Want to age well? You've GOT to hear this

Dr. Singh joins Dr. Gundry to discuss Urolithin A, a novel longevity compound and the connection between inflammation, aging and your mitochondria.

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The Dr. Gundry Podcast

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The longevity benefit of pomegranates may be connected to the postbiotic Urolithin A – a potent molecule that can support mitochondrial function, healthy aging, and an energy boost.

Topics covered

  • How mitochondria powers everything that you do and how the modern diet can damage them.
  • The new hallmarks of aging you need to know about
  • The three “P’s” that can revolutionize your gut health – and how to incorporate them into your lifestyle
  • Why most people lack the ability to produce life-changing compounds from pomegranates and what you can do about it!
  • How to determine if your body produces the molecule, Urolithin A
  • The ideal age to begin preventative health practices.
  • How combining Urolithin-A with other practices can increase the effects

Transcript

Dr. Gundry
Welcome to the Dr. Gundry podcast. The weekly podcast where Dr. G gives you the tools you need to boost your health and live your healthiest life.
Dr. Gundry
Welcome to the Dr. Gundry podcast. Well, you probably know that I think pomegranates are one of my favorite snacks. Not only are they delicious, but they're capable of supporting the body's natural production of something called Urolithin A. A potent molecule that can support mitochondrial function, healthy aging, and, a massive energy boost.
Dr. Gundry
But, before you go scarfing pomegranates or drinking pomegranate juice, there's something you should know. Most people don't have the right gut bacteria to benefit from this potent molecule. However, my guest today says there is a workaround and that anyone can benefit from this molecule with the right knowledge.
Dr. Gundry
I'm joined by Dr. Anurag Singh, the Chief Medical Officer of Timeline Nutrition, a biotech company focused on discovering and developing next-generation natural compounds that target improvement in mitochondrial health.
Dr. Gundry
After a quick break, Dr. Singh and I will share Urolithin A's connection between inflammation, aging, and your mitochondria, and reveal why it's one of the most exciting compounds in the health industry. And I mean that sincerely. We'll also share with you how you can take advantage of this potent compound to upgrade your mitochondria and experience life-changing health benefits.
Dr. Gundry
Dr. Singh, welcome to the program.
Dr. Anurag Singh
Thank you for having me, Dr. Gundry. Pleasure is mine.
Dr. Gundry
Quickly explain the importance to our listener of the mitochondria and its function.
Dr. Anurag Singh
Sure. Mitochondria are… Everybody's heard that mitochondria are the powerhouses of the cell, and that's pretty much where all the knowledge stops. But mitochondria are… Think of them as cell organelles that power everything you do, from moving, to thinking, recovering from exercise. They produce what is called this ATP, which is the currency, the energy currency in our bodies.
Dr. Anurag Singh
Think of mitochondria as the battery inside a Tesla car, for example, that has a certain capacity to keep driving the car, but after a while you need to give it more feedback and you need to nurture it. That's how these mitochondrial health is so key and mitochondrial function is so important to especially metabolic organs such as muscles, helpful muscle, cardiac muscle, and brain.
Dr. Gundry
Yeah. As I've written about in most of my books, particularly the last two, our mitochondria, in general, are on death's door. They have taken a beating that is actually unimaginable. From our Western diet, from our Western lifestyle, from our environment, environmental toxins, you name it, we have not been good caretakers of our mitochondria.
Dr. Anurag Singh
Not at all. You're absolutely spot-on right. There are actually two great ways to boost your mitochondrial health, and that's regular exercise and calorie restriction. But as you mentioned, we have not been kind to our own mitochondria by not paying attention to what we eat and how we move around.
Dr. Gundry
Now, something that's probably not on everybody's radar, even though I think most people remember high school biology and seeing this mitochondria in a cell, and it's the powerhouse of the cell. But there's an important relationship between our immune system and mitochondria. Can you elaborate on that?
Dr. Anurag Singh
Yes, sure. There's a big number of years back, the hallmarks of aging were described. These hallmarks of aging really all are deeply connected biological pathways. There's the DNA repair mechanism slowed down, you have the epigenetic alterations. Now, of course, the mitochondria are the central pillar to all these hallmarks and connect them. Now you have this chronic inflammation. As we age or as we have a more sedentary lifestyle, things like biomarkers like C-reactive protein, which is a marker of inflammation, go up.
