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Jan 09, 2023

How Postbiotic Urolithin A Upgrades Your Mitochondria

Dr. Anurag Singh joins Dave Asprey to discuss the research behind Urolithin A, a compound that renews mitochondria and improves muscle function.

Podcast

The Human Upgrade with Dave Asprey—formerly Bulletproof Radio

00:00

How food

Topics covered

Mitochondria and their essential role in the basic function of healthy cells.
The life-cycle of mitochondria and how as they get older they accumulate free radicals and reactive oxygen species, losing function.
The essential mitochondrial renewal process called mitophagy and how it changes with age.
Urolithin A, a novel postbiotic compound shown to repair mitochondrial health via mitophagy.
The introduction of Mitopure, the first and only highly pure, clinically tested Urolithin A supplement.
A review of clinical studies showing how Mitopure can improve cellular energy and cellular function with specific focus on muscle cells.

Transcript

Dave Asprey: You're listening to The Human Upgrade with Dave Asprey. Formerly, Bulletproof Radio.

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Dave Asprey: My commitment to you is that the time you spend with me on The Human Upgrade will always return more value to you than you spent on it. You're listening to The Human Upgrade with Dave Asprey, formerly known as Bulletproof Radio.

Dave Asprey: Today is going to be a really fun interview because we're talking about something you probably haven't heard of even if you're a cool biohacker like me or like our upgrade collective, live audience members. You've heard of probiotics because, hey, what the heck? I've been talking about those for a long time and so have many other people. You can buy them even at a normal grocery store, healthy gut bacteria.

Dave Asprey: If you read Fast This Way or Superhuman, I talk a lot about prebiotics, the food for them. But you know what a postbiotic is? Probably not. Well, you will by the time we're done with the show today.

Dave Asprey: I'm going to dig into studies on what happens after your gut bacteria digest something and then look at what it makes and what that can do to renew your mitochondria. Our expert today is Dr. Anurag Singh, who's an MD, PhD, and the chief medical officer from a company called Amazentis SA. He's designed big clinical development and translational research, which means he looks at the science stuff and says, "How do we turn into real-world stuff that you can actually use?" We're going to dig deep on mitophagy and how to turn that on.

Dave Asprey: What the heck is mitophagy? Why would you want to listen to something about that? Because replacing the dim bulbs or the dim batteries in your cells is important. If you want to live a long time, you want to function at your best today. You need to start that process even when you're young so that you don't get old. If you're old, you want to turn that up so that you can get young. It's just harder to do once you've already accumulated a lifetime of, well, dim bulbs. You don't want to be one of those. Dr. Singh, welcome to the show.

Dr. Anurag Singh: Thanks for having me, Dave. Pleasure to be here.

Dave Asprey: You're joining from Switzerland, where you spend most of your time. Thank you for staying up late for the upgrade collective and for me to make this work. I want to know, I've looked at your career and you've worked for big companies like Nestlé. You've authored articles in science journals. You're a super science nerd. I don't know if in Switzerland that's an insult, but here that's a compliment.

Dave Asprey: But you spent now seven years looking at just one compound called Urolithin A. I've covered it a little while back, maybe about a year or so ago we talked about it briefly. But I want to dig deeper in it because the idea of postbiotics has intrigued me a lot. What got you into just one postbiotic for that period of time, given that you've done a lot of cool stuff?

Dr. Anurag Singh: You summarized my career well. I've spent the last 15-plus years running clinical trials in the nutrition and consumer health industry, mostly on prebiotics and probiotics to start with with big consumer health companies such as Nestlé Health. After that, what I realized was that it was not the symbiotic bacteria in your gut or what they needed to survive, which is the prebiotics. But what got me really interested was the end result of this bacterial metabolism. That's this beautiful metabolite that was discovered at the Swiss Institute of Technology, of course. Then from there, commercialized by Amazentis, which is the company now I work for.

Dr. Anurag Singh: Seven years back, it was a lab discovery. I'm trained as a doctor, a clinician, and then as a scientist in the US. I often see scientists make a discovery and then say, "Okay, let's move on to the next big one and forget about it." The doctors, well, they take a long time to realize what's happening in the science field. It's come to 10-plus years. I said, "Hey, this is something big." I can actually take this forward from the lab discovery scale to clinical science and to the breakfast table and daily life of people. That's what we have done here for the last seven-plus years.

Dave Asprey: You got into this one because you're interested in mitophagy and you bounced around. I have to admire that. I have had the great pleasure to know a lot of what I'm going to affectionately call crazy inventors or crazy scientists. Not tinfoil hat-wearing crazy, but they're so into invention and creation that the idea that if you make something that no one ever uses or sees, or they only see it in a journal article that got referenced 14 times, so you feel good about yourself. It's like chasing likes on Instagram, but for smart people.

Dr. Anurag Singh: You got it.

Dave Asprey: You said, "All right, I can actually do the hard work of getting people to do something that works instead of just to make stuff that works and then throw it over the edge of a cliff and then go make something else," which is one of my motivating things. I'll curate as much as much as those things as I can find and then talk about it.

Dave Asprey: I just want to offer my respect and congratulations for deciding that you're going to do that hard work of taking one thing and moving it actually to the finish line instead of, like you were saying earlier, bounce around and do a bunch of stuff.

Dr. Anurag Singh: My mentor always said research is basically two words: re and search. You got to keep going back to the drawing table and asking the same question in different people, in different subjects, in different populations. That's what we've done. Now, we are doing our fifth or sixth clinical study with this beautiful molecule. A lot of times in nutrition world, people put extracts and blends of probiotics together and they just give it to healthy people and expect magic to happen.

Dr. Anurag Singh: Here we've actually done the deep dive of the science and hitting how this molecule hits mitophagy and mitochondrial health and then bringing it to human translation, I think, and to commercialization. As you said, this is really the holy grail for real-world evidence.

Dave Asprey: Can you walk me through mitophagy and what it is and then why you got into that out of all the fields you could look into?

Dave Asprey: It's possible that your gut bacteria are part of what's making you old. At this point, there is a huge amount of research suggesting that one of the secrets to living a long, healthy life is controlling what's happening in your gut and your specific combination of gut bacteria can determine how well you age.

Dave Asprey: One of your first lines of defense to protect your gut is a good probiotic. If you've been following me for a while, you've probably heard about P3-OM from BIOptimizers. If you're looking to completely transform your digestion, especially if you need help or you're looking for more energy or you just want to feel better, P3-OM is the thing to try.

Dave Asprey: Because you listen to the show, BIOptimizers is offering you a free bottle of P3-OM SUPER-strain probiotics. I've used them. I've talked about my experience on the show. All you have to do is cover the cost of shipping. There are no other strings attached. You know that it's all about seeing what works for you. If you don't notice an improvement, no problem. But if you do, it would be worth it, especially if you had to try it for free.

