← The Human Upgrade: Biohacking for Longevity & Performance
The Human Upgrade: Biohacking for Longevity & Performance
STOP Intermittent Fasting If You Want to Stay Young : 1409
01:17:18
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- [00:00]
A
A lot of people probably focus on the short term effects of things. They'll do something and they'll see what happens, you know, a month or two later and they try to extrapolate that into the rest of someone's life. But it doesn't work like that. If you look at 100 years of data, the only intervention to make mice and rats consistently longer lived is protein restriction. High animal protein intake have a major increase in diabetes, also a major increase in overweight and obesity. If you have high tor activity this tends to keep the system them in a pro growth modality but also pro aging. A lot of people like to hear about eat a lot of this or avoid that and in most cases is having it to get it exactly right. Growth hormone is clearly the most powerful that there is. When that becomes important, that's a little tricky. As you mega dose anything they're going to disrupt this equilibrium. Very sophisticated equilibrium that the human body has built. After billions of years of evolution, functions, strength and longevity are very closely connected. Short term effects and long term consequences are very, very different.
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A
Are you ready to.
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B
Plug into the latest science of longevity and human performance? Come to beyond the Biohacking conference where biology, longevity and consciousness collide in real Life. Join us May 27th through 29th, 2026 in Austin, Texas. Experience breakthrough tech, meet world class experts and connect with people who are also committed to being the best versions of themselves. Because strong community isn't optional. It's how we live longer. Register now at BeyondConference.com live longer live better Live Beyond. I'm excited for the episode today because it's about one of my favorite topics ever, which is fasting and intermittent fasting and things that are related to fasting with perhaps the most studied expert in the world on the effects of fasting, Dr. Valter Longo. This is his second time on the show and he's a professor of gerontology and biological sciences and director of the Longevity Institute at usc, which is a pretty good pedigree for someone who's going to talk about longevity and what happens if you don't eat every now and then. Or maybe you do eat, but you just eat the right things. Falter. Welcome back to the show. Thank you.
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A
Glad to be here. All right.
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B
You spent your whole career studying aging and thank you for that, by the way. If you had to explain the biggest thing that people still get wrong about aging, what would you start with?
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A
Probably focus on the short term effects of things. Right. So they, they'll do something and they'll see what happens, you know, a month or two later. And they extrapolate or they try to extrapolate that into the rest of someone's life, but it doesn't work like that. Right. You could have something that is extremely effective, short term, maybe even for years. I think probably GLP1 drugs are one of those examples. And then, you know, eventually it could still help you, but it might help you a lot less than something else. Right. So you know, again, GLP1, you could look at it as an anti aging drug or you begin to look at it as an anti aging drug, but then you have to say, I will compare to something else that maybe is much more effective. So, so yeah, so I think that's probably the, my number one complaint. Yeah.
- [04:37]
B
What's more effective than GOP ones for longevity?
- [04:39]
A
Yeah. So I think that if you look at what I call the longevity diet. Right. So, so but even if you just look at the Mediterranean diet, so now we know that for GLP1, there's a reduced risk for cardiovascular disease long term. Right. So somebody could say, okay, now you have the weight loss, you also have the reduce. And that's what everybody's saying, like you reduced risk for cardiovascular disease. So it's very good. But then you compare with just a Mediterranean diet. And the Mediterranean diet is two to three times more effective, you know, against cardiovascular disease. And so, and so in, in the Mediterranean, that is probably not the ideal in, you know, anti aging intervention. It's a good One, but I don't think it will compare with, you know, the, what I call the longevity diet, which has, say fasting mimicking diet, 1212 hour time restricted eating, intervene at the exercise and the sleep and all of. So, so yeah, so that's probably much, much more powerful and not necessarily not feasible. Right. So a lot of people will say, well, it's too many things. Yes, there's a lot of things, but not that big of a change compared to what people normally do. Right. And that's why, that's why we were talking, for example, fasting, making diet, and I'm assuming we're going to talk about that three times a year now we're testing it in Italy once every three months for the first time. Actually we're almost done with that large clinical trial. So what happens if you do this only three or four times a year versus once a month, which is what the previous trials were focused on.
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B
And for listeners who didn't catch the last time you're on the show, Prolon is a company that you helped to start that does the fasting mimicking diet. So you basically get a box of food that you can eat, but you're still getting the effects of a fast while you're eating it. I just did a Prolon fast recently and did it online with a bunch of people because it's easier than fasting for five days to just eat nothing. So the compliance is a lot higher with something like the fasting mimicking diet. Why does it work though?
- [06:43]
A
Why does it work? Well, probably lots of reasons. Right. And one of them, so we published a series of papers in both mice, rats and people. And so in mice we were seeing what we call multi systemic regeneration. Right. So you see effects in the pancreas, in the gut, in the nervous system, in rats. We just published on kidney. Right. So in some cases is increase of stem cells, so the fasting mimicking diet increases circulating stem cells or local stem cells and in some other cases is reprogramming cells. Right. So it's turning on what's called Yamanaka factors, sometimes multiple Yamanaka factors. The interesting thing is it seems to be different like so from study to study organ to organ. So for example, in the kidney we saw MYC being activated nanog and some other embryonic developmental factors. Whereas in the pancreas we saw Oct4Sox2. So different reprogramming factors and the Yamanaka factors basically have the job of bringing a cell, an old cell, back to an embryonic like state. But whereas when you force, let's say Yamanaka factors, you could have good and bad. The advantage of fasting is a very coordinated, very much evolved method or system. And so you don't have the good and bad. At least there may be some bad, but we haven't seen it yet because again, the great majority of organisms have undergone fasting periods in their history or in the history of the earth species.
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B
You know, so I guess we have multiple mechanisms. I usually look at insulin levels and MTOR as being the most important reasons we would fast. Can you explain what those are for people who don't know and what fasting does for those?
- [08:39]
A
Yes, so insulin is usually reduced long term. So insulin is responsible for allowing glucose to come into cells, but it's also controlling fat storage. Right. So high insulin level are associated with high storage of fats. So insulin after cycles of the fasting making diet come down and they usually stay down. But also something like insulin, like growth factor one, IGF one, it comes down acutely, but it also stays down for months after the fasting making diet is discontinued. So yeah, so then there is a reprogramming of a lot of these factors including insulin and IGF1. And part of the effects, at least even the ones that I just mentioned on reprogramming and on stem cells are due to TOR down regulation. So MTOR is a kinase, an enzyme that basically is involved in protein synthesis and lots of other and growth in size, let's say, of organs and cells. And so one of the messages that blocks this reprogramming and stem cel, the one given by torque. So if you have high TOR activity, this tends to keep the system in a pro growth, pro expansion, pro reproduction modality and, and, but also pro aging.
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B
If you don't have enough of this mtor, which causes tissue growth, you can't put on muscle though, and you don't regenerate. Like how do you balance that out?
