Do you want more energy? You need more Urolithin A

Dr. Anurag Singh joins Nat Niddam to explore the many benefits of Urolithin A including prolonging life span and increasing cellular health.

Podcast

Biohacking Superhuman Performance

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Nat and Dr. Singh discuss the mitochondrial renewal and repair compound Urolithin A, addressing the many benefits such as increasing muscle function, mitophagy activation, and increasing cellular health.

Topics covered

  • How Urolithin A impacts the mitochondria
  • Ways to induce mitophagy
  • Mitopure dosing
  • Does Mitopure help with fasting
Transcript
Nathalie Niddam
Welcome to the Biohacking Superhuman Performance Podcast. My name is Nathalie Niddam. I'm a nutritionist, a human potential and epigenetic coach. I created this podcast to bring you the latest ways to take control of your health and longevity. We cover it all, from new technology to ancestral health practices, personalized interventions, and a very special interest of mine, peptides. Enjoy the show.
Nathalie Niddam
Hey, folks, welcome back to the podcast. Today's episode is about one of our most favorite topics, and that is mitochondria. Mitochondria being the energy factories of your cell and hence your body are critical to our performance and our health and, well, our life, really. My guest today is a gentleman by the name of Dr. Anurag Singh, and he is currently the chief medical officer at Amazentis SA, which is an advanced nutrition biotech company based in Lausanne, Switzerland, that discovers and develops next-generation natural compounds targeting improvements in mitochondrial health.
Nathalie Niddam
These guys are all about the mitochondria. Dr Singh himself has been at this particular project for over 10 years. He has designed and led, for the last seven years, the clinical development program for the natural mitophagy activator. Mitophagy, meaning clearing out damaged mitochondria, urolithin A. The brand name of this product is called Mitopure. Mitopure comes in protein shake; it comes in powder; you can add to smoothies; or it comes in capsules. Whatever way you like to supplement, these guys have you covered. I'm using all three these days, and I frankly love them all.
Nathalie Niddam
Anyway, the work that he's done has led to the commercial launch of many branded consumer health products targeting improvements in cellular health. Mr. Singh has received his medical training in internal medicine from the Armed Forces Medical College, Pune, India, and a PhD in immunology from the University of Connecticut in the USA. He's authored over 30 articles and top peer-reviewed journals, holds over 10 patents, and has designed and led over 40 clinical trials over the last 15 years.
Nathalie Niddam
This guy is a bit of a heavy hitter, and yet he was a great guest. We talk all about mitochondria, mitochondrial health. We talk about what it is about urolithin A that's so special. There is a food source of a precursor of urolithin A, but unfortunately, most of us don't convert this food source into the active ingredient. One of the cool things that Timeline Nutrition, which is the holding company for Mitopure, does is they will send you a kit that allows you to measure your conversion of this precursor, which comes in delicious pomegranate juice, as it turns out.
Nathalie Niddam
Sadly, to make enough urolithin A to really affect our mitochondria and our performance, most of us would have to drink gallons upon gallons of pomegranate juice, which would be a lot of sugar, quite apart from anything else. However, they've got this really cool kit you can buy and you can test your very own conversion of pomegranate juice into your urolithin A versus measuring your before and after using their supplement. That's a really cool option if you're a biohacker and you love to do your own end-of-one experiments.
Nathalie Niddam
If you decide to buy the supplement, you can use discount code, Nat10, save 10% off of your purchase. Like I said, if you like a whey protein shake, that shake is amazing. The little powder packages are really yummy in yogurt. They taste like berry and it's not overly sweet, or there's the capsules.
Nathalie Niddam
Anyway, if you enjoy this episode and you get value from it, please make sure that you share it with your friends, your family, your networks, whoever else you think would get benefit from it as well. If you're feeling inspired today, please make sure to leave us a review because this is what allows us to be seen, to rise up the ranks, and ultimately to reach more people. Also, it allows me to get more amazing guests for you guys.
Nathalie Niddam
Thank you so much for being here. I've said it before; I will keep saying it every episode; I so appreciate you guys. I appreciate all your comments and questions, all of the connections I have with you, so thank you so much for being here and enjoy the episode.
Nathalie Niddam
Hey, folks, just a little bit of housekeeping before we launch into the episode. Please remember that all of the information provided in these podcasts is for information purposes only. We are never offering treatments, cures, whatever for any disease or medical condition. Anything you hear about here is going to be intriguing. There's some research around it, but make sure that you check with your medical provider before you go off and do any of this stuff for yourself. Enjoy the episode.
Nathalie Niddam
Also, if you're looking to connect with me for any reason with your comments, questions, whatever it may be, you can reach me through my website, which is natniddam.com, or you can find me on Facebook in the Optimizing Superhuman Performance group, or on MeWe in the Biohacking Superhuman Performance group. Of course, you can also follow me on Instagram, which is @nathalieniddam. Nathalie is with an H between the T and the A, the second A. Thank you so much for being here. I appreciate you guys. Enjoy the episode.
Nathalie Niddam
Hey, folks, just a quick minute to thank our sponsor for this episode. Have you heard of nitric oxide? If you were a listener in December, you may have caught the full episode we have on it. Nitric oxide is a vital molecule that is responsible for cardiovascular health and blood flow in the body. But as we age, we produce less of it. As a result, the health of our systems are impacted because we're just not getting the optimal distribution of blood and nutrients that we need.
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Nathalie Niddam
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Nathalie Niddam
Welcome to the podcast, Dr. Singh. It is such a pleasure to have you here today.
Dr. Anurag Singh
Thank you for having me, Nathalie.
