The Groundbreaking Science of Water Fasting w/ Valter Longo | EP #78

In this episode, Peter and Valter discuss the principles of the fasting-mimicking diet, which involves a 5-day period of reduced caloric intake to impact various diseases and potentially extend lifespan positively. The episode delves into the science and practice of dieting, intermittent fasting, and the importance of what, how, and how much to eat for optimal health and longevity. 19:17 | Fasting's Autophagy Effects 27:55 | Benefits of Water Fasting 56:20 | The Five Pillars of Longevity Valter D. Longo, an Italian-American biogerontologist and cell biologist, is a prominent figure in the field of longevity, dedicated to eradicating age-related diseases and educating people on living a healthy life. Known for his groundbreaking research on fasting and nutrient response genes, Longo's work focuses on their impact on cellular protection, aging, and diseases. He currently serves as a professor at the USC Davis School of Gerontology and as the director of the USC Longevity Institute. Learn more about ProLon here: https://prolonlife.com/MOONSHOT Learn more about my executive summit, Abundance360 ____________ I only endorse products and services I personally use. To see what they are, please support this podcast by checking out our sponsors: Get started with Fountain Life and become the CEO of your health: https://fountainlife.com/peter/ Use my code PETER25 for 25% off your first month's supply of Seed's DS-01® Daily Synbiotic: seed.com/moonshots _____________ I send weekly emails with the latest insights and trends on today’s and tomorrow’s exponential technologies. Stay ahead of the curve, and sign up now: Tech Blog Get my new Longevity Practices book for free: https://www.diamandis.com/longevity My new book with Salim Ismail, Exponential Organizations 2.0: The New Playbook for 10x Growth and Impact, is now available on Amazon: https://bit.ly/3P3j54J _____________ Connect With Peter: Twitter Instagram Youtube Moonshots Learn more about your ad choices. Visit megaphone.fm/adchoices

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• 1:00Peter Diamandis?

  What are you trying to do that's going to change the world?

• 1:04Speaker 04

  I think that...

• 1:07Peter Diamandis?

  There's a lot of work around these blue zones around the world, a lot of them in Europe, in Italy, in Greece, in Japan. What's going on there that is driving people to get to a centenarian and supercentenarian level?

• 1:20Speaker 04

  Thinking about the blue zones and thinking about what are the healthiest food in the world, ingredients in the world. So calorie restriction, as you mentioned, can extend lifespan, but what only fasting is something that maybe 1% of people could do, kind of like chronic calorie restriction, maybe 1 or 2%.

• 1:41Peter Diamandis?

  Everybody, welcome to Moonshots. Peter Diamandis here. The conversation we're about to have is with Dr. Walter Longo. He is a professor at USC and he's the creator of something called the fasting mimicking diet. Have you ever heard of it? It's a way to painlessly reduce your caloric intake for a five day period that has incredible impact on all kinds of diseases like diabetes, inflammatory disease, inflammatory bowel disease, even cancer. What you eat can change the course of your disease and really potentially extend your lifespan.

• 2:15Peter Diamandis?

  One of the incredible thinkers, the author of The Longevity Diet. We're going to have a conversation about intermittent fasting, about all the details around food. This is one of my favorite subjects because it's something easily done. So if you're a longevity fan like me, let's jump in. Before I do, let me just mention, I love sharing the incredible conversations I have with you. I'm committed to delivering the smartest individuals to you and having conversations that are in-depth in terms of inspiration and guiding and science and technology. If that's of interest to you, please subscribe. Let's do this together. When you subscribe, it lets me know that you're interested in these subjects. All right, onwards to our episode. Everybody, Peter here.

• 3:00Peter Diamandis?

  Welcome to Moonshots. We're going to be discussing a topic today that I'm super excited to learn about alongside with you. And we've talked about, you know, sleep and exercise and supplements. Let's talk about diet today. Dr. Walter Longo, as I introduced, is really one of the world's experts in this area. Walter, it's a pleasure to have you here. I'm looking forward to talking about the science and the practice of how and what and how much you should eat. Walter, normally you're at USC, just down the road from me, but today you're across the Atlantic. What part of Italy are you summering in right now?

• 3:37Speaker 04

  I'm actually in southern Italy, in a region called Puglia.

• 3:41Peter Diamandis?