- [10:18]
A
Yeah, so there is a minimum that you need to, to activate muscle generation, let's say. And so yeah, you need to hit the minimum. And it's usually, I mean, of course the fasting making diet is only five days every, let's say two, three, four, six months even. So you have all the time in the world to do that. But let's say that you had a very low protein diet, in particular a very low leucine methionine diet. Yes, those could bring TOR activity below a certain level. And let's say if you were maybe below 0.7 gram per kilogram of body weight and especially if that was mostly plant based. So if you have a combination of low protein and mostly plant based, yeah, you may have a problem building new muscle just because this, this levels of TOR is so low that it prevents muscle synthesis. Now, you know, in the fmd, you know, trial number four or five that is looked at musc mass, we see either very small reduction again compared to the GLP1s, we see lots of fat mass loss, very low lean mass loss, in some cases even increasing lean mass loss. And so this could be due to in the activation potentially of this PAX7 and some of these satellite cell muscle stem cell activation. And so we believe that maybe that's why in some cases we even see muscle increase after. For example, in this study we published together with University of Rome on six consecutive cycles of the fasting Mickey diet, once a month at least the estimation of muscle mass of lean body mass was an increase, a major increase after the sixth cycle. Now it was done by bioimpagentiometry. So I don't necessarily believe that there was this as big of an increase as we, as we saw. But even if there was a minor one, that's still a very good news because it suggests that there is a targeted loss of fat, especially abdominal fat and protection of lean mass.
- [12:40]
B
When people are too lean but still have adequate muscle mass, do they need to fast less?
- [12:45]
A
Probably yes. Right. So if somebody is say bmi, very low bmi, they are, well, you know, they could still benefit from the fasting, but because we're a caution, I would say they should probably fast less or a lot less until we know more or a lot more about it. I mean, so the people that my colleagues study calorie restriction, continuous calorie restriction, this severe continuous calorie restriction, they would say that the people, even males that go down to a BMI of 19 are very healthy. And so they may say well it's okay even if you're lean or very lean to keep fasting. But I think in our case we rather be cautious and say maybe not maybe do a less and let's wait until we have more years of reports and millions and millions of people having done this and then maybe we can make that choice.
- [13:50]
B
I'm kind of asking for a personal reason. I'm 6% body fat and I don't want to be lower than 6% because from what I've seen, not having adequate body fat might increase your all cause mortality risk. You maybe should be at 8% as.
- [14:10]
A
A guy, maybe even higher. But I think it's probably benefits and problems. Right. So, so, and that science is still poorly understood, you know, so why is fat and lots of even mouse studies, some of the mice that are able to retain fat are the ones that do better under calorie restriction. Right. So if you're calorie restricted, you undergo this severe diet, some of the mice that perform the best are the ones that are better able at keeping some fat. So, yeah. So is it the same in people? And of course there's data is indicating that, you know, older people that have a little bit more fat reserves, they tend to do better. And so, so yeah, it. I think what always emerges is this equilibrium or having to get it exactly right versus this idea of lots of this and little of that. Right. So a lot of people like to hear about eat a lot of this or avoid that, and in most cases is having it to get it exactly right. And fat is the same way, probably. Right. So although, you know, what is the perfect fat level? Well, probably changes between different ages. Right. So at your age you may be fine to be very low, but as you get older, it may be that a little bit more reserves are better.
- [15:41]
B
Through all the different biohacks and optimizations, I'm not lacking muscle, but it's very hard for me to put on fat now. And I come from a background of being obese. I was £300 and so all the people in my family are fat except for me. And I find it extremely hard now to put on another 2% body fat. And so I'm. I wrote a major book on fasting. I'm certainly a fan of it. And I do short, intermittent fasts, but I haven't done a longer fast other than the prolon fast recently in a while just because I'm. Maybe I should get a little chunkier. But it seems like the science is out on that.
- [16:16]
A
Yeah. And I mean, there are ways to gain some fat to then lose it again during the fasting or the fasting making diet. Right. So that's usually what we recommend to patients that are particularly fit and thin. They gain.
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B
I've been trying to gain fat. It just doesn't work. I mean, I can eat 400 grams of carbs and, you know, sticks of butter. I just don't get fat.
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A
It's kind of crazy maybe that you're in such a metabolic state that, that, you know, at least short term that those interventions don't work.
- [16:47]
B
It's an interesting conundrum because we have this kind of fetishization of you know, having abs, and especially in women that can be too lean. I think sometimes in guys it's too lean as well. I don't know that we have a ideal body fat. Like I said, it may change over time, but I think for listeners, being too lean is probably not ideal and being too fat isn't ideal. But we don't know the perfect middle. And it may vary based on your genes and your, your background. You know, if you're from a part of the world where people usually carry more fat, maybe you need more fat. Is anyone doing that research?
- [17:22]
A
There are probably people doing it, but I haven't seen a consensus on that. Certainly if somebody is, say, less than 60, low body fat is probably generally good. Right? Or very low body fat. I think once you get to. So in our studies, when we look at the enhanced database, after 65, the US population starts losing weight. Right. So losing weight means losing lean mass, but also losing fat mass. Right. And so probably that's when having low fat may contribute to the problem. Right. Because now the fat is also reserves, energetic reserves, maybe stem cell reserves. And, and so, so, yeah, so probably that's when it may be problematic to be extremely low fat, when, when things are starting to go, you know, the, the downward way.
- [18:26]
B
That makes sense. And I'm hoping that some research group comes out, maybe someone who's studying a PhD is listening right now, and. Yeah, optimal body fat based on what variables? Yeah, let's, let's do that research. I think it would be helpful for a lot like, like tens of millions of people. I want to talk with you about protein. And when I wrote my, my big longevity book, I, you know, thousands of papers and things, and it seems like 0.6 grams per pound of body weight. There's a bunch of research suggesting that, which is, you know, 1.2 grams per kilo or thereabouts. And there's also, though, another smaller but vocal group that says, no, it should be 1 gram per pound or 2.2 grams per kilo. I've tried both and man, my markers are better and my energy's better. My body composition's better when I do the 2.2 grams per kilo. And I'm trying to compare that with your recommendations, which are substantially lower protein than what I've found works. And it seems like there's these kind of two spikes of data around these, and there's a bigger spike that says 0.6, and you're even below that. So how do we make sense of the optimal amount of protein for Humans.