Nathalie Niddam
I've been looking forward to this podcast for quite a while, actually. I think I met... Well, I don't think. I know I met your team in September at the Upgrade Labs Conference, and it was a protracted back and forth since then. The cool thing is that they had sent me, and I'm getting a little ahead of myself, but they sent me the kit to establish whether or not my body makes urolithin A efficiently. They weren't able to send it to Canada. They had to send it to the States at the time anyway. It took until I got to Florida in December before I was actually able to run the test and send it back. It's been one of these long-time-in-the-making podcast. I'm really excited that we're here today.
Nathalie Niddam
Dr. Singh, I was wondering if you would start with a little bit about yourself because you've got a great big career behind you, and maybe talking a little bit about your career and how you ended up honing in on this one compound that we're going to talk about.
Dr. Anurag Singh
Sure. Thanks for having me again. My background is I'm a physician-scientist trained in internal medicine initially in India, then moved over to the States, trained in the University of Connecticut, got a PhD in immunology, and then worked a lot of time in the chronic diseases field and asthma, COPD, et cetera. Then moved over to Switzerland, working in consumer health space and consumer nutrition companies for the last decade and a half.
Dr. Anurag Singh
What became very clear to me that a lot of the products in the consumer health space were all, you have the probiotics, you had the prebiotics, and then you had the blends of plant extract and polyphenols that were based out of literature research and broad knowledge that they could deliver health benefits. But there was the deep-dive scientific approach was missing on how they were working, what exactly biological pathways they were hitting.
Dr. Anurag Singh
Then about seven years back, I joined Amazentis, which I learned was a company at that time formed with the same belief to bring in the deep-dive and the biotech approach to nutrition. That vision fitted perfectly. Amazentis' focus was on deconstructing the pomegranate, which is a fruit. Again, if you look at the scientific literature, there's hundreds of articles about health benefits of pomegranate, whether you take it in juice or extracts or concentrates.
Dr. Anurag Singh
At that time, we were studying and trying to deconstruct the pomegranate, which has about 300 plus bioactive compounds. It was really which compound is causing the health benefits. From that funnel approach, we focused and we realized that there was a group of polyphenols called the ellagitannins. It was these ellagitannins that needed to be then transformed by the gut microbiome into this wonderful natural molecule called urolithin A, which is really the subject of a podcast that we started finding these incredible effects. This was mostly because of the gut microbiome transformation.
Dr. Anurag Singh
We've been studying this molecule for the last 10-plus years, and the last seven years of my life, I've devoted to how it works in humans and what benefits it can bring.
Nathalie Niddam
Wow, that's incredible. Urolithin A, so let's talk a little bit about… Because this is really optimizing mitochondria and mitochondrial performance and health, really, and performance. But it goes about it in a very what people might think of as a roundabout way because it's not like urolithin A act on mitochondria, like makes mitochondria work better or do make more ATP. Maybe we can explain to people. I mean, most people listening to this podcast probably know what a mitochondria is, but we can give them a top-line little crash course on mitochondria, which I know people could spend years talking about.
Dr. Anurag Singh
Yeah, sure.
Nathalie Niddam
What we know and what we don't know. Then how does urolithin A really impact the mitochondria and why is that so important to people?
Dr. Anurag Singh
Again, not a crash course in mitochondria, but mitochondria are the cellular factories which are producing the currency of energy, which is ATP, as you mentioned. There are three different ways you can boost mitochondrial health. You can increase the efficiency of mitochondria. The pool of mitochondria you have in your cells, they're, let's say, compounds like creatine or l-carnitine that are known to make healthy mitochondria produce more energy.
Dr. Anurag Singh
Then there's another pathway that is called mitochondrial biogenesis. Now, this pathway is basically, well, you increase the pool of your healthy mitochondria in your cells, and by that, you increase energy. There are compounds, [inaudible 00:11:48] is touted as one; nicotinamide, NAD modulation is touted as one. But with aging, what happens is these pathways are all slowing down, but there's another third key, very well-conserved anti-aging pathway that is called mitophagy.
Dr. Anurag Singh
What is mitophagy? Mitophagy basically is your recycling pathway in your cells, specifically in your mitochondria. As we age, we are accumulating default or faulty mitochondria that are not able to produce optimal energy, for example. These faulty mitochondria occupy space, so you don't really have room for newer healthy mitochondria to come in, or even for your healthier mitochondria to produce more activity because these dysfunctional mitochondria are occupying space.
Dr. Anurag Singh
What urolithin A does, which is its novelty, is it activates mitophagy. By doing that, it revs up this cellular recycling process that then contributes to the building blocks of biogenesis, and of course, it cleans away the waste, so now you have more newer healthy mitochondria coming in and you have more energy coming in.
Nathalie Niddam
That's a great explanation. Thank you. That's an interesting concept around mitophagy, actually, that I think people sometimes forget is it's not just the nuking of the dysfunctional or poor contributors, if it will, but there's a recycling that happens and a reuse. The body is so efficient that way. It's going to discard what it can't reuse, but it is going to preserve and reuse elements that it can. I guess that somehow stimulates the biogenesis of new mitochondria or at least contributes to it.
Dr. Anurag Singh
Yeah, and that's what we're actually exactly seeing in our clinical studies and, of course, before that, in our preclinical study, that there is an initial phase of mitophagy where the body is cleaning away the waste. It is another concept we call as mitohormosis. When the body realizes that there's a perfect balance now between, let's say, the waste has been cleaned, then the body takes those recycled fragments and starts into biogenesis mode. That's what we are seeing is that we see in humans, at least, we upregulate after, let's say, a month of supplementation, genes linked to biogenesis such as PGC-1alpha. That indicates that first step is mitophagy, and then the biogenesis happens.