  Well, a pleasure. So let's begin. I'm super curious. Your work is the cornerstone of a lot of conversations around fasting, fasting mimicking, some of the terms we'll be talking about, the science. You've done a multitude of clinical studies here, and it really has changed the way I think about what I eat, when I eat, how much I eat. But how did you start this work? Where were you when you started thinking about dieting as part of the longevity area focus?

• 4:22Speaker 04

  Yes, I actually started very early. I was a student of Roy Wolf for the UCLA and he was my mentor, PhD mentor. And Roy was at the time probably the most famous person in the world for nutrition and longevity. And he was working on something called calorie restriction. And in fact, when I met Roy, he was not at UCLA. He was actually inside of this place called Biosphere 2, which was a sealed environment in Arizona. And him and other seven people locked themselves up in that environment and stayed there for two years.

• 4:59Speaker 04

  So it was, I guess I had a major moment, let's say, a major exposure to this world. And Roy was a little bit crazy, but I think he was a real pioneer and a real dreamer. And so that was, they made a big difference on me. And then after that, I end up back to the biochemistry department, working on starving bacteria and starving yeast. I think also influenced by Roy and the fact that he had been working on calorie restriction. But I went much further and so I just say, well, what if I starve bacteria and yeast? What happens then?

• 5:41Speaker 04

  And since then, it was 1992, 93. That's all I mean, I focused on that, let's say.

• 5:48Peter Diamandis?

  You know, I knew Roy and I was at the first Biosphere enclosure and then the coming out party. Two of my friends were there, Tabor and Jane, Tabor McCallum. And I remember it was an incredible story and just for our listeners, a A group in Texas decided they were going to try and create the first experiment for a biosphere with the thought if we eventually go to the moon or Mars or into space, we want to be able to grow our food and create a self-contained, closed economic environmental system. And so they put, I think it was eight people inside this enclosure, a glass enclosure.

• 6:30Peter Diamandis?

  The only thing that came in was sunlight. They had fish in a pond, they had crops they had to harvest and eat. And so they had to balance, they had to grow enough food for two years for them. And they had to balance the CO2 and the O2. And this grand experiment goes on. And the challenge was, the flying, the ointment, so to speak, was the engineers didn't realize that the concrete they had used to basically build this enclosure was absorbing CO2. It was absorbing CO2, wasn't it? That was the issue. And so as you started,

• 7:13Peter Diamandis?

  because the CO2 started getting absorbed out of the air, and they had eight scientists inside this biosphere, everything is going fine, going fine. And then all of a sudden, the CO2 levels are dropping, and the plants are not growing as well. And all of a sudden, they're on forced calorie restriction. And they reduced their caloric intake a lot, didn't they?

• 7:32Speaker 04

  I mean, different. Different members did different. Walford was the one, if you look at the charts, that lost the right amount of weight. I think maybe the other ones were cheating a little bit. But overall, they were probably at least 10% calorie restricted. And if you look at the data, it's a pretty impressive changes, which were then confirmed by randomized clinical trials by lots of other people. And by the way, Peter, we were at the same party then, because I was there when they came out. And I remember there's a lot of interesting characters, including Timothy Leary.

• 8:04Peter Diamandis?

  Timothy Leary was there?

• 8:05Speaker 04

  At that party.

• 8:06Peter Diamandis?

  Yeah, exactly.

• 8:08Peter Diamandis?

  Yeah, no, we're the same exact, exact same party, whatever that was 40 years ago, 30 years ago. Anyway, so if I were going to ask you, Walter, what your moonshot is, what are you trying to do that's going to change the world? What's your goal?

• 8:25Speaker 04

  Yes, my focus lab wise, but also the focus of two foundations that I started a while ago is helping people get to 110 healthy and with nutrition, but lots of other things. I mean, nutrition seems to be the safest and quickest way to go right now. But, but I think we're also working on drugs and other interventions to do that.

• 8:47Peter Diamandis?

  Well, I for one want to get to 110 healthy and then blast through that. And you know, a lot of people listening to this podcast, because we cover longevity and health a lot as well as AI and other subjects, you know, want to set a target. And, you know, in the past, I think people would set a target of 80 years old or 90 years old. Some might set of 100. A friend of mine, Dan Sullivan, set 156. When I was in medical school, I remember learning that, you know, bowhead whales could live 200 years and Greenland sharks could live 500 years. And I said, you know, well, if they can live that long, then why can't we? What's your longevity goal? How long do you want to live?

