[Transcript] – The Newly Researched Compounds That “Cleans Up” Mitochondria, Reverses Aging & Combats Sleep Deprivation, With Dr. Anurag Singh Of Timeline Nutrition.

Affiliate Disclosure


From podcast: https://bengreenfieldlife.com/podcast/timelinepodcast/

[00:00:00] Introduction

[00:01:23] Podcast Sponsors

[00:05:29] Podcast and Guest Intro

[00:07:41] How did Dr. Singh got interested in Urolithin A?

[00:15:25] The benefits of supplementing Urolithin A?

[00:19:22] What is Urolithin A doing in the body?

[00:24:57] Side effects from a higher amount of Urolithin A

[00:26:42] Timeline’s Urolithin A vs. Similar products

[00:32:06] Urolithin A in skin products

[00:35:57] Other compounds for age reversal

[00:38:30] A typical Dr. Singh’s day in terms of age reversal strategies

[00:43:11] The use of Urolithin A for workout

[00:45:30] What combines best with Urolithin A?

[00:48:22] Current Timeline Urolithin A studies

[00:51:20] Is there an excessively turning over mitochondria?

[00:55:33] Benefits of Urolithin A on brain

[00:58:46] Closing the Podcast

[00:59:51] End of Podcast

[01:00:22] Disclaimer

Ben:  My name is Ben Greenfield. And, on this episode of the Ben Greenfield Life podcast.

Anurag:  The five best ways to improve mitochondrial function if I have to put a priority list, one would be regular physical activity. So, try to do your 10,000 steps a day. Number two, in short of intermittent fasting, two meals a day with a very balanced nutrition profile probably does the trick. Stress. Big impact of stress on circadian rhythms and sort of how it impacts mitochondrial health. Sleep. Another big aspect that has a big impact on mitochondrial function at your cellular level. And then, the fifth is what I would say sort of advanced nutritional supplementation, things like urolithin A as we are chatting with or even hitting on some other well-known autophagy boosters, you mentioned spermidine as one, you mentioned other ways to boost autophagy. So, there's no one magic trick. It's really a concert with different tactics that you need to apply.

Ben:  Faith, family, fitness, health, performance, nutrition, longevity, ancestral living, biohacking and a whole lot more. Welcome to the show. 

Ahh, summer. I feel like that snowman out of Frozen, “Summer!” Brings warmth and sunshine and mud puddles and energizing opportunities to reconnect and move and play in a fair amount of sweat, sweat, sweat, sweat, and that [00:01:38] _____, alright, it gets minerals out of your bloodstream and that can lead to headaches and poor sleep and all sorts of nasty effects. And yeah, drinking water helps especially mineral-rich water, but you need the right fluid to electrolyte balance and that's a science. When I get that science right, I feel amazing, especially on hard workout days. And, this company LMNT that makes great tasting electrolytes just launched an amazing flavor titled Grapefruit Salt. So, you can balance your minerals all summer long and you can make really great recipes with this stuff. It may or may not be good in a cocktail, that's up to you but it's also fantastic over ice and ice water with a little bit of iced tea. It's good, believe it or not, in a lot of iced coffee drinks. It's great simply sprinkled into some kombucha or, like I mentioned, your favorite cocktail so you can mineralize and alcoholize at the same time.

Anyways, electrolytes are a science and LMNT has knocked the science out of the ballpark and getting the ratios right and the flavors that I mentioned are amazing. So, you get a free LMNT sample packed with any order when you order through DrinkLMNT.com/BenGreenfield. That's a DrinkL-M-N-T.com/BenGreenfield. 

Well, if you, like me, enjoy the occasional dose of good old nicotine to increase your focus, your creativity, your productivity, it's a very beneficial life hack, honestly, and you're looking for a way to do it without getting a bunch of toxins into your system, you should check out Lucy. They're a modern oral nicotine company that makes gum and lozenges and pouches, their cherry ice flavor, by the way, is amazing, for any adult who wants a really good responsible way to consume nicotine. So, if you want a nicotine product, you can actually feel good and guilt-free about, then Lucy is definitely for you.

Now, I have to warn you it does contain nicotine. Nicotine is addictive, so proceed with responsibility. But, if you enjoy nicotine or you want to feel what it really feels like to be supercharged on nicotine, check them out, lucy.co. That's L-U-C-Y.co and use promo code BEN20 at checkout.

Alright, guys, here's a fun pop quiz for you. How many sailors throughout history died from scurvy caused by vitamin C deficiency during the time of Christopher Columbus? Is it 20,000? Is it 200,000? Or, is it 2 million? And, I got your answer. Drum roll, please. Two million people. Would you believe 2 million people had to die before we figured that out? Well, here's where it gets crazier, there's a little-known deficiency right now killing millions of people around the world and the disease it's causing, insomnia. 

According to a study published by Academic Press, magnesium deficiency is a leading cause in sleep disruption in both children and adults. The problem is not any old magnesium will do the trick. Recent studies have shown there's actually seven different forms of magnesium and your body needs them in precisely the right balance for proper sleep. There's only one magnesium supplement on the market that has the full spectrum of all seven forms, it's called Magnesium Breakthrough. And, I got to tell you when I take this stuff, I just feel on like my body's finally getting something it's been desperately needing. And, Magnesium Breakthrough is now available at a 10% discount off your first bottle. And, if you're not satisfied in how it fixes your sleep, your digestion, your energy levels like it does for me or if you're not satisfied for any other reason, they give you a prompt and courteous refund on the spot guaranteed.

Here's how you do all that, MagBreakthrough.com/Ben and use code BEN10 to get 10% off your first bottle. Again, it's MagBreakthrough.com/Ben and use code BEN10 to get 10% off your first bottle of Magnesium Breakthrough.

Well, folks you've probably heard me talking before about something called urolithin A. So, you can find it in things like pomegranate and walnuts and raspberries, and my guest on today's show might know some other fringe sources of it. But, it seems to be kind of becoming one of these darlings of the age reversal and healthy aging community, right up there with the things you hear people talking about like NAD, and C60, and astaxanthin, and spermidine, and fish oil, and peptides and stem cells. People are talking about urolithin A now, but I've never really unpacked in detail on a podcast what it is because there's some subtle nuances in terms of its sources, its bioavailability, its dosing, the research behind it, and it's such a popular supplement and you're hearing about it all over the place now that I figured I should do a podcast on whether it's a reasonable thing to take in the first place, if you even need to supplement with it and what exactly it is and how it works in the body.

So, I found a guy who knows a lot about urolithin A. His name, and I hope I don't butcher your name Dr. Singh because I got the last name, S-I-N-G-H, but is it Anurag? Is that how you pronounce your first name?

Anurag:  Yeah, you got it correct. You can call me Dr. Singh.

Ben:  Nailed it. Alright, we'll go with Dr. Singh. So, for everybody listening in, Dr. Singh is an MD in internal medicine but he also has a Ph.D. in immunology because he's a total underachiever and he has worked with a bunch of different food companies including Nestle and different startups including one startup called Timeline, which has done a lot of this research and development of urolithin A, and they actually claim Timeline that urolithin A is backed by about 15 years of clinical research. And so, we'll be able to explore a little bit today about what exactly that research is and what Dr. Singh has found when it comes to urolithin A, which again I'm now taking as a supplement but I've never really done a deep dive into it. So, this is going to be fun to get into urolithin A. You ready to talk all things urolithin Dr. Singh?

Anurag:  Sure, love to share it with the audience.

Ben:  Cool.

