Urolithin A: The Miracle Compound - Dr. Dominic Denk : 1119

You're listening to the Human Upgrade with Dave Asprey. Formerly Bulletproof Radio. You're listening to the Human Upgrade with Dave Asprey. Today's episode is going to go really deep on mitochondria. We're going to talk about how to have more energy production in your cells and the relationship between energy production and even things like cancer. And this is working with a compound called urolithin A. With someone you haven't heard. Heard me talk with before. That was a really weird sentence. Someone you haven't heard from before. And his name is Dr. Dominic Denk. He's done some of the original research on what Mitopure, which is the brand name of Urolithin A, does at all sorts of different cellular levels. So this is talking with a researcher on a new compound in the world of biohacking and one that's in my permanent stack. And for reference, I, I have an entire cabinet full of crap that people send me. And some of it's actually good crap. I don't want to be, like, rude about it, but sometimes it's just poorly formulated supplements or whatever. And this entire cabinet is. People say, hey, Dave, can you try this? Like you. Either I try it, it doesn't do anything, or there isn't really good research, or it's not well formulated. So I end up sort of sharing those with friends in Austin, saying, hey, I have a bunch of extra supplements. One of the supplements that's never been in that cabinet is timeline, which is the, the mito pure that we're going to talk about today. When I saw the 10 years of research that went into it before it came out. And as a radical longevity life extension guy who's written a major book on the subject and another separate book on mitochondrial function, this stuff definitely meets the cut for me, which is why it's in my, my permanent stack. It's called Mitopure. If you're looking at Googling that now, Dr. Denk, you're in Germany, right?

That's correct. Frankfurt, Germany.

Now, I have a little story about Germany. When I was young, my grandparents, both my grandfather and grandmother were very senior PhD level researchers in the nuclear power industry. And they worked at Los Alamos National Labs for their entire careers. But they went to Germany specifically, what back then was called East Germany before the wall fell, to do a scientific exchange for a year. And my grandfather came back, who's really funny, and he said, dave, there's only one line of German you really need to know. I learned it for you. And I said, what is it? And he said, dubistein azel. So if you're listening, you don't speak German, which I don't. That means you are an ass, as in you are a donkey. So in seventh grade, feeling all full of myself, my teacher said she spoke German. So I said, teacher, teacher, what does dubistein azel mean? And she said, it means you are a donkey. And I was so offended because until that point, I thought it was the other kind of ass, which was why I asked her in the first place, just to put her on the spot. So that is the extent of my experience speaking German. But I love visiting. What part of Germany are you in?

I'm in Frankfurt, Germany, so it's pretty much the middle of the country.

Okay. Frankfurt is wonderful. Been there lots of times. All right, let's get into eurolithin A, number one. What got you into researching this?

It's actually quite the long shot. So I'm not an anti aging guy, I'm not a muscle function guy. But what we do in the lab that I work in is we work on cancer and immune function of cancer. So how does the immune system recognize cancer and fight the tumor? And one of our previous projects actually worked on the cancer cell itself. And we looked at mitophagy and we found that induction of mitophagy actually leads to detection of the cancer by the immune cells by mechanisms inside the cancer cell itself. So knowing this, we did this back then with a genetic model, we modified mice. We wanted to find something that induces mitophagy so we can kind of abuse this in a clinically relevant manner, and we can then maybe use it as a therapy for anti cancer purposes. And looking in the literature, as you always do, you start off googling, actually just google around, look at mitophagy inducers, something like this. We actually found this paper on ulithin a, which I guess your listeners have heard about this postbiotic that does just that. It induces mitophagy in all sorts of cells and it's only available and it's safe to consume. So we figured, well, let's start looking into this. And we fed mice ulithin A and we tried to see an anti cancer effect. And what we saw back in the day was, yes, there was, was an effect against cancer, but it wasn't an effect on the cancer cell itself. What you usually see when you study something in the lab. Right. But it was more of a remodeling of the immune system, and that led to tumors being smaller and being rejected, much better. And this is why I'm now very much into the immune system and seeing how mitochondrial function in immune cells actually regulates immune function.

That's amazing. And you are correct, some of our listeners, if they're new to the show and there's a lot more, more people listening to the show now, they may not know what it is. So can you explain what urolithin A is?

Yeah, sure. So EU is a postbiotic, which means in very broad terms what you take in is not what you get. So eulofin A is a compound that's made by the body, by the bacteria within the body, and it's derived from all sorts of fruits like pomegranates, berries, but also nuts. Some people, if, if they're fortunate enough and they have the right gut microbiome, they produce urine if they take in very high amounts of these nuts and, and fruits. But it has been shown that most people don't have the right gut microbiome, they don't have the right bacteria to produce eu. And as you get older, that adequate gut microbiome declines. So that's actually the big issue. Since cancer rises in old people, most people don't have the right gut micro to produce ufa. So most people don't actually have these benefits. And this is why the idea is to not supplement people directly with fruits and nuts, although it's also very good for multiple health benefits, but to give euphrate directly because then you bypass this whole need of the gut microbiome.

What are the nuts?

Walnuts in particular? I think pecans also, but I think it's mostly walnuts and for berries it's mostly pomegranates and high amounts and raspberries.