Dr. Anurag Singh
What we are seeing actually in a number of trials in older adults is that with declining mitochondrial health, there is this both gut dysbiosis and chronic inflammation. The immune system and the immune cells have mitochondria that basically power off and shut off as we age. That's the link between immune cells and mitochondrial health.
Dr. Gundry
I think one of the things that people, particularly during COVID, is immune function might be very useful. Plus, particularly in terms of cancer, we know that one of the theories, which widely accepted that the reason cancer becomes so prevalent the older we get is because our immune guardians against cancer cells, you're right, are underpowered or are not functioning the way they should be.
Dr. Anurag Singh
Sure. We recently published a fantastic paper in one of the highest ranking immune journals called Immunity. We showed actually in this that in certain cancer models, by improving mitochondrial health, via, of course, the compound we talk about, Urolithin A, you could actually lower the incidence in these models of cancer recurrence. More importantly, the thing we are seeing is, even once you treat the cancer, or once you do the chemo, radius, neoadjuvant therapy, the immune system is basically zero in the recovery phase. How fast it comes back to receive the immune system is the key determinant, is mitochondrial health.
Dr. Gundry
Yeah, it's interesting, as a transplant surgeon, one of the things we learned early on was that the older our patient was, who we did a transplant in, the much less immunosuppression we had to use. In a way, it was great. "Oh, you're 75 years old. This is going to be great because we don't have to give you a lot of immunosuppression because you're already immunosuppressed." In a way, that's actually very scary.
Dr. Gundry
This function of mitochondria in our immune system clearly needs to be given some attention. All right, speaking of aging, what new pillars of aging have we learned about in the last couple of years?
Dr. Anurag Singh
Well, I think if you look at the hallmarks of aging, there is these nine hallmarks of aging that link all the organelles of cell biology to the epigenetic alterations, as I was mentioning. In the last decade or so, a lot of emphasis has come on this gut microbiome dysbiosis. With aging, the gut microbiome starts to alter, and that leads to declining production of gut metabolites such as postbiotics, etc. What happens is, because of this chronic inflammation, the immune system detects upon that, and the mitochondral health and the declining mitophagy.
Dr. Anurag Singh
Now, this is a term your listeners may or may not have heard. One of the new hallmarks of aging is declining mitophagy. What that means is, basically, is that the mitochondria are working over time as we age to deliver us the energy, but then a lot of them get corrupted and they get faulty. The system that basically recycles this trash bin of poor mitochondria also slows down. How you can rev up and get all these bad faulty mitochondria packaged into garbage bin and then recycled so they can become healthy mitochondria is one of the new key pillars that is getting a lot of interest and excitement.
Dr. Gundry
All right. As I mentioned before in the introduction, we've known that pomegranates are pretty cool and that pomegranates have some very interesting polyphenols among the gallic acid. But it was really work on certain gut bacteria can transform these polyphenols into Urolithin A. Tell me all about that compound. Why is this such a miracle? What to do?
Dr. Anurag Singh
Yeah. Well, we've spent 15 years studying the pomegranates. We started with the whole fruit. I was trained in medical school where nutrition was not well-taught, but yet we all learned that, okay, nutrition needs to focus on certain superfoods. We started studying the pomegranate because there were all these… In the literature, some exciting studies on cognitive function, vascular health, etc.
Dr. Anurag Singh
When we looked, we brought the biotech approach to basically deconstructing the pomegranate. We looked around and there were all these great compounds, as you were talking about. There were these polyphenols such as punicalagins and the ellagic acid. But what we realized one day, as we were screening all these hundreds of compounds inside the pomegranate, we gave them to a famous professor just in the university campus we are in here in the Swiss Institute of Technology. He was running these assays trying to see if certain worms and rodents would basically run faster and live longer.