What got you interested in the first place?

Anurag:  Well, I'm trained as an internal medicine doctor and for long I was practicing as they call modern medicine, and I realized basically that a lot of times when we were seeing people with different chronic conditions it was too late in the sort of trajectory of health function and health dysfunction to intervene. And, I started working with a lot of natural compounds as I was training to be a physician-scientist. And yeah, from there, the interest grew and we started looking at bringing the biotech approach to nutrition and assemble it on urolithin A and it's a really great area of health benefits.

Ben:  So, besides having a really weird name, what exactly is urolithin A?

Anurag:  Sure. Yeah, it's a metabolite found from sort of–we all know the good foods that we eat, right? Things like pomegranate, walnuts, beacons, raspberries, all these, red and blue-looking stuff that we have, for long, said has packs a lot of antioxidants. Well, it does, so a lot of these antioxidants are polyphenols, they're natural compounds that are enriched in these fruits and nuts. But, when we digest them, our gut microbiome releases this metabolite called your urolithin A. So, it's basically a food metabolite.

Ben:  Okay. So, what's that mean the gut releases a metabolite? Would that mean the bacteria that are already in your gut would consume these foods or ferment these foods and produce some kind of like, I think it's called a postbiotic compound? Is that kind of how it's working or what exactly is the conversion here that's going on?

Anurag:  Yeah. So, these antioxidants or polyphenols are very complex sort of aromatic compounds. And so, when you digest so you're taking a glass of juice or a bowl of berries, your gut microflora basically will digest them and sort of break them down into smaller molecules that are more digestible and more well-absorbed and have health benefits for the host. Yes, you're correct, this is what I would also call a postbiotic compared to a pro or prebiotic, which is essentially the gut microbiome and prebiotic, the food that the gut microbiome needs.

Ben:  Now, based on that, I guess I'm wondering, let's say I'm eating pecans and raspberries and pomegranate weaving those into my diet so that I can then have the bacteria in my gut convert those into this metabolite urolithin A, is it going to kind of vary the conversion efficiency based on my unique biome? Because you got companies now out there like, probably Viome is one of the most popular. I know Genova Diagnostics has a test for this, but they'll tell you the genetic composition of all the bacteria in your gut. And, I'm curious if there's a way to know kind of your potential for urolithin A production based on something like that.

Anurag:  Sure. Yeah. So, basically, we have done a number of clinical trials all around the world. We've gone into French adult population, we've got into the Americans, the Canadians, name it, and basically, the best producers are the French. So, they must be eating closer to the Mediterranean diet rich and I guess a lot of fruits and berries and nuts, but they're also eating a lot of cheese and wine and a lot of fermented stuff. So, we do see about 30, 40% people in healthy adult population that have the correct gut microbiome. So, you're right, you need to be eating healthy foods but you need to have the right gut microbiome.

In the American population, we did a study we published a couple of years back. It's actually very low, it's like 10, 12%, and even those who will make it would make a very variable range. So, in most cases, it will be what I call sub-optimal ranges that are hardly going to give you a health benefit. For example, we also have developed a test that can accurately measure just with a few drops of finger prick blood swabbing sort of on a filter paper. We can tell you through a very advanced mass spectrometry methods if your body is actually naturally producing or not and how much you need to be taking it. I can drink 6 liters of pomegranate juice my body just refuses to make urolithin A as an example.

Ben:  That's interesting. This mass spec analysis that you can use on someone's blood like with a blood spot test, is that looking at the genetic makeup of your gut or is it looking at urolithin A presence in the blood or what exactly are you looking at?

Anurag:  Yeah, yeah. So, it's exactly looking at the presence of urolithin A in the blood that you're probably exposed from diet. And, it's a very precise test that we have developed. And, the end goal of that whole thought of developing the test was basically this molecule, this postbiotic is sort of the natural way for the body that exists. So, if you have a very well-functioning gut health, gut ecosystem and you're eating right, you could probably going to make decent amounts of naturally urolithin A, but a lot of us don't.

And so, the tests you were mentioning that other companies such as Viome or others have will tell you your microbiome sort of spread whether it's favorable, whether it's rich and diverse. So, we've actually done studies where we have looked at people who naturally produce and what's their gut microbiome look like and those who don't produce such as me. And, the answer really lies in the complex of that microbiome that you have to have a very rich and diverse gut microbiome. So, you could do that analysis but I think with our sort of end functional output, which is urolithin A, we can tell you if your body is making the end product or not.

Ben:  Yeah, it sounds to me like you could skip a lot of the hassle with doing a full biome test of the gut if you can simply test your blood, if you're already on a supplement that contains urolithin A or, I guess, perhaps some kind of a probiotic that might result in urolithin A production. I would imagine you'd want to stop that and then you could just test what your levels naturally are and know. But, I'm just curious, do you think it's more that some people don't have the genetics from an overall like a whole genome standpoint to produce urolithin A? Or do you think that these Americans, for example, who you mentioned are 10 to 20% of them capable of producing adequate amounts of urolithin A that it's more diet or epigenetic or environmental related? You know what I'm saying?

Anurag:  Yeah. I think actually it's more diet and environmental related and what kind of exposure you had. For example, I grew up in India, a lot of antibiotic usage early on for everything. It's a big practice to give antibiotics. My gut microbiome just basically, I think, is destroyed forever, and try as I might to eat a lot of fermented food and a lot of fiber, I don't seem to be able to rewire it. Now, those who are blessed, as I call them those who are producing and eating the right foods to nourish, they probably are getting the exposure to decent levels naturally.

Ben:  Okay, got it. So, would there be any advantage, and I realize this is probably kind of a question that you might be biased about working for a company that makes a product that supports urolithin A production, but would there be any advantage if you were getting, let's say, adequate amounts from your diet and you're eating things like these raspberries and pecans and pomegranate and a wide variety of fermented foods so you have the bacteria to produce the urolithin of adding more? Where's the benefit in supplementing with more? Have you guys kind of dug into the research behind that?

Anurag:  Yeah, we have. I do work for a company but before I'm trained as a medical doctor. And, I always say diet and exercise or the two pillars of your key health to longevity, right? So, yes, I think if you can know that your body is producing enough urolithin A, then you don't probably need to take a higher dose, you can probably just go on a maintenance dose and things like this because I assume not everybody is juicing four to eight pomegranates every day to drink a glass or two glasses of pomegranate every day.

Ben:  That sounds exhausting.

Anurag:  Yeah. And, you get the sugar exposure, a glass of juice is about 30 grams of sugar. So, yes, people should eat raspberries and pecans and walnuts and other good sources. And, if their body is producing urolithin A, then that's why we developed this test, they can actually develop a maintenance dose through dietary supplementation. Those who cannot, which is apparently a majority of us, then they need to rely on direct calibrated supplementation. Things like vitamin C, we all know orange juice is good for you, has a lot of vitamin C yet a lot of people take Vitamin C supplementation, right? And so, that's the way I look at it.

Ben:  Yeah, yeah, back to similar reasons you outline, maybe somebody is watching their calories and doesn't want to have as much of the pomegranate juice or fructose-containing foods, et cetera, which I know in the low-carb community is kind of a thing. But, kind of a nerdy question, I suppose, but let's say I worked a test, do you happen to know what reference range would be for adequate urolithin A levels that reflect some of the performance and recovery and mitochondrial benefits of something like elevated levels of urolithin A?

