In Blog, Diet, Exercise, Health, Health Professionals, Lifestyle

Could pomegranate polyphenols hold the key to longevity?

The 3 Hallmarks Linked to Mitochondrial Health

Having healthy strong mitochondria is necessary to have a healthy, strong body. It’s our mitochondria that generate the ATP through cells we use to drive the energy of life, the chemistry of life. And as we age, our mitochondria become less vigorous, and less vital. We know there are some ways to youthen your mitochondria. And this includes fasting, high-intensity interval training, and strength training—And there’s another compound Urolithin A.

This interview is with Anurag Singh, the current Chief Medical Officer at Timeline Nutrition, a Wahls Protocol® Sponsor.

Timeline 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 startups 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.

Don’t miss this interview (or read the transcript below) to learn how pomegranate polyphenols could hold the key to longevity.

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*These statements have not been evaluated by the Food & Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

Dr. Wahls: Okay. Welcome Dr. Singh. I’m so glad you’re joining me today. And now everyone, I’m here with Dr. Singh, who is the Chief Medical Officer at Timeline Nutrition. Now, timeline has developed nutritional products, and I’m really intrigued because they are focusing on mitochondrial health and vitality and what we can do using nutrition to energize our mitochondria so they’re more effective in supporting our cellular function.

Now, he’s an MD, trained in internal medicine like me. But he also has a PhD in immunology and he is instrumental in the Timeline development of the nutritional support products for the mitochondria. Now, Timeline is a Wahls Protocol® Sponsor. And I love these partnerships because these are companies whose products I use every day to support my healing journey. And so many people are asking me, so what is it that I do to maintain my health, maintain my vitality? In these interviews are really a wonderful way for you to see what it is that I do every day to be sure that I stay healthy, strong, and vital, because my goal is to thrive to 120 and still be doing this amazing, groundbreaking research. Okay, so thanks for joining me and Dr. Singh, let’s talk about mitochondria and muscles.

Dr. Singh: Sure. Thanks for having me on your show, Dr. Wahls. So we have been studying mitochondrial health in the context of health span and muscle as a key organ for longevity. And so that came first to our attention. Muscle is also—things like grip strength decline is associated with all cause mortality and a lot of these studies and literature were already out there. So we first started looking at 70 year olds who were running sort of 10K and a half-marathons and really studying at a molecular level, taking small chunks of their skeletal muscle here, what we call muscle biopsies and comparing them to 70, 75 year olds who were frail. So basically trying to take a look deep down into the molecular signature in their muscles. And mitochondrial health emerged as the number one determinant that was dictating muscle strength, muscle vitality. And that’s how, not only us but others have also looked into the space and found similar results.

Dr. Wahls: You know when I was very young, I was very into running. I ran 80 plus miles a week. It was only much later that I figured out, no, no, no, I should be spending a lot more time on strength training and a lot less on endurance training. So let’s talk about those biologic markers that you’ve identified that are key for healthy aging, because that’s my big goal is I want to live but thrive well beyond a hundred. So how do I do that?

Dr. Singh: Sure. So about a decade back, there was this seminal paper in the field of aging that’s called the Hallmarks of Aging and it came from Professor Guido Kroemer and what it described was all these cellular and biological pathways that basically decline during the aging process. Some of them are linked to stem cell exhaustion, some are linked to how we absorb nutrients. Some are linked to sort of collection of protein deposits in our muscle, in our brains that lead to a force disorders as we kind of grow older. But what was really striking was that the central hallmark that connected a lot of these hallmarks of aging was always linked to mitochondrial dysfunction. So mitochondria are these, think of them as your batteries powering a Tesla car and they’re really key to sort of cellular health and cellular vitality.

And more recently the three new key hallmarks that have been added are all linked to mitochondrial health in that there is decline in recycling and rejuvenation of faulty mitochondria process, which we will talk about called mitophagy. Then there’s chronic inflammation that is always happening as we are aging and then gut dysbiosis. So sort of looking in these areas, we were starting to look for solutions that could target and basically delay some of these hallmarks phasing as we grow.