So, so this is a, a really interesting conundrum in the world of longevity. If you were to eat enough walnuts, and there are studies that show walnuts are actually good for you. And this may be why. Actually because of, of the longevity effects of walnuts. But they also introduce a large amount of omega 6 fats which are bad for you. So if you're going to get the benefits of urolithin A, you would be consuming so much linoleic acid from walnuts that it would probably undo the effects. And then you could say, well, I'll eat raspberries. And then you could be like the hundreds of thousands of well meaning people, especially like I used to be like a vegan where you eat a lot of raspberries, you get a ton of oxalic acid and then you have to pee all the time. Or you get interstitial cystitis because it's causing problems because of this plant defense compound. And pomegranate has some, but not as much. But if you were to eat about 10 pomegranates, which is what it would take to make the same dose that you get in mitopure, you realize it is not feasible to use foods to get this effect on mitophagy. And for listeners who are newer to this or just are learning, Mitophagy is the idea of replacing the mitochondria with that are. That are dim, they can't run at full power, they're the weak ones. So we got to get rid of them so that we can grow new, healthy, young, strong ones. And this is like at the very core of. I would say three quarters of the biohacks involve mitophagy or autophagy, which is doing that for whole cells versus just getting rid of weak mitochondria. And turns out cancer and mitochondria, they have something to do with each other. Talk to me about genetic cancer versus mitochondrial cancer.

The whole notion of. Of mitochondrial cancer is actually not so deeply explored. And it's rather new actually. Cause we are now just starting to recognize what cancer is and how not every cancer is the same cancer. So generally we always perceived cancer as a genetic disease as a result of mutations in the cell. So our DNA undergoes changes as we age. And the older we get, the more changes the cell accumulates. And the body just gets overburdened those changes. And this is how then cancer rises in the elderly. And that's the genetic cancer, apart from some specific syndromes. And younger people that get cancer much earlier because some defense mechanisms against these alterations are not there. That's the one side of cancer, but the other side of cancer, and I think that's very interesting, is the mitochondrial part of cancer. And most importantly for the immune cells. So it has been shown that in particular inside tumors, immune cells are repressed in the mitochondrial function. And this is most importantly mitophagy that you mentioned. So immune cells inside the tumors, they don't have the adequate mitophagy programs. They cannot exchange their mitochondria, and they cannot create new healthy mitochondria. And that leads then to immune exhaustion. The immune system function as well. And this is one of the many pathways how cancer can then evade the immune system and keep growing and growing. And many other diseases also use this kind of pathway or are characterized by mitochondrial dysfunction, Most importantly, in your cells.

Okay, That I totally resonate with, with that I've been teaching for, since the start of, of biohacking, even before that in the longevity field. That way more than half the cancer, and at this point, I would say it's 75% of cancer appears to be more dysfunctional mitochondria than genetic. Like maybe 3 to 5% is genetic. And I've even had a couple experts on who said that you probably aren't aligned with that, but you may be getting there. If you had to just, you're not going to know. More research is needed, your grants aren't at risk. But if you had to throw a dart and guess with everything, you know, as an expert in the field, how much cancer is mitochondrial versus genetic?

Actually, you cannot separate these two that much because one leads to the other, right? So these genetic reprogramming inside the cancers, it activates aberrant signaling pathways. And then that might lead to this addiction to dysfunctional mitochondria inside the cells. That cancer cells use different nutrients, they function worse. With that being said, I think the mitochondrial component to cancers, you'll see many of those, more than a quarter, maybe half to those that have some sort of change in pathways regulating mitochondria regulating mitochondrial function. So you cannot separate these two. Although cancer is very diverse, in the end it often converges on very similar pathways, just by different means of getting there.

I, I see that. I've. I've read various books and papers about it. And what, what I learned was that there isn't a common cancer genetic marker. You look at two tumors, like the genetics are very, very different. It could be that this strange combination of genetics leads to mitochondrial dysfunction, or it could be that the mitochondrial dysfunction led to not repairing of DNA and that led to all the weird genetics. I don't know that anyone knows the answer to that yet, do we?

No, we don't. That makes it so. As brutal as this disease is, it's fascinating because not every cancer is the same. You can have two people with what you think the same cancer, for example, lung cancer. But they're largely different in their mutations, how they behave and what makes it so hard for us in the clinic, how they respond to therapy. So we don't just understand every single cancer. And I think that's the challenge of the next decades to, for every single patient, ideally, individually deconstruct their cancer, their tumor microenvironment, not just the cancer cell, but which cells are inside the cancer and support the formation of the tumor, and then find for that particular patient, the right therapy, the right targeted therapy to then tackle that, that just goes from this one tumor entity. Then just knowing that we have different organs that develop different cancers, even with the same genetic background, that makes it very, very complicated and shows that cancer is just not one disease. And there's much more research to do.

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But didn't you find that even if you didn't do any of that work, that if you gave larger doses of urolithin A to cancer patients, it magically turned on mitochondria and cancer got better?

So we did not see that in cancer patients yet actually. So, okay, the study we performed was on mouse models of cancer. So we took ufna, this mitochondrial compound, we gave it to mice, we saw the reduced tumor growth in a dose dependent fashion for sure.

Oh, so hold on a second. In Germany, mice are not considered to be human.

Mice are not considered to be human.

They are in the US we have a radical group of like animal rights terrorists who've made the argument that mice are the same as humans. And I soundly reject that. So maybe I'm more German than I thought. So thank you for being sane.

It's a very similar discussion around here, but in terms of immune function they are very similar. That's true. But we do know for what I'm going to be describing later for the immune function. We have done the work on immune cells and we have seen that if you take immune cells from people in the lab, treat them with Eulerin A, you see the same benefits in the lab. Of course now we're going one step further and actually testing these UL A compounds in healthy adults to see the same changes we've seen in the mice, then one go one step further in cancer patients. So we're doing the research from the most basic what you have, the hypothesis, two cells to then humans, one step at a time. And so far there's been no roadblocks. It looks all good. We've been hitting our targets from hitting hypotheses. We're hoping to keep this going. The Seinfeld is strong so far.