Anurag:  Yeah, so we've looked quite deeply both into the microbiome and exhaustively into the blood levels, both from, let's say, natural dietary exposure and with increasing doses of direct supplementation and we've published these in really top journals like Nature Metabolism. So, we start seeing really big effects in different human sort of trial randomized clinical trial settings at about 500 milligrams. So, this compound hits your mitochondria and kind of rewires them from being poor-looking mitochondria to healthy mitochondria. And, we can tell that difference in four weeks through blood biomarkers, et cetera. But, really the functional benefits you start seeing it about two months of supplementation.

We do see levels between, let's say, 10 to 100 nanograms per volume of, let's say, plasma that we can measure it would be the dietary exposure about 2 to 5%. People do have higher than that. With, let's say, direct supplementation, you can't consistently reach that. 100 would be, let's say, the lower limit and you'll always get an average about 300, 400, which there's a concept called a therapeutic range that we call in medicine. So, you always need to have enough exposure to the molecule and sufficient doses to sort of have the health output. And, that's what I believe you always need to maintain your blood levels at.

Ben:  Yeah, a lot of the research I was looking at leading up to this call digging in a little bit seemed to agree with what you just outlined in terms of around 500 milligrams of daily supplementation being something that elicited a lot of these performance and recovery enhancing effects. And, I even saw some particularly in the muscle endurance and performance realm albeit, I think it was with finger contractions and in human models, which might not translate directly to Iron Man Triathlon or something like that, but they were up around a thousand milligrams as far as the daily dosage goes.

And, I would love to get into some of the performance implications here in a little bit but just backpedaling, what exactly is urolithin A doing from an action mechanistic standpoint in the body?

Anurag:  Okay, great question. Yeah. So, you touched the bond and you talked about NAD, you talked about CoQ10, they are mitochondrial boosters out there. So, think about the life cycle of a mitochondria, we all are always ourselves typically highly energetic cells like your skeletal muscle, which is always moving, which is always climbing stairs, or a neuron cell which is always active. These are cell types that have thousands of mitochondria. So, they have a very high basically metabolic demand. And so, there's always a flux of healthy and poor healthy or bad functioning mitochondria. But, what happens is in the life cycle, healthy mitochondria accumulates what we call as oxidative stress, becomes damaged and then over time, it becomes really crummy.

Now, with things like aging or if you get injured and you're lying on a bed, you just shift the balance to more crummy-looking mitochondria in your cells and in your system. And, if you're not cleaning those faulty mitochondria, think of the trash bin in your house, if you're not cleaning your trash out regularly, your house is not going to smell right. And, that's exactly what happens in muscle cells and neuron cells and hard cells with aging or with obesity, for example, they just accumulate a lot of mitochondria. So, you could do NAD supplementation, which is targeting what we call mitochondrial biogenesis of trying to grow more healthy mitochondria or you could do things like CoQ10 or L-carnitine, which is just taking the pool of functioning mitochondria in trying to make them make more energy. But, unless you clear out the waste and there's space in your mitochondria, and this is a process we call mitophagy, which basically is autophagy of the mitochondria. So, a garbage disposal.

So, what urolithin A does is revs up mitophagy, cleans out the faulty mitochondria and now you have basically newer building blocks for near-healthy mitochondria.

Ben:  Okay, okay, got it. So, with this mitophagy then, arguably most of the effects we're seeing with urolithin A in terms of its impacts for recovery or longevity of performance are based on enhanced health of the mitochondria due to mitophagy. Okay. Does mitophagy result in greater amounts of mitochondrial density or number of mitochondria is impacting simply the quality of the already existing mitochondria? What exactly is going on there?

Anurag:  It's doing actually both. We do see higher mitochondrial abundance just because you're creating–as a result of mitophagy, you will clean the waste out and you will see things impacting mitochondria biogenesis so you will have more abundance of healthier mitochondria, but what you do see is mitochondrial quality go up big time. And, that just means that the cell is more energetic, your cellular health is more optimal and that has implications beyond just improving mitochondrial health into muscle performance and recovery as you said.

Ben:  Yeah, I'm curious what you guys have actually seen or what you've seen in terms of the implications for this as far as enhanced mitophagy from something like let's say that standard dosage of 500 milligrams or so of urolithin A consumption.

Anurag:  Yeah. So, we have run a number of randomized controlled trials, placebo-controlled trials. We've run it in older adults, about 65, 70-year-olds. We've compared those even doing regular exercise about those 70-year-olds who are doing 60 minutes of running every day to the frail sort of couch potato sedentary older adults and we've given those sedentary older adults about a 500 milligram or a gram of urolithin A. And, we've able to see basically a similar exercise mimetic-like impact on mitochondrial and cellular health. 

And then, we've gone into longer duration trials in, for example, 40, 50-year-olds and even older adults again and really seen, I think you mentioned some of the results on the sort of hand contraction. Believe it or not, one of the first muscles that declines with aging is this one. So, your grip strength basically is the first loss and that's why they say a handshake goes a long way to predicting your longevity. And, it's basically that.

So, we have seen not just hand grip strength improve but even leg endurance improve. And then, we have put people on our ergometer and seen that they basically have a resistance to fatigue, 20% more. They walk more in, let's say, if you do a standardized walking test and yeah, most importantly, you can measure a very simple test like PPO2, for example, goes up 10% in the non-trained population. So, these are some of the effects we have seen. In addition, we have seen also some of inflammation markers. So, as we all laid or if we are not eating well, our bodies get inflamed and things like C-reactive protein go up. Now, there's a big interaction between mitochondria and [00:24:37] _____. And so, what we see is actually down the road with longer a gram sort of supplementation given other benefits coming out.

Ben:  Interesting. So, up to a thousand milligrams or so, you can see even greater benefits from a performance standpoint, some of the research study I found?

Anurag:  Yeah, yeah, that's exactly what we're seeing now. 

Ben:  Any side effects? I mean, I'm curious if this is causing a shift in the gut bacteria in terms of their post-biotic production, I took some of the Timeline stuff, namely I like that little powdered packet because I could just dump it into my morning smoothie. I know you guys have a whey protein as well as a, I believe, soft gel that contains some of these urolithin A precursors. But, if you take it, do you ever notice anything like gut side effects or any other side effects from a higher amount of urolithin A consumption?

Anurag:  That's a great question. We have really characterized the safety aspect very well. Before we actually went into humans, we did a whole battery of safety tests that we wedded with even the FDA through a process called as GRAS, which stands for Generally Regard As Safe. And basically, in those experiments that we did early on, just even giving it like 5% [00:25:51] _____ and the diet didn't have any impact. And, in the humans, of course, we've done, gosh, about thousands of folks who have been in our randomized trials by now. And really, this is a natural molecule, so as we were discussing, about 30, 40% of us have been making it. A lot of us were probably in the evolutionary tree when we were eating fresh food and eating out sort of in the wild with berries and nuts. We were all probably exposed to it. So, it's a very safe molecule. We haven't really seen any product-related adverse effects. Now, certain people may have some allergenicity, for example. A lot of people when they take the rice-based or berry-based product may have some sensitivities to food ingredients. But, as a compound, as a pure natural compound, it's very safe.

Ben:  Now, based on the gut thing, I'm curious, there's some companies out there, I would imagine some are competitors to Timeline, that make probiotics that promise to shift the gut bacteria in such a way that you naturally increase your own urolithin A production. I think that, for example, the Seed Synbiotic is one that I think I've seen that type of claim on for the urolithin A production. What's the difference between your product and a product that would be more of a bacterial-based urolithin A support?

