I’m honored to connect with Anurag Singh today!
Dr. Anurag Singh is the Chief Medical Officer at Timeline Nutrition, where they develop next-generation advanced nutritional and skincare products targeting improvements in mitochondrial and cellular health. His background is in internal medicine and immunology. He has authored over 40 articles for top science journals and has more than 15 patents. He has designed and led more than 50 randomized controlled studies.
Today, Dr. Singh and I dive into his background, key biological hallmarks of aging, what accelerates aging, and what we can do to address aging proactively. We discuss sarcopenia, mitochondrial health, the gut microbiome, supplementation, and the differences between prebiotics, probiotics, and post-biotics. We also get into the benefits of Mitopure and the research behind it.
Mitopure is a supplement I have been taking for several years. I feel it has been instrumental in improving and maintaining the mass and strength of my muscles. Research has been emerging specific to brain health and cognition, immune and metabolism, and topical applications of Mitopure.
IN THIS EPISODE YOU WILL LEARN:
The key biological hallmarks of aging.
How healthy lifestyle choices can contribute to our health and longevity.
How can improving our mitochondrial health impact our lives and delay some of the comorbidities of aging?
The key role nutrition plays in everything we do, including how we age.
Some of the biggest contributors to the aging process.
Five lifestyle choices that can benefit mitochondrial health.
Dr. Singh gives a simple view of the mitochondrial life cycle and shares his approach to mitochondrial health.
How Urolithin A was discovered, and how it works.
The difference between prebiotics, probiotics, and post-biotics.
Dr. Singh discusses the research that resulted in the advent of Mitopure.
Dr. Singh dives into the natural aging process of muscles and sarcopenia.
Why is it critically important to boost and maintain our muscular health?
How modern-day lifestyles impact the gut microbiome.
What are all the benefits of Mitopure?
Bio:
Anurag Singh is currently Chief Medical Officer at Timeline Nutrition, which develops next-generation advanced nutritional and skincare products targeting improvements in mitochondrial and cellular health. With an M.D. in internal medicine and a Ph.D. in immunology, his experience includes work at top consumer health (Nestlé, Nestlé Health Science) and startup companies (Amazentis/Timeline). He’s authored > 40 articles for top science journals, been awarded >15 patents, and has designed and led > 50 randomized clinical trials. His research over the past decade across multiple clinical trials on the postbiotic Urolithin A and its health benefits has led to the launch of multiple consumer products.
“Practice a bit of intermittent fasting, do your eight or ten thousand steps a day. Just those two things have a massive healthcare impact!”
- Dr. Anurag Singh
Connect with Cynthia Thurlow
Check out Cynthia’s website
Submit your questions to support@cynthiathurlow.com
Connect with Dr. Anurag Singh
His websites are: https://www.timelinenutrition.com/ and https://www.mitopure.com/
Transcript:
Cynthia Thurlow: Welcome to Everyday Wellness Podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower, and inspire you to achieve your health and wellness goals. My goal and intent, is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
Today, I had the honor of connecting with Dr. Anurag Singh, who is the Chief Medical Officer at Timeline Nutrition that helps develop next-generation advanced nutritional and skincare products targeting improvements in mitochondrial and cellular health. Dr. Singh's background is in internal medicine and immunology. He has authored greater than 40 articles for top science journals, been awarded greater than 15 patents, and has designed and led greater than 50 randomized controlled studies.
Today, we dove deep into his background, key biological hallmarks of aging, our mitochondria, what accelerates aging? How we can proactively address this? The role of sarcopenia with aging and mitochondrial health, the impact of the gut microbiome, the role of Urolithin A and supplementation, the differences between pre, pro, and postbiotics, and lastly the benefits of Mitopure and the research behind it. This is a supplement that I've taken over the last several years and I feel has been instrumental in helping to improve and maintain mass and strength of my muscles. And there's emerging research specific to brain health and cognition, immune and metabolism, and also topical applications of Mitopure. I hope you will enjoy this conversation as much as I did recording it.
Dr. Singh, it's such a pleasure to connect with you. I've really been looking forward to this conversation.
Anurag Singh: Same here. Thanks for having me.
Cynthia Thurlow: Yeah. And obviously, I know quite a bit about your background and your work, but for the benefit of listeners, explain to them how you started in internal medicine with this immunology research background, how did you get to where you are today?