I'm interested when you say immune effects. So there are people who have immune dysfunction, autoimmunity, and I've seen multiple papers that say if you can increase mitochondrial function, autoimmunity can go away. In fact, autoimmunity itself may be a symptom of mitochondrial dysfunction. So mitochondria could be the root cause of at least some types of immune dysfunction. That's not to say that a toxin or something couldn't have poisoned the mitochondria which then turned on autoimmunity. So the toxin may be is the root cause, but we know they're in there somewhere with with immune cells. What was the dose for the mice that fixed immunity and did it fix excessive immunity? Did it just increase immunity? Like what is urolithin A doing for immune systems in mice?

So what we're studying for the most part is of course lack of immune function. When mice have a tumor, the immune system does not adequately cure it. And usually our body is built to detect cancers and cure them. Right. This is why we don't get cancer every single day. So with that being said, we mostly study the lack of immune function, not necessarily autoimmunity, but those are kind of similar in a way. What we used in mice is relatively high doses of 2.2 grams per kilogram of weight in those mice.

Wow, that's a big dose.

It's a big dose, but it is the big dose we show in the paper. Obviously we see effects with lower doses with half the dose for example as well in a true disease context background. So you have a whole manifested disease, do an intervention and you see an effect on that disease or a treatment of cancer. Of that being said, well, the whole notion of autoimmunity cells that attack the body by themselves, they're also deranged metabolically, mitochondrially, but we don't actually know so much about autoimmune disease and immune function if they have the same mitochondrial dependencies that T cells have that attack the body in a physiological way, or if they're completely deranged at this point, we think it's the latter actually. But that's a very interesting field of study and people actually checking this these days to see if we can abrogate autoimmunity with EUL as well. But in terms of improving immune function from immune system that doesn't work to immune system that works much better. UFN A seems to be very nice intervention.

Okay, that is. Huh. I. I guess we're saying we don't know. I would theorize that improving mitochondrial function is only going to help autoimmunity. And that is part of my strategy. And it's worked really, really well for that. And what I am doing right now is I am converting from the mouse equivalent dose to the human dose, which is basically. Here, I'll do this. Give me one second. It's 178, but that was in milligrams. That's actually not bad at all. It's not a hundred. Yeah, cuz that was 22. No, that was grams, sorry, 178 grams.

We will not, we will probably not need at high amount in a human context to see the health effects. We have some preliminary data of course and obviously before going to humans you test these kinds of things on yourself. Lower doses will be if there's an effect which you think there is, will be fine.

The other thing that, that we've talked about in previous episodes like this is a really fascinating compound. It is not a pharmaceutical. It is something that is made by your gut bacteria when you take it. It's called a postbiotic. The that means that as you start taking it your gut bacteria that can make your lithium a start to grow. The same thing happens with spermidine and the same thing happens with some of the other postbiotics that are really important in the longevity field. So probably you have some more onboard production of this as well. And if you take it over time, does it build up or does it just get metabolized and then excreted?

We don't know that actually on what the effects on the that microbiome are upon Uran a intake. So usually most of ufin a gets taken up, gets metabolized and then by products get get secreted as, as a waste product pretty much. But as this line of research is rather new also in terms of muscle function, cognitive function, euthanate, we don't actually know what the long term effects are in terms of you need lower doses after some time, for example, we don't know that. It's nice to hypothesize be possible but for now just seeing from the data I've seen on muscle strength endurance for example, because that's where you can really propose taking ur. I would say taking it for a long time consistently is probably the approach to go.

Well, like I was saying at the beginning, I wanted to have you on the show here because I, I take about a hundred and one hundred fifty plus depending on the day capsules every day. I'm planning to live to at least 180. And the reason for that is it's 50% better than our current best. And I'm counting on guys like you to do some real research to get us 50% better than our current best over the next hundred years. I think you can do it.

Gotta hurry.

So maybe I, you know, maybe I'll die trying. That's okay too. But that means when I add something to my stack, it's a pain. I have to buy it, I have to inventory it and I have to put it in a, in a bag and I take it with me places and I'd rather not, but with a timeline, I, I do it and I have no problem with it because the evidence is already so strong and it'll probably get stronger. And so it comes in, guys, you're wondering. It comes in pills, these little red pills. See if I can open this. You take a couple of these a day. And it comes in packets that I actually have in my smoothie. The packets are raspberry or ginger flavored and the ginger one tastes good with pineapple. I learned that at my conference at the biohacking conference. By the way, guys, you'll probably see Mito pure at the biohacking conference in Dallas end of the month of May. Go to biohackingconference.com if you'd like to meet some of the people behind the company and hang out with me. That's biohackingconference.com now you've seen what it looks like. And I was drinking a smoothie a minute ago that had one of the powder packets blended. So what you're, you're going to find is you may experience cognitive enhancement, you may experience improvements in muscle, you may want to up the dose, you may not need to up the dose, but what have you found around muscle health and muscle performance just from the doses that are recommended today.