Nathalie Niddam
That's really interesting. Again, it's an interesting concept in the body where sometimes you have to destroy, like you have to clean out. You can't build and clean out at the same time almost. There's an order of things. For people to get into mitophagy, just to... Mitophagy is probably triggered by more than just... Well, there's so many redundancies in the human body, thank God. What are some of the other ways that people can help to trigger mitophagy in their systems?
Dr. Anurag Singh
Yeah, sure. Intermittent fasting or fasting in general is one of the biggest, or caloric restriction in general, is one of the biggest ways how you induce just not mitophagy, but autophagy in general. Autophagy, the whole cell is now undergoing recycling, clearing of the waste. Aerobic exercise and a mix of aerobic and resistance exercise is another one that is known to induce mitophagy as well. These are the top two interventions that people can utilize already, fasting and exercise that are known mitophagy activators. Amongst the natural compounds, I think urolithin A probably would be the first and novel one that does this hitting the same pathways.
Nathalie Niddam
I mean, everybody's running around looking for this stuff. There is another compound I've learned about recently called spermidine that seems to help with mitophagy as well, but possibly not. It's a different compound altogether. Getting back to mitophagy and fasting, is it similar to autophagy, where you have to hit a certain threshold in fasting before the mitophagy really takes place?
Nathalie Niddam
Because we talk to people a lot, and so people are always wondering, how long do I have to fast for these tests to trigger? sis it 12 hours? Is it 16 hours? Do I need to fast for three days? What I've learned from a lot of the work I've done and the people I've spoken to is it depends person to person. Certainly, for autophagy, it is very dependent on metabolic flexibility. Is that true also of mitophagy, or is mitophagy maybe a bit more flexible than that?
Nathalie Niddam
No, I think it's pretty much true. Mitophagy is just more targeted autophagy of the mitochondria. That's what it is. Again, it probably depends on your feeding status, what are you eating in the day, your metabolic, if you're insulin-resistant or not, things like this that dictate a lot of the mitophagy flux, as we call it, similar to autophagy flux, as it's called.
Nathalie Niddam
It goes back to the question, why supplement—also, something like urolithin A or you mentioned also spermidine—when you can already get some exposure through diet? The reason is you get such suboptimal exposure from diet. These levels will never be enough to, let's say, sustain enough mitophagy activation. That's what we need to do with by short-circuiting this pathway, at least for urolithin A, by providing direct supplementation and making sure that mitophagy is triggered at an optimal level, with certain doses we know trigger autophagy and mitophagy, and then the physiological benefits will come in.
Nathalie Niddam
Then if you take urolithin A, and there's so many other things you want to talk about urolithin A, so by supplementing with urolithin A, you can be in a fed state and still trigger mitophagy. You basically circumvent this need to deprive yourself of food and work out because ideally, you probably do a big workout and then you do... If I'm doing an extended fast, I sometimes will kick it off with a workout.
Dr. Anurag Singh
That's a great question. We've actually tackled that question in some of our clinical studies where we have given supplementation on an empty stomach after overnight fasting and then with a hot, heavy breakfast just to A, see, if the bioavailability of the way it's absorbed is changed, because that will ultimately dictate the levels. And second, are you having an impact? Because if the fed status in the answer to long set of experiments is no, the fasting versus fed status of what you're eating, it doesn't really change how urolithin A is impacting mitophagy and its bioavailability as well.
Nathalie Niddam
Wow. Okay, so it's a hack, really?
Dr. Anurag Singh
It's really a hack. Yeah, it's a hack, and it's a short way to hit pathways you would otherwise struggle to comply with, for example.
Nathalie Niddam
Yeah, I know because fasting is not accessible to everybody. People find it hard, unpleasant, and cranky. In a perfect world, we can all do without food at least some of the time, but…
Dr. Anurag Singh
You can do it, yeah. You can do it for a certain time, but then compliance is a major issue in both exercise trials and in the intermittent fasting trials.
Nathalie Niddam
Absolutely. Let's talk a little bit about the gut microbiome, because the gut microbiome comes heavily into play here. In a perfect world, urolithin A is a byproduct of the metabolism of those pomegranate compounds, and the urolithin A is a byproduct. I did the test. I don't make much. I make some, but not a lot.
Nathalie Niddam
We were actually talking earlier before the podcast that, in my case and maybe in your case, there's a really good chance that the time in which we grew up, there were a lot of antibiotics involved in my childhood. I've always known that my gut microbiome… It's never really been optimal. It's been a work in progress, and it will be until the end of my days, ultimately, because it's set much earlier in life. But can we talk a little bit about the microbiome's role and what you found in your research?
Dr. Anurag Singh
This is, personally, as a physician-scientist, for me, one of the most intriguing aspects of this equation, the gut microbiome. Now, when we started studying this, it became very clear... The initial thought of the urolithin A, as you mentioned, was this is just a byproduct of metabolism of these pomegranate compounds. But when we started seeing the effects, whether it was on mitophagy or autophagy, or on muscle health and mitochondrial health in general, we started taking a deeper look into the gut microbiome.
Dr. Anurag Singh
Now, there are two biases you need, if you have a chance to succeed in nature, to be a good urolithin A producer. A, you need to be eating right. In addition to pomegranates, walnuts are a very rich source of the precursors. Some berries like raspberry or blackberries are very rich sources of... You need to be eating a bowl of nuts, berries, or drinking a glass of pomegranate juice every day. So that's one bias.
Dr. Anurag Singh
The second is then this optimal diet probably creates, or you're blessed with a healthy gut microbiome that is rich and diverse in nature. We've studied this in detail. We've done a clinical study where we gave a glass of pomegranate juice, which was pure 100% juice to 100 people.
