinsch: Well, it's more of the reverse. You start out with doses that you think might be suitable in an animal setting, and then when you translate that to humans, you then scale that up.

[00:23:33] Luke Storey: Ah, okay. Cool. And so, let me see where I want to go with this. With the microbiome piece, is it not that necessary? I mean, obviously, everyone wants to have a healthy microbiome, but in this case, since we're just taking the compound that we want directly and we don't have to go through that, how much does gut health play in the success of taking Urolithin A directly like this?

[00:24:05] Chris Rinsch: Well, it's a good question. I don't believe that the gut health plays an essential role there. Of course, it's always important to have a healthy gut. And so, it's hard to say what the impact would be if you had some type of, yeah, malfunction of your gut or disease. But for a general healthy person, which is the target audience that, of course, we go after with food supplements and nutrition products, I don't see there being an impact there.

[00:24:38] Luke Storey: Cool. And what are some of the other studies that you guys have done? I understand you're based in Switzerland?

[00:24:43] Chris Rinsch: We are based in Switzerland. We're based in the French-speaking part of Switzerland, over in Lausanne. And we basically developed after, of course, seeing these positive effects on muscle function in animals, we then took that next step of bringing this into humans. And so, we went through the whole safety analysis process that is required to get through the FDA GRAS procedure, which GRAS stands for generally regarded as safe. And so, we've gone through that procedure for Urolithin A that we've branded as Mitopure, and we've then gone on to run several clinical studies. So, we've run four.

[00:25:31] We've completed four clinical studies with that and we're engaging in a fifth one. So, the first clinical study looked at the bioavailability and the safety of Mitopure, and we also looked at biomarkers both in the blood and in the muscle after four weeks of taking Mitopure. And that first study, what we showed was that we were able to boost mitochondria function and that we saw that through looking at the biomarkers found in the muscle tissue. So, we took the biopsies before and after, and doing the analysis of gene expression in those samples, we were able to see that there's an upregulation in gene expression, particular to mitochondria.

[00:26:25] Luke Storey: Wow. After only four weeks?

[00:26:27] Chris Rinsch: Yeah, after four weeks of taking it, yeah.

[00:26:28] Luke Storey: Damn, that's crazy. And what kind of dosage where the participants working with?

[00:26:32] Chris Rinsch: Five hundred milligrams.

[00:26:33] Luke Storey: Just one a day? 

[00:26:35] Chris Rinsch: One a day in the morning, yeah.

[00:26:36] Luke Storey: Really?

[00:26:37] Chris Rinsch: Yeah.

[00:26:37] Luke Storey: That's crazy. I get so excited when somebody comes to market with something that actually works, you know what I mean? Not to disparage the supplement companies out there, but there's a lot of things that have claims and often don't have studies, or that don't work that quickly, or have something that you can actually quantify. That's pretty impressive. What are any of the other studies that are interesting to you, or that you've done, or that you plan to do?

[00:27:04] Chris Rinsch: Yeah. So, the two other studies that we've finished up recently that looked at more physiological function were four months in length. So, in one of the studies, we looked at 40 to 65-year-olds who were sedentary, and overweight, and had a lower mitochondrial function. We screened for that coming in through just physical activity and physical performance. And then, we had another study where we looked at individuals, 65 and older, and these people are also screened for low mitochondrial function. We used a more sophisticated way of doing that through a process called MRS, which is magnetic resonance spectroscopy. 

[00:27:45] And that allows us to look non-invasively at ATP levels and mitochondrial function in the muscle. In both of those studies, we observed similar impact on mitochondrial gene expression. Well, one, in the study, in the 40 to 65, we also performed biopsies. And then, in both studies, we looked at the levels in the blood of biomarkers, in particular, acylcarnitine levels that we saw were decreasing after this four-week period. And acylcarnitine level is a hallmark of mitochondrial function in general at a systemic level as the mitochondria use acylcarnitine. So, when you see acylcarnitine levels go down, that's an indication that it's improving.

[00:28:39] Luke Storey: Wow, that's pretty cool. And then what about where mitochondria mostly centered in your body? Are they highly concentrated in the heart and the brain? Is that kind of where we find a lot of them?