So, short disclaimer. I personally did not do the muscle studies, but I know about them obviously because I work on this compound. So the data on muscle endurance and health strength is actually quite solid. There have been multiple randomized clinical trials, which is the gold standard in research. You take two groups, one group taking ufl a line that they don't know what they get, the other group getting a placebo. And then without training or any other intervention, you test what happens before and after the intake. And what these colleagues in Switzerland actually from the company producing this have seen is that just the supplementation of UFNA leads to an increase of muscle strength by about 12%. I believe that's without any training in aged adults, sedentary people that don't work out. And that's very convincing. They've confirmed these in a second trial for a bit younger people as well. So there's a very big case to be made. Also, hypothetically, more basic research we have that muscle function indeed gets improved by urna and as many pathways are similar between neurons, muscles and immune cells in terms of what keeps the cell fresh, we are now moving to the immune part and the immune cells to see if we can actually see similar effects on the immune system, or what you would call rejuvenating the immune system, which would be very beneficial for treating cancer. Obviously mate filling, autoimmunity, and also things like response against chronic infections, for example, which are things that are all issues of the elderly people.

Do you use mitopure?

I actually have to test this.

Not today. Not today.

Actually, it's mostly a matter of when you have time. And I've taken it, I've checked before I conducted clinical trial. I'm not taking anything right now, just due to time, time, time and age. Being a doctor, I don't haven't found the time to build a stack myself. But I think there will be a time, it's not too far in the future, where I'll have to do some research to build one myself and find the right compounds too.

So do you worry about getting cancer yourself?

I used to. Not to. You always think these, these kind of things happen to other people, obviously. But knowing the data, one out of three people encounter cancer in their lifetime. Any kind of cancer doesn't have to be metastatic disease, obviously. And also being a clinician, you see people having cancer, you see young people with cancer that haven't done anything wrong in their life. Right. It's not always the people that smoke like a chimney that don't work out. Sometimes it just hits people.

It's weird that it hits people in America more than people in Germany. Is that just because cancer hates Americans?

Maybe. There's many reasons behind that. So several things drive cancer incidence and resistance to therapy, of course, cancer disease, obviously of genetic changes. But these genetic changes have to come from somewhere. And one of the main drivers behind cancer incidence and therapy resistance is obesity and lack of movement. And just compare the other. I know, obviously in some stereotypes way along the way. I guess that is an issue in the United States and an increasing issue.

Because Americans are lazier than Germans. I mean, those, those are some fighting words, my friend.

No, not necessarily. Not necessarily. But there, there is a change in nutrition and how certain products are manufactured in the western world, not the US but also western Europe, that is different from other countries.

And there's also a massive amount of glyphosate in the US that directly contributes to obesity, even if you exercise. And it also, in studies, reduces mitochondrial function. So if you're spraying something all over the place so you don't have to pull weeds, well, who would ever imagine that cancer rates could go up? Oh, wait, wasn't there a lawsuit about that? That almost Took Monsanto, slash Bayer down. Yes, there was. And I think RFK had something to do with that, which is even better. So I, I can just say that, that there's a lot of environmental things that are contributing. But end of the day, if you want to not get cancer, doesn't it make sense to, before you have cancer and before you get old, to start taking?

Might appear that could be the idea indeed. So what we're working on right now is, of course, work on aged adults where it has been shown that there is a decline in immune function starting around 45 years of age. I think we've seen other people that there's a decline there, but maybe there is a way to prevent this decline in immune function if you intervene early on.

There are ways.

Nobody has tried that really, in randomized trials. But that is the next frontier of research we should be doing to. Obviously, as a doctor, prevention is the best medicine and we should do something more about that.

Oh, man, you European doctors. So in the US prevention is the worst business model, but it's not the doctor's business model. It's the largest pharmaceutical company's business model over here. So doctors here are trying to heal people, but it turns out prevention is a bad business model. So maybe that's behind the US rise in cancer. I've kind of had enough of that. Like, we got to stop spraying these poisons everywhere and trying to convince other countries to do the same because it's kind of mean. So my strategy as someone who's in the US a very large amount of the time is to do everything I can to make my mitochondria work better, even if I'm exposed to the inevitable long list of more than 10,000 substances that have never been tested on humans that are floating around, and many of which we know are not good for us. So it's like, there's gotta be a way to do it. And I take even more when I'm on airplanes and if I go to Europe where there's different, a different microbiome, I'm going to take even more because I like my system to run as, as well as it can. And my resilience has gone through the roof. I'm 50% less than I used to weigh. My brain works ridiculously well compared to the brain fog I had in my 20s. And I believe it's all from mitochondrial enhancement and a few other things. Now let's talk about the interactions, if you're familiar with them. And I know you're on the cancer side of Things. It seems like you've already talked about this interaction between immune system decline and aging. Do you think aging causes immune system decline or do you think immune system decline causes aging?

It's both ways, but I think predominantly aging causes immune system decline. What we have seen in other trials, other people have very nicely described this, is that aging is characterized by some state of inflammation. It's subclinical. You don't feel it in everyday life, or you might feel a bit under the weather. But the older you get, the more inflammatory molecules you have in your blood. We call them cytokines, interleukin 1, beta C reactive protein. And those has been shown quite nicely in turn drive immune dysfunction. And very nice study has shown that one of Those inflammatory cytokines, interleukin 6, it's called, can actually lead to immune cell exhaustion. So a dysfunctional state that the cell enters, usually after prolonged stimulation, without the stimulation itself. And that's a state that's deeply ingrained in the cell. We call it epigenetically. And once the immune cell has entered that state, it cannot go back. So inflammation and what they call inflammating these days. So the mix of inflammation and aging causes immune decline, but also senescent immune cells. So old immune cells foster in turn the inflammatory process. So there's a very big case to be made to tackle the immune system to prevent the changes from aging and inflammation, but also to limit further inflammation as well. Very exciting field.