- [19:46]
A
I think we're going back to what I was saying earlier, right? Acute effects versus how do you make it to 110 healthy. And so if you look at 100 years of data, and maybe we talked about it a few years ago when I was on. If you look at 100 years of data, maybe the only intervention without calorie restriction to make mice and rats consistently longer lived is protein restriction, right? Or metallic restriction. You can do protein restriction, you can do metallic restriction or you can do calorie restriction. But that's really hard to do it any other way, right. Without calorie. Especially with that calorie restriction. So if you look at the monkeys, they live the longest or they were ancient restriction. In the Wisconsin study, you know, they had the 25% reduction of calories, but including proteins. And if you look at the Harvard data on, you know, protein intake and diseases, you know, one of the studies by Frank Koo a few years ago showed that, you know, this is the physician and nurse study indicating that those that have high animal protein intake have a major increase in diabetes and with that also a major increase in overweight and obesity. So and then if you look at their cardiovascular epidemiological studies, pretty considered one just came out I think a week ago. High protein intake associated with a major increase in cardiovascular deaths. If you look at, you know, I was having a conversation with Dan Buettner a few days ago and I say, Dan, you, you tour the world and you know, looking for people that live long. Did you ever meet a long lived population that are very high protein diet? And he's like, no, I don't, I don't recall a single one.
- [21:39]
B
What about Hong Kong? Like Hong Kong, they eat more meat than anywhere else on the planet and they have a well blue zone there, just without the beans. It seems like I always like to find the outliers because then they tell us that our, our hypothesis has room for corner cases. Right? Because that is a big red meat. Right, Right.
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A
But I mean we don't have any causality type studies, right?
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B
So we definitely don't have causality. That's what I'm asking.
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A
This is why I describe the epidemiological data, including our own, right. Looking in Haynes, major increase in cancer and major increase in overall mortality. But then the Swedish studies, the Harvard studies and the mouse studies, the rat studies, the centenarian studies, the genetic, the little people in Ecuador that we follow, well, guess where they have the mutation in the growth hormone receptor. So they have very low IGF1 and clearly protect it in the mice. Right. The mice that are growth hormone receptor deficient or the mice that are growth hormone deficient. 30 years of work by John Kapchik and Andrei Barkey and those are the mice that have the record longevity extension. Right. And where do they have the mutation? In the protein pathway, in the protein amino acid pathways. So it's like they were consistently and constantly on a very low protein diet. Okinawans record longevity in Japanese, historically traditional Japanese diet. Japanese have been number one in life expectancy for 25 years now. Right. Japanese have always had one of the lowest protein intake and 50, 50 plant animal. Right. So low protein intake and lots of plant based proteins which have very low essential amino acids. Yeah. So I think it's. You have all of this you cannot argue with Hong Kong. Right. I mean, you could say, hey, what if? But you have now 100 years of data and you need another 100 years of similar data to counterbalance that. And we cannot just pick a study or two and say, especially Hong Kong, where it sounds like we follow them for 30 years and we now know that the proteins are contributing to their, you know, high life expectancy. So they may be, it may be like they could have been even longer lived or healthier if they had the same healthcare system and everything. The same. But a low protein diet, right?
- [24:03]
B
Yeah, it's a conundrum. I just did a two hour show with Dan, who's just a wonderful human being. And so I don't play the takedown. I'm just genuinely curious and I'm always saying, well, if I can find one example. But you're saying that the Hong Kong example isn't strong enough from a data perspective to take action on. Might be a counterpoint, but we're not sure yet. Is that a good way to.
- [24:29]
A
Well, no, we're pretty sure that we shouldn't use it as an example. I think we should use the five pillars. Epidemiology, clinical studies, the mouse studies, the rat studies, the monkey studies, you, you know, all of it. Right. The centenarian studies, you know, the Mediterranean diet, traditional Mediterranean diet. Guess what? Fairly low protein, you know, two to one, plant based. The traditional one and the modern one is, is different. But so again, low amino acid. And by the way, I think we eventually, very soon we should stop. We're going to publish a few papers on this. We should probably stop talking about proteins. Right. Because it's really relevant because you can have a 3, 4, 5 fold difference in amino acids, two different sources of protein. Right. So so then, and I know we need application. We're going to need application because people are gonna. Are going crazy already as is. So it should be made easy. But I think it's really about amino acids. Right. So how much. What is the amino acid profile in the diet of someone? And you know, and, and then, you know, they can make decisions based on too much of one or more amino acids that are contributing to aging or they're contributing to frailty if they're, if they're deficient. Yeah.
- [25:50]
B
There's another variable for protein that people don't oftentimes talk about in just a common Instagram influencer world. It's the rate of absorption. So even if you have a certain amino acid profile, if it takes six hours for your body to absorb it versus two hours to absorb it, there's a peak of amino acid availability in the body that's probably important. Like slower proteins do something different than fast proteins. Do you have any opinions on that?
- [26:20]
A
I think that the opinion would be more about the timing. Probably we're working out. Right. So somebody was trying to build muscle, then you would probably want to time it. And there's lots of papers we cover, some of them and, you know, indicating different timings and different quantities of proteins being, you know. So the one I quoted some years ago, but I have not updated, it was, you know, 30 grams of good quality proteins will maximize muscle synthesis if timed correctly with the workout. So also, and there was many in my book, but yes, I think soon enough it'd probably be good to put it all together and see if there is any changes compared to what I had proposed back a few years ago. But yeah, so I think that. Because other than that, I think the body is pretty good at absorbing what it needs. I mean, unless there are gastrointestinal issues and then utilizing it for the purpose of protecting the muscle and the bone density.
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B
I saw a couple studies recently showing that it doesn't look like there's an upper limit to the amount of protein we can absorb. They were doing 100 grams per meal and finding that the body was making use of it. Is there any, any case to centralizing all your protein to one meal in a day versus spreading it out?
- [27:52]
A
I think that in general, probably again, going back to the 30 grams, if somebody has a goal of muscle growth, probably good to have at least that level. I think it was leucine had to be so high, and I think it was because of leucine effects on tor. And so you have to meet those. Otherwise probably the Synthesis is limited, but in general, I would, I mean, of course, I recommend 0.8 grams per kilogram of body weight, as many medical associations around the world are fine with. So, so it's fairly low. But you know, I, I agree that, you know, if you look at, for example, southern Italians and Italians in general, they were more frail, they were longer lived, more frail compared to central and northern Europeans. Right. So probably is telling you about trade offs. Right. And I'm sure, I mean, there's data indicating the Japanese were more frail compared to lots of other countries, at least traditionally. So they live very long. But they did give up some things. And, and so again, we need to find that, that balance that reduces cancer, reduces cardiovascular disease and, and reduces obesity and diabetes. And at the same time it, it optimizes strength and function in an age specific manner. Right. So, yeah, so we're about to publish several papers on that and. But they're not. Yeah. So. So, you know, hopefully six months from now we'll be able to sort of say more about. Exactly, you know, what is the way that you orchestrate, you know, longevity, disease prevention, function and strength. Yeah. Wow.
- [29:45]
B
I will come back on when those come out because I'd love to go deep with you on it. What is the, the best amount of total leucine per day if people want to live a long time? Yeah, yeah.