Anurag Singh: Yeah, so I started out pretty young in the internal medicine field. Yeah, I was a young medical intern in my early 20s even. And then I was always fascinated by the field of medicine, but I always felt like medical doctors were taking sort of a very later approach to symptom management and not really kind of figuring out what they could intervene early on in the process of the disease when the first pillars of disease symptomatology are forming. That led me to kind of in the US where I trained probably one of the top immunologists at that time, who really educated me in how to become a physician-scientist and I was also lucky to have a co-mentor who was trying to figure out how a compound from pineapples was a very potent anti-asthmatic compound and that got me into the natural product space. And from there, I ended up doing a lot of research in gut microbiome that journey led to the discovery of these postbiotics we'll talk about.
Cynthia Thurlow: it's really exciting. And I think for so many of us, we might start in a more traditional role within the medicine community. And then as we become more seasoned or more vested in the research, we acknowledge there are limitations to the traditional allopathic paradigm as it pertains to prevention of disease. And so, that's why I find your research, in particular, to be so interesting. And I haven't really had an expert on speaking to kind of the changes that go on with aging, the hallmarks of aging. And so, maybe we'll start the conversation there. There are some very well-documented biological hallmarks of aging that I think might be interesting to kind of from a 30,000-foot level, kind of providing some context for the conversation.
Anurag Singh: Yeah, so the whole field of aging today is segmented into two camps. One that is sort of more proponent towards lifespan extension and the other is more health span extension. If you look over the last 10, 15 years, we certainly know the different biological pathways that you can modulate with nutritional interventions, with exercise, with dietary restriction like intermittent fasting, and with nutrients such as either NAD modulators or the postbiotic we'll talk about. And the way I see it is really before, these were nine hallmarks of aging before all targeting very complex biological process. But if you really look at what are those out of those pathways, ones that you can modulate to have a health impact? The key one is mitochondrial health. And just for your listeners, mitochondria are sort of like your Tesla batteries that are producing energy and with aging we all feel fatigued, etc. And you so, can actually reverse some of that mitochondrial dysfunction. And that's where we feel we are positioned very well.
Cynthia Thurlow: Well and I think it's so important for listeners to understand that some of this is under our own control, whether through lifestyle-mediated factors, meal frequency, nutrition, as you mentioned, exercise, supplementation, all can be very helpful for preserving, maintaining the health of the mitochondria because most of Americans-- because that's the research that I'm most familiarized with. Most Americans by the age of 40 have mitochondrial dysfunction and it's really at the basis for most chronic disease states we see here in the United States and I would imagine in most Westernized countries.
Anurag Singh: Yeah, you know when we started out studying the mitochondria in context of aging, there was already literature out there that in your 70s and 80s that mitochondria were declining in organs that have a lot of abundance of mitochondria, which is your skeletal muscles, your cardiac muscle or your brain. But then we start sort of even looking younger in the 40s and 50s. And we would find already the signature out there. And so, you mentioned the two pillars of health is really diet and exercise. But I think that cellular health and really nurturing good cellular health is a third pillar. And so, that's why we believe that targeting improved mitochondrial health can have a bigger impact down the road. And even delay some of the comorbidities that happen with aging and improve our health span, so when you're in your 80s and very mobile you can play with your grandchildren.
Cynthia Thurlow: And I think that's so important. It was interesting when I was pulling up statistics for our conversation, 8.5% of the world's population is greater than 65. So, I'm thinking about my parent's generation. And they have these age-associated comorbidities. So, the things that we think are normal, that people have chronic pain, people have poor sleep, people have weight loss resistance, diabetes, metabolic poor health. Unfortunately, there's this prevailing limiting belief that these are just a normal byproduct of aging and yet they don't need to be.
Anurag Singh: I fully agree. And trained as a physician, they're not teaching good nutrition in medical schools or other healthcare practitioner training. And this is a lesson I learned after my medical school that nutrition has such a key role in everything we do. Our gut microbiome is absolutely the foundation of good health linked to inflammation, linked to poor mitochondrial health, and even nutrient absorption options. So, yeah, I totally agree with that. That improving mitochondrial health can have really impactful changes in our life.
Cynthia Thurlow: And what do you think are some of the biggest compounding variables or the biggest contributors to accelerating the aging process in a traditional kind of Westernized society? What are the things that stand out to you that are of greatest concern?