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You mentioned one of my favorite compounds ever, IL6 or interleukin 6, and few people are familiar with this other than longevity doctors and immune researchers and inflammation specialists. In the the beginning two weeks of that three year period of global insanity which shall not be named for fear of deleting podcast episodes, I wrote a large paper about every compound I could find that reduced or controlled IL6 levels. In other words, if you want to prevent a cytokine storm that causes damage to your body from any cause, viral or, you know, exposure to pollution or whatever, you would want to inhibit that cytokine. So there's a long list of natural compounds that do this. And magically within a couple weeks of writing that, I got a nasty warning letter from an agency telling me that I had to take it down. So it ended up being on my Telegram channel. So I would say, guys, there's a strong argument if you want to live a long time, is don't have too much IL6 floating around in your body. And it seems like if you increase mitochondrial function, as you're saying here, Dr. Dank, then IL6 goes down. Is that right?

There's a strong association indeed between immune cells that dysfunctionally produce excessive IL6, the ones with accumulation of dysfunctional mitochondria, and the ones that don't that have healthy mitochondria. And there's a very important balance. IL6 is not inherently evil. Of course we need it for acute responses to infection. But as you mentioned, too much IL6, too much inflammation causes all these adverse effects. It can be the magnitude too much being a cytokine storm, for example, in infections which may kill you way more than the Infection itself is the excessive immune response or the chronicity. If you have constant slight elevations of that cytokine, such as in obesity, such as in aging, you will then have this reduced immune function, which by nature is actually a normal response to the body to just get used to high levels and limit autoimmunity. But it's highly detrimental because then you cannot fight infections as well and you have large issues in your everyday life.

It, it just, it seems like the totality of evidence is pretty strong on, on that stuff. There's also the totality of evidence for mitopure in general or at least for urolithin A, because there are 3, 300 plus studies that have talked about urolithin A. And timeline, the makers of Mitopure has done six published studies and five preclinical studies. I would just say this is a very well studied compound compared to many other things that people are taking. So it's one of those things where no one's heard of it. And I'm actually really grateful that a few years ago, timeline reached out and said, you know, hey Dave, you should learn about this because you're a leader in the longevity field. And as soon as I read the papers, I said, I'm so in on this stuff. And by the way, guys, timelinenutrition.com use code Dave is where you can get the stuff. Code Dave will save you 10%. And if you want to see what it does for your heaviest lift, to set a personal record to see what it does for your cognitive function before your next big meeting or your test or just to make you reverse your age over time as a part of a comprehensive longevity strategy. I'm just a true believer in this stuff. And so timelinenutrition.com and code Dave, talk to me about T cells. What are T cells?

Oh, it's fine.

What do we know about the potential effects of T cells and urolithin A?

It's my favorite topic actually. I think ever since this whole three year span that you didn't want to name. We all know what the immune system does roughly about that. There's B cells and T cells and T cells are part of the so called adaptive immune system. They're the cells you would imagine when you think about immunity, they're the cells that patrol the body, kind of like the trained assassins looking to fight cells that are infected by viral infections, for example, or malignant cells. So they're the ones that really protect us by direct cytotoxic function. So as a T cell Circulates the body and finds such a cell, it recognizes it and directly kills it. And that's what happens every single day, every single moment. Probably right now, as we speak, your body detects a malignant cell and takes it out.

There was one. Oh, I got it.

Yeah, it was. And that's what makes it so interesting. And there's very clear associations shown that the more T cells, for example, you have inside your established tumor, the better your outcome is, the better the response to therapy is. And this is why the whole notion of cancer therapy has changed in the past decades. It used to be that we tried to kill the cancer cell, right? It used to be chemotherapy. You nuke everything with the whole idea that, of course, cancer cells divide faster. So if you apply an agent that stops proliferation, you will cure cancer cells predominantly, but you will also probably cure your gut a little bit, your bone marrow, many side effects. But now that I've known this for a long time, that the T cells and the immune system are a natural defense against cancer. What if we just enhance their function and we see what goes wrong in cancer and then improve that? And this is where this new therapy called immunotherapy, comes into play, where we have identified pathways where we can see which T cells are what we call exhausted, dysfunctional. They cannot fulfill their functions. We try to prevent that state by specific antibodies to boost up immunity. And this is why T cells are so important. You cannot have an immune response against cancer, against infections, without T cells. And there's a huge diversity in T cells as well. We've described in my recent paper that, of course, you have these T cells that you imagine they have these effector functions, they kill a malignant cell. But way below that, you have an entire pool of what we call memory T cells that just sit in the shadows. Cells that have seen something bad, something infected years ago, and they sit dormant for a long time, just waiting to once again encounter this pathogen, to then re. Proliferate and re attack with the immune system. And this is why certain diseases, for example, we don't encounter twice in our life because we've seen them before. There are these highly trained immune cells in our body that just wait to counterattack.

It almost sounds like you. You talked about natural immunity.

It. It is natural immunity. I mean.

Oh, that's.

That's not.

That's not legal over here in the US it only works in other countries.

I see. Yeah, we. I talked about medication, though. That's fair enough.

Okay, Fair point. Talked about medication. We're okay then. Whew I thought I was crossing onto some thin ice there. I, you know, I want to just make sure I'm respectful of our pharmaceutical overlords. This is a question outside of our general conversation here. What's the German take on pharmaceutical overreach versus the American one? I know it's worse over here. We have direct advertising and all that. Is there more trust in the pharmaceutical world in Germany?