Dr. Anurag Singh
One compound really attracted our attention, and it was a molecule called Urolithin A, which is basically the result of gut microbiome digesting these polyphenols and releasing this postbiotic, which is the Urolithin A. This professor, Professor Aubrix, came running to our lab and he said, "What is this compound? Because it's boosting lifespan in worms by 50%. The older animals are running faster by 60%.
Dr. Anurag Singh
That's really the whole journey of the last 10 years for us. We got more interested into Urolithin A, and we started studying in different human populations its producer status in terms of, what is the percentage of population and people actually making the molecule. We looked in the French, the French were doing better, 30-40%, and I'm guessing because French are probably eating a lot of fermented food, etc. Then we looked in the American population and the Canadian population, it was much lesser, 10-15, 20%, probably, again, a mix of diet and physical activity contributing to it.
Dr. Anurag Singh
That's led to us synthesizing the molecule and starting to directly supplement and randomized trials in humans, in older adults, in overweight adults, and really seeing these remarkable effects on muscle health translate into humans with improved endurance and improved strength.
Dr. Gundry
How exactly does it work? It's great that I'm going to have stronger muscles and I might live longer. What is it doing at the mitochondrial level?
Dr. Anurag Singh
Yeah, sure. The first studies we did was we were looking in older adults, and we took about 70, 75-year-olds who had been running half marathons and training for half marathons all their adult life, for example, and we took little chunks of their muscle. This procedure called a muscle biopsy, where you can take small chunk and look into how the mitochondria are behaving in the muscle tissue.
Dr. Anurag Singh
Then we took age max 70, 75-year-olds who were really what we call as frail and they were sedentary. They didn't have good functionality, they didn't have very good levels of physical activity, and they had lower muscle strength for sure. We looked in the same way into their skeletal muscle tissue. We saw that both mitophagy and mitochondrial health was super compromised in the frail people. We took these same people, the sedentary, frail people, and we started supplementing them with Urolithin A, as a first randomized trial.
Dr. Anurag Singh
We saw then when we took four weeks after, again, these muscle biopsies, we saw a big signature of improved mitochondrial health that was mimicking basically months and years of exercise. Basically it's hitting the same pathways of improved mitochondrial health and enhanced mitophagy that, for example, a six-month aerobic exercise regimen would give you. It's basically biologically hitting the same pathways.
Dr. Gundry
Oh, my gosh. You mean exercise in a jar?
Dr. Anurag Singh
I don't think I can put that claim. But scientifically and biologically speaking, yes, the pathways are pretty much similar to trials done in humans with aerobic and resistance exercise and with calorie restriction. They all point towards improved mitophagy and improved mitochondrial health.
Dr. Gundry
Is that the only human trial that's been done or are there multiple?
Dr. Anurag Singh
There are multiple. This is what I described to you was the first one, where we only supplemented for a short period of four weeks just to see the biological effects. Then from there, we have done multiple randomized trials that are now published in journals like JAMA and Cell Reports, really the top of the top journals.
Dr. Anurag Singh
In these randomized trials, we supplemented all the way for four months, much longer to see improvements in muscle function. What we see in older adults, and by the way, the oldest participants we've had is an 89-year-old, very spiky, robust lady who was a blinded trial, but she was convinced she was taking the active and she kept coming to me. It's like, "You have to tell me if I'm right, if I took the right product, if it was not a placebo." When we unblinded, she wasn't reactive, so she actually felt more energy. She felt resistance to fatigue. What we are seeing actually in older adults is improved endurance and more energy, and these people can do exercise longer. In little, younger populations like the 50 and the mid-50-year-olds who are also a bit sedentary. We have done another trial where we see improvements in things like VO2 max.
Dr. Anurag Singh
This is a marker of, a defect marker of improved mitochondrial health. We also see improvement in a test that a lot of clinicians use called the six-minute walk test, which basically measures how much of a distance you can walk in six minutes. We see about a 10% increase there. Then, of course, the muscle strength is a standout improvement we see in these trials.
Dr. Gundry
You mentioned the cancer trial. Again, that you find is because of the improved mitochondrial function in the immune cells?