Dr. Wahls: Okay, so everyone is listening. Mitochondria key, mitophagy is a big deal. That’s the renewal or the ability to self-renew the mitochondria, keep them young. Okay. So why don’t we talk a little bit more about what that mitophagy process looks like.

Dr. Singh: Sure. Yeah. So my mitophagy is one of the very well-conserved anti-aging pathways that we all have. And what happens is that, especially in organs that have a lot of abundance of mitochondria such as the skeletal muscles, such as the brain, which of thousands of mitochondria in each cell. What happens is that you start having or accumulating with aging a lot of faulty mitochondria. So a good analogy I can give you is your trash can in your home. If it’s filling up too much and it’s not being regularly recycled or removed, the waste is not removed. Your house will not smell well, right? And that’s exactly what’s happening in these cells is that you’re accumulating a lot of bad mitochondria and cellular waste. And so mitophagy is this process that you need always running in your background to remove this cellular waste and that slows down. And so you need to find ways to really amp up the mitophagy process as we age and that will lead to newer healthy mitochondria.

Dr. Wahls: So we can do part of this through strength training, lifting weights, high intensity interval training, calorie restriction, fasting and I do those things. But you guys found another way, an additional way to support this.

Dr. Singh: Yes. So absolutely, you nailed it. The two known interventions that are known to amp up mitophagy are sort of strength training and intermittent fasting. And we always have compared our results in initial, let’s say experimental models to that sort of how would it compare to caloric restriction? And so when we started out, we started, gosh, 15 years back and our whole goal was to be sort of the bring the deep biotech approach to nutrition a and natural compound discovery. And so we looked at a pomegranate at the start and we found through hundreds of natural compounds in pomegranate, there was this one molecule that attracted attention that was actually not coming from the diet. It was coming from the precursors in the diet that we call as polyphenols, present in pomegranate. And the gut microbiome was basically the key factor that was involved in generation of this compound.

So this compound is called urolithin A. And that’s what we have been studying. We have been studying how it improves muscle health, how it improves vitality, and how it improves mitochondrial health. And we have shown that in multiple species, including many clinical trials in humans, it activates mitophagy.

Dr. Wahls: Okay. So do I just eat more pomegranate then?

Dr. Singh: For certain lucky few, yes, you can up your pomegranate intake and you can eat more balanced fiber-rich diet. So you need two key variables. You need to be eating very healthy and you need to have the right gut microbiome. Now we have run studies around the world in French population, in American population at fact, in downtown Chicago on hundreds of people, we found only basically 12% people had some circulating levels of urolithin A coming from the diet and gut microbiome.

So yes, you can eat a lot of pomegranates, but a lot of us don’t have the right gut microbiome and that’s the key variable.So we’ve done studies where we have even given the right diet. So we’ve given folks a glass of pure pomegranate juice and we see only 30 to 40% people can actually do the conversion. So somebody like me growing up in India, taking a lot of antibiotics, my microbiome never had a chance and I can drink six glasses of juice, my body won’t make your urolithin A. So yes, you can definitely try to eat more pomegranate, you’ll get the sugar from there, but there’s a 60% chance you won’t produce it.

Dr. Wahls: And of course, many of us have taken many antibiotics and so our microbiome is not as diverse. And I can look at myself, I had early antibiotics as a child, recurrent strep, and so I certainly would be in that group that would be at significant risk of not having the right microbiome. So how would we sort out, I should be taking urolithin A or maybe everyone should take some urolithin A. Is there any risk from getting too much of urolithin A?

Dr. Singh: Well, I don’t think so because to your first question, how do we know who is producing urolithin A or not? We are actually just built a prototype test that involves a little prick in your finger and a few drops on a spotting card that you send to a lab and then you drink a glass of juice and you will know along with that test kit if your body is making a urolithin A or not. And then you can actually take a calibrated supplement with the pure molecule urolithin A and then you can see the difference.

Dr. Wahls: Okay, hang on. Everyone who’s listening, I want to be sure we understand. So this is a way that one could answer that question on your own without going to your physician. And is that something that people can request or could obtain?