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Dave Asprey: Can you walk me through mitophagy and what it is and then why you got into that out of all the fields you could look into?

Dr. Anurag Singh: Yeah. Mitophagy is basically recycling of the faulty mitochondria. As we age, our cells accumulate faulty mitochondria. Now in the life cycle of a mitochondria, what you have is basically, you get new growth of mitochondria, and these are called... There's a process called the mitochondrial biogenesis.

Dr. Anurag Singh: As you age, these healthy mitochondria, they accumulate free radicals and reactive oxygen species, and they start to lose shape and they stop communicating well with each other, much like... Think of it like a battery. If a battery is not wired with each other, you're not really producing enough energy.

Dr. Anurag Singh: This recycling process, as you put it, dim bulbs as you age. That's what this molecule, Urolithin A, does is it revs up the recycling. Think of recycling your trash can in your house. If you're accumulating waste in it but never cleaning it out, your house won't smell very nice. That's what mitophagy is. You need to have mitophagy up and running as we age so that you're creating space for new or healthy mitochondria to always produce energy, which is ATP.

Dave Asprey: That idea of recycling is really elegant. When you look at any of the anti-aging things that are out there, most of them anyway, there's some aspect of recycling there. You've doubtlessly seen probably Bruce Lipton is the one who talks about it the most, but a lot of people reference a study where a researcher kept a cell culture alive for a ridiculous amount of time by changing the medium all the time until his grad students got drunk and forgot to change the water and lo and behold, the experiment ends.

Dave Asprey: It seems like that's happening inside each of the major components of our cells. It's happening extracellularly. There's a lot of cleanup work to do if you want to stay young and over time you're going to accumulate metals, you're going to accumulate dysfunctional cells and all of that.

Dave Asprey: Are you feeling hopeful that we're going to be able to do enough cleaning of all the different systems, including obviously mitophagy, but all the other stuff that we're going to be able to extend human lifespan that way?

Dr. Anurag Singh: Well, I'm very optimistic that we'll be able to extend human lifespan, which is when you're 90, you're able to go about your activities of daily living. Now, how that translates into extended lifespan, this is something where active research is going on with what is the diet and certain blue zones where people live longer. But I am very optimistic that you can be a fit 90-year-old and play with your grandchild much.

Dave Asprey: I don't know, Dr. Singh, I think that's a bit of a cop-out. I'm going to share a little story here. Back when I was studying what we called computer information systems, it was one of the first degrees you could get in what would now be called artificial intelligence. I asked my professors, "Hey, why don't we just call this what it is?" They said, "Oh, we can't call it artificial intelligence because no one believes artificial intelligence is real. It'll never happen."

Dave Asprey: That wasn't that long ago. That was certainly within my lifetime. It was only a decade or two. When I hear that, "Oh, we're going to extend healthspan," it's sort of like that, "Oh, we shouldn't really say what we're doing because people might not believe us." Do you really think that a healthy 90-year-old who's playing with his or her grandkids isn't going to live longer as well?

Dr. Anurag Singh: No, that's what I'm saying. You need to first… You need to rev up the machinery to make the motor run well. When the motor runs well, maybe the car will have a longer lifespan. I'm just saying that I'm very optimistic that the data today says that healthspan can be extended. I think that ultimately may translate to extended lifespan, as you were saying.

Dave Asprey: You're hedging our bets so no one thinks you're crazy.

Dr. Anurag Singh: No. I think given the knowledge we have today, we probably can realistically extend human lifespan. But what I'm saying is that as a focus, as a clinician and physician and scientist, my first aspiration... There's many layers. You want to go to the Moon before you want to go to Mars. Right now, we just want to aim to get to the Moon and then I'm sure we'll get to Mars.

Dave Asprey: I like that. It's a goal. We'll probably get there and when and exactly how is open for interpretation. I hear you on that, and I actually agree with you there. I'm just willing to say within the next 100 years, we'll get there. That's good enough for me because I'm planning to be there.

Dr. Anurag Singh: Okay, great.

Dave Asprey: How old do you think you're going to live?

Dr. Anurag Singh: I think I want to beat my father and my grandfather. In terms, they both lived to 80-plus. If I can, as a third generation, outlive them, I'll be happy with that.

Dave Asprey: Excellent. So you want to do better than the previous generation. I certainly expect my kids to outlive me. Hopefully, they can double my age if our tech keeps doing what it can do and we don't destroy the soil and the insect life on the planet because I'm pretty sure they're going to need it. But those are different issues that may affect longevity. Or maybe we'll live in bubbles on Mars. Just ask Elon. By the way, Perchlorate, Elon. Perchlorate. Different issue.

Dave Asprey: Now, when we eat something, we know that our gut bacteria will transform it. When I say eat something, we're talking about pharmaceutical drugs. It turns out many, many of the actions of pharmaceutical drugs are mediated by your gut bacteria. We're figuring that out now. If you don't have the right gut bacteria, this drug doesn't work nearly as well or may not work at all. Yet some drugs work regardless of your gut bacteria. It all depends. Then we're getting all these natural compounds. I'm well known for saying, "Hey, maybe you should have more polyphenols in your diet because they do all sorts of good stuff."

Dave Asprey: Polyphenols are colored compounds if you guys are listening and you're new to the upgrade collective, new to the show. Colored compounds that give red things their color and dark things their color like black rice or black coffee, tea, chocolate, et cetera, and of course, pomegranates, which is where we're going to go deep today.

Dave Asprey: Pomegranates may make something called ellagic acid. I'm one of the few people actually knows that I don't have gut bacteria that convert ellagic acid into the active compound that gives pomegranates most of their good benefits. There's two reasons pomegranates work. One is ellagic acid. The other one is PON-1 enzyme if it's fresh pomegranate juice, which is a detoxing enzyme that's probably not as important as the other thing.

Dave Asprey: I used to have a pomegranate tree in my backyard. Didn't matter how much I ate, I could raise my blood sugar, but I couldn't raise my levels of beneficial mitochondrial compounds. So some people can, some people can't. The biohacker in me says, "What would happen if we could just take the compound that the bacteria make? Wouldn't that be amazing?" We have here with Dr. Singh, one of the guys who's been studying this for seven years.

Dave Asprey: Can you help me explain the discovery process for you of saying, Wait a minute, how did we know this was the one? Why Urolithin A, which by the way is a terrible marketing name. You guys should have some… Oh, you do. Timeline is the marketing name for it. But Urolithin A, why that compound out of all the other stuff you could have looked at?