Dr. Anurag Singh
Yeah. This is a preclinical trial that was published. We are now translating these findings into two trials. The effect is primarily even in the immune cells, is because of improved mitophagy. Now, what happens in the immune system, there's a very specialized cell called a memory T-cell. This is a cell that basically has an imprint or a memory of how cancer cells look like or how viruses look like, etc.
Dr. Anurag Singh
What we see basically is that mitophagy is compromised in cancer patients and cancer models in this particular memory T-cell. And by supplementing with the postbiotic Urolithin A, we are reactivating mitophagy in this memory T-cell, and that contributes to better immune function. That contributes to clearance and better recovery from the cancer, and so that comes on the immune system.
Dr. Gundry
I want to backtrack for a second because you're using the term postbiotic, something that I've written about in my last two books extensively. But most people know probiotics, friendly bacteria. They know hopefully prebiotics, what friendly bacteria like to eat. But this concept of postbiotics is, for most people, they either haven't heard of it or what the heck is that? You go ahead and define it, I'll out if I want to add more. How's that?
Dr. Anurag Singh
I've read your book and your speeches on the three Ps, the prebiotics, the probiotics, and the postbiotics. The way I see them is that prebiotic is basically food for these healthy gut bacteria that coexist with us, and there are millions of them, billions probably, and that's by using probiotics, you're trying to modulate this gut ecosystem that exists. It's all good for them and all good for their ecosystem.
Dr. Anurag Singh
But then as a benefit to the host, which is us as humans, they take our food and nutrients from our food and they process them to release what are called as postbiotics that are beneficial to us as humans. That's a field that is coming up, postbiotics. There are a lot of them like short-chain fatty acids, typically butrate and acetate. Then there are from polyphenols derived metabolites such as urolithin A, which is a postbiotic. But I'll let you add to it.
Dr. Gundry
No, I think my book I'm writing right now does an incredibly deep dive into this incredibly complex ecosystem that we're just now beginning to understand because the amount… If you actually look at PubMed searches about the gut microbiome in 2006, there's maybe 1,000 searches, and now there's 30,000, and it goes on and on.
Dr. Gundry
What I think is fascinating is that these are communication systems that we now know exists between the gut microbiome and their host, us. We are actually dependent on these messages, these postbiotic signaling molecules. What I think exciting, particularly for Urolithin A, is yeah, pomegranates got lots of really cool polyphenols. There's history of how important pomegranates are in various brain health, heart health. But what you mentioned before is, particularly here in the West, America, in Canada, we're screwed because we don't have the probiotics that are able to take the prebiotics in pomegranates and make the active postbiotic compound that's going to do all this good stuff.
Dr. Anurag Singh
Yeah.
Dr. Gundry
You're right, we're not the French. The Swiss are actually very close.
Dr. Anurag Singh
The story I tell, and it's my personal experience, I can personally... I grew up in India, where there's rampant use of antibiotics. For everything when I was probably a kid with a little flu here and there, everything was antibiotics. My microbiome just never recovered, just never recovered.
Dr. Anurag Singh
I can drink six glasses, and I've done this challenge with myself. I've had six glasses of pure pomegranate juice, and then I have bled myself at different times to see if my body would make Urolithin A. Guess how much it makes? Zero.
Dr. Anurag Singh
Because maybe there is hope if I eat a lot of fiber. Maybe I figure out, and we have spent years trying to figure out what's the right mix of probiotics that will basically do the conversion. The answer is it's very complex. The ecosystem is so complex.
Dr. Anurag Singh
We have gone in and taken people, these lucky 10, 20, 30% people who are producers, we have really taken their stool samples, and we have really done a high throughput gut microbiome sequencing. We don't know. What we do see is that they have a very rich and diverse microbiome, which is rich in things like Akkermansia, which now also, you hear it so much.
Dr. Anurag Singh
But to get there, you need to give your system, A, eat better exercise and then probably third pillars, what we are talking is supplementation for cellular health and postbiotics.
Dr. Gundry
All right, so that's why Timeline and Mitopure exists. The workaround you guys have synthesized. What is Mitopure? How does it work?
Dr. Anurag Singh
Mitopure is a trade name for our proprietary Urolithin A, which we synthesize with a patent-protected methodology, and it's 99.9% identical to the natural molecule. The workaround is essentially... We have actually, even in the works of developing a small health kit where people can actually measure themselves in a lab or in a clinic if their body is actually...