Anurag Singh: Well, our diet is definitely number one. We are all not nourishing our gut microbiome health. We're not all eating a lot of fruits and vegetables and we'll get into it. But we've looked into the gut microbiome of different populations, the French, the Canadians, the Americans, and the gut microbiome was I would say, is the richest in places where the Mediterranean diet is followed as a practice right. In the US and Canadian sort of healthy adult population, the gut microbiome is not very rich, not very diverse and I think that's the central tenet.
And then inflammation is another one. We see a lot of healthy adults who are, let's just say, not symptomatic of a disease. But if you just take a little blood and look at their blood levels, something like C-reactive protein, they are super inflamed. And being overweight is another, inactivity is the second we touched upon that. And those really boil down to this accelerated aging which we are seeing even earlier now today in 50s and 60s as you said, the population is growing older and older. And so, there will be a point where we'll start to think about how can nutritional interventions delay some of the health economic impacts?
Cynthia Thurlow: Well, and it's interesting. For context, my entire background as an NP up until seven years ago was cardiology. So, I got to see more often than not people who had already gone on to develop chronic inflammatory vascular disease. And I would sometimes try to find an angle with patients to convince them that the lifestyle piece was equally as important as taking their medication. And occasionally I would have someone that would say to me, “Cynthia, I'm not going to sleep more. I'm not going to stop smoking. I'm not going to change my diet. Just give me the pill and let me go on my merry way.” And I really think that on so many different levels, we've done patients such a tremendous disservice. I think about the pharmaceutical industry that spends millions and billions of dollars a year trying to market to consumers instead of saying, “Hey, instead of taking an additional diabetes medication, what you really would benefit from is eating less often, moving your body, and eating less processed foods.” It really is that simple but we make it more complicated than it needs to be.
Anurag Singh: And now 200% totally agree. I mean, if all cardiologists or even geriatricians or even just your family doctor is telling you to eat, practice a bit of intermittent fasting. Do your 8,000-10000 steps a day, already just those two things has massive, massive healthcare impact that of course, there's no incentive to our healthcare systems to do that. And I train as a medical doctor where I can see you see a few patients a day, and you build the wider sort of for the etiology and the symptomology, but you're not thinking at a big picture. And that's one of the reasons why I got into research, actually, was whatever I'm working on should impact hundreds and thousands of people eventually. Yeah, exercise and diet is not the easiest to comply with. I think that's probably the number one problem with these interventions. To tell an older adult to do three days of 30-minute walk is easy to say, but not the easiest to comply with long term.
Cynthia Thurlow: Right, and for anyone that's listening, lifestyle changes are not meant to be easy. If they were easy, everyone would do them. And sometimes it can be as simple as you stated. Taking a walk after dinner 10 or 15 minutes. We know it can help with insulin sensitivity and reduction in blood sugar and glucose, but yet we've kind of and maybe the pandemic, I know for sure has contributed to this. But I think on a lot of levels, we've gotten so conditioned to be very hedonistic. We want everything right away. We want to lose weight instantaneously. We don't want to do the work. And I think a lot of that is human nature. And things are so easy now. I think of the example I have teenagers and unbeknownst to my husband and I, during the midst of the pandemic, when weren't really going anywhere, they were doing Uber eats at night when went to bed.
And things are just too easy. It's easy to get access to foods we probably shouldn't be eating. It's easy to get access to binge on Netflix. It is much easier to sit at home or sit all day long than it is to move around. But I think for so many people, once they make those lifestyle changes, they feel so much better. It just reinforces the good behavior. So, it's finding one thing you can do a little differently every day to contribute to health and longevity. Now, when we talk about proactively impacting mitochondrial dysfunction, you mentioned fasting. But what are some of the other kind of lifestyle pieces? Maybe things we haven't talked about in terms of hormetic stressors that can be of benefit to the mitochondria, that can make our mitochondria more resilient?
Anurag Singh: Well, I think the top five would, of course, starting in the order would be diet. If you're all eating a good antioxidant-rich diet, we call also polyphenols and these are complex nutrients that are in our diet. If you're eating a lot of berries and nuts that are known to have antioxidant effects, those are good for your mitochondria. Mitochondria do accumulate what is we call a lot of oxidative stress. So, think of them like turbines or Tesla batteries that are working all the time in the background and they get damaged. And so, that's part of the problem that we are not feeding the right nutrients to these mitochondria, to the cells, and then less stress. We all talk about the blue zones where people live till 100, 120. They really have three or four things that they're getting a lot of sunshine. So, probably vitamin D is the key. They're moving around a lot because in these islands, Japan or Costa Rica, that five zones, certainly physical activity levels is not a problem.