Dr. Anurag Singh
First, we say, "How many were producing?" There were only 12% in an American population that were producing in real life. Probably American diet is not super healthy anyway. Most of the people when they took it, only about 40% were able to convert, which means that, well, the 60% are still missing out, even if you were to give them a diet, and that's people like me, and you mentioned you are also a low producer.
Dr. Anurag Singh
We have found that there are species such as Akkermansia that are enriched in these people who are "blessed," as I call them, who can make urolithin A. Again, this is a very imprecise, imperfect process that nature has created. Some are gifted; some are not. What we saw is that by short-circuiting this process by direct supplementation, we could then give all the 100 people levels that were much higher and about six-fold higher. That, in essence, is the story of the gut microbiome.
Dr. Anurag Singh
Now, probably you could train it, you could improve it to improve the production of the urolithin A naturally, but I doubt that it will reach therapeutic levels that you see with supplementation.
Nathalie Niddam
It's actually Akkermansia that converts?
Dr. Anurag Singh
Like biology, there's never a magic bullet, so I don't think it's one magical species. It's really a consortium, I believe. We've put our heads over the years trying to figure out if there's one magical gut microbiome species that is responsible. The answer is very difficult. Gut microbiome is like a concert. You have these millions of bacterial species all in harmony, and then there are others that are not in harmony with the optimal gut microbiome.
Dr. Anurag Singh
If you eat a good diet rich in fiber, if you're eating, as I mentioned, the precursors over a period of time, you could probably train your microbiome to do better. But again, if the damage has been done, as you touched upon, in my case, growing up in India, taking a lot of antibiotics, and then migrating and being on different diets, Indian diet to American diet, and now more European diet, I think the microbiome is always evolving and not really there to optimally produce urolithin A. But Akkermansia is definitely one of the interesting candidates.
Nathalie Niddam
That is interesting because I've done some work with a program by a gentleman by the name of Joel Green, and he's all about restoring bacteritis and Akkermansia to the microbiome and doing it with food, but using certain supplementation, like he has an apple peel, an HMO protocol, and then he adds polyphenols at the end.
Nathalie Niddam
He's definitely in that world of using nutrients to try to, the way I think of it is, recultivate these gut bugs that we lost, if we will. But at the end of the day, you also need starter fuel for that. If it's been wiped out to begin with, then it doesn't matter what you feed it. If it's not there, it's not going to grow.
Dr. Anurag Singh
Yeah. Exactly. I can drink 6 liters of pomegranate juice, my body will make zilch of urolithin A. That's not [inaudible 00:25:12].
Nathalie Niddam
And you'll be on a massive sugar high.
Dr. Anurag Singh
Yeah. Exactly.
Nathalie Niddam
Tastes good.
Dr. Anurag Singh
Tastes good, yeah.
Nathalie Niddam
Basically, the supplement, ultimately, it's a total shortcut to the end product. This supplement, at this point right now, this is this whole postbiotic concept. This is the concept of, in essence, taking the microbiome out of play and just providing the body with this end product that we know.
Nathalie Niddam
What's really interesting, I think, about urolithin A is that it seems to make it to the cell, which is not always a gimmie. One of the big arguments around all of these NAD precursors and NAD is, is it actually getting to where we want it to go? Just because you take something, doesn't mean it's going to go to that one place. It seems, at this point, you seem to have proven through your work and the studies and the clinical trials that it's definitely getting into the cell or getting to the cell or that place where it needs to activate mitophagy.
Dr. Anurag Singh
A couple of years back, we published a paper in Nature Metabolism where we showed actually that as you increase the dose, you'll get more inside it in the blood. As you went from taking, let's say, 250 milligrams of urolithin A to 500 milligrams to a gram, you would get dose-dependent increases. Then in these studies, we also take small chunks of muscle tissue, which is called muscle biopsies, just to study the mitochondrial health in these-
Nathalie Niddam
That sounds pleasant.
Dr. Anurag Singh
Yeah. It's like a wasp bite, a bee sting. But most people, they opt for it because they're in trials. They want to know if it's actually reaching much like the question you're asking. In these studies, we looked at two things. We first asked, is it actually getting into the muscle cells? Because if it's not getting into the muscle cells, then how is it doing? Is it making other...
Dr. Anurag Singh
We saw that it's getting into the muscle cells at the same level as plasma, which is great because that means it's hitting the cells. It was rich in mitochondria, which is muscle cells are one of the richest cells with the richest abundance of mitochondria. Second, we saw that mitochondrial genes and mitochondrial biomarkers were all upregulated in the skeletal muscle cells in older adults and overweight middle-aged or healthy middle-aged adults.
Dr. Anurag Singh
We've looked at a spectrum of different age population, and we always see that it's very bio-available, and it hits the target organs, which are rich in mitochondria, for example.
Nathalie Niddam
You've picked skeletal muscle because it's the easiest to measure, is that right? Have you ever looked at cardiac muscle? Because cardiac muscle, again, is very, very rich in mitochondria, obviously.
Dr. Anurag Singh
We picked skeletal muscle for two reasons. It's one of the first things people notice as they age. Everybody notices a lack of energy, a bit low in strength. You're used to exercising for an hour, and then suddenly after a few years, you start to feel it. It's one of the endpoints in clinical studies that people can recognize and we can measure very easily. We can put people on a treadmill or an ergometer and see how long they can last. We can give them tools to do grip strength measurements. It's easy to measure.