So with that being said, of course, I'm no legal expert. I'm only a medical doctor. I'm talking about societal from personal experience and my, my everyday conversations with people. Since I work in the hospital, there's way less contact with pharmaceutical companies. There's way more barriers in place for pharmaceutical companies to contact us. And just as I turn on the tv, for example, there's barely any advertisements on therapeutics, as in, if I watch the NFL, for example, I will see in every commercial break some commercial on chemotherapy, actually on cancer agents. We wouldn't have that in the European Union, so that's a bit different.

Yeah, you have to create demand for cancer therapeutics before you can advertise them. That's a good point. So my experience in Europe, and I've spent a good amount of time over, over the years, is that because of the lack of advertising that it feels like there's less manipulation? What I see in the US is that people have recognized the cancer statistics that you shared, and they're saying, wow, you know, if I don't want to die and I want to live longer, I'm going to have to avoid getting cancer. Right. So I've talked with companies who do cancer early, early stage detection, companies like Viome, where they can do esophagus cancer with just bacteria from the mouth, which is remarkable. And then companies like Prenuva, who can spot tiny, like MRI, whole body, MRI stuff. And when I ran that episode, 25 people who were probably going to die found that they had urgent treatable problems that had no symptoms and they were able to go and get treated, which I feel really good about. And those are relatively small numbers compared to the prevention side. All of those are after you have cancer. So my big thing is, if you want to live a really long time, do everything in your power that's economically feasible and is worth it. For instance, for you, you're young and you don't have enough time to take a handful of pills, so you're not doing it right now because you're balancing your risks and benefits. So just for listeners, it's your job to not get cancer and you still might get cancer, but it probably won't be as bad if you do. If you're taking some steps to have a healthy metabolism and you can read any of my books, listen to thousand plus shows and I, I just know there's so many levers you can pull to reduce risk. And all of them essentially may mean you make better energy and your cells work better so they can fold proteins properly, so they can make the compounds they're supposed to make. And I can say it's not that hard because it's just one thing. But that one thing is influenced by millions of variables. You don't have to be perfect, you just have to get some of them right. And that's why this episode. Urolithin A kind of is a big gun, I would say, for working mitochondria, which is why it's in my bucket of tricks, we'll put it that way. Talk to me about treating cancer holistically. And this is something else where Germany is so far ahead of the US If I had an advanced cancer, I would probably end up in Germany or maybe Austria at some kind of a clinic because there's all kinds of magic over there. But if someone you cared about in Germany wanted to holistically go after their cancer, what are some of the things that you might think of that may include Urolithin A, but maybe wouldn't.

First of all, of course, as you mentioned and we talked about, is the prevention side of things, of course doing it in the first place. But often case, when you think about cancer treatment and the whole oncology side of things, of course, I'm a doctor, we think about medications and that's very important, very fine to advance research here. But there's a whole different side of things, the non medication part, which is I think what we are becoming more and more aware of, at least in European Union. So what you want to do, I believe at least to give your immune system, the body, the best chance to fight cancer itself, but also survive the treatment in the best manner. The many, few basic steps pretty much is getting right amount of sleep, regular exercise, even if you do have cancer. There's very nice studies showing that regular exercise have very good health benefits. If it's due to mitochondrial function, could be probably. But it's a very important take to have that on top of dietary interventions such as intermittent fasting. There's some, some studies here just looking at the patient as a whole and not just what can we do as a doctor, but what can the patient do. For themselves. And it goes even further beyond that that if you have cancer, for example, there's no new approaches here, that before you go into surgery to have that cancer removed, you go into what you call prehab. For example, you'll be sent to essentially a rehab institution for two weeks. And you train your body before you go into surgery so you come out much stronger, you can get out of bed much faster, all with the idea that you reduce infection rate and you give your immune system and your whole body more to work with in the first place.

It's funny, you talked about prehabbing and even the post surgical techniques are important too. I did a documentary. You guys can get it for free. It's daveasprey.com heal where I talked about everything I could do before, during and after surgery to heal faster. And I recovered more than twice as fast as anyone expected. And funny enough, was mitochondrial enhancement, including mitopure, part of my strategy in the documentary? It was. So the surgeon was just blown away. Just say, I've never seen anything like this. You don't even need antibiotics. This is nuts. It was a bone surgery for that one. And also because you mentioned it, I'm having a surgical procedure abdominally done tomorrow. I have had for several years a very, very tiny hernia on the lower abdominal wall. And I'm getting it fixed while it's tiny so that my functional movement patterns will continue working as I reach on my way to 180. I'm using dissolvable mesh, but you can bet that I'm prehabbing before I go in for that, because I don't want the recovery to interfere with my life. I'm just going to have it and then be done with it. So every step of that is planned. And I'm doing everything that's in the documentary. That's daveasprey.com heal Did I take a quadruple dose of urolithin A today? If you had to bet, what would you bet?

I would assume so.

There you go. So thank you, Timeline, for making that possible because you couldn't buy this stuff and I would have gotten sick if I ate that many pomegranates. So this is the only way to do it. I want to ask you a couple of questions that we don't have studies for. So you're not accountable for these answers. You're an expert in your field, so it's given everything you know, what would you guess the answer would be? Knowing you could be wrong. Would it be appropriate or most appropriate or most beneficial to take mito pure before getting in a sauna or after getting out of a sauna. Ooh.

Oh. I was kind of saying earlier prevention is the best medicine. So I would personally two before. But we don't know. I don't know.