They are eating fresh, as they say, farm-to-the-table kind of food and less stress and sleeping better. And those are things-- circadian rhythm has a big impact on mitochondria. And then I believe that the fifth is really sort of where the research is headed, is really these advanced nutrients that have an impact on mitochondrial health, so together, some of these four or five exercises and diet are obviously the two key ones.
Cynthia Thurlow: Yeah, and it's interesting because those advanced nutrients that you're alluding to are things like NAD and NR and Urolithin A. And maybe it'd be helpful to differentiate how these three advanced nutrients are different from one another because I think there's a lot of misinformation, especially about NAD and NR in particular in the blogosphere on social media, but maybe helpful to differentiate how they are different from one another and how they benefit us, too, in terms of repletion.
Yeah, and I think for that, I think a very simplistic view of a mitochondria life cycle is needed there. A young, healthy mitochondria is producing the currency of energy, which is what we call is ATP all the time in the background. And so more of mitochondria, so things like muscle and neuron cells have thousands of mitochondria. And as they're young and healthy, they also will, in parallel, accumulate damage to what we call as oxidative stress or free radicals. And their architecture starts changing and we have looked at old people's mitochondria. It's really like electrical wires and they just start sagging inside the mitochondria.
And what happens is some of the faulty ones then are sort of labeled or tagged to say these are the faulty ones and your body needs to recycle them. And that's what slows down with aging. And so, what happens is basically, instead of always having a good pool of healthy and unhealthy mitochondria, your cells shift towards bigger pool of unhealthy mitochondria. And so, typically, things like NAD modulation or things like NR or targeting is basically a boost in NAD production, which will then lead to more newer healthy mitochondria. So, putting that in picture of a mitochondrial life cycle.
There are other nutrients like CoQ10 and creatinine, etc., that are also targeting. They take a healthy mitochondria and make it produce more energy. So, now you have more energy efficiency. But what has never been taught, only intermittent fasting or regular exercise was known to activate this process that is called mitophagy, and mitophagy is the final end of this mitochondria life cycle. And if you're not cleaning out the waste and all these faulty mitochondria are accumulating in the garbage disposal bin, then your cells don't look right. And that's what happens basically with all our aging cells. Where we just have spent a good part of 10, 15 years of research is figuring out how to activate mitophagy during the aging process that can then clean out the waste and result in more healthy mitochondria and then you can use NAD supplementation on top. So, that's how we approach mitochondrial health improvement.
I think that's probably one of the best, most concise explanations that I've heard yet. So, thank you so much for that. I think it makes the science accessible to listeners, and they're very familiar with the concept of autophagy. And so, mitophagy is talking about this specific to the mitochondria, the waste and recycling process of disease-disordered organelles that we're getting rid of. And so, I'd mentioned Urolithin A and so, obviously, this is something that I think is really exciting in terms of not just as an advanced nutrient, but potentially what it has the ability to do within the body. So, how does it work and how was it discovered?
Anurag Singh: Yeah, it was discovered over 15 years of very hard sort of biotech approach to nutrition. When we started timeline, the whole concept was to bring the biotech approach to nutrition to really understand how some of these nutrients in our diet were impacting cellular and biological hallmarks of health. A lot of times in nutrition, everybody was blending nutrients and probiotics and prebiotics and starting to selling as multi-pronged approaches. So, we said, let's change that. We started with sort of a high throughput approach where we took thousands of look at compounds and our everyday fruits and nuts. So, we started deconstructing the pomegranates, for example. Now pomegranate has about 500 plus bioactive compounds in it, and we narrowed it down to a group of polyphenolic compounds much like antioxidants that are called punicalagins or ellagitannins. And these are just not in pomegranates, these are in your pecans and walnuts, these are in your raspberries and other red berries.
For long there have been studies in pomegranate juice and berries and walnuts having these great health benefits similar to Mediterranean diet. So, we started looking at them and we found that independently a lot of these bioactives were not having an effect. And then we started looking at the gut microbiome transformation which is needed to take these complex polyphenolic bioactives and break it down into simpler what we call postbiotic molecules. And so that led us to the Urolithins which are one of the most prominent and produced byproducts from the gut microbiome is Urolithin A. And we found that this had some remarkable effects and a lot of this research was done with the Swiss Institute of Technology where we are based here and basically showing these remarkable effects on muscle endurance and energy production that led us to the whole journey.