• 9:26Speaker 04

  I wouldn't mind making it maybe to 125 or so. I mean, realizing how difficult that is. But yeah, I think I've seen that 110 with Salvatore Caruso here nearby in Calabria. I followed him for my entire life. And, and I see 117, I've seen 117 with Emma Morano in northern Italy. And she was at the time the oldest person in the world. So I've seen it happen. And I'm thinking, why not? You know, maybe. Maybe I'll get to 125, or maybe I die tomorrow.

• 10:04Peter Diamandis?

  Before we jump into the whole conversation around your particular research, and this idea of fasting-mimicking diet versus an actual diet or a water fast, and we'll get into that. I'm curious your thoughts on the blue zones. There's a lot of work around these blue zones around the world. A lot of them in Europe, in Italy, in Greece, in other look, in Japan. What's going on there, you think, that is driving people to get to a centenarian and super-centenarian level?

• 10:38Speaker 04

  Yes, so I go there a lot, especially to the one in Sardinia and to Lomalinda. And I think that Sardinia, when you look at Seulo and Villa Grande Strisaili, you realize, but also Calabria now, we've seen lots of little towns that have a very high prevalence of centenarians. And I think you realize that the genetic factor is probably much higher and more important than previously described, right? Meaning that you see lots of the centenarians saying, you know, I had three or four brothers and sisters, and one made it to 95, one 98, one 102. And in fact, this was the case for Emma Morano.

• 11:21Speaker 04

  Emma had six brothers and sisters, all of them, I think, made it over the age of 88, which is extremely rare, almost impossible to happen in a single family. So, yeah, so I think that in at least some of these blue zones, there is a genetic factor. And some of them, there's a lot of inbreeding, like Seulo and Villa Grande, there are these little towns on top of the mountains. Maybe a few families represent, you know, 70 or 80% of the population. So a lot of inbreeding, and we suspect that the may create this like super longevity, almost like gossity, right? So that they get two copies, they eliminated the bad genes, and then they get two copies of the good genes. And that's what I suspect.

• 12:06Speaker 04

  But obviously, the lifestyle is also right on, right? So a lot of exercise and really good diets. And so probably, I always say not to be Michael Phelps, you probably need everything. And so you cannot, you just, you gotta train, but, but you also have to be born, right, with the right genetics. And yeah, so I, it wouldn't be surprising if these world records by these little villages are there because of the combination of genetics and also all the lifestyles that you can think of.

• 12:38Peter Diamandis?

  You know, we talk a lot about extreme longevity and even the idea of longevity, escape velocity, that science extends your life for more than a year, that every year you're alive. And I ask folks like David Sinclair and George Church and Ray Kurzweil, you know, is there a limit on the human lifespan? In other words, if we're able to alter epigenetics or alter your genetics and so forth, is there any reason why we can't make it past 120, past or to 150 or greater? How do you think about that? What's the evidence you're seeing? Do you think we can get to over the next decade using AI and quantum chemistry that

• 13:20Peter Diamandis?

  we can move the needle and extend, you know, to super, super centenarian, so to speak? Is that science fiction? Or is there some rational reason to believe that's going to be within the hands of science in this next decade?

• 13:33Speaker 04

  Until you say then, within the next decade, I had a very positive answer. So yeah, I think that the eventually, obviously, we're going to live a lot, lot longer. And it's not going to be just 110. But I always cite my, my lab, it wasn't my discovery, but somebody in my lab in the 90s discovered the gene, the SOD mutation for leukoarthritis disease, right? And when we discovered that, when they discovered that, we thought, yes, you know, within 10 years, we're going to cure this disease. And so, you know, there was

• 14:12Speaker 04

  a point in 1994, 95. So 30 years have gone by and we're still nowhere even beginning to cure ALS, leukoarthritis disease. Yeah. So unfortunately, the, the reality, even if you consider the exponential growth, and the exponential growth was also for ALS since 1992 now, right? So we were much, much better than 30 years ago in lots of different things. But You know, people still die and suffer miserably from from leukatic disease. So yeah, it's wishful thinking in ten years. I think as you get to twenty or thirty years, may not necessarily be wishful thinking,

• 14:52Speaker 04

  depending on on what happens in these thirty years and some really key, you know, key discoveries, especially on the safety, right? You can reprogram all the cells you want, but you know, are you gonna put the person at risk? And remember when gene therapy was first started, you know, one person died and this this delayed the the use of it. But it was a great technology and it was just, you know, one person was enough to to cause a big problem for twenty or thirty years, right? So.