- [29:57]
A
You have to calculate it. But you know, leucine is, is fairly low in legumes and lots of other plant based protein sources. And so the, to live long. And there's data, you know, where leucine restriction makes mice live longer. And, and you know, if you look at the traditional okinawans, they had 39 grams of proteins per day, at least according to some of the traditional okinawan diet papers. So 39 grams of all plant based proteins. Right. You know, these, these Okinawans had such a long lifespan and health, you know, at a ridiculously low amount of, of amino acids, including leucine. So, so yeah, so I think that again, probably very low levels are promoting high levels of protection against aging and diseases, but also promoting frailty. And so leucine will probably eventually have to be dosed based on, again, age, what age, what muscle mass you have, and what risk do you have of developing one of a number of diseases for which high levels of this amino acid could be a risk.
- [31:19]
B
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- [34:42]
A
Well you know we've been working on that with, with John Kopchick. Right. And, and so John is the, is the Ohio University a professor who came up with something called Pigvisomant and Pigvisomant is a FDA approved drug for acromegaly. Right. So excess growth hormone. And so John and I for a number of years have been, have been trying to start up a company where we will focus on let's say oral growth hormone receptor inhibitor. So this is the same growth hormone receptor that is blocked in this very long lived mice. And the people in Ecuador that are, you know, don't develop disease or develop diseases a lot less than everybody else. So I think that's probably the best way also because there's all this data coming from all these direction and very consistent so blocking the growth hormone receptor. Now you know the FDA is, is not that interested in, in aging and so and investors are now very interested in aging. But that's, that's a drug that, whose path has not been funded yet. So we'll see right? We'll, we'll keep on trying. But yeah, I think if you think about safety and efficacy that is probably the best way to go.
- [36:03]
B
That's interesting. About two weeks ago I interviewed the new Head of the fda, and we talked about aging and longevity, and I was blown away. He seemed very committed to pulling out the stops, not taking 10 years to come out with new substances and embracing longevity. And this is in front of an audience of 500 people. So I was actually pretty excited. So I'm hoping they become more friendly real quick here, at least for the next few years. Are you seeing any benefits and not.
- [36:37]
A
Just friendly to longevity, but friendly to a much quicker and less expensive system of getting things approved? Right. So, for example, we're working on cocktails or drugs for cancer that we combine with the fasting mimicking diet. And it's really not a path to go forward with the FDA approval so that we can go fast and we can have these technologies used to treat cancer patients. So I think that it'd be nice if the FDA begins to look at, you know, what's beneficial to patients, you know, regulating, of course, more than what's beneficial to drug companies that, that are trying to get, you know, monopolies and sometimes on drugs that are out there. Right. So I don't think the system right now is set up for, let's say the cancer patient or the diabetes patient. It's more set up and. Well, yeah, the, the drug company puts a lot into it. And then the FDA process is so expensive, it's so difficult that nobody wants to even, I mean, unless you have a sure thing, you don't want to, nobody wants to touch that. And now we approach, for example, the FDA with the fasting mimicking diet. And they were very nice, but you know, there's already 60 ingredients in the fasting mimicking diet. So the discussion was like, well, maybe you can have seven. Right. And we go from 60 to seven. So the FDA is not set up for big changes. So hopefully they'll open up to these changes because they're badly needed.
- [38:17]
B
They are for sure. The national institutes of Aging seem like historically they were in favor of aging, not trying to stop it. So maybe they'll change their tune. Let's talk about cyclical keto. A lot of listeners will go into ketosis for a brief period of time or they take ketone supplements. What does a fasting mimicking cycle with Prolon give them that they're not getting from intermittent fasting and, you know, an 18 hour fasting window.
- [38:49]
A
I think that the main thing is this coordinated 3 billion year old process. Right. So the main, the body during fasting shrinks a little bit. Not very much, but it shrinks. And even in our clinical trial we showed that the people, based on MRIs, we see organs becoming smaller and then they re expand. Right. And so if you look at our mouse and rat data, they indicate that probably also in people, especially when we saw very similar results in mice than we saw in rats, we gain a good idea that this is probably conserved. And so, yeah, in these five days, the system shrinks and at that point the stem cells, the Yamanaka factors, the autophagy, and by the way, autophagy, in a recent study, which I think is not published yet, it took about five days to see markers of autophagy. Right. And this is also consistent with other work that was done before. So it takes a long time for lots of cells in the human body to activate these self eating processes. Right. So yeah, so you want to allow enough time so that things break down and then the system decides, okay, activate the stem cell, reprogram lots of different cells that may be damaged, and then begin the process of re expanding. Right. And that's in the next five days or seven days. And by the way, if you look at rats and mice, if you do, when you do refeeding, you see these Yamanaka factors go up at the end of the diet, let's say on day four or five of the diet. Right. And then on day one refeeding, you see many of the embryonic developmental genes still up, but sometimes you see them after three days and maybe even later than that. Right. So there is a process post refeeding that in some cases it could last weeks. Yeah. So this is just a brief description of why you, I mean, you can biohack your way to it and, and that has some effects. But this coordinated, really beautiful response that is fasting and refeeding, it's hard to match with anything else that I, you know, I always challenge people and I'll challenge you with the, you know, give me an intervention that will cause more changes in the human body than long term fasting and refeeding. Right.
- [41:17]
B
Oh, you and I are both pretty firmly in the fasting camp. I wrote the first major book on intermittent fasting and a second book because people were doing it wrong. So I think it's the most powerful other than maybe getting your circadian biology working. I think having bright light in the morning and having actual darkness at night and eating before it gets dark may be as important as fasting. Other than that, I couldn't come close.
- [41:41]
A
Yeah, no, but I was talking about actual molecular changes. Right. So if you, you took a cell, cells of a human body and you, you disrupt the circadian rhythms or you, you're on day five of the fasting Mickey diet and then you refeed, you see, you know, I mean, I don't know that anybody's ever done that, but I'll bet money that you see many more changes in there. I mean, everything after five days of fasting is revolutionized in the human body. Now if you disrupt this rhythm, you, you have some changes, but not, you would not have a revolution of your gene expression, let's say in the brain, in the liver, in the gut and everywhere else.
- [42:20]
B
Not in five days. If you did it for six months, you might see similar magnitude changes. Again, I'm just guessing, but it's so broad spread. The more I look into it, the more I'm like, wow, POMC and all the things that are activated even by UVA and uvb, there's a lot going on in the mitochondria that has chromophores that. I just think we're starting to understand that better than we have. But I'm with you. If I have five days going on a good prolon fast is the fastest thing you could possibly do with everything we know, including peptides and everything else.
- [42:53]
A
And by the way, I agree completely because we recommend FMD every, say three or four times a year and then 12 hour of time restricted eating per day. Right. So this is part of the longevity diet. And so. Absolutely, I mean, aligning with the circadian rhythms is very, very important.
- [43:08]
B
It's funny, I just personally have experimented with the lower protein things and it's, I almost wonder if there's a genetic thing. I'm Basque, like 28% or something. And Basque is the land of ribeyes, so there could be a genetic thing. Have you explored whether your ancestry affects the amount of protein or specific amino acids that you need in order to maintain your health?