It's really exciting because I think listeners are familiar with prebiotics and probiotics but a postbiotic is probably terminology that they are less familiarized with and how do you find the differentiation in terms of looking at each one of these and how does a postbiotic differentiate from a pre and probiotic?
Anurag Singh: Yeah, so the simplistic, if I can break it down, prebiotic is food for your gut microbiome. Basically, it's the sort of breakfast, lunch, and dinner that you need to give it to your gut microbiome. The probiotics are things that you would like to see it as part of your gut microbiome ecosystem. So, you want more healthier bacteria in your gut microbiome. And postbiotic is basically the end product the sort of from the foods and nutrients we are eating. What the probiotics are harnessing and releasing which are beneficial to us as human hosts is what is postbiotic. So, these are bioactive molecules that have immense benefits for us who are hosting the gut microbiome.
Cynthia Thurlow: And it's my understanding that these help to stimulate mitophagy. This is kind of the big picture is these postbiotics are helping to stimulate mitophagy, autophagy getting rid of these disease-disordered cells.
Anurag Singh: Yeah, so, there are a number of postbiotics, so typically certain vitamin B or vitamin K is a postbiotic because you require your gut bacteria. Now, I don't think all postbiotics will stimulate autophagy or mitophagy. There are things like short-chain fatty acids, butyrate, propionate, they are known to have big impact on cellular metabolism. Now, Urolithin A is a postbiotic and what we found was that it was triggering this very specific form of autophagy that I described previously which is specific to mitochondria called mitophagy.
Cynthia Thurlow: Yeah, it's really interesting. In terms of your research and how you've been looking at Urolithin A. How did Mitopure come about through that process? Because I'm sure it was very exciting to realize that there was all the potential and how did Mitopure kind of come out of that research?
Anurag Singh: Yeah, so Urolithin A, when we started out, had been described as being present as one of the byproducts that nobody had really paid attention to it. It was known to be in Iberian ham because they were eating a lot of acorns and things like this. But when we took a closer look, we started-- aging has always been our focus. The Timeline has always been a longevity-focused company. So, we started in worms, these are the first species you would do your first experiments to really tease out what is the key nutrient out there. And so, compared to, let's say, ellagitannins or even other nutrients, Urolithin A, or as we have trademarked it, Mitopure was shown to have about a 40% to 50% increase in lifespan in these worms. And that was the eureka moment that led us to take it even forward to older experimental models, where we would give it in the daily diet of older rodents and we would start seeing them being 60% more endurant and having about 10%, 15% percent better muscle strength.
That led to the whole journey of multiple randomized trials. So, we started out actually with two key studies, which I think are absolutely key to how nutrition field needs to do research. First, we actually went and asked the question, can we measure mitochondrial health during the aging process? And we were able to show that in 70-year-olds who were running marathons versus 70-year-olds who had difficulty moving around, if we took a look at their muscles, their mitochondria were very bad in those we call as frail people versus those who were running marathons.
And then we took a look at the gut microbiome of people and how many could produce it naturally, this molecule Urolithin A. The answer was about 30% of people were making this molecule and not enough in levels to give you the sort of health benefits associated. And that led us to developing a proprietary almost 100% pure Urolithin A that you could then directly supplement and raise the blood levels by about six, seven-fold and do randomized trials where we saw in 70-year-olds improved endurance and overweight 50-year-olds, we saw better strength. And now we're even running trials in elite athletes looking at things like muscle recovery. So, it's been a process and the research process takes long, but you have to be patient to get the data.
Cynthia Thurlow: Yeah, no, it's a very exciting process I would imagine. Now, for the benefit of listeners, they're familiar with the term sarcopenia. They understand that muscle loss with aging is a real thing, you also can lose strength. And so perhaps kind of walk us through the natural aging process if we're not working against it. And this contributes to a lot of the chronic health problems that we see because muscle is so critically important for insulin sensitivity and metabolic health.
Anurag Singh: Yeah, muscle is one of the most key longevity organs as I always say. If you can move around when you're 70 and 80, you really have cracked the code of aging well. So, what happens after? We all peak our muscle mass and strength in about a third decade of life. As we age with every decade, you're losing 10% and by your 70s, 80s that's when all these issues with mobility and you mentioned sarcopenia, so sarcopenia is basically the accelerated loss of muscle mass with aging and loss of muscle strength with aging. And nobody's really cracked it. And there's not yet a single pharmacological intervention approved for sarcopenia.