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Dave Asprey: Urolithin A, why that compound, out of all the other stuff you could have looked at?

Dr. Anurag Singh: Well, there's a great story behind how that name came. Urolithins were actually discovered maybe 40 years back in 1980. They were discovered in the urine of beavers. The nerdy professor who discovered it said, "Well, I discovered it in urine," so that's the uro part, and he saw them as crystals. That's the urolith.

Dr. Anurag Singh: Now, beavers, we wonder why this discovery was made in beavers. Well, beavers eat a lot of tree bark of oak trees. These oak trees have a lot of polyphenols. Your favorite topic there, Dave. Typically, Ellagitannins. That's how this molecule was first discovered.

Dr. Anurag Singh: Fast forward 30 years, Amazentis has been studying Ellagitannins in pomegranates for almost 14 years now. We started with the theory that we could bring the deep science approach to nutrition and natural product discovery.

Dr. Anurag Singh: We started by just deconstructing the pomegranate because the last 30 years, there's been so many studies and health benefits associated with pomegranate. Out of the hundreds of compounds that we put, you start aging research typically in using worms and animal models. When we put the Ellagitannins or ellagic acid, as you were mentioning, on these worms, that didn't seem to be extending the lifespan of the worms.

Dr. Anurag Singh: But when we said, "Okay, let's try these byproducts of the metabolism of the gut microbiome called Urolithin A," and we sprinkled that on the worms and they started living by about 45% longer, that set the alarm bells ringing and it was the eureka moment.

Dr. Anurag Singh: From there, we gave it to old rodents who were... In just six weeks, we started seeing about 40%, 50% increase in aerobic endurance and increase in grip strength by about 10%. The native polyphenol compounds were not doing it. That triggered the whole discovery around Urolithins and how we focused and zoomed in and started moving. It was really, as you put it, this postbiotic process.

Dr. Anurag Singh: You need two biases to really produce Urolithins. You need to eat the right diet. As you said, you can eat fruits and nuts and drink a glass of juice, and then you need your gut microbiome. I can also share, I have tested myself and I don't have... I can drink six liters of pomegranate juice. My body will not produce this molecule. We said, "Okay, this is how we're going to move forward. There's a need for supplementation."

Dave Asprey: What would happen if instead I went out and I found some species of bacteria that converted ellagic acid from raspberry or more heavily in pomegranates and converted that into Urolithin A? Could I just take that probiotic and expect it to work?

Dr. Anurag Singh: Conceptually, it sounds appealing. Believe it or not, we have spent a long years looking in that direction as well. It's not easy because our gut microbiome is very complex ecosystem with hundreds or millions of different species interacting with each other, and they need to be interacting in perfect harmony to release these postbiotics, which is the way I look at it, is the perfect gut health relationship with these microbiome. It's not one bacteria, it's not one strain that you can isolate and give. It's really got to be multispecies.

Dr. Anurag Singh: I think you can probably conceptually find that strain or probiotic that could do it, but the process will be so inefficient that the best way, and that's the way we have come up within the company, is to short-circuit it and provide the postbiotic, which is Urolithin A directly in a pill or in a food product.

Dave Asprey: What you're saying is that if someone took a probiotic that was actually stable enough to be delivered to their house and then to make it through the acid in their stomach and it took root, or maybe they just stick the probiotic in the other end, which is actually probably a better strategy for a lot of probiotics. It's just less attractive to take a pill that way because it's not a pill anymore.

Dave Asprey: Let's say you could get it to take root in the gut, then the environment around it, it'll be outcompeted by other things unless you have a constant supply of pomegranate juice and there isn't something more aggressive. It's really a difficult thing to do to say, "How do I balance this stuff?" It's one thing to say, "How do I get what my body considers is enough for me to live a normal life?" like your parents who made it into their 80s. I want to do better than that. So what you would do is say, "Okay, I want more of this compound." If they had pomegranate and they have the gut bacteria, that's not enough to matter.

Dave Asprey: Now you take Urolithin A as a purified compound. That's something that works for everyone then, right? Is there a genetic susceptibility to which pathways for mitophagy are going to be activated by Urolithin A, or is pretty much it just works?

Dr. Anurag Singh: Yeah, pretty much it works. It doesn't matter what levels of Urolithin, whether you're a producer, natural producer or not. In our clinical studies, we have both healthy people who come in, and we see great effects on muscle, and muscle strength, and the physical performance. This also works for me.

Dave Asprey: If you compare a dose of Mitopure, and this is the Urolithin A stuff from Thailand. A dose of that, it comes a little packet or a pill. How much pomegranate would you have to eat or drink in order to equate that dose?

Dr. Anurag Singh: Yeah, that's the study we just published. You will actually need to eat and drink about six glasses, so about a liter and a half of juice to be equivalent, if you were blessed with the natural microbiome to get the equivalent of 500 milligrams, which is in this food sash here. So yeah.

Dave Asprey: Wow. Six glasses a day. Having been a raw vegan, guys, I know it's a shameful part of my past. I do my best not to talk about that. I'm embarrassed that I did such harm to my health, and I did such harm to the planet by not supporting grass-fed agriculture. But those are different things. I did eat substantial amounts of fruit and lots of pomegranate juice because I had a tree in my backyard.

Dave Asprey: Strangely enough, my blood sugar wasn't very well managed because six glasses of pomegranate juice has enough sugar to raise your triglycerides and probably give you fatty liver if you drink that much every single day, because fructose is a major cause of fatty liver after alcohol. That doesn't seem like a good strategy to get mitophagy by overdosing on high amounts of fructose. At least I don't think it is. That's all accurate, right?

Dr. Anurag Singh: Yeah, that's perfect. The other thing we saw was, well, maybe if you provide the pomegranate juice as a perfect diet to the people, maybe the gut microbiome will now see it and start converting. Even when you provide this amount of pomegranate juice with a perfect diet, we do see somehow the microbiome evolving in certain amount of people.

Dr. Anurag Singh: From 2%, you can maximum push this percentage. Let's say if you studied 100 people, you can have about 40% of the people, 30%, 40% of the people now making it. But those amounts are so variable, so subtherapeutic that you will never really be able to harness the health impact that you will get by direct supplementation. I'm happy to share the paper that we just authored and shared with your audience because I think it makes for great reading.

Dave Asprey: All right, I'll put that up in the show note links on daveasprey.com, because it's fascinating. If you're saying, "Look, I'm not interested in the research, just tell me what to do." Well, the bottom line here is the product is called Mitopure, and you take a packet of this stuff. On the last podcast I did about it, you can put it in your coffee if you want to. It's heat-stable. Just confirm that with you.

Dr. Anurag Singh: Yeah, absolutely. It's very stable. I still take pills from like, I don't know, three or four years back, and I still get great absorption by availability, so it's very stable.