Anurag:  Yeah, I just think it's an indirect way. And, for example, I've been running clinical trials in the nutrition industry for 20 years. I started actually a lot of trials that you can probably pick up in probiotics are probably trials that I ran about a decade back. Problem with probiotics is if you're taking these billion CFUs hoping that a certain percentage of them will colonize your gut–and we've looked at the gut, I spent a good amount of five, six years trying to study what is that bacteria. The gut microbiome is so complex. It's never one bacterial strain or two bacterial strains  or 10. It's really the whole ecosystem needs to be there. So, I think it's, as I said, if you can induce urolithin A production through diet and probiotics or eating fermented foods by all means, do it. But, I just think for a majority of us, that indirect way of supplementing will be imprecise and that will lead to a lot of wearability in just human clinical trial settings but in real life. With direct calibrated supplementation of 500 milligram or a gram, we know what we are giving and what levels we expect. And, those are probably leading to more consistent clinical trials or real-life results.

Ben:  Yeah. I need to actually try this blood spot test that you mentioned because I take the Seed probiotic. I take three of those little capsules when I get up in the morning, but then I've been putting the powder of urolithin A into my smoothie, which I have five mornings a week. So, it'd be interesting to actually test my levels both with and without the Seed and then with and without the urolithin A just to see. Because I would imagine I don't know what you think about this, but it seems to me you could potentially do both, support the gut bacteria and also supplement in the same way that you could eat a wide variety of fermented foods and then also weave in things like the pomegranate and the raspberries and pecans, et cetera. Have you ever thought about that?

Anurag:  Yeah, I agree and that's why I said that I really see this as part of the three pillars of human health. One is you need to be exercising regularly. You need to have a good diet, rich in fiber, probiotics, vitamins and minerals. And then, at the base of this is the third pillar, which is really adding on sort of very advanced calibrated supplementation that is boosting your cellular health and will help, I don't know, better nutrient absorption, for example, or better cellular health that even you will have better additive effects. So, I do think this merit into doing complementary approach.

Ben:  Yeah, you say advanced supplementation, how is Timeline's product any different? I guess, I'm curious if you've somehow patented your process or if there's a special form of urolithin A that you use. Is there anything that particularly differentiates Timeline or is it just these variety of delivery mechanisms like the protein or the capsule or the packet?

Anurag:  Well, one thing we know the molecule in and out, as I mentioned, we've started for 15 years. We have probably a whole array of patents protecting health benefits but more importantly, it's how to deliver the molecule right. It absorbs well in lipid medium-chain triglyceride kind of matrices. So, we have put it in soft gels that are rich in these MCTs. And, that helps even enhance the bioavailability of this natural molecule. And, of course, we have proprietary ways to manufacture it from scratch. So, we know that the purity of this molecule is over 99% and we do it with really the top manufacturers that, of course, are GNP compliant and very high quality.

Ben:  Okay, that's interesting. So, arguably taking it with lipids would be better. If I were to take it with fish oil in the morning or if I were to have other fats like coconut milk or something like that in my morning smoothie, that's going to enhance the bioavailability?

Anurag:  Yeah. We've done even a head-to-head. It needs a sort of a food matrix protection. So, you've done a trial with mixing it with high protein Skyr-like yogurt, so Icelandic yogurt is very rich in whey protein and sort of branching amino acids. And, that gives it a sort of a better effect than sort of protecting and the digestion of it. And, that's one of the reasons why we blended it with the whey protein. If you mix it and blend it with the fiber, it also helps but all the trials actually have mostly been run with the MCT formulation and soft gel. So, I do think that gives it an edge in terms of a little enhanced absorption.

Ben:  Okay, got it.

Now, what about the transdermal part of things? I noticed that you guys have a skin product. You send me like a day lotion and a nighttime cream. Is that actual urolithin being applied to the skin?

Anurag:  Yeah, it is. It is. So, for long, when I would go to top conferences and presented top medical conferences, the first question everybody would ask me, “Well, what will I feel? How do I measure mitochondrial health?” I would say, well, you would measure kind of subjectively because you'll feel more energy, you'll feel less fatigue. If you really want to test it out, you'll measure your sort of VO2 max and by going on into a special lab that can put you on a treadmill and hook you up with all kind of measuring instrumentation. So, people say, “Well, what will my first thing, will I see it in the mirror that I'm aging less?” And, I said, well, this is not a youth in a fill or exercise in a fill, this is improving, hitting many of the pathways that are important for cellular health and recycling. 

And so, those questions also triggered, “Well, what will it do?” It's just not the muscle cells that are abundant in mitochondria are our skin cells have a lot of mitochondria, our immune cells have a lot of mitochondria. So, we started looking in these different verticals and really seeing if urolithin A, when we would sprinkle it on human skin cells, for example, from older donors, we started seeing the same effects as we were seeing in muscle cells. And, that led to formulations and in sort of day creams and night creams and now we've just run many randomized trials again that we are trying to publish in JAMA with the skin formulation.

And, what we see is basically improve cellular energy and less inflammation in the skin, which is practically what happens when we grow old is because of sun exposure, our skin gets inflamed and wrinkles start appearing. So, we thought skin aging goes in parallel with longevity. And so, now we have products that hit skin longevity.

Ben:  That's interesting. So, you'd see a difference between say oral consumption and the effect that would have on the skin versus direct transdermal application?

Anurag:  That direct comparison, we have not done yet. It's something in the works. Not compare direct but to even combine the oral supplementation with the direct topical administration. Now, the reason is that when you take something orally, about 80% gets absorbed in GI and then probably disseminates, but then the 20% that comes in, some of it goes to the muscles, some goes to the brain, some gets taken up in plasma, hits your immune cells. So, probably all of it is not going to the skin. And so, we thought, well, if we could do something synergistic and additive by applying a very calibrated so that we're giving like a 1% urolithin A or Mitopure in these topical products, and we know it penetrates well in the skin and it hits a lot of the skin cells similar to the muscle, so yeah.

Ben:  Yeah, that's super interesting. And, by the way, I'll link to this stuff if you go to BenGreenfieldLife.com/Timelinepodcast. Because like I mentioned, they had a stick pack and a gel cap and the protein powder, and then they also have these transdermal applications. So, a lot of different delivery mechanisms for this urolithin A. 

But, there's so many other things out there. I mean, Dr. Singh, in the introduction and then you alluded to it I mentioned NAD and C60 and fish oil and astaxanthin and all these other compounds, I recently interviewed Bryan Johnson, he say he takes 120 different supplements when he gets up in the morning. He runs that Blueprint age reversal website. So, I'm curious for you because it seems like you kind of have your ear to the ground for a lot of this stuff, are there other compounds that you think would kind of like appropriately fall into an age reversal supplementation strategy that might go above and beyond urolithin? And, if so, have you been particularly impressed with what you've seen on any of these?

Anurag:  Well, I think there's promise in the NAD field quite a bit, but I do think that there's sort of untapped synergy out there by combining. A lot of people just blending stuff. The problem with the nutrition field is, oh, let's blend X, Y, Z and hope miracle happens. I think there's a lot of interactions between molecules. And so, one needs to study that. Having said that, I think if people were to think, well, if you clean the waste away and then you apply something like an NAD booster on top, probably there's reason to believe that there will be synergy, so I do think there's merit in all these molecules, vitamin B3, nicotinamide, riboside or NMN kind of known to be biogenesis boosters.