Dr. Anurag Singh
Heart health. It's a bit more... You're absolutely right. Aside the skeletal muscle, the human heart and the human brain are the two richest organs that have mitochondria. We've started looking at it now. When your small company is starting to build the science, of course, we spent years building on evidence and muscle health. Now we do see metrics like peak VO2, for example. This is a perfect metric to also assess cardiac health, and we see that peak VO2 is improved by 10%. Now we are starting our experiments on looking at cardiac health, but you will see trials in the future where we are starting to look at cardiac health, just not muscle health in isolation.
Nathalie Niddam
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Nathalie Niddam
Logically, you would think that for people who've had cardiovascular issues where there's been damage done to the heart muscle that optimizing mitochondrial health is going to... It's going to be a big piece of their recovery.
Dr. Anurag Singh
Mitophagy is well-known also to be impaired in people, as you mentioned, those who have heart issues. Mitophagy is well-known to be impaired and autophagy as well. I think it's the logical second application as we move the science forward.
Nathalie Niddam
How about crossing the blood-brain barrier? Have you looked at that at all? Because again, when you think about the possibilities in people with... As we age, natural cognitive decline. Of course, we have a population that's looking to optimize. But to your point, it's easier to go look at a population where there's been a decline so that you can more easily see if there's been a restoration of function. Are you looking at that at all?
Dr. Anurag Singh
Yes. We do know today that it does cross the blood-brain barrier. We haven't done specific studies looking at what aspects of human cognition, for example, it is improving. We started the research, and we identified it as a mitophagy activator. Since then, there's a lot of top labs around the world that have picked up on our research. Of course, we can do research in isolation ourselves.
Dr. Anurag Singh
There are groups in the National Institute of Health and the Buck Institute of Aging that are in breath have got millions of dollars of grant funding to look at how this beautiful molecule impacts cognition and brain health during the aging process. They've come up with some spectacular findings. I think some of them are published as well, where they see that mitophagy declines in the brain of, for example, these aged models that they have published in, and that out of 300 odd compounds they screen, urolithin A was one of the most potent in recovering neuronal health and neuronal function in their system. This is another aspect we are very excited about research.
Nathalie Niddam
No kidding. It's interesting. I think that in all of the things we do, certainly for me, I'm always looking to see how far upstream can we get? How far up the chain of command can we go so that if we improve this one thing, the downstream effects are just going to cascade out of it? It's almost like the lowest intervention you can do that allows the body to then just go and do what it's going to do. Optimizing mitochondrial health, I think, is just one of those things. It's like giving fuel back to a machine. All of a sudden, the machine can work again, and it just does what it does.
Dr. Anurag Singh
I think that's exactly what it is. Cellular health is the bedrock of our overall health. I always say that these are the three pillars: good diet, good lifestyle, being active. But then you need to think about your different cells. Improving mitochondrial health is a great tool to improve cellular health, whether it's brain health or heart health or skeletal muscle.
Nathalie Niddam
In your clinical trial, you've done a lot of work with high performance athletes. Now, I think you mentioned you've moved into more regular people, as it were, like your weekend warriors or your aged populations. Are you moving into the-
Dr. Anurag Singh
Yes, the other way around. We started with aged populations or older adults because this is where we know very well-characterized that mitochondrial health declines. That was the logical step. We took out older adults; we gave them a month of, in our first trial, a month of urolitihin A Mitopure supplementation. Then we looked at what mitochondrial health biomarkers were improving. As I mentioned, we also took some biopsies. There we figured out the doses. The doses, 500 milligram and a gram were the two most top doses that we found that effects that.
Dr. Anurag Singh
Then we run two studies. One we just published where we saw that after two months, older adults had more resistance to fatigue. Meaning if you make them do a muscle function task over time, whether it's leg press or lifting a weight on the hand, the muscle exhausts itself after repetitive tasks. It accumulates lactate, for example. But with the urolithin A supplementation, it just went about, for example, 20% longer. There was more endurance and more resistance to fatigue.
Dr. Anurag Singh
There's another trial we are just trying to get published. It was done in about 40-, 50-year-olds and middle-aged, so we moved a bit in the younger, healthy aging population. These are again people who are not athletes. They're everyday Joe. They're working. They do a little bit of exercise they can, but more or less sedentary. Then in this population, we saw really good robust effects on leg strength and improving the VO2, which is a marker of mitochondrial health.
Dr. Anurag Singh
Now we are moving further into younger, Olympian athletes because the idea is that with over training or training or repeated competitions, these athletes, they compromise their mitochondrial health, and so can mitochondrial health be a way to recover faster after competition or after training? That's where we are today.
Dr. Anurag Singh
Then we're also going into hospitalized populations where if you're admitted into hospital and you have prolonged bedrest, where we know that muscle wastes very faster, can we see an impact there? These are the next steps we're doing.
Nathalie Niddam
Fascinating. I actually think that's such a great point on the athletes because we all think of athletes as these superhuman people. They can do amazing things, and if I only have the time to train like these guys. And I think what we forget is the degree to which they train is actually they've gone over to the hump of benefit and now on the other side of too much of a good thing where they age faster and their body is not able to recover really from all of the stress and strain on their systems, and it actually works against them.
Dr. Anurag Singh
It's really accumulation of cellular stress over the years of training and not giving enough time for the body and the cells to recover. I think that's what it is in the end. We are very interested in seeing if urolithin A can now accelerate this recovery process and give them breathing space so they are again ready for the next competition or next race in a better way.
Nathalie Niddam
Then maybe even avoid some of the long-term damage that they sustain. I had recorded another podcast with a gentleman who had looked at the biological age of an Olympic. It turned out that this amazing Olympic medalist, her biological age, I think it was 10 or 15 years older than her chronological age. Again, it's one of those things where people go, "Well, wait a minute, that shouldn't be." I think it'll be really interesting to see as your research continues how helping these athletes recover faster, if that's able to...