Dave Asprey: Okay, good. You can do that. I will tell you, I got tired of raspberry flavor in my coffee. I like my coffee with butter. The fact that Mitopure makes capsules is convenient for me. But the raspberry stuff is nice and it's got some other prebiotics in it, I believe, as well. That's a good thing. I sent the powder out to people who are in the Dave Asprey Box—go to daveaspreybox.com—and every quarter I send out a box full of cool stuff worth way more than you pay for it. People and the upgrade collective who are members of the box have definitely given it a try. I'm seeing all the comments here saying, "I like it. It's the real deal."

Dave Asprey: I do have to say, I take it the vast majority of days. Every now and then I miss something. But I want to know, in fact, several members are asking, what's the best time of day to turn on mitophagy? Because we know a lot about circadian timing of vitamins and vitamin D in the morning, magnesium in the morning, and maybe at night, but certainly in the morning. When do I want to do a timeline? Is this during a fast? Even though it has some raspberry powder, end of a fast, in morning, night? What's your take?

Dr. Anurag Singh: All our clinical studies are done where we see great health improvements in muscle strength and mitochondrial health. They're done first thing in the morning. Participants usually take it first thing in the morning in a fasted state just before taking the breakfast. The idea is that you peak the absorption. If you know the kinetics of absorption of this beautiful molecule is it peaks about 6-8 hours after the intake. It's hitting the peak when you're at the peak daily activity in a day. Overnight fasting is also known to be inducing autophagy and mitophagy. Take it and amplify with Mitopure in the morning.

Dave Asprey: During a fast?

Dr. Anurag Singh: Yeah, during a fast, it will work.

Dave Asprey: I think there's what, 10 calories or something in a packet? It's not enough.

Dr. Anurag Singh: Yeah, it's really nothing. I think it's hardly got any sugar, so I think probably-

Dave Asprey: I don't think it's going to raise insulin in any way that would shift mTOR. I haven't measured it, but it's such a small amount. People are saying, "Wouldn't it break a fast?" Guys, it doesn't look like... I don't think it would, but I haven't measured with one of my glucose meters. I've thrown in my coffee during a fast and seen no difference, but I wasn't specifically studying just that.

Dr. Anurag Singh: That's with the powder. We also have the pills, as you said. You can pop two pills and you would... Yeah, that's-

Dave Asprey: That won't break a fast with the pills. That's what I do now after I used all the packets that I had. I had like six months worth of packets.

Dave Asprey: To be really clear, this is one of the superstar anti-aging supplements that I plan to be taking daily for a long period of time just based on the the strength of the research. I do about a hundred pills a day, 150 sometimes if I'm traveling. Some of those are because they're large molecules like magnesium or glutathione or something. But definitely this is in my stack, and I'm expecting it to be there for a very long period of time because of my aging goals. I basically only talk about stuff that I think is worthwhile and that I'd be willing to do. But I want to know something. You've done seven trials on this stuff now?

Dr. Anurag Singh: We are on our sixth trial.

Dave Asprey: Oh, you're on your sixth. Seven years, six trials. How are you measuring mitochondrial health? Because at Upgrade Labs, I'm helping people train and improve it, but measuring it is really a pain. What's the mechanism there?

Dr. Anurag Singh: It's not easy from a scientific or clinical assessment. We measure two ways in our trials to mitochondrial health. We either do some biopsies in the muscle, which is... Well, I can imagine it's not the easiest to do in real world, in clinical setting.

Dave Asprey: Yeah, those hurt.

Dr. Anurag Singh: But we look at mitochondrial gene signatures, we look at respiration and live muscle. That's what we do. That's the most validated way. Then we do what is called as magnetic resonance spectroscopy, which is non-invasive, which is basically you go in an MRI-like setup and you exercise in a limb MRI, and as you exercise, your ATP levels in that muscle that you are studying or the brain will go down, then you see how fast the ATP is coming back and how fast it comes is really a measure of your mitochondrial health. Involves heavy machinery, involves having magnetic scanners. That's seven Tesla and all.

Dr. Anurag Singh: The other old-school way is to look at biomarkers, which is something we have been investing a lot of time to study. We've been looking at a panel of molecules in the blood called acylcarnitines that basically are involved in fat oxidation. They are de facto markers of good mitochondrial health. If you really had to go at a high level, you could look at your VO₂ as well as a de facto marker.

Dave Asprey: That's what we do at Upgrade Labs. We've got some proprietary tech for that. But that's a pain. You're on a bike, you have to be fasted, breathing through a mask. It's not one of those things you're going to do unless you're really a nerd, right?

Dr. Anurag Singh: Right, yeah. I think there's still a long way to go to crack that holy grail of what's the perfect biomarker of mitochondrial health. But yeah, in real life, you'll know it from fatigue and energy levels down to your VO₂, and then at the molecular level to these biomarkers I was mentioning.

Dave Asprey: Long-time listeners have probably heard me talk about acetyl-L-carnitine as something you might want to take when you're on the bulletproof diet or you switch into a high-fat diet or you just want mitochondrial function. You mentioned members of that family. I think that would probably change test results if people were supplementing that, right?

Dr. Anurag Singh: Yeah, that's what we see as well in our studies, that hopefully some of them will also get published very soon.

Dave Asprey: Okay, very cool. What about urine organic acids? Useful?

Dr. Anurag Singh: No, we haven't really seen them. We look at some mitochondrial crep cycle metabolites in addition.

Dave Asprey: Succinic acid, things like that?

Dr. Anurag Singh: Things like that.

Dave Asprey: All right. I'm wondering how many of our audience is completely like, "What the hell are they talking about? They're bored." Or how many of my functional medicine doctors jumping up and down in their cars going, "Someone finally said succinic acid."

Dave Asprey: But it's fascinating because I'm going a little deep with you there. I've written a major New York Times bestseller about how to enhance mitochondrial function, yet measuring it is always looking at the shadow of it instead of looking at it directly, looking at evidence it was there, looking at smoke instead of the fire. In fact, that's the best analogy I can think of.

Dr. Anurag Singh: Yeah.

Dave Asprey: You're saying the best way is those acylcarnitines?

Dr. Anurag Singh: Yeah, from biomarkers. The best way is ultimately to look at ATP in real-time with imaging and those tests. I think from going from imaging to something that is point of care will take some time.

Dave Asprey: All right. I think for all of our listeners, I don't have an answer for you guys about mitochondrial health, but when you have a clinical researcher with a massive NMR equipment, they can do it. Or you have some of the gear we have down in LA at one of our research piece of equipment for VO₂. It's not VO₂ Max, it's a different algorithm. It's hard to do it, is the short answer.