Dr. Singh: Yes, part of a clinical study people, we can provide you the link. Some folks who are interested can participate and already know what their levels are of urolithin A from natural sort of consumption through the diet, et cetera. But even if you make, and of course we have looked into the microbiome of these people who are, as I call blessed because they have the right gut microbiome and as you pointed out, they need to have a rich and diverse gut microbiome. The levels vary because you’re not going to drink a glass of pomegranate juice and squeeze four pomegranates every day on your own, right? And so what we do see is even if your gut microbiome is there, there’s a lot of variability in the levels that are in some cases what we call therapeutic levels, which you would get sort of the health benefits out of.

But in most cases there are suboptimal levels. So you would not probably get enough as a clinical trialist, I say not enough exposure to the molecule to drive the health benefits. And that’s why we created this route of short-circuiting the whole natural process and creating the direct supplementation.

Dr. Wahls: So I can either eat lots of pomegranates and then maybe have enough urolithin A or I could take the urolithin A supplement. And I just take it once and then I’m done?

Dr. Singh: So the way it works, we have done a lot of clinical studies. So we’ve done studies in older a adults, healthy olders, we’ve done studies in healthy middle-aged adults, and now even in young athletic individuals. And so the way it works is that you take it, mostly in our trials, people are taking it fasting. So in the morning because that’s when probably after overnight fast, you already have some levels of autophy, mitophagy with the 12 hours of fasting. And so you take the pill, you kind of augment that process even further. The half-life of the molecule is about a day. And so in our trials, what we are seeing is at a molecular level, you start turning these bad faulty mitochondria out of the system and having newer healthy mitochondria come in about a month that that’s when we are able to catch the effect. And then in about two months you start seeing physiological benefits like improved improvement in endurance, and less fatigue, all linked to improvement in mitochondrial health. And in four months we see really statistically significant improvements in things like muscle strength.

Dr. Wahls: So this would be something that the benefit continues to accumulate as my mitochondria get better. So we’re talking muscle strength. I’m thinking of other health challenges that many people with chronic diseases have such as fatigue, cognitive decline, maybe they have a little bit of heart insufficiency. So have you had any information on how quickly people may see a change with a reduction in fatigue or an improvement in mental clarity?

Dr. Singh: Yeah. So there’s the real-world data we have and then there’s the clinical trial compared to a placebo in our RCD setting we have. So in most of the RCT’s takes about a month to two months to see an effect. That’s why we actually even sell only month and two month and four month kind of subscription. So people allow, it’s not a magic pill that will kind of in a few days of use, clean out all the waste and use expect to exercise. It’s like thinking of fasting and exercise. You need to be on it for months to really see the benefits of it.

Dr. Wahls: Correct, correct. Okay. So is there a dosing guide? It’s one capsule that I take every day then and is there a runup phase?

Dr. Singh: Sure. So we have different product format. So we good signs that we have invested 15 years on before we launched products. We believe that good signs should be complemented with different product options and good tasting products. So we have both food products and dietary supplements. The food products are basically fruit flavored powders, either berry, pomegranate or ginger that people can mix in smoothies, et cetera. And these have the clinically studied dose of 500 milligrams inbuilt into them.

So you mix it in your muesli or yogurt or protein shake, et cetera. And then we have the pills, the soft gels, which each have about 250 milligrams in each capsule. So you need to take two a day to get that 500 milligram dose that we have studied. Now some people who are more kind of athletic and a lot of athletes ramp up the dose and we have studied in these clinical trials about a gram as well. At the higher dose of a gram, we also start seeing additional benefits to just the mitochondrial and muscle. We see even inflammation being dampened, so things like C-reactive protein in older adults or obese adults or overweight adults, we start to see that mitochondria linked to even the inflammatory pathways. And so yeah, you start getting additional benefits. So about 500 milligrams is the sort of starting dose in a gram is the really the top dose we see effects on.

Dr. Wahls: Any negative effects or anything that we have to be concerned about?

Dr. Singh: I don’t think so. I mean this is an evolutionary natural molecule that has been, a lot of is, as I mentioned, 30 to 40% I’ve had. We’ve changed our dietary patterns, we are no longer eating out in the forest, fruits and berries and now we are kind of all eating fast food and all these diets that has shifted our microbiome. So it’s been present in a bodies for, I mean it’s what I call it post-biotic. Right. So this has been around for centuries. And in our trials, which are now, we have studied almost a thousand participants in our consumers, which is many, many thousands of people. We have not seen many, in fact, we’ve not seen anything in terms of side effects.