- [43:32]
A
I have not explored it. But when you look at, for example, The Harvard studies, 120,000 doctors and nurses, you know, it's, it's probably all kinds of genetic backgrounds, right? So, so I would say overall it's probably pretty consistent. But yeah, there could be, there could be people that they need another level of, of proteins and amino acids to reach their goals. So. And it makes sense, right? It would make sense that the different people may come from, from different histories and, and with different needs and. Yeah, but seems to be fairly consistent. When you look at, you know, epidemiology or any other type of, you know.
- [44:26]
B
Pillar, I'm seeing kind of a breakdown of Some epidemiology over the past five years, as personalization gets bigger and bigger because, you know, you have the middle of the curve and you're designing. 80% of people are above this part of the curve. But if you're one of the 20% of people that's on either edge, the stuff that's supposed to work doesn't work for you. And we're finding 20 different things beyond MTHFR issues and things like that, where it's getting to be more and more and more personalized, where we might say, well, you're average for this part of your biology, and then this other part isn't average. So for instance, in a folic acid metabolism is a classical one. So I'm guessing that with AI over the next five years, we'll be to the point where we can say you should, based on your genetics and maybe based on your current state, you should do a prolonged fast every month or every six months, or we're already doing this. You need more of this nutrient, less of that nutrient, where if you look at a population of a million people, you don't have any granularity to be able to pull those people out. But when you look at pathways, we're getting better and better. Are you hopeful on that front where personalization is going to move in?
- [45:42]
A
Yeah, no, I agree completely. I think AI is going to do it fairly soon, and we're working on that, and lots of people are working on that. We're combining everything we know with what AI can do to personalize it. Absolutely. So I have foundation clinics, and in the foundation clinic, historically, we've done it one person at a time, one professional at a time. But this is why in the foundation, we have physicians and we have the PhDs, and that's the job, the PhD to do the AI work. The PhD will have more time and they can sit there and they can start thinking about you. Right? Well, we did this and it's not working, you know. And so, for example, we do the longevity diet. It's like pescatarian, low protein and, you know, mostly vegan diet. And some people, you put them on it and they lose a lot of weight and they do great. And some people, you put them on it, nothing happens. Right. And then, you know, a year later, but then you put them on and nothing happens. Then you start the fmd and that unlocks the insulin resistance. And so then it starts working. Right. So I think the toolkit, we have five or six different things, and with this, and when we personalize, we are pretty successful with most people in trying to achieve the things that we want to achieve. But yeah, AI is just going to probably do a much better job than, than even we can do it with lots of scientists and physicians.
- [47:11]
B
Yeah, it's getting better and better as long as we have an understanding. Another question that I've been just wanting to ask you ever since our last interview. I've become more and more convinced that oxalate is a driver of systemic inflammation which drives aging in a meaningful number of people. Because there's abundant studies showing direct mitochondrial harm from oxalate in foods. And when I look at a lot of the plant based diets, things like black beans are just full of it and beets and some of these other things. Do you have any perspective on oxalate and whether we need to limit that?
- [47:48]
A
I think that that's where I will go to the, to the pillars. Right. And say, you know, if you look at study after study after study, you will see these ingredients and the legumes coming, you know, at the very top among the top of the foods associated with expectancy increase. Yeah. So I would say that, you know, something could look bad. I mean there's data on olive oil. Right. Because in inflammation and, and so. But you know, overall I think that the, the, the overall effect is very positive. Positive or very positive? Now could it be that there's something even better? Yes, maybe there could be that if you eliminate certain food that have, you know, one of many potentially toxic molecules, you could do better. But then what would you miss? Right. So, so now you're removing a problem and maybe you're introducing a bigger problem. Yeah. So that's why I think that we have to focus on, on the multipillar system and say if this ingredient. So I really like, for example, Harvard's Francus latest study looking at how do you get to 70 or 75 healthy with no diseases. Right. And you know, and what are the foods that gets you there and what are the type of diets that, that are associated with an increased ability to get to that, to get to 70 or 75 cognitively and overall healthy. And yeah, so I think a lot of these studies point to the same vegetables. You know, sometimes the fruits are there, sometimes they're, they're not as high. So absolutely, fruits and vegetable can have inflammatory effects, but I think you have to personalize that. And this will again what we're doing in the foundation. So we have these diets that basically get rid of any inflammatory component. And some people, you know, gluten plus many, many hundred more ingredients and we just exclude them all right. And a lot of the people when do that, they feel they do a lot better. But it's a, it's a, it's not a small percentage of the population but I would say it's you know, maybe 1 in, in 5, 1 in 4, 1 in 5 that for whom we have to remove lots of ingredients that they may be inflammatory or you know, they cause problems or sometimes severe problems.
- [50:24]
B
It's interesting because we can metabolize about 200 milligrams of oxalate depending on your gut bacteria and some other metabolic pathways. But some of the western superfood diets have people on a gram a day and it does contribute to kidney stones and things. And when earlier we talked about well maybe it's not the meat, it's the amino acids in the meat. And if you're looking at say lentils, the light colored lentils are very low in oxalate, almost as low as white rice. So they're a source of carb, they've got some protein in them. If you're not sensitive to lectins, no big deal. But if you switch to like navy beans or pinto beans, those are very high in oxalate where you're getting 100 milligrams, half your total daily amount in a single serving. So it's like maybe we should recommend the right lentils the same way we recommend the right amino acids for people. And it's this level of personalization and it's kind of harm minimization that that is a part of this conversation because I'm not a carnivore but I do eat a lot of red meat because my markers improve when I do it and I feel like crap when I don't. But I also may be a Neanderthal, I'm just an n of 1. And so we're saying how do we make population level recommendations then? How do we tune them for people? And my prediction is that we're going to figure out more and more about oxalate but it's mostly because we paid attention before 1950 and then kind of stopped thing tension so.
- [51:53]
A
Absolutely right. So eventually some of these could end up being toxic. But it could also be that, you know, lots of people, they, they start on legumes, they, they feel terrible for two or three months and then they start feeling really well. So yeah, you know, so is there redistribution, rebuilding the microbiota with that, you know, bring it down to a level that is non toxic or could it be that, in fact that oxalate is stimulating certain responses that are more beneficial than bad in the long run? Right. So this is why you need the multipillar, because you don't want to say, well, oxalate causes this problem acutely, and so it's bad. You want to say, well, let's look at people that have been eating that pinto beans for 30 years. Are they all dead of, you know, colorectal cancer or maybe are they protected from colorectal cancer? Right. So, you know, hormesis. You know about hormesis. And so there's a lot of complex responses that the body goes through. But this is why we always say, stick with your. Among the foods of the longevity diet, what I call the longevity diet, which also learns from Harvard and from lots of other people. Pick the ones that your grandparents used to eat all the time. They always very good with. Yeah, yeah. So it's basically saying if your brain. Parents never ate pinto beans, you know, don't start having a ton of. And this is also the recommendation in the, in the foundation clinics, you know, don't all of a sudden, because it's part of the longevity diet, start, you know, get rid of everything you do and start eating, you know, beans six times a week because you might have a problem. Right.