Dr. Anurag Singh
What we do is we send you the pomegranate juice, you take the challenge, you just take a few drops of blood from your fingertips, put it on a card, and we can tell you if your body is already conducive to making Urolithin A or not. Then you take the direct supplementation, so you take a dose of 500 milligrams of Mitopure, and then you see the change in bioavailability.
Dr. Anurag Singh
I can tell you that the average is about sixfold higher in even people who can make it. For people in the community who don't make anything, you go from 0-400 levels of Urolithin A pretty fast in about six hours a week. That's what we have done. We've basically short-circuited the whole natural process of getting it from a diet or relying on the microbiome to produce it.
Dr. Gundry
Everybody's going to want to know, is it a pill? Is it a liquid? Is it a powder? How can I take it?
Dr. Anurag Singh
All our randomized trials at the start were with the pill, very calibrated dose of 250 milligram in each pill. The doses we are seeing that have the best effect in clinical studies are 500 milligram, and then the gram gives even a much better response and a much quicker response. But most people do take the 500 milligrams, so it's basically two pills.
Dr. Anurag Singh
Since then, we have also gone in... Because science and good nutrition should come with good taste as well, so we've developed a lot of food products. There's these berry and ginger-flavored powders now that you can mix in your smoothies, in your high-protein shakes. There's even a product with 20 grams of weight protein hitting on muscle mass and muscle energy at the same time.
Dr. Anurag Singh
This is the whole breadth of our product portfolio, whatever lends with your lifestyle.
Dr. Gundry
How long has Mitopure been available?
Dr. Anurag Singh
After a good 13 years of research, we launched it in 2020, and launching a new product in the mid of COVID crisis is not always easy. We only started ramping up sales in '21 and '22 and started selling it. We got what is called as a grass designation from FDA. We showed all the high level of safety data from Human Studies and from different safety dossier that FDA requests for what is called as a generally regarded safe designation.
Dr. Anurag Singh
We got that in 2018, but only now since the last couple of years have you start selling it in the US. Now we have thousands of customers who are taking it and swear by it.
Dr. Gundry
Now, you mentioned early that, obviously, mitophagy is a good thing, basically recycling our damaged mitochondria. I've written about the last thing you really want to do is have these mitochondria simplistically explode and throw their pieces out into the cytosol because the membrane of mitochondria...
Dr. Gundry
Mitochondria are actually engulfed bacteria, ancient. Our immune system actually views mitochondria, at least the wall mitochondria, as an evil bacteria. It can actually produce inflammation as these mitochondria die inappropriately. You're right, recycling these guys is really beneficial in lots of ways.
Dr. Gundry
You mentioned that fasting does this. As you know, I'm a big fan of time-restricted eating, intermittent fasting. Is it the same mechanism that Mitopure hits?
Dr. Anurag Singh
Yes. Fasting induces autophagy at the high level. Autophagy is basically recycling of the whole cellular machine. A focus autophagy is what we call it. It's just focused in the mitochondrial recycling. That's what we call as mitophagy. Both Urolithin A and fasting are known to induce autophagy.
Dr. Anurag Singh
Now, what we see very specifically with Urolithin A in different trials and different models is this unique ability to activate mitophagy specifically. We have compared different markers in different experimental systems comparing covered restriction to supplementation with Urolithin A, and it's pretty much similar in terms of autophagy. It's both a combination of autophagy and mitophagy.
Dr. Gundry
Getting back to the earlier studies, particularly in worms, worms are actually a really good model for lifespan, and actually, believe it or not, gut health. Worms with this compound were literally living 50% longer?
Dr. Anurag Singh
Yeah, one of the reasons why a lot of aging research is done in worms is they live about 20-25 days, mat tops. One of the most potent compounds that are known to extend lifespan, do it about 25%, things like Resveratrol trial and NAD boosters. One of the reasons we got so excited was Urolithin A in these initial experiments that we published in Nature Medicine was doing it by 45%, and that's unheard of, and that's what got us excited.