Dr. Wahls: Well, as I’m listening to all of this, I’m thinking that I need to have another separate conversation with you about some clinical trials in progressive MS. I think this would certainly be a very interesting molecule to investigate. And I’m thinking about some of the huge challenges with remyelination because myelination declines as we age. And I think mitochondrial dysfunction is certainly a big part of why people experience cognitive decline, difficulty with memory, difficulty with repairing myelin. And so this could be certainly a very helpful support for anyone who’s looking at the goal of healthy aging, the goal of not only living to 70, 80, 90, 100 but thriving with clear thinking, clear energy, plenty of strength so I can live and thrive independently. What is the next innovation that Timeline’s going to go off? What are guys working on next? You’re a very innovative, interesting company.

Dr. Singh: Yeah, I mean at the core of everything we do, we put people’s quality of life and health span. And of course we are company founded by scientists and doctors. So science and high level science and clinical evidence is the core. So you’re doing a number of clinical studies. We are looking at studies, as I mentioned in elite athletes now because elite, even you would think elite athletes probably have the best mitochondrial function. The over training actually in a lot of these Olympian long distance runners causes mitochondrial dysfunction and inflammation. So we are looking one area there. You’re looking at immobilized sort of setting where, so if you get into an accident and you’re in a hospital for two weeks, if somebody puts a cast on you, if you fracture your leg. That induces very rapid muscle dystrophy and mitochondrial dysfunction. So you’re looking in those settings. Adding on the standard of care there is basically giving high protein to preserve muscle mass.

So you’re trying to change the game thereby targeting bioenergetics. And in addition to muscle mass. And then immune metabolisms really the field whereas the train immunologist, I think where mitochondria have a big role to play. There’s a new study that just came out showing that, albeit in an experimental model where they showed that supplementing the urolithin A really turbocharged the memory T-cells. So now they were more efficient at sort of clearing the way in things like cancer in these models as in these colorectal cancer models. So we are now translating this into two trials and post-cancer recovery sore, really trying to see if we can rev up the immune system after post-cancer treatment. And second is in healthy adults if we can already show that the mitochondria of the immune cells, especially the T-cells are revved up. So these are the trials we are running.

Dr. Wahls: Wonderful. Very exciting stuff. Well, Dr.Singh, if you wanted to give our listeners what would you give as the single takeaway key message that you have for them?

Dr. Singh: Yeah, I mean I’m a trained doctor, so I always say you have to focus on the two key pillars of health, which is diet and exercise. You have to be compliant with that to. And then the third pillar I think, which a lot of us are either not taught about in medical schools or being educated in our real life is that you need to, the third pillar is really your cellular health. And that’s the sort of pillar where we think we can make a difference by complimenting the other two pillars of diet and exercise by targeting improved mitochondrial health through nutrients such as urolithin A.

Dr. Wahls: Okay. Well thank you Dr. Singh. This was just marvelous. I look forward to ongoing collaborations and I will be chatting with you about potential clinical trial collaborations.

Dr. Singh: Sure.

Dr. Wahls: Now all of you who are listening, please tell us down below what were the key takeaways that you took from this? What will you be trying to do next to support your healing journey? Be sure to go also over to my website, Sign up for a newsletter to get alerts for other wonderful interviews as they come up in our research updates. And as always, thank you for all that you are doing. Keep eating well, keep exercising and focus on those mitochondria.


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About Dr. Singh: Anurag Singh is currently Chief Medical Officer at Timeline which develops next generation advanced nutritional and skincare products targeting improvements in mitochondrial and cellular health. With a M.D. in internal medicine and a Ph.D. in immunology, his experience includes work at top consumer health (Nestlé, Nestlé Health Science) and startups 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.

About Timeline: Timeline is a novel nutrition brand developed by Amazentis on the belief that uncompromising research can unlock a new class of nutrition that is backed by cutting edge science. As scientists, we know that physical decline from aging can’t be stopped. However, through its groundbreaking science, Timeline is committed to developing products designed to help reduce the impact of time on health. For more information, please visit

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