- [53:39]
B
So, yeah, it's bad for your dating life, if nothing else, at least for.
- [53:42]
A
For the first couple of months. Yeah.
- [53:47]
B
Going back to fasting, is there a point where fasting starts to break things? And how do people know if they're fasting too much?
- [53:55]
A
Well, I think fasting, and I don't know if we talk about this the last time, but I hate the word fasting. Right. I always say it's eating. Is eating good for you or is it bad for you? You know, it's pointless. Right. So I think we need to move from fasting to exactly what we're talking about. For whom, Right? So like, like fd, Right? So you have a medicine, what's the dose, who takes it, when you take it? Otherwise we probably going to do more damage than good. Right? So because people hear that word and say, well, it must be good. You know, I could do three weeks, I could do two weeks, I could do one day. So, yeah. So then, you know, for example, we know that if you fast for long enough, your. Your body goes into a more of a hypometabolic or a thrifty mode. Right? And so. And so if you enter that modality, that could last a long, long time. Right. And we know this from the calorie restriction studies in humans and lots of other studies. So this is why for example we pick five days with a fasting mimicking diet and not five. I mean beside the fact that water only would be very tough, but also the fasting mimicking diet, for example in mice when we compare the fasting mimicking diet with water only fasting, water only fasting increased the leakiness of the gut and the fasting Mickey diet did not. Right. So but the point is that the length but also the composition has to be tested in mice and different organisms and then in people randomized trials and then at a certain point I think the medical community is going to say this looks good or no, this does not look good. Yeah. So I hope we can, can have that to avoid fasting disappearing. So fasting comes around every 50 years and disappears after 50 years because people, people are damaged by it, doing it wrong. Right. And then, and didn't do it too much and doing it too long and, and, and, and so it would be the same as, as people start taking their own drugs. Say you know, I come up with my own, my own medicine and you know, I, I think I understand it enough so I can decide what drugs I should take in and what kind of dose. Right, right, yeah, you can do that. But most people are going to be.
- [56:06]
B
Hurt by it unless they have ChatGPT.
- [56:08]
A
Right. I mean in probably five years. Right, in five years. I don't want to offend any doctors but I mean five or six years, you know, maybe that, that, that's going to get, you, going to get a better response. I don't know.
- [56:23]
B
Yeah, you wouldn't be the first high end medical professor who has said that AI is doing better than doctors real soon now on at least some things. So yeah, it seems like we're heading in that direction and not better than all doctors, just better than average.
- [56:38]
A
Somebody is already popular I think. But yeah, no, I'm not saying that that's what it's going to be but AI in fact is using a multi pillar system. Right. So AI, I mean least eventually it's going to get trained to say I'm not just going to look at epidemiological studies, I'm going to look at all and then, and then put it all together into a recommendation that keeps all of it in consideration. Right. So that's why I think eventually it's going to be more powerful than, you know, the individuals each focusing. Oh, I'm an epidemiologist and I'm an Endocrinologist and I'm a PhD, so. And each with an opinion, Right? So yeah, at some point, of course, we're not there yet because the sophistication is not there. And where do you learn? Right. How do you pick the good studies and separate them from the bad ones? Right. So yeah, so I think doctors and scientists can do a better job now, but for how long? I don't know.
- [57:54]
B
I've got a question for you. You're probably one of the few people who could really answer this because you've worked on IGF1, MTOR, PKA, and other longevity pathways, not just one. Can you stack, rank them from most important to least important for longevity?
- [58:09]
A
Yeah, I would say most important, I would go up to the master regulator, growth hormone. Right. Growth hormone receptor and growth hormone, because that's very, very consistent. Now the complication is, is it important lifelong or is it important during development? Because it just switches you to modality B, the long live model. So it's clearly the most powerful that there is. Right. But you know, when, when that becomes important, that's a little tricky. Now if you do, and if you look at studies then that start at advanced ages, at least in mice, then TOR seems to be the most promising because the studies on TOR started a fairly long old. In fairly old mice, and they still work and they still make a tremendous difference in the mice longevity and health. Right. So Taurus seems to be the. And rapamycin. And now rapamycin is a drug because arabamycin also causes hyperglycemia and lots of other problems. See, finding a way to modulate it in an optimal way. And of course the fasting diet modulates all of it. The growth hormone and the IGF1 and the TOR and the PKA. But yeah, so I would say, number one, growth hormone receptor modulation and number two, torture. And, and you know, insulin and IGF1 and TOR are all regulated by growth hormone, growth hormone receptor. So I think all of them are important, like, you know, high insulin, high IGF1, high TOR, you probably want to have low levels, but also you want to have. So we always. So if you think about fasting, right, you love low of all these, but then when people refeed, they'll have high levels of all of this. Right. So I think we've underestimated the alternation of low and high. Right. And so low it protects you. It gets rid of maybe autoimmune cells and maybe of cancer cells or pre cancerous cells and lots of other things. But then high is, is There to rebuild maybe parts of the immune system. Right. It's rebuild muscle and et cetera, et cetera. So yeah, so these growth factors have to. So. So this idea of restricting and blocking all the time is probably not the right one. It's probably better to alternate times of low levels in times of rebuilding.
- [60:48]
B
I certainly believe that about mtor. It should be chronically low and occasionally elevated so that you have regrowth. Right. So it makes a lot of sense. And you said something really important that people miss about fasting. If you fast for five days on water, the gut bacteria start eating the lining of your gut and you get a leaky gut, which can cause allergies and it certainly lets lipopolysaccharide toxins come in. They cause brain fog and systemic dysregulation. And one of the reasons I like Prolon and the fasting mimicking diet concept is that I. My first book I wrote about something called protein fasting and it was you can have a thousand calories a day with no protein. It was under 10 grams of protein. Protein. And you pretty much get the effects. But you've commercialized it and tested it in such a way going down the fasting mimicking diet that you're not creating the leakage in the gut. Which is why I think it's much more sustainable to do a Prolon fast multiple times per year because it's much less aggressive on the GI tract than just having a water only fast or something like that. Do you have concerns about people who are doing water fasts for multi days multiple times a year because of this?
- [62:08]
A
Yeah, I mean, not just because of this. Because of hypotension, because of hypoglycemia, because of the difficulties in. You know, I've done it once and I still remember every day of it. Yeah. So I think that's. There's lots of issues. That doesn't mean that I cannot, you know, help a lot of people. And a lot of people have been doing it even for religious reasons and they do great and it. So I don't want to go against it, but really, you know, the FMD is, we think of it as a drug made of food and it's got lots of things like glycerol, for example. Glycerol is there to protect muscle and to protect from, you know, to have a gluconeogenesis ingredient. Right. That can feed the muscle when can substitute to amino acid come from the muscle when the body's trying to make new glucose. So. So I think that, that's the idea of the FMD is trying to have the prebiotic components, is trying to match the longevity diets of the world. Like you know, the blue zones and, and, and what people. Some of the areas of the, of the world that have been the healthiest. I mean there was my idea from the beginning. Let's take the healthiest ingredients that you can think of and then match them with the fasting mimicking properties and then add things like glycerol to it that can improve it even more. Right, so yeah, so that was the idea.