Dave Asprey: But the easy way is, how do you feel when you wake up in the morning? Do you have athletic endurance? Does your brain work all the time? If so, your mitochondria are probably working better. But here's my question for you about Urolithin A or Mitopure. There are some supplements that I'll take that are direct stimulators of ATP creation and mitochondrial stuff, and you feel like, "Yeah." Even MCT oil changes the amount of electrons available because it carries more than sugar, so you're like, "All right, I've got myself back today. My brain is where I want it to be." I don't get a buzz from Mitopure. Do you?

Dave Asprey: How long does it take to feel a change in mitophagy? Because if you change a light bulb and you have a million of them and you change 1% a day, you're not going to notice a change in brightness maybe ever because it's a slow change. What's the rate of change when people start using Mitopure?

Dr. Anurag Singh: Yeah. What we have seen in our studies, and then I'll mention some of the folks I chat with were on the product. In our clinical studies, around one month after or four weeks after, we start noticing biologically relevant changes, so changes that you would expect from exercise regimens of many years. That's the level of impact on mitochondrial gene signatures or biomarkers.

Dr. Anurag Singh: Then about two months, we really start seeing about 10% improvements in VO₂. In things like muscle strength would take a little bit longer than four months because physical performance and improving muscle strength takes time. It's not on off that in a week you will improve your muscle strength. It's a constant remodeling. You have to clean the waste out, you have to create new mitochondrial biogenesis, and you have to create... Those mitochondria need to be then efficient. It takes about, I would say, about a couple of months.

Dave Asprey: Okay, a couple of months. This is with daily use of the recommended dose. Is it body weight dependent? The reason I'm asking is right now, given how ripped I am, I'm around 230. I vary between like 210 and 230 depending on what experiments I'm doing and other stuff like that. I have very large legs, so it's easy. I just do a few squats every day and magically I put on muscle, but it's all... It just makes my pants not fit.

Dave Asprey: Most of the supplements I take, they're meant to be a safe dose for a 90-pound woman, and that's what we have to do at supplement companies. I usually double dose things. Should I be doing that as a larger person with my BMR? Let's see. My BMR is something like 2,900 calories a day. Does that mean I just need a higher dose, or is it you take it and it works regardless of your body weight?

Dave Asprey: How many times have you heard someone tell you that restricting sodium is heart-healthy? Well, here's the thing. If your body is an engine, salt is your battery. It plays a really important role in nerve impulse conduction, muscle function and water and mineral balance, and contrary to what you've probably heard, you get the best health outcomes at sodium levels that are two to three times higher than the current recommendations.

Dave Asprey: Your need for sodium increases even more when you're fasting or when you're on a low-carb diet. That's because when you eat low carb, your insulin levels go down, which causes your body to release too much sodium. That leaves you with low electrolytes. If you've ever felt the keto flu, now you know why.

Dave Asprey: To avoid all that stuff, I get my sodium and other electrolytes with LMNT. It has a science-backed ratio of sodium, potassium, and magnesium with no sugar, no fake ingredients, no fillers. It's also low-carb-friendly, and it won't break your fast. When I take LMNT, I notice reduced hunger cravings, I have better energy levels, my sleep is better and my mental clarity is better. It's actually a big gun in making you feel good no matter what you're doing. It comes in single-serve packets that I take with me every single time I travel. Their new grapefruit salt flavor drops May 25th, and that is my second favorite. Order now at drinklmnt.com/dave and get a free LMNT sample pack with your purchase.

Dave Asprey: You're listening to The Human Upgrade with Dave Asprey.

Dave Asprey: My BMR is something like 2,900 calories a day. Does that mean I just need a higher dose, or is it you take it and it works regardless of your body weight?

Dr. Anurag Singh: Yeah, it's a good question, actually. It's a great question. We have seen impacts at the 500-milligram dose on muscle strength and on mitochondrial health and cellular health. Now, we have done what is called this dose escalation study. You take a quarter of people, you give them a low dose, and then you raise the dose, and then keep on doing. We've done that till 2 grams. The best data we have is actually on 1 gram, which means double the dose.

Dave Asprey: That's what I was doing just because I always double the dose.

Dr. Anurag Singh: That improves mobility, you have more bioenergetics, you're walking better. As I said, the VO₂, 500 milligrams and 1 gram is also a very safe dose. We have data on this molecule that you can up it. There is no limit to it where you will get a safety signal. I would say, yeah, if you want to try out upping the dose, sure. By means, I take double the dose myself.

Dave Asprey: You take double the dose as well. This is a very different situation. Years ago, I interviewed a guy from Vanderbilt University. I call him Dr. Nicotine. He did the first study of pharmaceutically separated pure nicotine versus using tobacco. He was looking at Alzheimer's disease studies. That came out in 1986 and showed a reversal of Alzheimer's disease. My hypothesis would be probably through PGC-1a effects, but who knows? Maybe it's for some other reason.

Dave Asprey: At the end of the interview, I said, "Have you ever used nicotine? What's your favorite form? Are you taking some now?" He says, "No, I've never used it. I want to keep my research pure." I'm like, "No." If you believe it works after 25 years, I feel like you really should be doubling down on it, which is exactly what you're doing. You're saying, "Okay, I'm doing it."

Dr. Anurag Singh: Yes, in one of the markers we actually look in the muscle is this PGC-a. In one month, we have actually published that this molecule can increase the expression of PGC-1a, which means biogenesis is already starting to happen.

Dave Asprey: Wow. Guys, if you haven't read my books or you just didn't remember it, PGC-1a is what happens when you exercise. It's an exercise, mimetic thing. Things that raise PGC-1a. Funny enough, they make you lose weight, they suppress hunger, and they're generally good for you. Although too much nicotine is probably not good for you, but a little bit probably is. Reminding me I should stick a patch on or chew some gum or something, but I'm not going to chew gum on the show because it's gross.

Dave Asprey: All right. Are you up for a question from the Upgrade Collective? Lisa has a good one that I love to work in here.

Dr. Anurag Singh: Sure. Absulute.

Dave Asprey: All right.

Dr. Anurag Singh: Sure.

Dave Asprey: Chris, let's patch her in.

Lisa: Okay, so I'm wondering, is a higher dose of Mitopure better for mold toxicity or any mast cell symptoms one might have?

Dr. Anurag Singh: Good question. We have not studied, let's say, the immunological effects of might appear. This is an active area of research. A lot of academic groups since our publication have started studying it. They've been studying models of IBD, they've been studying models of neurodegeneration. In these at least the model of IBD they looked at, they saw that it had an anti-inflammatory effect. Hypothetically, I would say probably yes, but we have not done any clinical studies or looked into that direction.