I like CoQ10 even though the literature is mixed because it's a molecule that directly goes into mitochondria and is important in the whole sort of energy metabolism pathway and that improves efficiency of whatever, a healthy pool mitochondria you have. And then, I think just the two best drugs ever developed to improve autophagy, mitophagy or regular exercise and intermittent fasting. So, if people do want to boost autophagy and mitophagy, that's one additive way to do it right. And, that's what I do practice also intermittent fasting myself.

Ben:  Yeah, yeah. A few days ago on Twitter, I published an interesting study showing that low-dose aspirin, of course, not only has some of the heart health benefits, particularly if you're careful not to combine it with a lot of other blood thinning agents but it seems to induce cellular autophagy mechanisms in a similar way that fasting does. And, I kind of like some of these autophagy or mitophagy agents that particularly for lean active people, pre-menopausal females, et cetera, don't necessarily require hefty bouts of fasting, which I think can be overdone or particularly problematic for the endocrine system when combined with a lot of exercise or training for a triathlon or a marathon or CrossFit or something like that. And so, I think that some of these things that you can do to improve mitophagy or autophagy separately from fasting can be a pretty good idea. I'm curious for you. It sounds like you incorporate some of this stuff into your lifestyle, what a typical day would look like for you as far as some of the age reversal strategies or mitochondrial support strategies that you do in addition to using something like urolithin?

Anurag:  Well, I always say that probably the five best ways to improve mitochondrial function if I have to put a priority list, first would be regular physical activity. So, try to do your 10,000 steps a day. Number two, eat. You don't have to eat a lot but in short of intermittent fasting two meals a day with a very balanced nutrition profile probably does the trick. Stress. Big impact of stress on circadian rhythms and sort of how it impacts mitochondrial health. Sleep. Another big aspect that has a big impact on mitochondrial function at your cellular level. And then, the fifth is what I would say sort of advanced nutritional supplementation, things like urolithin A as we are chatting with or even hitting on some other well-known autophagy boosters that you mentioned spermidine as one. You mentioned other ways to boost autophagy. So, yeah, I think there's no one magic trick, it's really a concert with different tactics that you need to apply.

Ben:  Yeah, that's sound advice. I'd agree with all those principles. What do you do for sleep? How do you prioritize sleep or enhance your sleep? What's that look like?

Anurag:  I stopped looking at my phone screen as I leave work and I play with my kids and that relaxes me. And, I go to bed around 10:30-11:00. And, I mean, everybody's different when it comes to sleep. Honestly myself, I was trained as a medical guy, so I'm used to doing more with less sleep. So, I just need about six to seven hours of sleep, but I think exercise, whenever days when I do a 5 or 10K, I sleep the best. And, I do think that even with things like urolithin A and any of this supplementation, there is literature coming out that things have the potentials to sort of hit on some of the circadian rhythm through bioenergetic modulation and results in better sleep cycles. And, people have more wakefulness early on, so it needs to be studied further.

Ben:  Yeah, NAD beyond the shadow of a doubt, particularly for me from an anecdotal standpoint, significantly combats any effects of sleep deprivation. I'll even use a heftier NAD oral dosage or a transdermal patch of NAD. I get it from a company called IonLayer when I need more NAD or if I'm doing long-haul flight and want to combat some of the DNA damage.

Anurag:  Oh, sure.

Ben:  And then, creatine seems to act similarly just a slightly higher dose of creatine. And, we usually take 5 grams. If I'm sleep deprived, I'll bump that up to about 6 to 8 grams. What about urolithin A, have you noticed that that seems to have any type of effect either anecdotally or from a research base standpoint on the sleep deprivation?

Anurag:  Yeah, we haven't run any randomized trials, yet there are some in the works. But anecdotally, we've heard people making a fresh sort of they feel like they wake up early and they are much more fresher early in the morning. But again, this is anecdotal.

A lot of our studies are now kind of gearing up to we've done a lot of studies clinical trials in older adults and middle-aged adults. A lot of our new clinical researches is moving towards more healthy–there's a study, for example, we're just doing on elite athletes. Believe it or not, you would think that their mitochondrial health is optimal but the problem there is overtraining. Overtraining also induces mitochondrial dysfunction. And, we are even in the works discussing to do our trial with sort of the elite Army professionals or the Green Berets that have both sort of the cognitive decline with stress and hypoxia and the physical demand. So, we're doing a lot of work that probably you'll hear about in the next year or so, but I do think there's potential in those aspects.

Ben:  Yeah, yeah. For sleep deprivation, I've noted that acute dosing as soon as you get up in the morning, if we're looking at NAD and creatine seems to be best for timing. And, I would imagine urolithin A might be similar, maybe take a thousand milligrams or something on a sleep-deprived day and bump up your dosage when you first get up. And, I'm actually going to experiment with that now that I know and I'm aware of its effects on that. 

But, what about for something like a workout? I know a lot of these studies have looked into performance, but what's the dosing–well, we talk about the dosing, 500 up to a thousand milligrams, what about the timing? Is this something that chronically accumulates in the body like loading with creatine throughout the year or is it something that you can literally notice the acute effects of if you're let's say take 500 milligrams for you tell me how long before workout?

Anurag:  Yeah. So, the way the kinetics of absorption of this molecule works, the moment you take, it takes about a few hours for it to start absorbing. And, it really peaks in your blood about six to eight hours after you've taken it. So, most of our trials are done giving to individuals in the fasting state in the morning with or without breakfast. So, that would be about, let's say, 7, 8 o'clock in the morning and would start beating, let's say, midday, mid-afternoon sort of. That's where we see a lot of, let's say, the acute effects. But then, it has a kinetic where its half-life is really about a day. So, it kind of will peak at six to eight hours and then will start dipping down and go below what I call subtherapeutic or suboptimal levels of exposure to the molecule. So, you would need to then again take it the next day or bump it up even to a lot after.

So, a lot of the recovery work is with the gram. So, I was just telling you about the study in athletes that was only focused on recovery. So, a lot of these individuals before a big season of competition, they go into training camps and they're all eating the same food, they're running downhill, they're kind of training in extreme conditions. Well, we are sort of seeing in some of this early data that is coming out is profound effects on recovery and muscle damage. So, I do think that even in in sort of these settings, recovery will be boosted in this sort of populations with this molecule in a cute way. So, during training or post-workout would probably make more sense to take it.

Ben:  Okay, got it. When you look at creatine post-workout, co-administering with caffeine seems to increase absorption a little bit. We talked about with urolithin A how co-administration with either lipids or perhaps even some type of a ferment or probiotic might enhance the effects. But, are there any other things, a lot of my listeners like to stack stuff or know what combines best with what, have you looked at any research or even just anecdotally yourself looked into stacks, things that would go well when paired with urolithin A to either enhance bioavailability or enhance the mitophagy effect or anything else as far as kind of upgrading the urolithin A that you actually take?

Anurag:  Yeah. I know that there's sort of this bioptimization with stacks and taking a few things and then building on top in the protocol that people follow. Yeah, I'm a try list and then evidence-based person, so we have studied is things, as you mentioned, the lipid matrix like MCTs probably. That's probably going to.  So, if you're taking a sort of a keto diet perhaps probably that would result in improved absorption. A lot of folks are taking high protein. High protein does seem to have a very sort of, not in terms of enhancing but a protective effect around the molecule. So, when we give it with high protein shakes or things like high protein yogurts, we do see a slightly better sort of absorption of the molecule. And, that could mean that it blends well with things like branch and amino acids like leucine isoleucine. So, those would be my top two things to stack with. And, as we mentioned, other mitochondrial optimizers probably are additive as well things like CoQ10.