Exercise is probably the only and nutritional supplementation with high protein, a high amount of 10 grams plus is probably another well studied. And frailty is similar, it's a similar syndrome as sarcopenia except that it comes with underlying inflammation as well. So, the problem is if you wait too long, you're on the wrong end of the trajectory. And where we believe we could act is that people started early in their 40s targeting improvement in their cellular health and could maintain their muscle mass and strength trajectory, where in your 70s and 80s, you're looking almost like your 40s and 50s that you would basically have the normal healthy health span you're supposed to have and that's what we think we have cracked now.
Cynthia Thurlow: Yeah, it's really interesting for those of us that are clinicians, we probably have seen these patients over and over again in the hospital. But people that were my own age who couldn't get off a bedside commode or they would end up being in bed for two, three weeks and they had lost so much muscle mass that they then were too weak. So, you talk about that frailty and the inflammation will accelerate the sarcopenia. And this is why I'm so outspoken and Dr. Gabrielle Lyon is a good friend of mine, I know shared friend of both of ours. This is why I think it's so important for listeners to really understand that muscle is this organ of longevity. We need to preserve it, we need to maintain it. It is critically important for so many different things. If but nothing else, we want to remain physically active. That's why strength training is important. Those macros as you kind of alluded to are so beneficial.
And so, we know that or at least based on what I was looking at in terms of clinical research, there's a lot of research about muscle health in relationship to Urolithin A, which I think is really exciting for many people that are saying, it's really hard for me to get to the gym and lift heavy multiple times a week, maybe my protein intake isn't where it needs to be, knowing that there's some degree of supplementation that can be beneficial. And there was a study, obviously, I know you're familiar with it, that was in JAMA in January of 2022 looking at supplementation on muscle endurance and mitochondrial health in older adults.
Mean age was 71, mostly white women, randomized to placebo or four months of supplementation. And the primary endpoint was a change from baseline in a walk distance and change from baseline to four months in maximal ATP production in hand skeletal muscle. And really compelling information. I mean, granted the study was small, but still when I was looking, kind of looking at current research that was ongoing, definitely something that's suggestive of why this might be of tremendous benefit for us, especially as we're getting older.
Anurag Singh: Yeah, so high protein is a great way and exercise is a great way to boost muscle health. But I think the paradigm that we have been trying to change is there's been a lot of focus on muscle mass and muscle mass is important, but you have to also focus on muscle quality. And what I mean by muscle quality is really the energetics and the energy supply of the muscle. So, now you have better muscle health, you have better muscle strength, and when you have both good muscle mass and strength, you're a winner.
And so, one of the first studies that you were talking about, the JAMA study, it's a study I was very close to. We ran this at the University of Washington in the US also with Fred Hutch in partnership with Fred Hutch there. Now, the participants were about 70 to the oldest participant and I remember talking to her, was an 89-year-old lady. These were folks who are like our parents perhaps, who have fatigue issues, who are healthy. They're going about their daily activities, but at the end of the day, they would like to have a little extra 10%, 20% more so they can play with their grandchildren or go about and socialize with their friends.
And when we did this trial, the number one feedback and this is the 89-year-old lady who told me and this is a blinded study, so we didn't at that point know, she's like, my recovery after gardening has just got so much better. I don't feel sore. And she was like, I swear I'm on the right product and not the placebo and we didn't know. And when we finished the trial about six months after, she was right, she knew she was actually on the active product. And so, I think what we saw in this trial was that people just had that extra 20% more energetics.
And that's the keyword that I've been trying to tell most clinicians that it's just not boosting muscle mass. You have to improve the bioenergetics of the muscle. And if you get both together, if you're eating a lot of good protein and then you improve your mitochondria, you're really going to have a winning strategy in practice.
Cynthia Thurlow: And I think it's really important for people to know that and to be selective about what they choose to supplement with. I think that we as consumers are really overwhelmed with choices and helping my listeners or my patients or clients understand the quality of these things is certainly very important. Have you seen any negative side effects from supplementation? I didn't see anything in the literature so I thought I would just ask.
Anurag Singh: Yeah so, today we have about 15,000 consumers on the timeline product seemed very safe. We have done a randomized trial in at least 900 to 1000 participants. Older, young, even now middle aged. So, this is a natural molecule. That's the beauty of it. It's been around as long as we've been eating fruits and nuts, evolutionary, we've had it. I have lost the capability because now we are now developing a test that can tell you if your body is making it or not.