Dave Asprey: Thanks, Dr Singh. The bottom line, I would say, from everything I've studied is that if you want to live a long time and you want to turn off inflammation, inflammation is the opposite side of the coin for mitochondrial function. When mitochondria work better, you have less inflammation almost by definition.

Dave Asprey: Then to make them work better, there's stop using toxins that directly affect mitochondria and make sure that the weak ones get the hell out. Mitopure is that latter part. As you do that over time, of course, athletic performance is going to go up because you're doing a better job of turning air and food into electrons. That means your immune system to work better, too.

Dr. Anurag Singh: Yeah, immune cells have mitochondria, too. We just chose to study muscle because an active muscle has about 2,000 mitochondria. It's just the most active organ or cell in our body, the muscle cell, that it requires ATP and consumes ATP at a higher rate. Immune cells, on the other hand, about 200 mitochondria. Anything that is having an impact on mitochondria and mitophagy, it's going to be irrespective, just not muscle cell is going to have an effect on other cell types too.

Dave Asprey: In my mind, the number one thing you can do at any age to either age backwards or not age and perform better is mitochondrial enhancement. Because it seems like even mitophagy itself, once your mitochondria start working a little bit better, maybe because you took some compound that helped and that wasn't for mitophagy, you have to have enough electricity to run the body and enough electricity to rebuild the body.

Dave Asprey: If you kick your energy levels up a little bit maybe with acetyl-L-carnitine, maybe with d-ribose, anything like that, and you have Urolithin A or Mitopure on board, the body says, "Oh, now I have enough energy, too." Then it says, "All right, what's the repair system that's next on the rung of priorities that it has?" It's a relatively simplistic model, but at the end of the day, when you boil out all the network effects, it seems like that's what the body does. This one was more important than that one. Let's fill that part of the waterfall and then go up to the next one.

Dave Asprey: I feel like you want to have enough energy to build new mitochondria instead of just run weak ones. There's a little bump that's required, which may be something like combining fasting with this. You have some ketones present. Does that seem like a good strategy? I know you probably haven't studied that.

Dr. Anurag Singh: No, in a lot of studies that we published, actually not in clinical studies, but in our animal models and worms that were fasting, this actually increased the autophagy. Fasting induces autophagy and adding Urolithin A to that regimen actually had a very additive effect, and that was shown in this beautiful Nature Medicine paper. Exercise would be another way. Exercise is another way to stimulate mitophagy. You just need to be doing it regularly.

Dr. Anurag Singh: That's where I see, and that's why we are actually running studies now in athletes where we are starting to ask the question, can we actually take high performance people, people with VO₂s of 70? Can we add this to their regimen and can it help boost their performance or most importantly, their recovery? Because training does have an impact, or training sometimes has an impact on mitochondrial health too.

Dave Asprey: That is fantastic. You've got to get a stimulus in as well. You should probably sprint every now and then or do some squats or whatever high-intensity interval or for cardio endurance and specifically. Even that, it seems to be that high-intensity interval training works followed by longer walks or very slow jogs. If you were doing any of those things for an endurance event and you're taking Mitopure, you're likely to, over the course of a couple of months, see some improvement in mitochondrial function, even if you're already a pretty good athlete.

Dave Asprey: You did a study with a very well-known scientist, well-known amongst scientists, Dr. Louise Burke, who spent 40 years as a sports dietitian and has 350 papers published, and has written a few textbooks on sports nutrition. What did you guys find when you collaborated on the latest research you've done on Mitopure?

Dr. Anurag Singh: This is an ongoing study, Dave. This is a study that was designed by Louise. She came to us and said, Well, a lot of elite athletes, runners, triathletes, they typically go before a big race. They do training. Sometimes they have to do multiple races in an active season. They struggle to maintain their level of performance and so recovery is a big issue. The muscle recovery and to maintain their peak performance from race to race is a big issue.

Dr. Anurag Singh: She said, "Well, I think being on Mitopure could help these athletes potentially recover faster and maintain. The way it could do it is through mitophagy, recycle the waste and the toxins accumulated by overtraining and overstimulation of the muscle machinery." This is what we are testing. We don't have the final results yet. We are dealing with COVID-19, throwing a spanner in some of the clinical research programs. Hopefully early to mid-next year, we will have great data. This is being done in Australia with really Olympic-

Dave Asprey: You picked the worst country ever, except for maybe Canada to do anything. Your hypothesis for this is one that made me happy that you're doing research on it. It was that overtraining in athletes induces mitochondrial dysfunction.

Dave Asprey: I think I experienced this when I was a younger person. I was maybe 24. I had weighed 300 pounds and I said, "I'm going to work out six days a week an hour and a half a day." I'd max out all the machines at the gym, except for two. Then I'd hop on the treadmill with weights at an angle in a weighted backpack. I just did it six days a week and went on the low-fat, low-calorie diet. Didn't lose any weight over 18 months. I got stronger. I think I had even worse mitochondrial function because I just didn't do any of that recovery stuff. It's one of those things where something is good, more must be better. You do it until you're exhausted.

Dave Asprey: What are you seeing around over training and do you think that you've proven the hypothesis so far? I know it might appear as helping with that, but did you find a result that you could say, "Yes, 100% clear," that that's a problem?

Dr. Anurag Singh: Yeah, this is something that is being investigated a lot. Not by us but a Swedish group, who recently published a very high-impact paper in the Journal, cell metabolism, where they took athletes and they kept on adding training regimens week after week, the intensity of the training increased. Over time, of course, with any training, they saw improvements in mitochondrial health. After a while, the system started to crash. It's been known this is called overtraining. Some folks call it overreaching, some call it plateau, whatever.

Dr. Anurag Singh: What they found was that this over-training induced performance dip was because of poor mitochondrial function. That was just not offsetting performance. It was offsetting the athlete's metabolism, especially they had higher blood glucose peaks after. Then there was a recovery period after which the athlete stopped training and then the body recovered and they were back to, but what was very key was this window where athletes were over-training, where the performance dip and that was ascribed to mitochondrial dysfunction.

Dave Asprey: Very interesting. We get mitochondrial dysfunction from over-exercising. Interestingly, in that study, it also decreased glucose tolerance. A lot of people who are listening are going through that where they say, "Okay, I understand I don't want to have high glucose." These are mitochondria that are so damaged or stressed that they can't actually handle sugar, which they should love. It's a disrupted network, you could say.

Dave Asprey: They found this in free-living elite endurance athletes. I've said for many years now that endurance athleticism isn't a good way to live a long time, but there's one or two studies that show ultra-extreme 100-mile runner types if they can do without getting injured, which is a very small number but they do have lengthened telomeres. Have you seen any association between Mitopure and telomeres being longer?