- [63:46]
B
I absolutely love it that you're talking about glycerol. And most people even in the influencer health community are unaware of this. But there are studies that show it like that taking glycerol can have an effect similar to taking creatine on cognitive function and mitochondrial output. It's really good for hydrating cells as well. So I love that they actually have added instantized glycerol to electrolytes. I just put a little bit in a glass of water. The only problem is if you get too much of it, it gives you gi upset pretty quickly. So you're using the appropriate dose. I haven't seen that from Prolon. And that's like a, it's going to make people's brains work better when they're on the fasting mimicking diet. And it's just unacknowledged in this space.
- [64:33]
A
And it is a fasting response molecule. Right. So glycerol will go up as you fast for of course from breaking down triglycerides. So that was also the reason for putting in there. It wasn't, you know, a biohacking supplement. It was more like consistent with the fasting response months. What would the human body have in relatively high levels during fasting? And glycerol is one of those molecules, right? So yeah, so I think that's the way I approach the development of the fasting making diet. And by the way, I give everything to charity. I don't take a penny from El Nutra, the company that sells the product. And even my shares will all be donated to charity. So just to make sure that people don't think that I'm here advertising for a product.
- [65:22]
B
Valter, you're working for the good guys. And so is Dan Buettner, by the way. There's some people in the carnivore community who are just hating on Dan and he's a true believer in longevity and just a great human being. And the fact that we don't all agree on everything, it doesn't matter. But I have no questions about your motives. You've been studying this for 30 years because you care. And thank you for that. You've moved the, the, the knowledge forward. What's your take on creatine?
- [65:47]
A
I'm always worried about supplements and you know, because I always, I in my book years ago, I talk about vitamin C, right? And say, well of course, you know, Linus Pauling and many, many people have talked about vitamin C, but, but I'm afraid that you know, creatine and, and vitamin C and lots of other molecules, they are going to do good and bad and, but the main thing is they're going to disrupt this equilibri. This is very sophisticated equilibrium that the human body has built after billions of years of evolution. As you mega dose anything, of course it's gonna maybe a very powerful effect for whatever it is that it does. But then what happens to this equilibrium, right? What happens to everything else that, that, you know, so, so if you think about a hybrid car, right, and it has been designed a certain way to alternate between using the combustion and, and the electric engines. And so you know, what happens if you put it, if you try to force it together, right? Well, it could maybe go faster for a while, right? And you get a lot of benefits. But, but then what, right? It wasn't designed for that, right? So, so yes, you add in mega doses of molecules, you could have very beneficial effects. But then you're pushing the system in direction and GLP1 is another example, right? And are you pushing this glucagon receptor, agonist receptor with an agonist and you keep pushing and pushing and pushing in a, in a, to a receptor or a receptor that is not, it was never stimulated like that, right? Not in combination with all this food that is coming in and all these, this, you know, molecules that are normally not associated with high levels of GLP1. So yeah, so what happens that after two or three years of that, a mixture, this mismatch between a drug and, and what the body normally did when GLP1 was in fact elevated and you know, and how long is normally GLP1 elevated for? And you know, and what, what does it coordinate with when, when it's elevated? Right? So we think like that, you know, and it doesn't mean that there could be exceptions where, where hey, it just happens to be good. Okay. Then we say okay, show me the mice living longer, right? And creatine does not make mice live longer. I'm pretty sure it's been tested by the intervention program in mice. And show me the rats who are living longer. And show me the epidemiology. If you don't see this up, I mean, clearly positive in each, say, maybe not in all five pillars, but say three pillars out of five, say, hey, if you give creatine to a mouse, it consistently lives longer. Okay, that's a good start, right? And, you know, epidemiology is like 30 days Meta analysis on creatine levels and, you know, longevity, extension or life expectancy. That would be another good one. Yeah. So if those come up, then I'll say, okay, that looks interesting.
- [69:21]
B
The idea of equilibrium is something I've really struggled with because I recognize that there is such a thing, but we've already disrupted it. I was in Dubai last week. I'll be in Paris tomorrow. I'm sitting under LED lights. I'm surrounded by microplastics and endocrine disruptors and all sorts of things that create disequilibrium, unnatural EMFs, glyphosate in food. There's a lot of stuff out there, there. So part of my goal with biohacking is, say, well, if you're not in equilibrium because you're not living in the forest, the way we evolve to, how do you use selective interventions to bring yourself back to equilibrium with the environment that we live in versus the one that we evolved in? And it's a delicate dance. So I also seek equilibrium. I also know that if I can increase hydration in the brain and my cognitive function goes up, even if I, I don't extend my life, if I'm smarter, more focused and more awake and it's not going to shorten my life, I'm totally okay with that. So there's something in the middle. And it's just my hope that as we get better at doing RNA testing, so we can see what's actually going on in there and we start just getting better and better data that pretty soon we'll be able to say, yeah, creatine, that was a fad, or maybe it wasn't, but we'll actually know instead of guessing pillars.
- [70:48]
A
Right? So pillars are. You can test it. Right. So we are bombarded by all these chemicals and, and, and devices and problems. But okay, why don't we see. So are the mice right? Mice probably have microplastics and, and they're exposed to lots of, lots of bad things even in the lab. But yeah, why don't we see that? Right? Why don't we see it consistently? Right? So if the mega dose mouse did something. You should start seeing it over and over and over. Right.
- [71:19]
B
For longevity. Agreed. We're not measuring like the mouse's subjective well being.
- [71:27]
A
Ability to focus.
- [71:27]
B
You can measure that. Right?
- [71:28]
A
You can measure the well being. You can have quality of life testing. A lot of epidemiological studies have that. Right. And the Harvard and Montreal study that I was referring to earlier, you know, they were not even looking at longevity. They were looking at can you get to 70 or 75 healthy. Right. With cognitive function. And, and yeah, so. And what was in there? They came up, you know, it was vegetables, it was nuts, it was so. And they made a big difference. Right. So there was maybe 10 different things that you shouldn't do at any things that you should do. And that's one pillar. I mean, so I would say yeah, if creatine builds that type of data behind it then and maybe it is effective.
- [72:19]
B
But there is good data not for longevity, but in mice it reduced anxiety like behavior. Creatine had antidepressant like effects, enhanced cognitive performance in mice in multiple studies and it also increased exploratory interest. None of those are longevity, but all of those are useful for humans. So I'm like, okay, if it's not going to make me live less and it's not going to give me cancer, there's that. I don't like the word hellspan. I think it's kind of dumb. I would like to extend life, not just be healthy and die at a normal age, but I also want to have full energy and vibrance. And that's one of the motivations behind biohacking. But the fastest thing you can do is restore equilibrium. But it's got to be equilibrium matching the life you're living. And it goes in a different direction than longevity. But I think longevity is the final goal. I just don't want to feel like crap and live twice as long as.