And probably I took a lot of antibiotics growing up and my microbiome never recovered. So, a lot of us have lost it. But we always were supposed to make this molecule naturally and it was supposed to be safe and what we are doing basically now is we've found a way to short circuit the natural process, a little bit of inefficient process and directly supplement with the molecule Urolithin A. So, it's very safe.
Cynthia Thurlow: Yeah, and I would imagine and this is the perfect tie-in to the gut microbiome because inevitably people will say well if Urolithin A is contained in food can I just get it from food and what would your response be to that?
Anurag Singh: So, it's not in the foods. It's derived from let's say precursors present in food. These polyphenols that I was talking about in pomegranates or walnuts or pecans, if you're eating a lot of these fruits and nuts in parallel, if you're also taking a lot of fiber and eating a good diet, chances are that you probably have a good microbiome that has a chance to make it. Now, we have done studies where we have given a glass of pure pomegranate juice and we see only about 30, 40% of people make it.
Even in that population, you get a lot of variability. Not everybody's going to squeeze four pomegranates into a juice and have all the high glucose sugar coming anyway with it. So, yeah, there are folks who make it and they make it at decent levels and this is probably going to be downstream research where we're going to see if some of these people who are naturally making it perhaps have longer health spans and longer longevity much like all the other key nutrients that we know of.
Cynthia Thurlow: Yeah, it's really interesting. We certainly have had a lot of experts talking about the gut microbiome on this podcast and admittedly when I was in school, which seems like 20, 25 years ago, the gut microbiome was not a thing. But now we're starting to acknowledge the net impact of our lifestyle on the health of our gut microbiome and why antibiotics? There may be, in fact, instances where we need them, but we want to limit the use of antibiotics knowing that it can kill off beneficial bacteria. What are some of the other things about our modern-day lifestyles that can impact the health of our gut microbiome?
Anurag Singh: Well, inactivity, we know the gut microbiome is in many ways an organ in itself now and that's how people are approaching it. It changes from your infancy to your teenage years to your adulthood and then stabilizes in your adult years, and then again starts changing as we grow old. And so, gut dysbiosis is now one of the new hallmarks of aging, in addition to some of the new hallmarks of aging. They were 9, now they're 12. And so, mitophagy was added and chronic inflammation was added and gut microbiome dysbiosis was added.
And so, I think in the last 10 years, the field of gut microbiome has just exploded. We still don't know the right techniques to look at it, I believe, and we are still scratching the surface of it, but if people are eating right, then they have no-- as I mentioned my own example growing up India, taking a lot of early-life antibiotics, I think I eat rice today, but it was set in stone probably early on with the antibiotic use.
And you could have issues with gut microbiome dysbiosis, such as irritable bowel syndrome or inflammatory bowel diseases, is pretty well documented. But now even the gut-brain axis is coming up that a lot of diseases of the brain, like Parkinson's disease, actually start in the gut, which is thought 20 years back you would have laughed at, but now that's where the research is coming in.
Cynthia Thurlow: Well, and it's always interesting “Know better, do better.” And certainly, this is a product for full transparency that I've been using for a long time and really enjoy the powders in my daily smoothie that I consume, which allows me to take in supplements that I otherwise wouldn't have the opportunity to consume. And so, what is your practice? So, do you use the oral supplement? Do you use powders? What are you using day to day?
Anurag Singh: Yeah, so, I tend to have a preference of popping pills. That's just me. Again, that's maybe my bias as a trained physician early on. A lot of our trials were actually initially done for compliance reasons. It's easier to tell people to pop two pills, each pill is about 250 mg of Urolithin A. So, if you take two, you meet your 500 mg targeted dose that we are seeing all these great effects on muscle and mitochondrial health. Powders are great and they blend in with lifestyle. So, if you get bored with sort of taking pills every day, it's just when you travel or when you don't have yogurt or you ran out of the muesli to put your powder, that's where I feel, so, my preference is on the pill side, I do take a bit higher dose of a gram because the evidence we are seeing at the higher doses, you start to also get anti-inflammatory effects associated with this molecule, such as lower CRP levels, your CRP levels start going down and you're less inflamed. And so, I run a lot, so I try to take a bit higher dose and I take it in the morning because after overnight fasting, probably your autophagy is already hitting the wheels. And so, if you supplement on top, it's probably going to be even more effective.