[00:28:52] Chris Rinsch: Well, in skeletal muscle, cardiac muscle, the brain, of course, mitochondria found in essentially all of our cells, with the exception of red blood cells. Yeah. And as we were saying, the muscle in the brain are key organs where mitochondria are playing an important role.

[00:29:15] Luke Storey: And so, if somebody's mitochondria are in tip top shape, what's the subjective experience of that? Does one have clearer thinking, athletic performance? If somebody's just rocking with their mitochondria and ATP production, what's the difference between that person and someone who is having a dysfunction in that area?

[00:29:37] Chris Rinsch: Yeah, for sure. I mean, if you're having your mitochondria firing on all cylinders, so to speak, from an athletic performance perspective, you should be at the top of your game, right? It should also, in terms of your muscle functions, your muscles should be just generally functioning better. So, yeah, if you think about older people who have problems walking, we did a study before all of our interventional studies with Urolithin A, we did a study where we looked at older people who are, on average, about 70 years old.

[00:30:20] And we looked at and we compared people who are for very active running on a regular basis to those who are considered pre-frail, and pre-frail are people who have a problem sort of getting up out of their chair and they can't walk very fast. And what we saw, the main difference between these two populations was the decline in mitochondrial function in that pre-frail population.

[00:30:45] So, it's a really good indication of where you don't want to be. You don't want to have impaired mitochondrial function, because in the end, it becomes sort of a vicious circle. If you have impaired mitochondrial function, your muscles won't be as, yeah, you won't have that same endurance that you will have when you have a robust mitochondrial function, and then you'll move less. And then, as a consequence of moving less, you'll have even lower function.

[00:31:19] Luke Storey: Ah, kind of a vicious cycle, right?

[00:31:20] Chris Rinsch: Yeah.

[00:31:21] Luke Storey: I mean, who wants to work out when you don't feel great and you don't have the energy to do so? Right?

[00:31:26] Chris Rinsch: Right, exactly. 

[00:31:27] Luke Storey: So, it's like self-defeating cycle. So then, you just start working out, and moving, and exercising less, and less, and less over time. And then, your mitochondria suffers as a result of that inactivity, essentially, too. Well, that's interesting. So, I'm assuming that Urolithin A would be something to improve athletic performance, do you have any anecdotal or studies regarding like high-performing athletes that are improving their performance, muscle function, et cetera?

[00:31:58] Chris Rinsch: Well, after these most recent two studies where we showed an improvement in muscle strength, after four weeks in this 40 to 65 population and muscle endurance in the 65 and older population, this encouraged us to continue our clinical investigations. And so, we've launched another study that we announced earlier this year in professional athletes. And so, now, we're in the process of evaluating Urolithin A in athletes.

[00:32:33] Luke Storey: Cool. Is the mitochondrial dysfunction part of what makes it more difficult as you age to build muscle, like density of muscle? I'm 50 now. I notice within my own body, I mean, I'm working out fairly regularly now, but the minute I stop, I just get gooey. You know what I mean? It's just different. The muscle is different than it was in my earlier days. How much of that has to do with mitochondria, and your ability to put on and keep muscle on basically?

[00:33:04] Chris Rinsch: Well, they're slightly different things, but what we do know is that mitochondrial function is very important for the functioning of your muscle cells. And so, however large your muscles are, what's important is that they function well. And so, there have been previous studies in the pharmaceutical space where drugs have been tested and they've improved muscle mass by a few percent, but no improved functionality. So, I think it's the functionality that you need to really think about and one aspect of having improved mitochondrial function is that you're ensuring that you're at least putting yourself in a position that you have an optimal functionality from a bioenergetic standpoint.

[00:33:51] Luke Storey: Got it. And are there any issues with a high-performing athlete that would supplement with something like Mitopure in terms of doping and things like that?

[00:34:04] Chris Rinsch: No. Mitopure and Urolithin A does not contain any banned substances. It's a pure substance and we've been exposed to it for literally centuries, because we've been taking pomegranate juice and nuts, yeah, since the dawn of time.

[00:34:21] Luke Storey: What is the history of pomegranate culturally around the world? Is there documentation of kind of health benefits of pomegranate in general? And if so, what culture is kind of gravitated toward that? I think of Middle Eastern food often incorporates pomegranate, for example. Is there anything you know about that, like the early origins of people identifying it as a beneficial food?