Ben:  Yeah. I'm personally a bigger fan of essential amino acids than branch-chain amino acids, which I think are kind of like overpriced flavored water because you just have the isoleucine, the leucine and the valine. I like the essentials because you get all nine of the amino acids.

Anurag:  Yup.

Ben:  And, I haven't done much experimentation. I've tried putting it in whey protein. You know what's funny is I haven't actually used your guys' whey protein but I've used the Kion protein before and combine that with the urolithin A based on some of what you were explaining about. It seeming to perform pretty well when combined with protein. But, your guys' whey protein, is that something that you're just adding to urolithin to and it's just pure whey protein with urolithin?

Anurag:  Yeah, that's the blend with the whey protein and we're developing alternative protein shakes as well as we speak. We're even running a head-to-head trial in sort of individuals who are immobilized. So, think of an athlete who got injured and we're giving them 20 grams of high protein supplementation seeing the effect it has in muscle and comparing them to how it will be in that particular population if you were to supplement with high protein and the bioenergetic aspect with urolithin A. So, we do think there's synergy in the two ideas to boost muscle mass and muscle quality and energetics.

Ben:  Interesting. What else are you guys studying up right now at Timeline? Because you have the transdermal products, the protein, the soft gel, the stick packets. What else are you looking at right now if anything?

Anurag:  So, I'm a trained immunologist and I do believe there's big impacts of the molecule and the immune system. And so, we have pretty good evidence already but, of course, since the big discovery of the molecule about a decade back when we made and published our first papers, a lot of other top labs around the world have got interested into studying its effects and cognitive health. So, I would put probably these two are the most at the top and gut health because so much of it is getting absorbed in the gut. And, there are some top obligations. But, for the time being, the trials we are running, one is in post-cancer patients. So, typically though let's say cancer patients have kind of cured themselves of cancer after chemo and radiotherapy, they basically end up with also no immune system because the chemo and radio is hitting their functional healthy cells too.

And so, we're trying to see if we can rev up mitophagy in sort of the stem cells that seed the immune system, and that will lead to a better seeding of the immune system because stem cells get exhausted in this kind of both aging and post-cancer. So, that's one of the areas we're working. And then, we're working with National Institute of Aging on really looking at the impacts on cognitive health and how we can boost brain energetics with the molecule.

Ben:  Do you think it would have any type of protective effect on stem cells? I just ask because a lot of my listeners, they'll go out and do stem cell injections and I always advise against flying on an airplane for a couple of days after and engaging in some strategies to enhance stem cells health like PEMF and antioxidant-rich diet, avoidance of vegetable oils, alcohols, all the things you do if you have little tiny fragile baby newborn cells floating around in your body. As far as urolithin A goes, do you think it would support or protect stem health cells somehow in that type of context?

Anurag:  Yeah, I do believe, absolutely. So, there's a great paper we put out end of last year in probably the top immunology journal called Immunity. And, the data is pretty remarkable that it targets this sort of pool of stem cells that is always in our bone marrows, in all the organs where the immune cells and the stem cells are sort of hanging out and they're activating mitophagy in these pool of stem cells really resulted in better sort of receding of the immune system, kind of even better muscle stem cells. So, we do things, so we are studying, we have a lot of trials, actually studying what you were just mentioning the impact on stem cells.

Ben:  Yeah, that's interesting. It's good to know. Maybe I'll throw up my bag for my next stem cell protocol and load up with it. 

Related to this concept of mitophagy, Dr. Singh, there's a lot of people developing senolytics to prevent the accumulation of these so-called zombie or senescent cells, but the idea is that quieting those senescent cells particularly early in age when someone is going through growth phases, production of growth hormone, higher amounts of anabolic type of activity that could be hampered by quieting cellular senescence too much dictates that you wouldn't want to overdo a senolytic compound and possibly even not do a lot of senolytics early on in life. When it comes to mitophagy, is it also like that? Is there a law of diminishing returns and in excessively turning over mitochondria and related to that, an age at which that type of approach might not be advisable? 

Anurag:  I don't think so. So, basically the process of mitophagy is when mitochondria gets stressed and really damaged, they put out an “eat me” signal. So, if this is the mitochondria, it puts out an eat me signal on the top of its surface. And, that's what basically when people are activating mitophagy through either urolithin A or exercise or other things, those tagged mitochondria put in the sort of garbage disposal machinery, and then these become the building blocks of held in your mitochondria. And, that's a fundamental important thing to know is that you can overdo mitophagy. Our cells are always in what I call mitohormesis. So, there's always a balance between good and sort of the yin and yang. So, you will always just take this faulty tag mitochondria and then put them into more healthy mitochondria. Mitophagy is always happening, it just slows down with aging, it slows down with a lot of other things like prolonged immobilization. But, we haven't really talked that overstimulating my autophagy will be–we haven't really seen it. I think it's more as what I call a modulator of mitochondria than approached and sort of overstimulating mitochondria.

Ben:  Yeah, I've always wondered if the body will have a natural modulation mechanism to where mitophagy-supporting compounds present would not result in, let's say, excess mitochondrial turnover just based on natural modulation although I don't know what the mechanism of the action for that would be. The idea, it seems reasonable at least.

I'm curious based on that and kind of back to your blood levels of urolithin A and this blood–by the way, where do you get that blood spot test kit? Do you guys mail it out from Timeline?

Anurag:  So, we're still prototyping it and there's a clinical study that I'm running with hundreds of folks just to make sure that we have the sort of the right test before we launch it. But, happy if we want to participate, we can send you a kit and to your some of your listeners if they are intrigued as well. We can offer that as well.

Ben:  Yeah, that'd be interesting to test. I'd love to test based on what I was saying earlier. So yeah, I'll hunt that down and link in the shownotes if you send me over more information on it.

Anurag:  Yeah, sure.

Ben:  And again, the shownotes are at BenGreefieldLife.com/Timelinepodcast. But, the reason I ask is, have you compared what gets your urolithin A levels highest, the little soft gel that you guys make, the stick packet or the whey protein? Have you broken that out at all?

Anurag:  So, we have put them in those different matrices because we think all those different matrix help in the absorption. So, we have studied for example independently the soft gels in a lot of trials and also study the berry powder or now we're studying the protein shake. And, I would say within a 10-percentile difference, they all in the similar levels of boosting as I'm mentioning to the therapeutic range of 300, 500, and some people even more depending on the dosing they're taking. So, I think they're fairly equivalent I would say.

Ben:  Okay. Have we not touched on any benefits or research that you're aware of about urolithin A that you think that would be important for people to know?

Anurag:  There's a lot of excitement as you mentioned. We, of course, started doing the research 15 years back but now, I was approached by the National Institute of Aging that said, “Hey, we ran a library of thousands of national compounds and repurposed drugs trying to study the best effects on neuron cells where typically in things like Alzheimer's disease, mitophagy declines, it's well-known in neuron cells and we think your compound is really one of the top inducers and really is neuroprotective.” And so, I think a lot of excitement now will come from these top professors, and Harvard has the same sort of research stream that I was told about. So, I think that is the next big frontier, what are the levels that we can see in the brain getting into this molecule if we can image sort of the ATP levels within six hours of peaking and look at brain energetic capacity. This is where, I think a lot of research is headed now.