Nathalie Niddam
Obviously, your first metric will be their performance, because that will be the most obvious. But then even if you were to dig deeper and start looking at these deeper markers of damage and-
Dr. Anurag Singh
That's exactly the study we're running with the Australian Institute of Sports in Melbourne and Canberra. We're working with Professor Louis Berth. He was really one of the leading researchers studying elite athletes. These are exactly, as mentioned, the two metrics: performance and recovery and oxidative stress that we're measuring in this study.
Nathalie Niddam
Cool. Amazing. Do you have an opinion, or in terms of what you've seen of the... You mentioned that it's somewhere between 500 milligrams to a gram dosage is ideal. Is a gram definitively better, but you recommend 500 milligrams just because it's easier for people to get their heads around, or does it depend on the individual? Someone like me, for example, who makes some Urolithin A, would I be one of those people that might get away with a bit less? Or is it just that the optimal dose is a gram, and then is there a point of diminishing returns over that? Or you just don't see more benefit?
Dr. Anurag Singh
I'll tell you what we have seen. Research is "re" and "search," so you got to always continue building up…
Nathalie Niddam
Going at it.
Dr. Anurag Singh
Going at it. What we know is that both starting 500 milligram, we can impact mitochondrial health. We see upregulation of genes linked to improved mitochondrial health. We see improved systemically in the blood biomarkers linked to mitochondrial health get better. Physiologically, we see at both doses statistical improvements on muscle strength, for example, at the same level.
Dr. Anurag Singh
Where the one gram starts to get better, maybe it's a kinetic, it does it faster, is metrics like more related to aerobic endurance and performance. Peak VO2, we get more better effects. Typically, the way I think is 500 milligrams is enough for getting benefits linked to cellular health and mitochondrial health, and if you continue longer, you get benefits linked to muscle strength.
Dr. Anurag Singh
If you're sports, if you're into the weekend warrior or even into sports health, then maybe a higher dose is needed because, as we were talking just before, you need to accelerate the clearance process much faster, and you need to act on different levels. What we also see the higher dose do is it's a bit of a little anti-inflammatory, and there's a lot of new literature coming that links mitochondrial health to immune health, which is a new field of immune metabolism.
Dr. Anurag Singh
That's where I think the one gram… Again, a lot of athletes have inflamed bodies. With aging, we also have inflamed aging. That's where I think depending on your… What is the right dose for you? I think that's where we've started thinking about this kit that we chatted at the start. How does precise nutrition fit in if you're already a producer or you're making low amounts? Maybe you start off with the lower dose and then you ramp it up. For someone like me who body will never make anything, I go straight with the higher dose.
Nathalie Niddam
That's really interesting. I guess it makes sense that the higher dose. Basically, people who have a higher need, whether it's someone who's more elderly or you're a high-performance athlete or someone who just... Maybe someone who's been obese for a very long time, they've got a lot of inflammation in their body. We know that their bodies are struggling to meet their needs anyway. Whereas maybe someone who's essentially healthy and in pretty good shape might be able to get away with a 500-milligram dose for a period too.
Dr. Anurag Singh
I think this dose is a work in progress because, as I mentioned, research needs to be done over a certain period of time. Again, think of urolithin A, the way I think is like the vitamin C of aging, except that with vitamin C, we all are told to take our four orange equivalent of juice or take a gram of vitamin C, which who knows how much of it gets absorbed and how much is needed.
Dr. Anurag Singh
What we are aware, and that's why we've been working on this concept of providing a kit to people that people can measure what they're starting out at and then titrate accordingly if they want. 500 is the dose we know will improve cellular health, so we're very confident about that. Then if you want to ramp up to a gram to get better physiological effects, you ramp up.
Nathalie Niddam
Have you ever thought about or looked at, and maybe it's still early days because I guess it's funny. We don't always think about how long it takes to accumulate the knowledge that we need on things like this. Still very much in its infancy, even though you've been at it for so long. Have you ever or do you think you might… This is a funny question to ask of drug company, because at the end of the day, their perfect world is everybody just takes it every day, and it's [inaudible 00:43:36] in the world.
Nathalie Niddam
In terms of cycling this as a supplement for people, do you think there might be some benefit in maybe going higher dose to the one gram for a period of time? Let's say three months, because we know we need a couple of months before you actually experience any real benefits. You get that extra month with the superior function. Then if you were to cycle off it for one or two months and then go back to it, is this something you think there might be any value in? Or have you even looked at that yet, or it's going to be down the road?
Dr. Anurag Singh
I think it's going to be down the road. Dosing, should I take half the dose in the morning and half the dose in the evening? Is it the peak levels that matter, or is it the exposure and the time? As you're saying, do you need X amount of time and then you can taper off and then bring it back again?
Dr. Anurag Singh
I don't really have answers to all this. As I mentioned, these are more longer term research as a continuum of time. We've been at it at 10 years. I think we need another five-plus years to figure out all these questions. What I do think is, and we are a science-based nutrition company, is that think of exercise. If you just thought of it, we know exercise is hitting the same pathways as this molecule.
Dr. Anurag Singh
If you said, "Oh, let me do exercise for two months and then stop doing exercise, and then come back again two months after," that's not what we know about exercise science. We know you need to be added regularly over time to get the best effects out of it. What we do know is the kinetics of this molecule, and it peaks about six hours, stays about 20 hours, 24 hours, and then the levels start declining. In my opinion, if you want to take it, it's best taken a day, for example, as long as you can until you see the effects, and then it's up to you to decide how much. To draw the correlation with exercise, that's how I tend to think about it.