Dr. Anurag Singh: Honestly, no. We have never looked at telomere biology. One of the reasons is we have such a specific mechanism of action through mitophagy and renewal of these mitochondria that, yeah, in honesty, we haven't explored that biological pathway.

Dave Asprey: I don't think you'll see a difference. I don't think you'll see a lengthening from what Mitopure does. If you took Mitopure for quite a while and someone had more free electricity for repair processes, I think you probably would see a slowing of the shortening of the telomeres.

Dr. Anurag Singh: Maybe, I think. You'll need to do long-term studies for that.

Dave Asprey: Yeah, those are expensive and hard to do and probably will never be done. That's one of the challenges for all the anti-aging stuff that I do. Well, here's a mechanism action. We understand it pretty well. We know the basic direction. If you had to bet which one of these is going to make you live longer, I'll take the bet that I think is most likely. I could be wrong. Given the alternative, which is eating hotdogs and drinking diet soda, I'm pretty sure I'm winning. There's always that.

Dave Asprey: Here's a question from Hara in the Upgrade Collective who's put it through in our little chat window here during the show. She's wondering whether you could combine this with breath work practices, which are reducing oxygen and increasing carbon dioxide. Any thoughts on breath work plus Mitopure?

Dr. Anurag Singh: Potentially, yeah. Breath analytics could be utilized. That's how a lot of exercise tolerance studies are done looking at the gas exchange. That's how we look at two levels. I think the question is referring to certain breath biopsy.

Dave Asprey: Like pranayama or Wim Hof exercises or any of the other things like James Nestor has written about recently. There's a lot going on with carbon dioxide versus oxygen levels and retention.

Dr. Anurag Singh: Yeah, this is, let's say, upcoming field of research but we haven't looked into it, Dave.

Dave Asprey: You can always count on the Upgrade Collective to say how do we combine all these cool bio-hacks that we've learned about to get the most effects? Another question. Well, actually, guys, it's a question about how do we make Mitopure available for more people. I don't think asking a research scientist about that is the right thing. You're not in charge of pricing, packaging, and distribution. Is it easy to make though, as a molecule? Or are you mostly just getting it already made and then you're seeing what it does in humans and animals and stuff like that?

Dr. Anurag Singh: Yes, it's not too difficult to make with the right chemistry knowledge. One of the things, and this may interest your audience, one of the things we are developing is a Mitopure challenge test. It's a kit, it's a consumer health kit that looks like this.

Dave Asprey: Oh, cool.

Dave Asprey: You have to take a small blood prick test in a card called Before. You just prick with a lancet and you put some blood spots. You can drink juice as well. You can drink juice or eat bowl of nuts. You can know if you are actually a natural urolithin producer. Then you can take this one sachet and then repeat the test, call after with a few blood spots and send it to our lab and we'll be able to tell you if you are a natural producer and the delta difference you will get from just taking this. This is a test. We are actually running a home-based study. If your folks are interested, we can share the link and they can try the beta version.

Dave Asprey: I will send this out to the Upgrade Collective members. There's all kinds of discounts and other cool things that you get when you're in the Upgrade Collective. By the way, if you're listening and going, "I want to be in the live audience," ourupgradecollective.com is how you sign up for my mentorship and membership group.

Dave Asprey: It's intriguing. You guys haven't even sent me one of those test kits yet, but I have great respect for that. The idea that if you're taking a vitamin and you can test that it's working, that's a really good thing to do. You can see if it's worth it for you. In fact, everyone's exploding with excitement right now on our group chat during the episode. So that study, I'm excited and I'll…

Dr. Anurag Singh: Happy to send you one. Happy to send you. We just got the first 200 beta kits. Happy to send you one if you want to participate, send your samples to our lab.

Dave Asprey: Does it matter if I take Mitopure with a larger amount of prebiotic, a bunch of acacia gum or something, or with fat or with protein, do any of them help with absorption?

Dr. Anurag Singh: No, not at all. Actually, in our first human studies, we actually tested this. We gave it on an empty stomach in a fast state or with a high protein and in a yogurt matrix to see if high protein and the levels we get in the blood are identical. In fact, we now even have a product with high protein, 20 grams of protein plus Mitopure 500 milligrams because with the idea that protein builds muscle mass and then the Mitopure gives you better energetics and strength. Now actually, it's, I think beneficial if you combine them.

Dave Asprey: Okay, got it. There's no… There's really not stability issues. You can take it, you can mix it into hot coffee and it works fine. You can take it with protein or anything. The absorption rate is pretty much as if your gut bacteria had done it.

Dave Asprey: When I take timeline, I know... Let me rephrase that. I know that there are certain compounds. When you take them, they cause your gut bacteria to make more of them. Glutathione is one of them in some people and things like butyric acid. If you take a butyric acid capsule, you're more likely to make gut bacteria that make butyric acid.

Dave Asprey: Part of my anti-aging strategy is I'd like little manufacturing plants called my microbiome to make the good stuff and not the bad stuff. It's easy, but of course, you don't have much control. It's a very complex system. It's like managing an ecosystem. It's hard to do. Look what a great job we're doing on the planet right now. Monsanto, I'm talking to you. I mean, Bayer. Aside from all of that stuff, what about just taking Urolithin A for a while and then having your gut bacteria make more of it and actually make those producers of Urolithin A and then taking a month off?

Dave Asprey: There are people in Upgrade Collective who are on different budgets. Some people saying, well, can I pulse this? Is there benefits to pulsing it? Can I teach my bacteria? Talk to me about pulsing, cycling, and training your gut bacteria to handle ellagic acid.

Dr. Anurag Singh: It's fantastic. There's a lot of questions hidden in that one question.

Dave Asprey: Sorry, yeah, I'm a bad interviewer at this point.

Dr. Anurag Singh: No, butyrate is a great example. By the way, butyrate is a perfect example of a postbiotic. Urolitin A, butyrate is good for your gut health. Similar analogy is Urolithin A is great postbiotic for your muscle and mitochondrial health with the axis of microbiome and mitochondria. On the pulsatility, we have not done once a day or twice a day what is the impact on absorption. This is something that is currently in the works and we are planning that. Longer-term studies, longer than four months, we haven't done as well.

Dr. Anurag Singh: What we have done is in one of our studies, we have looked at the gut microbiome of people… Well, a couple of studies. We've looked at the gut microbiome of people who actually make it versus don't make it. Definitely, the gut microbiome of people who produce Urolithin A is much richer and more diverse compared to those who don't make it.

Dr. Anurag Singh: What we have seen is over time, if you supplemented over four months, for example, and then again, look at if the gut microbiome suddenly changed, no. The answer is you don't really… It's a postbiotic. It's the end result of a healthy microbiome, but it doesn't really induce big changes on the gut microbiome per se.