Ben:  Okay, interesting. Related to the brain, a lot of people take nootropics, they take smart drugs, they'll pop methylene blue, do red light therapy, do a lot of things that apparently increase activity of some of those cytochrome C oxidase pathways in mitochondria resulting in enhanced production of ATP, mitochondrial biogenesis, et cetera. I'm curious if you've ever thought about or if you know anything about the idea of, well, if I'm making my mitochondria work harder, produce more energy, make more of them, if combining urolithin A with things like smart drugs, nootropics, some of these mitochondrial enhancing agents in terms of things that kind of push the gas pedal harder would be a good idea. Have you ever looked at that?

Anurag:  We haven't but I do think it's a good idea and something we are exploring in the background. I do think there is potential in that to even combine it with a certain amount of, for example, even ketone bodies or ketone esters just to induce sort of better cognitive effects together where you can recycle the poor mitochondria neurons and then give them alternative fuel supply to rewire them. So, we are looking into that.

Ben:  Yeah, I've kind of discovered the same thing. If I take DHA and choline to replenish a lot of nutrients that I'm burning through more quickly than ketone esters and NAD on any cognitively demanding day on which I might also be using let's say methylene blue or psilocybin micro-dosing or some type of nootropic agent like Qualia Mind or some of these Nootopia products or something like that. I find that stacking choline, DHEA, NAD and ketone esters to just blast through, let's say, a 16-hour creativity/focus work day with some of these nutrients on board seems to help. But, I haven't really brought in something like a mitophagy-enhancing agent into that equation. It'd be interesting to experiment with.

Anurag:  Sure, yeah. I think future research is headed that way.

Ben:  Yeah. Well, this is fascinating, man. I really appreciate the research that you've done on urolithin A and with Timeline. I know we have discounts and codes and things like that for timeline. I'll hunt them down and put them in the shownotes at BenGreenfieldLife.com/Timelinepodcast. That's BenGreenfieldLife.com/Timelinepodcast. And, over there, if you'd like, you can also leave follow-up questions, comments, feedback, et cetera, for Dr. Singh or myself and we'd be happy to jump in and help reply and point you in the right direction.

But, in the meantime, Dr. Singh, I really appreciate you filling me in on all my silly questions about urolithin A because I've been fascinated by this for a while and kind of looking forward to getting you on the show and asking all these questions.

Anurag:  They're all great questions, so love chatting with you, Ben.

Ben:  Awesome, awesome. Well, I'm excited to put this out. And folks, again, the shownotes are at BenGreenfieldLife.com/Timelinepodcast and until next time. I'm Ben Greenfield along with Dr. Anurag Singh signing out from BenGreenfieldLife.com. Have an amazing week.

More than ever these days, people like you and me need a fresh entertaining, well-informed, and often outside-the-box approach to discovering the health, and happiness, and hope that we all crave. So, I hope I've been able to do that for you on this episode today. And, if you liked it or if you love what I'm up to, then please leave me a review on your preferred podcast listening channel wherever that might be, and just find the Ben Greenfield Life episode. Say something nice. Thanks so much. It means a lot.

In compliance with the FTC guidelines, please assume the following about links and posts on this site. Most of the links going to products are often affiliate links of which I receive a small commission from sales of certain items, but the price is the same for you and sometimes I even get to share a unique and somewhat significant discount with you.

In some cases, I might also be an investor in a company I mentioned. I'm the founder, for example, of Kion LLC, the makers of Kion-branded supplements and products which I talk about quite a bit. Regardless of that relationship, if I post or talk about an affiliate link to a product, it is indeed something I personally use, support, and with full authenticity and transparency recommend in good conscience. I personally vet each and every product that I talk about.

My first priority is providing valuable information and resources to you that help you positively optimize your mind, body, and spirit. And, I'll only ever link to products or resources, affiliate or otherwise that fit within this purpose. So, there's your fancy legal disclaimer.



You've probably heard me talk about “Urolithin A” before. Naturally found in pomegranate fruits, walnuts and raspberries, Urolithin A seems to be gradually becoming – like NAD, C60, Astaxanthin, Spermidine, Fish Oil , peptides, stem cells, etc. – one of the “darlings” of the age reversal and healthy aging community.

But I've never really unpacked in detail on a podcast exactly what it is or how it works. Turns out that there are some subtle nuances in terms of Urolithin A sources, bioavailability and dosing. Since it's such a popular supplement that appears to have many benefits I figured I should probably interview someone who knows about all things Urolithin A.
Dr. Anurag Singh, my guest on this podcast, is  Chief Medical Officer at Timeline, a company that develops 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  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.
Dr. Singh's work with Timeline includes advising on what Timeline claims is the “first and only purified Urolithin A supplement backed by 15 years for clinical research with human trials and thousands of consumers taking the product every day”.  If you want to try the products we talk about on the show, you can click here and use code BEN to save 10% off your purchase.

During our discussion, you'll discover:

-Dr. Anurag Singh…05:28

  • Urolithin A (use code BEN to save 10%)
    • Popular age reversal supplement
  • Dr. Anurag Singh
    • MD in internal medicine
    • PhD in immunology
    • Worked with different food companies, including Nestle
    • Worked with different startups, including Timeline
  • Worked on research and development of Urolithin A

-How did Dr. Singh got interested in Urolithin A?…07:41

  • Worked as internal medicine doctor
  • Realized that for a lot of chronic conditions, it was too late to intervene
  • Started researching natural compounds
  • Was looking at bringing the biotech approach to nutrition
  • Stumbled at Urolithin A

-What is Urolithin A?…08:25

  • A metabolite found in food like pomegranate, walnuts, pecans, raspberries
    • Foods are full of antioxidants – polyphenols
  • When digested, the gut microbiome releases this food metabolite called Urolithin A
    • It is a postbiotic compared to a pro or prebiotic
  • Does the efficiency of Urolithin A depend on our own unique biome?
  • Viome
  • Genova Diagnostics
  • Done a number of clinical trials all around the world
  • The best producers are the French
    • Eating closer to the Mediterranean diet
    • Fruits, berries, nuts, cheese, wine, fermented foods
  • 30-40% of people have a healthy gut microbiome
    • American population – only 10-12%
  • Timeline has a blood test; finger prick blood swabbing 
    • Shows if your body is naturally producing Urolithin A
    • Looking at the presence of urolithin A in the blood
  • Some people naturally produce Urolithin A, while there are those who don't produce it, like Dr. Singh
  • Is it genetics or diet?

-The benefits of supplementing Urolithin A?…14:54

  • If your own body produces it, you don’t need to be supplementing
  • People should eat good sources of Urolithin A
  • Those that cannot produce it need to take supplements
  • It’s like vitamin C
    • We all know it is in orange juice, but still take the supplement
  • Ranges of adequate Urolitihin A levels for mitochondrial benefits
  • Dr. Singh has looked deeply into the microbiome and blood levels
  • Published the results in Nature Metabolism Journal
  • Starts seeing really big effects at 500mg
    • The compound rewires the mitochondria from poor looking to healthy 
  • Functional benefits after 2 months of supplementation
    • Dietary exposure – from 10 to 100 nanograms per volume
    • Direct supplementation – average of 300-400 nanograms

-What is Urolithin A doing in the body?…19:27

  • Highly energetic cells, like skeletal muscle or neuron cells, are very active
    • Very high metabolic demand
  • Healthy mitochondria accumulate oxidative stress and become damaged
    • You need to clean those faulty mitochondria
  • NAD supplementation is targeting mitochondrial biogenesis, trying to grow healthier mitochondria
  • Also CoQ10 or L-Carnitine or Fish Oil or C60 or Astaxanthin
  • Need to clear out the waste in a process of mitophagy – autophagy of the mitochondria
  • Urolithin A revs up mitophagy and cleans out the faulty mitochondria
  • Mitophagy leads to higher abundance of healthy mitochondria
    • It also improves the quality of mitochondria – cells are more energetic
  • A number of control trials showing
    • Strength and endurance improved
    • 20% resistance to fatigue
  • Up to 1000 milligrams have even greater benefits from a performance standpoint