Dr. Gundry
Obviously, you can't make any qualifications that my taking this product now for a year and a half has already extended my lifespan by 20 years.
Dr. Anurag Singh
That's not what we are about, I think. The goal is healthspan.
Dr. Gundry
Exactly.
Dr. Anurag Singh
Today, the whole longevity space has been split into two. One says, "Oh, we want to live to 120, 130 years," which is really increasing lifespan. I think you can achieve that realistically if you focus on the lifespan extension.
Dr. Gundry
All right, back to Urolithin A. Is there a time to take it? If I'm a 20-year-old athlete, is that going to improve my performance? Or I'm a 50-year-old and noticing that I'm losing muscle mass every year no matter what I do. When should I start this stuff?
Dr. Anurag Singh
Most of our early studies focus on older adults and over the middle-aged adults because that's where we knew the mitochondria were impaired, and mitochondria would be compromised, and we could see it. We could detect signals to show the efficacy.
Dr. Anurag Singh
But when we launched it, to our surprise, we thought this would be mostly advanced nutritional product that a lot of older adults would be taking. But to a surprise now, a lot of our consumers are very active. They are these weekend warrior profile that wants to focus on health, wants to preventively address their health issues in their 40s and early 50s rather than wait for the symptoms to happen like modern medicine would wait for frailty and sarcopenia to manifest before starting to think about it.
Dr. Anurag Singh
A lot of athletes, two of the France cycling teams are on it, and a lot of top NBA players are taking it. That actually made us think, why are these players so much believe in Urolithin A when the science is still emerging on that aspect. That motivated us to launch a big study in Australia with one of the most revered sports nutrition researchers, a lady called Professor Louise Burke in the Australian Catholic University.
Dr. Anurag Singh
She's been studying elite athletes for a good part of three decades. She said, "A lot of times overtraining impairs mitochondria." That's what I think where young compound is actually acting is that some of these players are playing five NBA games or riding a bike for 50 kilometers to 60 kilometers, uphill, downhill for months, and the body just doesn't have the time to recover.
Dr. Anurag Singh
Now we have just finished this study, and the results hopefully will come out midyear, is that we think that by using the postbiotic and even elite athletes, we can blunt the muscle damage and accelerate the muscle recovery. That's one stream of research that is happening.
Dr. Anurag Singh
The other is in the hospitalized patient settings. Now, each day you spend in the hospital and you put it very well, you start losing muscle mass at a very accelerated phase. We think by supplementing in that hospitalized, immobilized setting, we can also accelerate the recovery of these people. The research is just building up, and many more people are starting to study this.
Dr. Gundry
Going back a second. Fasting is one way to produce autophagy. Can you combine fasting or exercise and Mitopure and get an even additional effect?
Dr. Anurag Singh
Yes, we've done it. We've looked at different models where we've added exercise regimens and showed that endurance improvements and strength improvements are even add-ons with supplementation with Urolithin A. The study that I was just describing with elite athletes, these guys are basically exercise gurus. That's all they do.
Dr. Anurag Singh
If we can improve somebody with a VO2 max of 70 and make their VO2 max better, gosh, that's really the holy grail of all clinical research. But you're right, the timing is very key as well. Overnight fasting induces autophagy, and so we use a similar approach in our trials is that we supplement early in the morning in a fasted state, so we get the best induction of mitophagy. That's what we even recommend consumers today that take the pill or the powder first thing in the morning.
Dr. Gundry
Good point. This all started because you guys were interested in pomegranate juice?
Dr. Anurag Singh
It all started with the pomegranate, the fruit and its magical healing powers and everything inside it. That's how it started.
Dr. Gundry
Now, there's obviously lots of other historic compounds that have purported history of health benefits. I would assume there are other compounds that you're also interested in. Can you share any of your other research?
Dr. Anurag Singh
For example, a lot of fruits and nuts also have ellagitannins. The majority of the urolithin is Urolithin A, but there are other urolithins that the body could make as well. There's Urolithin B, C, and D, and we have looked at them. It's just that Urolithin A is just so much more potent than the others, which is why as a small research company, you can only put so many research dollars into one area.