Cynthia Thurlow: That's really helpful and I think for the benefit of listeners that may not be familiarized with your product right now, you can use it in things like I've done protein balls, I've done smoothies. In fact, if you purchase the products, you get a really nice, essentially like a recipe book. So, it gives you a lot of creativity and I'm always tinkering with recipes, but I like it in my smoothie because that's usually how I will break my fast tail end of my fasting window. And so, before we kind of wrap up, when we're talking about the clinical research, you mentioned a great deal about muscle health. What are other areas of health that are investing that you're seeing the benefits from Mitopure beyond the muscle health piece and reduction of inflammation?
Anurag Singh: Sure, yeah. When we started out about 10 years back into the clinic realm as a small focus company, we had to take one focus direction that was muscle health. And since we’ve published our first publications, a lot of other top scientists and clinicians around the world have started looking at it from a different angle. So, we have basically three top groups who have looked at its effects on neuronal health, brain health, and how it impacts in cognitive decline or brain aging. And they've found spectacular data. So, there's a group in National Institute of Aging that published a few years back, really one of the top authorities in the field that even out of, like, a whole library of thousand national compounds and even drugs compared to Urolithin A, Mitopure was having very potent effects on how as you age in your neurons, you accumulate a lot of protein deposits and that sets off this whole process of neurodegeneration.
So, he was having this sort of unclogging the clogged neuronal cells and, of course, that leads to neuroinflammation and seems having effects neuroinflammation. We have now moved also our research a lot into immune metabolism. So, for your listeners, this is a field which is now starting to see how key role mitochondria have in immune health and immune function. What that means is that, for example, a recovering cancer patient, after chemo/radio, they basically have no immune system left because chemo/radio knocks off the good healthy cells as well.
And so how fast with your receding of the mitochondria can you get immune function at the top level so they can fight off infections and things like this? So, this is one of our focus areas of research is really immune health and how we use improving mitophagy and mitochondrial health to improve immune health. And the other is we are starting to look at how can we deliver Mitopure just not orally, but topically also.
A lot of folks ask me "How do I feel that your product is working?" And that led us to the road of people. What do people see first as you age? It's really visual aging signs, right? And then you bypass all the oral sort of uptake and absorption issues by just giving in the topical delivery. And so, that's the line we are pursuing skin aging and how topical formulations of Mitopure can have a big impact on aging.
Cynthia Thurlow: That's really exciting and for the benefit of my listeners because most of my listeners are middle-aged women. So, 35, 45, 55, 65, and beyond and for so many of us, as we go through perimenopause into menopause, and women if they're not taking HRT, they've lost predominant estradiol is now made in weaker formulations in estrone and fat tissue. And so, the degree of immune impact of this loss of estrogen is pretty profound and actually very humbly the more as I kind of navigate these changes in my own body, the changes that I'm seeing. I think if anyone's listening and they're trying to kind of think of other ways that Mitopure can be of benefit, it's with the understanding that with this loss of estrogen signaling, as we're transitioning into menopause, we're increasing inflammation.
And what many don't realize is that estradiol has a potent net impact on immune function in the body, significantly so in the gut microbiome, and as I stated before, as I humbly learn these things, I like to share them. So, yet another reason if we tie in women in particular and the changes that are going on hormonally with age, that loss of insulin sensitivity, less metabolic health that they're not being conscientious, also can impact us on an immune level as well. So, I love that you're doing research in this area too.
Anurag Singh: Yeah, yeah. Sure, happy to share new data as it comes out with your audience. And yeah, as I mentioned, we are also developing this test. If anybody is up for trying our beta version where they can test if the body is making Urolithin A or not, we can offer that as well.
Cynthia Thurlow: Yeah, I would love to hear more about that. Well, Dr. Singh, I want to be respectful of your time. Please let listeners know how to connect with you. Obviously, Mitopure is a podcast sponsor, so we'll make sure that all those links are included. What's the easiest way to connect with you and your team to your research to Mitopure to connect with you online?
Anurag Singh: Yeah. So, of course, if they want to learn more about the scientific discoveries and the products, they can go to timelinenutrition.com. We also have a sort of education website called mitopure.com and they can go to that and learn about all the published literature and all the upcoming new science.
Cynthia Thurlow: Well, thank you so much for your time today. This will be an invaluable resource for listeners.
Anurag Singh: Thanks for having me, Cynthia.
Cynthia Thurlow: If you love this podcast episode, please leave a rating and review, subscribe, and tell a friend.
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