Dave Asprey: It's a postbiotic, but it's not one that causes a change in the behavior of gut bacteria. It's really just bypassing them to give you the benefits as if you had stupendous numbers of the good ones making your Urolithin A. What would happen if I was on Mitopure for 10 years straight?

Dr. Anurag Singh: The analogy I like to give is, I always show the slide where I show muscles of exercising people who have been exercising all their life and how they're looking at 70, 80 years old. Then I show in parallel, four-week intervention how muscles look like, and they look almost identical. The question is really, how long should I be exercising? We are hitting the same biology, same pathways.

Dr. Anurag Singh: Of course, we have not done studies longer than four months, as you mentioned, over two years but it's a nutrient. To make another analogy, it's like vitamin C of aging. Would you stop exercising? Would you stop eating a healthy diet? No, you'll take it. The kinetics, the way it works is, as I told you, it has a half-life, which means that it disappears from your bloodstream in about a day. It's daily administration that you need to maintain enough, what we call as therapeutic levels in the blood.

Dave Asprey: Got it. That's a pretty clear answer. Guys, what you'd want to do is take it often. I take it pretty much straight all the time because I think the research is there. The fact that you've seen improvements in exercise performance is a really good sign and that you're doing really hardcore science way more than you would see for a typical supplement, which has me excited.

Dave Asprey: I think that you're looking at a foundational thing. If someone said, "All right, I'm going to do this for one month and then take a month off and do it for a month," is it better to do that? Versus two weeks on, two weeks off, there are people on budgets.

Dr. Anurag Singh: I think you have to stick to the first two months at least to see the impact. Then the question is, can I lower the dose or up the dose? Or how should I switch it? The honest answer. We are a science-driven company, so we still-

Dave Asprey: You don't know.

Dr. Anurag Singh: We don't know. We need to-

Dave Asprey: Honest answer.

Dr. Anurag Singh: We need to do more trials and we need to add more evidence on the plate.

Dave Asprey: Here's what I would do in answer to the question from our collective member who asked it, I would do it for two months the way we just learned from Dr. Singh. Then if you have to take a month or two off, great, then do it for two months. You may go up, you may go down, you may go up, you may go down. If I've learned anything about keto by testing it out before I wrote the bulletproof diet and all, cycling is always at least okay, and usually better than steady state.

Dave Asprey: In this case, I think steady state is a good idea for Mitopure and that's what I'm doing. If you had to do it, I don't think cycling is going to cause more harm. You're saying, I had a period of great mitochondrial refreshing and a period of less good and a period of great good. Then you saved some budget there, which is okay. My recommendation would be just do it all the time if it's within reach and your goal is to live a long time.

Dave Asprey: My final question for you, Dr. Singh, what about cognitive performance? I'm into my neotropics, have been for years, and I got 40 years of Zen, where I have people coming doing very high-end brain work. Have you done any studies or seen any anecdotal results around measures of neurological performance versus just physical performance?

Dr. Anurag Singh: Great question, again. There's a lot of research going on around this molecule, actually. Buck Institute of Aging in California just got a multi-million grant from the National Institute of Health to study the effects of Urolithin A on cognitive aging and how it can reverse some of the neuronal circuitry to look youthful. We are actively looking at it, but we are keeping our eyes and ears open for exactly feedback like this because brain cells are also, after muscle cells, have the highest number of mitochondria that decline with aging.

Dave Asprey: You know it would be really cool. They have these places where you can go and you can bet on almost anything, like an election outcome, just any random thing you can bet on. It turns out that betting markets are ridiculously good at predicting outcomes.

Dave Asprey: We need a scientific betting process because having written a book on cognitive function improvements via mitochondrial function, I'd put a lot of whatever cryptocurrency, gold or rapidly declining Fiat currency on a bet that that study is going to show positive results. In fact, if we had a scientific betting market, we could probably just go doing science. We'd all just bet and we get the same results. What do you think?

Dr. Anurag Singh: I think you're onto something there probably. It's not a bad idea to make scientists more aware of how they can commercialize stuff. I think I'll talk about my experience there. As I mentioned, I've been taking it for about a year. I'm a busy guy with young kids who wear me down. Since I have taken the product...

Dr. Anurag Singh: Here, I'm at 8:30 at my time talking to you and I feel more attentive, I feel more energy. Energy is just not in the muscle. I think you're probably right. Time will tell, research will tell in the long term, but probably it's an area to focus on and do some research with your Urolithin A or might appear in your cognition.

Dave Asprey: There's more to be found there. I thought that was my final question, but Joanne just jumped in. Thanks, Joanne, right at the end. Great question. Any changes in sleep from what appear that you guys have come across?

Dr. Anurag Singh: No, but we have heard some, let's say, anecdotal that people are seeing impact on waking up more fresh and this does have an impact. This is again something we need to look further in. That's the beautiful aspect of now seeing it go into real world is now we're getting these great feedbacks, and now you can hear the consumer feedback and actually see where to focus your research beyond just focusing on muscle health. This would be something on the top of our research table.

Dave Asprey: There you go. If you can focus on muscle stuff, you should look at erectile dysfunction and hair growth. If you can just conquer those markets, you guys are going to be co-billionaires. Unfortunately, if you look at where people spend their dollars, that is a ridiculous percentage of it. Probably Brazilian butt lift should be in there as well. I'm glad you're focusing on aging and the performance you're doing because those actually matter more. Those other things are very far downstream outcomes from having good health but that's where people want to put their money there first.

Dave Asprey: Well, Dr. Singh, thank you for the work you're doing with Mitopure. Guys, timeline.com. You can use code upgrade 10, and they'll give you 10% off the plan of your choice. I'm on the whole year-long subscription plan. It just arrives every month. It comes in a nice case and all that stuff. I just think it's worth your time if you're on either an athletic angle or an anti-aging angle or potentially we don't have proof, but I'd bet on it, a neurologic, I want my brain to work better angle. Or you just want mitochondria that are stronger than your neighbors. You could just be a mito geek. That's cool too. So timeline.com and it's code upgrade 10. Dr. Singh, thanks again for being on The Human Upgrade.

Dr. Anurag Singh: It was an absolute pleasure Dave. Thank you for having me.

Dave Asprey: You're listening to The Human Upgrade with Dave Asprey.

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How Postbiotic Urolithin A Upgrades Your Mitochondria

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VO2 max and longevity – Optimizing your healthspan

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How Postbiotic Urolithin A Upgrades Your Mitochondria

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VO2 max and longevity – Optimizing your healthspan

Boosting skin health: plant-based foods that keep you young

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