Dr. Anurag Singh
But we are now getting excited. We talked about adding on with high protein because I think for the whole muscle space, and I've done trials looking at muscle function improvement for the good part of two decades, adding 20 grams of A protein or alternative P protein, for example, was supposed to be the only way to build muscle mass. Those studies wouldn't work without adding exercise regimens because you needed to start the whole muscle protein census via mitochondria, I'm assuming.
Dr. Anurag Singh
We think that's where a lot of known ingredients in the space, whether it's immune with vitamin D, for example, there's a lot of synergy with Mitopure. That's how we are approaching it with Mitopure as the base bio-active that can boost cellular health. Then we add on well-studied, well-clinical research ingredients that add further benefits. These will be products we'll be launching in the duration of the year.
Dr. Gundry
Have you looked at the effect of Mitopure on, say, the gut microbiome or probably more importantly, at least to me, on the gut wall integrity? I happen to think that the gut wall is the holy grail of health span, among other things.
Dr. Anurag Singh
We have started translating it. There's a lot of research emerging now with excitement, as you mentioned, around this molecule. There's a group out of US that has just basically published, and again, a very top journal showing that the barrier junction was improved following Urolithin A intake. This was again done in preclinical models of inflammatory bowel disease and colitis and Crohn's disease, where they basically showed that supplementing with Urolithin A was improving gut barrier junction, and it was hitting on all these leaky gut that gets compromised with aging again.
Dr. Anurag Singh
This is now leading to human translation where we are starting to think of how to translate this in people who have irritable bowel syndrome or even irritable inflammatory bowel disease. That's the one area we are actively looking at, as you mentioned.
Dr. Anurag Singh
The other that excites us, just because the science is coming from the National Institute of Aging and the Buck Institute of Aging, is the potential Urolithin A as a molecule has on improving brain health and really counteracting neurodegeneration. They've screened thousands of compounds, and they'll found that basically Urolithin A is the top that prevents by activating mitophagy again.
Dr. Gundry
It's going to work from top to bottom is what you're saying?
Dr. Anurag Singh
It's going to work wherever. There is an organ and links to high metabolic demand, which is either A, a skeletal muscle, B, could be the cardiac muscle or the gut, as you were talking about. But the brain cells have thousands of mitochondria and they get compromised.
Dr. Gundry
Oh, yeah. All right. What makes Mitopure different from other products or solutions that are... You see across the Internet, "Oh, this is improving mitochondrial function, or blah, blah, blah."
Dr. Anurag Singh
What makes it different is... My answer is a twofold answer. One that makes a difference is that probably there are very few compounds that people have studied and put the efforts to study with the biotech approach for 15 years, and only when they believed that this molecule had health benefits have we brought it from the bench scale to the human research to the breakfast table, as I say, of people now that people can take it in their daily routine.
Dr. Anurag Singh
The second is that it's such a safe molecule. It's a natural molecule. It has been evolutionary present through a diet, and of course, a lot of us have lost the ability to make it. It's a very unique mitophagy activator, which is such a well-conserved anti-aging pathway.
Dr. Anurag Singh
There are other mitochondrial nutrients that are known to improve energy production like COQ10 and L-carnetine, for example. Then there is the biogenesis side of mitochondrial improvement where you can take respiratrol or certain NAD boosters like nicotinamide, ribocytes.
Dr. Anurag Singh
But those, in my opinion, will only work if you take out your trash bin. You can't keep putting more trash and suddenly expect that it will clean away and there'll be empty space to have healthy mitochondria. That's where I think this is so unique, is that it takes out your trash basically, and that allows new healthy mitochondria to come in.
Dr. Gundry
That's a great description of where this fits into our health span armamentarium. All right, I'm going to have to let you go. What's next for Timeline?
Dr. Anurag Singh
Well, we are a research-focused company founded by scientists and doctors, and so we continue to invest a lot of dollars into R&D on our own, but there's a lot of excitement. We are collaborating with, as I mentioned, the National Institute of Aging and really the Harvards of the world out there to really expand the universe of health benefits associated with. We are focusing today on studies in cancer recovery patients, we are focusing on immune health.