-Side effects from a higher amount of Urolithin A…24:57

  • Conducted a lot of safety tests
    • Thousands of people in randomized trials
  • It's a very safe molecule, no product related adverse effects
  • As a pure natural compound, it's very safe
  • Certain people may have some allergies to some components
  • GRAS – Generally Recognized As Safe

-Timeline’s Urolithin A vs. Similar products…26:42

  • Some companies claim their probiotics can naturally increase the production of Urolithin A
  • Seed Synbiotic
  • Dr. Singh ran clinical trials in the nutrition industry for 20 years
  • The gut microbiome is very complex
  • Direct calibrated supplementation leads to better and consistent real life results
  • Three pillars of human health
    • Regular exercise
    • A good diet rich in fiber, probiotics, vitamins and minerals
    • Advanced calibrated supplementation to boost cellular health
  • Is there anything that particularly differentiates Timeline’s Urolithin A? (use code BEN to save 10%)
  • A whole array of patents protecting health benefits
  • The way they deliver the molecule
    • Coated in soft gels that are rich in MCT's to enhance absorption

-Urolithin A in skin products…32:05

  • Very common question is how to measure mitochondrial health?
    • More energy, less fatigue
  • It’s not a youth pill
    • It’s hitting the pathways that are important for cellular health and recycling
  • Skin cells have a lot of mitochondria
    • Started looking into its effects on skin
    • Saw the same effects as in muscle cells
  • Formulated day and night creams
  • The result is improved cellular energy and less inflammation in the skin
  • Oral consumption vs. direct transdermal application
    • Making sure skin mitochondria gets Urolithin A (use code BEN to save 10%)
  • Podcast with Bryan Johnson
  • Bryan Johnson's Blueprint

Other compounds for age reversal…25:57

  • Biogenesis booster molecules NR, NMN
  • Dr. Singh also likes CoQ10
  • The literature about it is mixed
  • A molecule that directly goes into mitochondria
  • It’s important in the whole sort of energy metabolism pathways
  • The best things for autophagy and mitophagy are:
    • Regular exercise
    • Intermittent fasting
  • A study about low doses of aspirin
    • Induces cellular autophagy mechanisms in a similar way that fasting does

-Dr. Singh’s typical day in terms of age reversal strategies…38:30

  • Dr. Singh's priority list to improve mitochondrial function
    1. Regular physical activity
      • 10,000 steps a day
    2. Two healthy meals a day with intermittent fasting
    3. Avoiding stress
    4. Sleep has a big impact on mitochondrial function at the cellular level
    5. Advanced nutritional supplementation
  • How Dr. Singh prioritizes sleep?
    • Stops looking at his phone screen after work
    • Plays with his kids
    • Goes to bed around 10:30
  • Ion Layer transdermal NAD
  • Creatine
  • No trials for Urolithin A for sleep deprivation
    • Anecdotally, people say they wake up earlier and feeling fresh

-The use of Urolithin A for workout…43:10

  • It takes about a few hours for it to start absorbing
  • Peaks in the blood about six to eight hours after taking it
  • 1g for recovery
  • The study on athletes that was only focused on recovery
    • Showed profound effects on recovery and muscle damage
  • Best to take during training or post workout

-What combines best with Urolithin A?…45:14

  • Evidence based:
    • MCT
    • High protein
  • CoQ10
  • Aminos
  • Kion Protein
  • The blend of Urolithin A and whey protein by Timeline (use code BEN to save 10%)
  • Developing protein shakes
  • Running trials with injured athletes
  • Boosts muscle mass and muscle quality and energetics

-Current Timeline Urolithin A studies…48:21

  • Dr. Singh, as an immunologist
    • Believes there's a big impact on the immune system
    • Also, a big impact on gut health
  • A paper put out last year in the journal Immunity
    • The data is pretty remarkable
    • Use in post cancer patients
    • Impact on cognitive health
    • The protection of stem cells
  • Other studies

-Is there an excessively turning over mitochondria?…51:20

  • You can’t overdo mitophagy
    • Take faulty mitochondria and put them into healthier mitochondria
  • It’s a modulator of mitochondria
  • Blood test by Timeline 
  • Mitopure is the highly pure form of Urolithin A (use code BEN to save 10%)

-Benefits of Urolithin A on brain…55:32

  • Timeline has been approached by the National Institute of Aging
    • They study the best effects of natural compounds on neuron cells
    • Mitophagy decline in neuron cells in diseases like Alzheimer's and Urolithin A is one of the top inducers and really is neuroprotective
  • Combining with  
  • Combining with ketone esters
  • Qualia Mind
  • Nootopia (use code BEN10 to save 10%)
  • Future research – how to stack Urolithin A with smart drugs and nootropics

Upcoming Events:

  • Disrupt Healthcare: September 29 – October 1, 2023

Join me for the Disrupt 2023 Event in Atlanta, Georgia between September 29th – October 1st. This highly practical and immersive workshop will feature live Q&As, my top secrets for career success, and much more! Head to bengreenfieldlife.com/disrupt2023 to claim your spot today.

  • Couples Collective: October 25 – 29, 2023

Join Jessa and me for an exclusive and immersive way to explore health, wellness, and mindset with your significant other in Napa, California October 25th – 29th. Head over to ownitcoaching.com/couples-collective to apply.

Resources from this episode:

– Dr. Anurag Singh:

– Podcasts:

– Other Resources:

Episode Sponsors:

LMNT: When summer brings the heat, LMNT brings the Grapefruit Salt — to help you enjoy that balance all summer long. Consider Grapefruit your ultimate summer salt companion. Receive a free LMNT Sample Pack with any order when you order through drinklmnt.com/BenGreenfield.

Lucy Gum: If you are looking for a cleaner and tastier alternative to other nicotine products, Lucy is for you. To save 20% on any order, head over to lucy.co use discount code BEN20.

BiOptimizers Magnesium Breakthrough: The 7 essential forms of magnesium included in this full spectrum serving help you relax, unwind, and turn off your active brain after a long and stressful day so you can rest peacefully and wake up feeling refreshed, vibrant, and alert. On top of the promo code ben10 for 10% discount, you can unlock a special gift with purchase – for a limited time only. Go to magbreakthrough.com/ben now and get your gift.

BioStack Labs: BioStack Labs have formulated their NAD Regen to increase your energy, enhance your cognitive function, and slow the aging process. When you buy a 3 month supply, they'll send you a 4th bottle 100% FREE. Simply go to biostacklabs.com/ben to get this awesome deal!

Kion Aminos: Aminos are building blocks for muscle recovery, reduced cravings, better cognition, immunity, and more. Go to getkion.com/ben to receive 20% off on monthly deliveries and 10% on one-time purchases.

Fart of War: The Fart of War is a hilarious, slightly odorous card game designed by my sons and me as part of our first-ever father-son gaming company, Fried Pickles Games. Head to fartofwar.com to learn more about this unique game and to grab your own. Your family will never sit around the table for game night the same way again. 

Do you have questions, thoughts or feedback for Anurag Singh or me? Leave your comments below and one of us will reply!

Ask Ben a Podcast Question

Leave a Reply

Your email address will not be published. Required fields are marked *