[00:34:45] Chris Rinsch: Well, certainly, pomegranates are growing best in these arid climates. And so, the Middle East and in the Mediterranean, there are lots of pomegranates that are growing. And yeah, whether it's in Turkey, or in Southern Italy, or yeah, even in Egypt, I guess I've seen, yeah, some documents around how pomegranates were used back in the Egyptian times and consumed back in Egyptian times, and linked to health and prosperity, if you will. So, in terms of how that all came until today, I thin people continue to eat it because of its health benefits, I think in general, and yeah, it's great to-

[00:35:40] Luke Storey: Yeah. It's interesting, when you look at different foods that have health benefits throughout history, I wonder, sometimes, just how much of that is folklore and how much of it is ancient wisdom that's legitimate. It seems like humans gravitate towards certain natural foods. And sometimes, there's a mythology around certain foods, that they have these superpowers, and maybe sometimes, they do, and sometimes, they don't. But the fact that you guys have found something in there that is this meaningful and you're starting to validate scientifically is really interesting. And I wonder how many other things we're going to discover that our ancestors ate that are actually superfoods in the truest sense.

[00:36:22] Chris Rinsch: Yeah. I think at least today, with all the tools we have in terms of on the biologist bench, if you will, that now, this opens the door to exploring a lot of the foods that people have been taking, yeah, for centuries for different types of medicinal benefits and exploring what actually inside of them causes these benefits.

[00:36:49] Luke Storey: Yeah. Well, it's like with Urolithin A, I mean, I think if it weren't for science, we wouldn't really even understand that we just go, oh, my grandmother ate pomegranates, and she said they're good for you, but we wouldn't really know. So, I think, as you mentioned earlier, the ability that we have now to extract the stuff that really matters from these foods and actually create supplements out of them.

[00:37:14] Do you see there any potential downside when we're kind of, in a sense, bypassing nature's wisdom and creating isolates from things when there are other components of those, like cofactors and other molecules that the creator or nature put into foods, and now, we're kind of going, oh, we want this one thing? Like thinking of willow bark with aspirin or something like that. Are there things that we might be missing there by extracting isolates?

[00:37:46] Chris Rinsch: Well, certainly, we consume foods for the ensemble of all the benefits of all of the components, whether it's, yeah, the phytocomponents, or the vitamins, or the minerals, or even protein levels. And so, it's important not to sort of take that dramatic shift and go directly to only taking supplements with specific components. Well, you have to maintain a very healthy diet.

[00:38:22] But I think the message is really that even if you eat a healthy diet, you don't necessarily get the levels of certain components that you may need. And so, that you may need to supplement them in order to get those levels. And that's particularly the case of Urolithin A, where the active compound isn't really found in the foods you eat and it's your body that develops it, basically, and converts it. And so, if you're not able to convert it naturally, then you can eat all the foods you'd like that contain these ellagitannins and you won't be exposed to Urolithin A.

[00:38:58] And so, that's the best—and when you can take a supplement like Urolithin A at a particular dose that's been tested to show a certain benefit, I think that's where, when you have that science around those specific components and the specific levels, that's when you should feel the most comfortable to take a product, as opposed to other products that have been less rigorously evaluated in the clinic and are offered at all kinds of different doses, or even, you're given the opportunity to take whatever dose you'd like, where you're making a decision without having that really robust science to help guide you.

[00:39:47] Luke Storey: Speaking of robust science and the studies that you did, so if you did the studies that you did with humans, based on one serving, one of these, that's 500 milligrams, is there any diminishing return or waste if someone wanted to take four of these? Because it's always the way I think, well, I'm like, 500 milligrams is good, then 25 must be better. Is there any point to one that's a high-performing person, whether they want mental prowess and acuity or physical performance, is there a cutoff point where you're kind of wasting your money by taking more or is just more and more better?

[00:40:24] Chris Rinsch: Well, in our first two studies, we evaluated 500 milligrams and 1,000 milligrams, and we showed that there was a slight increase in performance or in mitochondria activity at 1,000 milligrams. And then, in the third study that we conducted, we only used the dose of 1,000 milligrams in our 65-plus population and we showed an improvement in endurance there. And so, I would say that anywhere between 500 milligrams to 1,000 milligrams, you should expect to see some improvement of your mitochondrial function.