Yeah, we, we don't know. There aren't studies. But the cool thing is once you know how something works, you can guess how it's going to work. You might be wrong, but your guess is better than just your random coin toss. So we're just, you know, playing odds. This is how most biohacking works. Well, there isn't a study that says this, but it makes sense. So let's try it and see if we got results. And if we did, like, okay, it works even, you know, probably no pharmaceutical company will ever do a double blind placebo controlled trial of parachutes, but I'm gonna guess that they work based on what I've seen. So. Okay. I would also do mito pure before based on the idea that the heat shock proteins and the idea that, that, that they will form better and also that under heat. We just recently discovered that instead of discarding damaged proteins, even ones in senescent cells with the right amount of heat is relatively hot saunas. The body can actually unfold the proteins and then refold them, which is more efficient electrically rather than just making new proteins. So that process must be driven by mitochondria because it's not driven by windmills. So therefore I would want to have more mito pure before I went in. But I could be wrong. Maybe having a lack of it and then a surge afterwards is better. We don't know cold therapy. Any guesses there?

Before, after cool therapy.

Yeah, cryotherapy, we do upgrade labs. We don't have one in in Germany yet, But we're opening 27 locations in the US with the franchises. So people go in to do cryotherapy with 160° below zero air.

I mean, I'm sticking with the same answer because you are essentially preparing your body for either prolonged or acute stress. And cryotherapy is that sort of stress. So the better you can walk into this with your cellular functions, which are essentially your mitochondrial functions, the better. So personally, I would also do that before if I were to choose.

Here's another one I've written about something called tripling down on mtor. Now you know what MTOR is, I'm assuming because of what you do for a living. A lot of listeners don't. Mammalian target of rapamycin this is a compound that causes tissues to grow and heal and you put on muscle. It also causes tumors to grow. So, so we have this conundrum where we want to be young, but we don't want tumor. So how do we balance it? My strategy has been to keep it low by doing intermittent fasting and manipulating the type of amino acids you eat on sometimes. And then when you want to put on muscle, you suppress MTOR as much as you can, and then you do everything to make it spring forward. So the higher you push it down, the more of a surge you get afterwards. And during the surge, you put on muscle. So the three things that I know suppress MTOR are exercise, intermittent fasting, and coffee. So you wake up intermittent fasted, you have some coffee and then you exercise. And now your MTOR is maximally suppressed. And then when you finish exercising, you have, if you really want to grow, you actually have some carbohydrate to raise insulin, which causes you to grow. And then you have some protein, which is a building block that also raises mtor, but the carbohydrate raises MTOR more than the protein protein. So this would create the ideal suppression of MTOR and the ideal rebounding surge in mtor. So you guys got that. So, Trip, three things you do. If you want to grow muscle the most, then what the heck do I do with timeline? Do I take it during the fast, do I take it before the exercise, or do I take it during the surge after exercise?

It depends on what kind of dose you're taking, obviously. Right. So what has been studied for this particular product you're talking about is mostly the, the twice daily intake.

And you would want to, you'd want to be on it twice daily, you wouldn't do an extra dose or I.

Would do it twice daily and stick with that for the most part, I think the more stable, the better. That's of course of the whole idea of now mitochondrial function, muscle function, not entirely sure about the immune function part of things we're starting right now. The once daily dose. Well, we'll have to see.

Okay.

But you have many interesting research questions that we'll have to tackle in the future for sure. So.

And some of these probably aren't worth funding research for, but we can just make educated guesses and you're not going to go wrong with any of the answers. But one answer may be 10% better than the other. I just find that by talking to someone who's really thought deeply about it, you probably have some ideas. I tend to, after I've exercised especially, and almost all of my exercise is driven by AI and it's at upgrade labs. And I exercise all of 20 minutes a week. And I'm in better shape and leaner and stronger than I have been in a very long time. So when I load my muscles, let's just say they're sore the next day. And when I load my muscles, I take extra mitre pure because I'm assuming my body is going to be working really hard on building new muscles, so I might as well have extra mitochondria. So I'll take my. I take it morning and night, um, and then on those days I'll take a couple extras or like, I'm going in for surgery, might as well preload with a bunch of it. I have no evidence that my surgery will be better. It just makes sense. So I'm willing to do it. Uh, and I want to be really clear too. You're not making any of these recommendations based on, you know, medical advice or even based on science. We're hypothesizing and guessing what would probably work best given what we know. And you know, we have permission to be wrong on this because we've identified it as being questionable.

Exactly. And that's why I've been saying that there's a few things we still have to study, a few things we're actively studying. And of course, none of these things are right now, me as a medical doctor giving advice to people to take certain supplements. But we'll get there in a few years. I think to really be able to answer the question yes or no, in which circumstance we'll have to do it.

Mito pure mitochondria and sleep. Know anything about it?

Not too much, unfortunately. I'm not a sleep expert. But what I do know, though, in terms of immune function at least, is that sleep is very important for adequate immune function. Lack of sleep goes hand in hand with accumulation of dysfunctional mitochondria and also promotes or fosters the inflammation phenotype. So more signaling molecules, cytokines, are associated with this low grade but chronic inflammatory state. So I would assume, just based on what I've known from before and what we know on immune function, that sleep is very important for mitochondrial function and mitochondrial boosting euphemia, for example, and sleep would go hand in hand. It's not. No replacement for sleep. Very important to know that sleep is not replaced by anything.

Are you sure?

Personally? Personally, I think so. And there's very strong studies showing in all kinds of conditions that sleep is rather important.