Nathalie Niddam
That's actually a really good point. Unless you were cycling your building and burning periods. There's someone that I've worked with in the past who he has these building phases where he has his clients build, build. Then he has what he calls, and he actually would start with a teardown phase, where you're stripping the body of what it doesn't need, so you would use your senolytics. You might use something like this a little more heavily because you're doing a bit more fasting. You're not as focused on the building phase. You're trying to get rid of things, and then he would go into his build phase. Then you could make an argument that says, but now you're going to want to take your urolithin A to fuel the muscles.
Dr. Anurag Singh
For example, what we are doing in terms of research—again, and we don't have answers, so I don't pretend to have an answer to your question—but we are starting to see doing a time course. Is it a week when we start seeing in humans, this mytophagy? Or we know in a month? Is it earlier? Can we still see effects? We know we are seeing physiological effects and we're seeing biogenesis. Again, back to the question, is cleaning the waste upfront for a week or a month more key than…
Dr. Anurag Singh
But I think there's a maintenance phase. The way, again, I think of it, to give you a second example, is you're recycling in your home. You accumulate waste in your home, it fills up, and then you recycle, and then you fill more. That's how this molecule we know works today. You have a waste, then you fill it up. It cleans it up, then you get more space to grow new mitochondria, and then you again accumulate waste. It's a cycle.
Nathalie Niddam
I think actually it's that one of those things you want mitophagy to be going on all the time. To your home analogy, you don't want to fill your house with garbage and then just take it out.
Dr. Anurag Singh
At some point, you get biogenesis, which is what I call the mitohormosis concept. There's always a balance that the body has, and with aging, the balance shifts towards declining mitophagy. You activate it and then the body switches back to more of the biogenesis mode.
Nathalie Niddam
Got you. Another question for you is the dosage, and I'm going to guess not because you haven't talked about it at all, but have you found it to be dependent on the person's size? Like do bigger people need more? Or have you found that generally speaking, it's pretty even-steven across the board?
Dr. Anurag Singh
I think it's pretty much similar by availability, whether it's BMI or different. We've looked at the French populations. There's more mixed ethnicities. We don't see an impact of gender, body weight, or ethnicity on how it's absorbed. It's pretty much similar effects across the board.
Nathalie Niddam
Not size-dependent, gender-dependent, or ethnic-dependent. It's really about are you making the stuff or are you not making the stuff?
Dr. Anurag Singh
Are you more athletic and do you need more? We are still doing the experiments and the research is ongoing, so we'll know more about that.
Nathalie Niddam
I think as we've talked about, there's a reasonable chance that your high -performance athlete is going to have a higher knee just because they're pushing their body that much harder. Similarly, the complete antithesis of the high-performance athlete, the person who's more challenged might also benefit more.
Nathalie Niddam
In that vein, one of the populations I come across a lot that are really struggling and very much struggling with energy at a very foundational level are people who are dealing with something like Lyme or mold or EBV, like these co-infections that just seem to zap, or chronic fatigue syndrome, like these things, these low-lying chronic infections that just seem to drain people's energy. Is this an area that you have looked at at all or you might look at in the future?
Dr. Anurag Singh
We haven't, to be honest. We have not looked at these areas, but we do know we have real-life feedback now because we've been selling the product for the last year and a half, and there are a lot of folks who have these, as you call, chronic fatigue issues who swear by it, and they think whether they're recovering after a viral illness or anything similar, that it does help them recover better.
Dr. Anurag Singh
A lot of times when you have these conditions, you're also taking a lot of medications that are also known to have detrimental effects on mitochondria. That's where again, not studied it and it's mostly anecdotal, but that's what we're starting to hear, that it's helping folks who have fatigue. We've seen in our studies at least muscle fatigue is improved. That's a key element to overall fatigue. We do think that it does have a role that needs to be studied in more detail.
Nathalie Niddam
It's a piece of the puzzle. I guess the next one that would come down the pipes on that line, not to say a bad word or anything, that would be your COVID-19 long haulers, which again, these are people who are just they just can't seem to get themselves going.
Dr. Anurag Singh
The condition needs to be studied more. Is it a mitochondrial deficit, or is it more something else in that population? I think the studies will… The goal when you're studying a new ingredient or a new natural product is to set the foundation of science that people say, "Wow, this is interesting." Then as a small company, we can do 50 trials. Then now since we published our last paper, now I'm getting calls exactly in all the different topics that you mentioned saying, "Maybe it could work for this population, or maybe it could work for…" I think that's how the aspiration is, is to build the foundation of science and then get real-world feedback, but also other top labs testing it out for different conditions.
Nathalie Niddam
I guess that's the goal. I never thought of it that way, but I guess when you come out with a novel ingredient, a novel compound like this, the hope is to inspire other labs around the world to grab the flag and run with it kind of thing.
Dr. Anurag Singh
I can see it validated because… That's what we aspire here in our company, is really work with the top labs, and that's what we have done since our 10-plus years, is really partner with the top labs and let them study the molecule.
Nathalie Niddam
No, that's, I guess, more brains. The more people you have on it, the faster it'll go and the more we'll learn. Is there anything we've not touched on here? What else should people know about urolithin A? We know that it can be taken fasted or with food. Do you think there might be some additional benefits if someone was doing a fast to take it while they were fasting as well, just to give that extra push?
Dr. Anurag Singh
We haven't studied in humans, but we have done comparison head to head similar in other models of aging where we do see that the effects on, for example, autophagy and mitophagy are very similar to fasting. I don't think we have done a combination of fasting. We have done exercise. We have given exercise regimens in addition, and it's additive. The effects of exercise are boosted if you add urolithin A into the diet. So that, we know. Now, of course, we're running trials in elite athletes who are exercising, so that will add to the body of evidence. With fasting? No, to be honest. But we know it hits the same pathways.