Dr. Anurag Singh
But the other stream, which we didn't talk about, is topical. We've now done a lot of work on topically delivering this compound because there's also, believe it or not, a gut-skin axis where a lot of the skin aging is probably the number one. Visual aging is what people see with aging the most, and of course, muscle that people feel and functionally.
Dr. Anurag Singh
We are now starting to get a lot of amazing data on skin cells mitochondria showing mitophagy can be upregulated, and that's a way to boost energy production in the skin cells. And we've done trials showing better collagen synthesis, showing again, mitochondria are key to even things like wrinkle formation as we age.
Dr. Anurag Singh
That's where all the research is coming, and just this last week, we launched products targeting with skin creams, and day cream, and night cream. That's the future of mitochondrial research.
Dr. Gundry
Well, Dr. Singh, thanks so much for joining me today. Can you share with everyone where they can learn more about you and Timeline, please?
Dr. Anurag Singh
Sure. They can go to our website, www.timeline.com, and they can also go to a knowledge science-only website called www.mitopure.com, where they can read all the signs and blogs around cellular and mitochondrial health.
Dr. Gundry
All right. I guess you've got a couple of generous offers for our listeners.
Dr. Anurag Singh
Yeah, sure. No, for all the listeners of your podcast, we're offering 10% on any Timeline Nutrition product, so they can use the code Gundry10, and I'm sure in the footnotes of this podcast, we would direct our audience to it. They can go to www.timelinenutrition/gundry and put the code that I just mentioned, Gundry10 and a real 10% on any products they want.
Dr. Gundry
And to the first thousand listeners, we are offering free samples. This is basically a three-day pack. They can try and see how the product tastes. I mean, not saying that in three days they'll feel amazing energy and start moving, but at least they can see how it fits in their daily lifestyle. And then if they like it, they can avail of the bigger offer on the 10% on the products.
Dr. Gundry
Well, that's fantastic. Thank you very much. Now, don't everybody flock. You guys will all be there in the next five seconds, so don't crash their computer, please. Now, this is great. And people, I've actually been using their product for, gosh, I think about a year and a half. And the reason I wanted to have you on is I'm personally recommending this to many of my patients. Specifically, we've seen some really very interesting effects on brain health. Yeah, I'm a big believer, and I really wanted to have you on. You guys are really on the right track. I appreciate it.
Dr. Anurag Singh
Pleasure was ours being on your podcast. It's such a great medium to take cutting-edge research and bring it to the consumers. Thank you for having us.
Dr. Gundry
All right, we'll let you go, and hopefully we'll talk again soon.
Dr. Anurag Singh
Sure. Thank you, Dr. Gundry.
Dr. Gundry
Now, time for the review of the week from Christian G. On YouTube. He says, "You always cut through the fat and provide the most accurate current information to optimize health. Thank you for your tireless work. Your research has improved my quality of life."
Dr. Gundry
Well, thank you very much, Christian. I always try to cut through the noise out there. There's a lot of noise on the Internet. There's a lot of gurus out there. Here's the deal. I spend six days a week learning from my patient. We call this the practice of medicine because it is a practice. I want to see what happens when people adopt certain things, get rid of the no list, start on the yes list, take a supplement, not take a supplement.
Dr. Gundry
I see that with blood work that we do every three months on our patients. And I can actually see those effects. I've spent now over 25 years cutting through all the chatter out there. I get to change my mind because as new evidence comes up, as new research comes up, as my new research changes my mind, I'm happy to tell you, because if I'm not learning something over the last 25 years, quite frankly, you don't want to listen to me.
Dr. Gundry
So thank you very much, Christian, because I'm Dr. Gundry, and I'm always looking out for you. Just like you said, Christian. We'll see you next week.
Dr. Gundry
I hope you enjoyed this episode of the Dr. Gundry Podcast. If you did, please share this with family and friends. You'll never know how one of these health hacks can completely transform someone's life when you take the time to share it with them.
Dr. Gundry
There's also the Dr. Gundry Podcast YouTube channel where we have tens of thousands of hours of free health insights that can help you and your loved ones live a long, vital life. Let's do this together because I'm Dr. Gundry, and I'm always looking out for you.

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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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