Sleep is super important. The reason I was kind of laughing is that in the 50s, in a uniquely Russian way of thinking, Russia said, well, it's expensive to send astronauts into space just to pay them to sleep and all that rocket fuel for one third of their day being taken out. What if we could invent a device that caused them to only need two hours of sleep? They did that. And it has to do with running small amounts of electricity over the brain while you are getting your two hours of sleep. And I have the gear, I've used it. And yeah, you can get a full night's sleep, at least for a substantial period of time in two hours. But we don't know the long term effects on things like the glymphatic system and washing things out. But from a mitochondrial and a brain function perspective, you could do it for least a couple months. So maybe there's a short term replacement for sleep. But I'm with you if you want to live a long time. Right now, sleep is still necessary. And we don't even know why, despite the why We Sleep book and its author's been on here. But we have ideas. Just like we don't know everything about mitochondria, but we're learning more like we are with a Urolithn A. Are there side effects or downsides to urolithin A?

So as you mentioned, it has been amply studied in multiple clinical trials. And in those studies there were no major side effects observed. I'm saying major out of habit, but there were no significant side effects observed, not even diarrhea or headaches that were with urfinase compared to placebo. So, so far from the data that we do know, in the time it has been taken in the studies, I think up to four months, there's a trial coming up for 12 months soon. There hasn't been any side effects observed. And that's why it's very easy for me to talk about this today, because I know there I'm not doing damage to people right now.

I already know that urolithin A is heat stable. You can put it in your coffee if you want raspberry flavored or ginger flavored coffee, you could. The ginger's terrible coffee, by the way. But the raspberry stuff is not bad in coffee. But I prefer my coffee without raspberry in it. But it's heat stable. So we know that isn't an issue. But I never asked, are there any foods that would make it more absorbable? Is this a water Soluble or a fat soluble compound?

Actually, I do not know. I do not know at all. Gotta refer to the people that make this product, actually, to be sure. I didn't know it was heat stable, but it's a good thing to keep in mind.

It's heat stable, but I. I wonder. I'm 99% sure that it's water soluble.

That would have been my guess as well.

So I. I'm pretty darn sure of that. Which means you should be able to just take it with anything. Uh, and then if you were to look at things that might block the mitochondrial or the cellular uptake of it, food things, you know, is having it with a ton of glucose or a ton of fat or a ton of protein likely to help or hinder the absorption of this?

Well, also there I have to pass. Unfortunately, I don't really have the real clinical data on this. But hypothetically, what would be prudent to do is to combine that with protein. Obviously, since you are having these building blocks for your muscle, and combining that with UFNA would be very, very feasible. What I wouldn't do is take anything that empties your stomach rather quickly because then you lose the effect. You just get stumped into your gut.

So probably not during Oktoberfest.

Probably not. Maybe in that case, I wouldn't take it right before. Maybe a bit afterwards.

Yeah, a bit after. It probably would help with hangovers. It wouldn't surprise me, although I doubt there's a study for that. Do we know anything in humans or mice about the pharmacokinetics of the absorption? Like how quickly is it absorbed?

It's absorbed relatively quickly within the first three to four hours. Actually. There's been extensive trials. Of course, when you bring a product like this to the market, you have to do all these trials on rodents, mice, rats, and 10 times the maximum amount of dose. And there you could see that it's very quick. And also in the human trials, when they measured the metabolites upon URFUM A intake, it was very quickly detected and peaked, I think after 12 to 24 hours. I believe so. But it's very fast when you see the first effects inside the blood.

Okay, got it. So it hits you pretty fast, which is beautiful. And one of the Upgrade Collective members. And by the way, if you're listening to this, and what would it be like to be live with Dave in the studio on Zoom, looking at me, looking at the other live audience and chatting with me, which is what a large group of people are doing right now you can join the Upgrade collective. Go to ourupgradecollective.com and I'd love to have you here. And our community of people who know each other and are part of my thought process for the show, we would welcome you. Our Upgrade Collective. So one of our members, whose name is conveniently iPhone4, I'm not sure that is because they're moving, says that it seems to really improve heart rate variability. Have you seen anything in any of the studies you're doing that look at nervous system response, vagal tone, which are both of those are correlated with cancer, or anything around heart rate variability?

We have not studied that in particular. So in the clinical trial we're performing right now in healthy adults, taking this for one month, we looked at base heart rate and we didn't see a change there. Also owed to the way it's measured. Of course, people come in, you measure the heart rate, but the variability is a very important parameter I would look at. But then after a prolonged time, after like up to four months maybe, and seeing how that affects the nervous system on base heart rate, we did seizure, for instance.

Yeah, I wouldn't expect it to drop heart rate unless they were doing some other kind of cardio training or something. And it probably would improve results from cardio or muscle training just because if your mitochondria work better, you get better results from exercise. But it hasn't been studied. This is such an interesting compound and I really appreciate that you're doing the the hard work of testing a natural compound for cancer because there are large forces that really only work. Want you to buy the $20,000 intravenous chemicals for cancer. I know that we can reduce our incidence with our diet and our lifestyle. That's. That's core to longevity. It's core to biohacking. And I know that there are supplements that can make a massive difference. So thank you for studying urolithin A and thank you, Timeline, for manufacturing the stuff so I could finally start taking it. Guys, go to timelinenutrition.com use code Dave, save 10% and give it a try. See how it changes all of the things you want to change. I think it's foundational. Thanks again.

Thank you.

You're listening to the Human Upgrade with Dave Asprey.

The Human Upgrade, formerly bulletproof radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purpose purposes of diagnosing, treating, curing, or preventing any disease before using any products referenced on the podcast, consult with your healthcare provider carefully, read all labels and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of Guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by by Bulletproof Media. A Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of diagnosing, treating, curing, or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider provider carefully, read all labels and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of Guests are their own and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. This podcast may contain paid endorsements and advertisements for products or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by Bulletproof Media.