Dr. Anurag Singh
It won't hurt, that's for sure. Is there anything we've left out? Is there anything else you'd like people to know? Are you still running those tests? Are you still sending out the test kits? Can people get the test?
Dr. Anurag Singh
Yeah. Actually, it's running as part of a virtual clinical study, so people can participate in the study and sign up and they get a kit in the home and with instructions on how to do it. Then it's too small with the capillary fingerprick blood, a few drops of blood, you get to know, A, first if you're a producer or not, and then you take a single dose, and you see the difference the dose can bring in terms of blood levels.
Dr. Anurag Singh
The next, I think you may want to ask, what is the future? Yes, it's important to know if you're a producer or not, but what do I do with that information? I think as we think about the next building block or the next version, we're starting the thing you mentioned, biological age. We are actually starting to think of a more precise nutrition kit that will allow people with a set of mitochondrial biomarkers and biological age to track their cellular health, because that's what we are actually trying to improve is cellular health.
Nathalie Niddam
It's what we were talking about as far upstream as you can. We have talked a lot about physical performance and athletic performance, but really, the big win for so many people who listen to these podcasts that we're all after is this improved healthspan and longevity and function as we age and keeping those little energy power plants going.
Dr. Anurag Singh
Exactly. I think that's the holy grail. Can we improve our healthspan and can we make people continue to go out and do activities of daily living like they were doing 20 years back?
Nathalie Niddam
What do you think is the optimal human lifespan or maximum human lifespan? Have you thought about that much yourself?
Dr. Anurag Singh
To summarize, a quote I read somewhere, about 50, 60 years back, the average lifespan was about 35, 40, if I'm not correct. Of course, the wars and the infectious disease that were rampant. Now we're an average of living 80 years. I'm sure if we address the three pillars of diet, lifestyle, and of course, eat the right nutrition for ourselves, I think we can extend it further for sure. But I think the goal is to be 90 and do the things that you were doing when you were 60. I think that should be an easy goal to set. Let's achieve first and show we can achieve that, and then we can aim for Mars. Let's go to the moon first.
Nathalie Niddam
I totally agree with you. I think that as we improve the time that we live, next is first, let's improve the quality of that time, and then let's think about the next.
Dr. Anurag Singh
It's possible. We know there are these blue zones around the world where people are living 100. They're not doing anything extraordinary. They're just eating right. They move around a lot, and they eat fresh fruits and nuts, and they're all at hundreds, still very active. That certainly can be done.
Nathalie Niddam
I think sometimes it's what you don't do. We're always looking to see, what's the next thing I should do? What's the next thing I should take? What's the next thing I can buy? Sometimes what we forget is it could have a lot to do with what we don't do, what we don't eat, what we don't buy.
Dr. Anurag Singh
Yeah, you got it. You're right.
Nathalie Niddam
It's going back to the mitochondria, right? Mitophagy first and biogenesis next. It's getting to that balance. How can people order their test kit? How can they get their hands on the magic Mitopure?
Dr. Anurag Singh
We can send you the link to the study and it's a link people can register on the link. If they're approved, if they fulfill the different criteria of the study, they'll get a kit of their own. If they're interested in buying the product, they can go to timeline.com. If they want to learn more, they can go to mitopure.com as well.
Nathalie Niddam
What's the difference between those two sites? Mitopure.com is more for-
Dr. Anurag Singh
Mitopure.com is just a science-based website where people can learn more about the science and how the discovery was made and how cells age and why should we care about cellular aging and things like this. Timeline Nutrition is the nutrition brand that sells Mitopure, and they can go to timeline.com and purchase if they prefer. We have three products. Most people prefer to take pills, so we have the pills.
Dr. Anurag Singh
I see nutrition as just not pills that you need to pop it, but also something that should taste good as well. We do have two products. One is a berry-flavored, pomegranate-flavored powder that you can mix in your daily yogurt or loosely. Then we have a high protein shake with the Mitopure hitting muscle mass and strength, bioenergetics in one combo. People can choose what fits their lifestyle.
Nathalie Niddam
Nice. Well, I mean, or a combination, right? I think-
Dr. Anurag Singh
Or a combination, there's a-
Nathalie Niddam
I think it would be probably optimal because you're getting it in food form; you're getting it with your protein on maybe days you're working out, and then you're taking the pills.
Dr. Anurag Singh
You can choose a one month of each, so that's also an option. You can choose to try all three products in the package.
Nathalie Niddam
I think that's great. timeline.com and mitopure.com, all these links will be in the show notes, guys. We'll also have a link for a discount code for you. We didn't have it in time for the episode, but if you're listening to this, you probably heard it in the intro, so it doesn't matter. Dr. Singh, thank you so much for your time, your evening, my afternoon. I really appreciate you sharing.
Dr. Anurag Singh
Totally enjoyed my conversation with you, Nathalie. Thank you for having me.
Nathalie Niddam
Thank you so much.
Dr. Anurag Singh
Thank you.
Nathalie Niddam
Thanks so much for joining me on this episode of the Biohacking Superhuman Performance Podcast. If you enjoyed the show, please remember to leave us a five star review on iTunes because that's what helps us to be heard and to be seen. If you'd like to connect with me directly, or if you'd like to leave any comments, or if you have any questions about this episode, please reach out to me directly through my website, natniddam.com.
Nathalie Niddam
Of course, if you're not already a member of the Biohacking Superhuman Performance community on Facebook, that's where you'll find me every day. It's a short application. Just answer a couple of questions, and you're in and interfacing with other amazing Biohackers. Thanks again, and we'll look forward to seeing you on the next episode.

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

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© 2024