[00:41:04] Luke Storey: And how long does it take in terms of dosing in the immediate? Like I took a packet of this, this morning, and thank you for bringing those up, because I didn't get a lot of sleep. I was like mitochondria function, ah, I'm interviewing the right guy. In the immediate, so I take a glass of Mitopure in the morning, how long in the immediate does it take for me to actually metabolize that and start to see the effects? And then, in the longer term, and I don't know how long these studies are, but is there a cumulative effect after three months, or six months, or nine months, or something like that?

[00:41:39] Chris Rinsch: Yeah. Well, so in terms of an immediate effect when you consume Mitopure, about six to eight hours after intake, you'll have a peak in your blood in terms of the level of Urolithin A. And what we've seen in our studies, after seven days, you sort of reach a steady state in your blood. And yeah, we've done studies as long as four months, and we see, this is the time point where we start to see improvements in muscle strength. In the separate study that's still yet published, we start to also see benefits as early as two months on muscle function and muscle endurance.

[00:42:24] Luke Storey: And what's your consumer business model? Do you guys do like a subscription of this, or do people just order it off the cuff, or how do you guys actually market your product? I'm curious.

[00:42:36] Chris Rinsch: Well, we're a digital native brand, and so we sell it through our website, timelinenutrition.com, and we sell two-month, four-month, and 12-month plans, and we provide those to you right when you purchase them.

[00:42:50] Luke Storey: Oh, cool. Awesome. And in terms of Urolithin A and the world outside of your company, are there other people doing research, or trying to develop products, or looking into this, or is this just really a very narrow niche that you guys have found and focused on?

[00:43:06] Chris Rinsch: Well, in terms of the research, there are a number of labs around the world that are doing research Urolithin A, which is very encouraging to see? When we published one of our first papers in Nature Medicine several years ago, this sort of encouraged other scientists to look at Urolithin A, because it was the first compound that was shown to be an inducer of mitophagy. And so, this then, yeah, led to additional research in other areas that are outside of the muscle health space, if you will. And yeah, so what's nice to see is that there's a lot of scientists going after Urolithin A in terms of exploring its benefits, and its activity in the lab and in preclinical setting.

[00:43:57] Luke Storey: Yeah, that saves you guys, the research work, right? What I'm thinking about with mitochondrial function, as we've talked about muscle health, and physical performance, and endurance, and things like that, are you guys or any of those other scientists that are starting to get hip to this, looking at brain function, cognition, memory, things like that, because your brain obviously is using tons of energy to process, and I'm assuming that that energy comes from ATP also to some degree?

[00:44:28] Chris Rinsch: Yeah. So, we're not particularly studying the impact of Urolithin A on brain function, but there have been other publications by other laboratories that are working independently of us, nd there was one publication showing that your Urolithin A was in animal models of Alzheimer's disease, that it was improving function in the Alzheimer's disease mice.

[00:44:52] Luke Storey: Oh, wow.

[00:44:53] Chris Rinsch: Yeah. 

[00:44:54] Luke Storey: That's a pretty compelling.

[00:44:55] Chris Rinsch: Yeah, it's very encouraging, of course, translating from mouse to human in Alzheimer's disease is a huge step.

[00:45:04] Luke Storey: Yeah. How did they give mice Alzheimer's? I'm just curious.

[00:45:08] Chris Rinsch: Well, there are genetic models of Alzheimer's disease. And these genetic models, the mice have a slow degeneration of the brain and, yeah, of their neurons, and that leads to this type of memory loss. And so, in this publication, by administering Urolithin A, they were able to show that there was less of a memory loss and there was an improvement in the memory function.

[00:45:40] So, I think it would be interesting to, of course, assess the benefits of Urolithin A on the brain. We've been very focused on the muscle. We see the muscle as sort of ground zero for health. If you stop moving, then all of your health kind of declines after that. So, trying to keep people, muscle at the peak performance, and then perhaps in the future, we'll take a look at the effect of Urolithin A, yeah, on memory. We'll have to see. 

[00:46:10] Luke Storey: If somebody is using this for physical performance, is there an optimal time to dose? Say, someone takes amino acids, and creatine, and beetroot powder, and things like that, is there a time like before intense workout or something that this would be beneficial, or is it more generalized and just long term?