- [73:15]
A
Those don't go along. Right, so. Meaning that if it's something that is making the mice healthier, like growth hormone receptor knockout, it's also making them long lived, making them healthier all the way. Right. And more, more vigorous and better memory. And so they usually go along. Function, strength and longevity, they're very closely connected. And you know, and now the argument would be, well look at what this mutation that where the mutation is that is making the biggest impact on healthy lifespan is growth hormone, the same growth hormone that people inject for short term impact on health and longevity. Right.
- [74:01]
B
And you're saying having a lower Growth hormone over time extends life.
- [74:04]
A
Yeah, I'm not saying, I'm saying this is what 100 years of data indicates.
- [74:09]
B
Yeah, you're saying it backed by the science because you generally only say things backed by science, in my experience of you.
- [74:16]
A
I'm saying this is the same growth hormone that people take for short term effects, which, which have a lot of the features that you just described for creatine. Right. So a lot of people will have great benefits short term. Right. So the question is, we already know from acromegalaxy the very high levels of growth hormone, and they die very young with lots of problems. Right. And same thing for the mice and the rats. So I think that we have to be careful, right, because short term effects and long term, you know, consequences are very, very different. So we, you know, ideally you want to have both. Right? You want to have short term effects and then you want to have the support of the, of all the data indicating that you're going to live longer and you're going to prevent cancer and lots of other diseases.
- [75:07]
B
And sometimes we just have to take a flyer like, I, I think I'm there with creatine in part because getting Alzheimer's and Parkinson's is bad news. And, and even in mice there are studies showing that creatine protects the dopaminergic neurons in the brain over time. So if I can lower my Alzheimer's and Parkinson's risk, it's probably good for longevity. But I could be wrong. And it's the not knowing and then just kind of making a bet and then tracking your numbers over three years and, oh, that was a dumb bet, and then going another direction. Not everyone's going to do that, but the people who are, are curious about this are probably going to do that. And hopefully we share enough of that with AI and on Reddit and everywhere else that it starts to bubble up into something that maybe you'll study in the lab. Not necessarily creatine, but just any of the things where people are doing things that seem stupid, but they seem to be getting results, and we scratch our heads and go, man, we should test that. Because I'm hopeful that more things will pop out just from looking at, not epidemiology, but from looking at a massive, massive data set that has enough data behind it that we can personalize it, like, oh, only people with this gene does that work for. I'm actually feeling like we're right on the cusp of the golden age of personalized longevity, where the things that you've found with the fasting, mimicking, diet, I think they're foundational and that there's going to be other little tweaks that become more and more not just backed by science, but backed by science for you, but not for your wife or your best friend, because they're just not the same. Do you think we're close to that?
- [76:42]
A
Yes, I think we're very close. Right. And I think it's a combination, as we were saying earlier, of AI and the right group of people because as you know, with anything you have, I always say if you're going to get surgery, you're going to look at, you know, what university this surgeon has graduated from and you know, how many years of residence, I mean, residency, where did he do it or she do it, etc. Etc. And so I think that AI is the same way. Meaning, like you have to pick the best of the best. Right. And lots of people, each with different expertise. And if you do that and combine it with AI, I think it's going to be very powerful, but I think the filtering is going to be needed of all the junk. Right. Because if you insert a lot of bad information, AI, at least right now, doesn't seem to be doing very good at bouncing it. But yeah, see, once the good group of people gets together with AI and yeah, then the personalization is very close. Right. Because the ability to process the information is going to be a million times faster than any group can imagine.
- [78:05]
B
I'm similarly hopeful and it's an exciting time, even just getting daily heart rate variability changes and all. I'm stoked. And without the mechanistic pathways that you've been pioneering, we just don't understand. I don't understand it. I want to ask you one more question about growth hormone here. Is there a case for suppressing growth hormone in people in order to live longer?
- [78:28]
A
I think there is a case for suppressing it in those that have high levels of it. Right. Or not high levels of growth hormone, but high levels of the growth axis. Right. Growth hormone, insulin, IGF1, TOR. So if somebody is consistently and constantly in this pro growth mode, because, you know, the Laurent, for example, and the mice live longer, they have very high growth hormone and very low IGF1 because the growth hormone receptor doesn't work. Right. So that's probably very good. But what's not good is very high growth hormone, high insulin, IGF1 itor. And yeah, so in that group, which is probably maybe half of the people that are relatively young in the United States, yeah, they probably would Benefit now in know, we don't know. I mean nobody has done that test but I mean I, I wouldn't be surprised if eventually we look at IGF1 as we look at cholesterol right now and we say, we wrote a meta analysis on that where we said well between 120 and 160 seems to be ideal for mortality and people that have much lower they do poorly and people that have higher, they do poorly. So yeah. So then the possibility would be check your growth factors level levels and then if you do have 280, yes. Maybe you want to bring it back to less than 160.
- [79:57]
B
It makes good sense. So we want to have it at the level where we have enough muscle and we're not losing our brains but not too low and not too high and so equilibrium yet again. Valter, your work is fascinating and it's groundbreaking and, and I think your innovation with a fasting mimicking diet is absolutely worthy because a lot of people, they're just not going to do a five day fast for a long period, over and over for long periods of time. It is burdensome and this is an option and you've shown with really clean science that this works, why it works, how it's put together. So this is a really good innovation. I'm glad you did it. And I'm still not certain that I'm going to go down to what was it, 0.36 grams of protein per pound of body weight. I think I would blow away and not feel so good but I recognize that that might work really well for some people and not for others and I'm happy to play with my levels to see what works and I'm truly grateful that you're just open minded and asking questions and, and sharing the science. So keep doing what you're doing for hopefully another 100 years.
- [81:09]
A
Hopefully, yeah. And if you do lower your protein then that way I would love to know what happens. Right. Is there a major impact on your muscle or anything else? Right. So yeah, that would be interesting.
- [81:20]
B
I'm, I think if I can find a time when I'm not going to be on an airplane and like for a month or something I would do that with the amount of travel that I'm doing now I, I know that if I lower the protein my cognitive function goes just not, it's not a good thing. But I also have very weird biology compared to most people so. But I'll play with it and I will share the results with you and with everyone else too. If I radically cut my protein for long periods of time and nothing bad happens. That'd be amazing. So give me six months to find a window. In the meantime, I'll just eat some Prolon occasionally.
- [81:52]
A
Sounds good.
- [81:54]
B
Okay, thank you my friend.
- [81:55]
A
Thank you, Dave.
- [81:58]
B
See you next time on the Human Upgrade Podcast Podcast. 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 carefully read all labels and heed all directions and cautions that accompany the product. 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. 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.