[00:46:32] Chris Rinsch: I would say taking it in the morning is the way that we suggest that people take the product. I know some people take morning and evening. Sort of everyone has to try for themselves to see what works best. Yeah, all of our clinical studies are built on this concept of taking it in the morning around breakfast time. And the product itself, I mean, it's a berry powder, you can mix it in yogurt, you can mix it into smoothies, put it on cereal. So, it's designed to allow people to incorporate it easy in their morning routine.

[00:47:11] Luke Storey: I noticed that. The past couple of days, I was just putting mine in water. I have my little hand blender and it has a very mild flavor, actually, which is kind of cool, because oftentimes, people put so many kind of artificial fake fruit flavorings and things. And I'm sure, speaking of like amino acid powder or something like that, because amino acids taste really nasty, but if you think about you're consuming something day after day, after day, that's kind of a lot of even natural flavoring, which is a bit suspect to me. So, that's one thing I noticed about this. It didn't have a lot of that fake fruity, sugary masking. It's just relatively innocuous in terms of its flavor profile. So, it would be easy, I think, to mix in just about anything and you wouldn't even really notice.

[00:47:55] Chris Rinsch: Yeah, and that was the purpose. We felt that a berry powder is something that is appealing to most people, and there's also pomegranate in there, so that sort of links to our origin story as well.

[00:48:10] Luke Storey: And is there any issue with heating the Mitopure? I mean, I don't know what hot food you would put into. I'm just curious if you could use it in a baking recipe or something like that, in muffins or some kind of dessert, or anything like that,

[00:48:24] Chris Rinsch: Mitopure is very heat stable, so people can use that, yeah, in hot beverages., if they want, or if they want to cook, they can do that as well.

[00:48:40] Luke Storey: Do you foresee in the future any way to increase the bioavailability of it, doing a liposomal or something like that, where you're getting maximum absorption, or do you find that just natural digestion is enough to get it all in there?

[00:48:56] Chris Rinsch: I think the formulations that we develop already are very bioavailable and I don't think, at least for the moment, we need to focus on that, because what we've seen from our clinical studies is that the levels that we're administering are actually bioactive in the body and giving people benefits. So, I think now, it's more about expanding the applications, studying it more in humans for different types of health benefits that would be linked to mitochondria. And that's where I see the future going in terms of the clinical studies.

[00:49:35] Luke Storey: Cool. Yeah, I think it's very compelling that you guys have targeted the mitophagy, because other than, as you discussed, fasting and different things like that that require a lot more discipline of someone, it's kind of one and done. And what keeps coming to mind is a compound called spermidine. I'm sensing you might be familiar with this. Spermidine is in certain foods like Japanese natto, fermented soybeans, and it's in foods that aren't very palatable and it's hard to get a lot of it.

[00:50:06] So, I interviewed a woman named Leslie Kenny from a company called Primeadine and the spermidine is cellular autophagy, and it really improves that, and there are tons of studies similar to yours that prove that. So, I was thinking, that's a pretty good one-two punch if you can get the mitophagy and autophagy boosted up at the same time, I just had an idea for a stack. Are you familiar with that? Have you looked into spermidine at all?

[00:50:30] Chris Rinsch: Well, I'm familiar a little bit with the science, although I don't think it's translated clinically, so what I can say is that, currently, the only nutritional product that is translated clinically for and shown an improved mitochondrial function that's a mitophagy inducer has been Urolithin A. It'll be very interesting to see what will happen with spermidine and if the findings that they've shown in animals and in cells actually translate into humans.

[00:51:03] Luke Storey: Yeah. Cool, man. Cool. And what do you see in the future? Do you guys have any ideas of further developments or studies? What's happening next for you guys, because you're a relatively new company, right? How long have you guys been doing this?

[00:51:16] Chris Rinsch: Well, we were actually incorporated back in 2007, so there's over 10 years of research behind this. Yeah.

[00:51:24] Luke Storey: I just figured, well, I just saw it come to market, and I kind of am on the cutting-edge, so I think of this stuff.

[00:51:29] Chris Rinsch: Yeah. So, we just launched the product just over a year ago.

[00:51:32] Luke Storey: Wow. That much R&D went into it?

[00:51:34] Chris Rinsch: Yeah. So, significant amount of R&D has gone into this. So, I think this also should let consumers feel comfortable taking products where they've been really deeply studied over the years, as opposed to taking a product and just sort of putting it out in the market before it's even been evaluated properly.

[00:51:54] Luke Storey: I'm curious from an entrepreneurial standpoint, when you're taking that long of a runway to do R&D, how do you guys pay your bills in the meantime? Were you guys independently wealthy or] had other careers and you did this as a side gig while you were in the R&D, and then finally went, alright, we're going all in with this?

[00:52:13] Chris Rinsch: Well, no, it's like most startups that we have an investor base that stay with us over the years, yeah.

[00:52:19] Luke Storey: Oh, cool. Awesome. Well, thanks for sticking it out, man. That's a long time to really work with something before coming to market. I think a lot of people that are kind of in the supplement game tend to, in some cases, and not to disparage them, but I think in some cases, somebody discovers something, they just kind of throw it on the market and start marketing it heavily. And then, we find out later, ah, it's not really doing what it's supposed to do, or in some cases, even maybe have some side effects.

[00:52:47] Chris Rinsch: And I think that's one of the big problems in the dietary supplement space, that there's not enough robust science that goes into the development before things are launched. And so, that's why we're really glad about our product and bring our product to people. And yeah, we think that people should be able to benefit from this, and the ongoing science and research that we will be doing in humans, so they can understand how it will affect different aspects, yeah, of their livelihood.

[00:53:18] Luke Storey: Awesome, man. Well, thank you so much for taking the time to dive into this with me. It's very, very compelling and I'm definitely going to be grabbing some more of this from you guys and giving it a shot. I think as we age, as we've discussed, energy is a huge factor. It's like if you don't have energy, you don't have life, you don't have anything. So, I'm always kind of having my antennae up for things that have to do with mitochondria, and energy, and just performance in general. Yeah. So, thank you for doing that and putting in the possibly unrewarding work in some respects along the way to actually take your time and do it right. It's very cool.

[00:53:56] Chris Rinsch: Yeah. Well, thank you very much for having me today. This has been great.

[00:54:00] Luke Storey: Yeah, man. So, I got one last question for you. Who have been three teachers or teachings that have influenced your life and your work that you might share with us, in any category?

[00:54:11] Chris Rinsch: Oh, good question. Well, I think teachings in entrepreneurial and entrepreneurship, I think one of the key teachings in entrepreneurship is just persistence. I mean, we spoke a little bit about that in the length of time that it takes, sometimes, discoveries take time, and that, yeah, being persistent pays off, and there's no sort of magic solution that happens instantly there.

[00:54:46] Luke Storey: Except cryptocurrency. I'm just kidding. So they say. I don't know. I'm no expert. But yeah, I think there's a lot to be said for that principle. I think a lot, especially younger people that have entrepreneurial ambitions, it's like the get rich quick kind of mindset and some do, and many don't. Two more.

[00:55:06] Chris Rinsch: Good question.

[00:55:09] Luke Storey: I love when I spring this on people. Some people are like, they rattle off three, and it could be like my mom, my grandma, my dad, something like that. And some people are like Buddha, Jesus. So, it's fun for me to see people squirm. But think of like a book, or a public figure, or a philosophy, or something. So, I love that, sticktoitiveness and patience in entrepreneurship. That's a great start.

[00:55:33] Chris Rinsch: Yeah. I don't have another one for you right now. I'm sorry.

[00:55:37] Luke Storey: That's fine. I'll let you off the hook. That's one of the reasons that I like that question, is sometimes, people are like, ah. But you already provided us, Chris, with tons of value today and great information, and you're on to something super cutting-edge that's validated. And I appreciate that and I appreciate your work. So, thank you for coming on. I guess in closing, just give us any websites or social media links where people can find you guys.

[00:55:59] Chris Rinsch: Sure. Timelinenutrition.com. This is our website for the Timeline Nutrition product. And then, of course, we're also on Instagram and Facebook, and you can find us there as well.

[00:56:12] Luke Storey: Awesome, man. Well, thank you so much for joining us.

[00:56:14] Chris Rinsch: Thank you.

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