• 15:28Peter Diamandis?

  Yeah, no, I remember that very well. I was I was in the field at MIT and Harvard at the time, and I remember the promise of gene therapy and it stopped cold, like you said, until the safety was put in place. But, you know, even even the promise of twenty or thirty years from now. So if someone's in their forties, fifties, or healthy in their sixties, if you can make it, you know, an extra twenty or thirty years, get it get to ninety, then the potential to intercept these technologies may be may be there. And I think the other thing to remember is it's a nonlinear progression. It isn't like we're just incrementing the same amount every year.

• 16:10Peter Diamandis?

  We're doubling in power with massive compute capabilities coming our way.

• 16:16Speaker 04

  Yes, and I mean, I guess the goal in thirty years will be maybe to to get an extra twenty, thirty years and then, you know, and then go from there, right? So so, yeah, I think if we achieve that, it's very achievable in the next thirty years that we add thirty years to the life. And I mean, I always said it's gonna be two populations, one that does all the right things, and they may live twenty, thirty years longer. And the other group, I think, is gonna live probably about the same as now. But of course, yeah, with the technology, maybe we'll we'll, I mean, I'm talking about nutrition. And fasting and fasting mimicking diet and all that. But yeah, with the technology, I think it is possible.

• 16:57Speaker 04

  Maybe we have initial technologies that get us another 20 or 30 years. And then we have, you know, now 60 years to, at least the ones of us that are in our 50s to get there. But, you know, it's a fun, for sure, it's a fun moment, revolutionary moment. And we just have to see what happens.

• 17:25Peter Diamandis?

  Well, I can guarantee everyone listening to our voice and our podcast today is doing, gonna be doing the right thing. So let's jump into that. So you start your graduate work or postgraduate work starving bacteria and yeast. And then getting to the point and realizing, I mean, there's actually, there's a few very concrete things that one can do to extend the human lifespan. And caloric restriction is definitely one of them. You may not want to live that much longer if you're restricting your caloric intake radically. But it is definitely one of them. If you could walk us through the work you did at your postgraduate work through to

• 18:08Peter Diamandis?

  the development of this fasting mimicking diet. But let's, let's begin with FMD fasting mimicking diet. What is that? And how does it compare to a regular diet?

• 18:18Speaker 04

  Yeah, so, so calorie restriction, as you mentioned, can extend lifespan. But if you look at even mice, about a third of the mice that are placed on severe caloric restriction actually live shorter. About a third live the same and a third live longer, right? So it's more complicated than people appreciate. And I think the FMD, coming out of Wolford Lab, the FMD was a way to say, well, maybe there is a way that makes it a lot less hard for people. You could do this maybe once every two or three months. And you don't lose muscle mass like you do for calorie restriction. And you know, and you can get all the benefits of calorie restriction.

• 18:57Speaker 04

  So the fasting weekend diet is something that lasts five days, is plant-based, is low calorie, low sugar, low protein, high fat. And has the job really of shrinking, at least partially shrinking the human body or the mouse, and then re-expanding, right? So it's something very simple, but incredibly powerful, right? So why? Because when you shrink, you start this self-eating process, this, you know, repair process. And when you re-expand, actually, as we've shown in lots of different papers in mice, you turn on embryonic developmental genes, right?

• 19:38Speaker 04

  So I think that, you know, and this is all coordinated. I talk about three billion years of R and D, right? Because this is really nature's way to rebuild organs and systems. And so I think it's probably going to be the first success. I mean, I'm biased, obviously, but the first success in causing multi-system regeneration and rejuvenation in a safe way, in an effective way, just because we're already there and so, and it is safe and we already have data showing that it's effective.

• 20:16Peter Diamandis?

  So let's introduce the term autophagy, which is a term which obviously you've done a lot of extraordinary work in as well, which is when you're in this fasting mode, your body will begin to autophagy, which means to eat oneself in one sense, to start killing the senescent cells, and as you said, to shrink the body and put yourself. It's the equivalent in the seasons of life, it would be fall, where you're shedding. And spring would be the return if you would. How much dieting does it take to trigger autophagy in the body?

• 20:56Speaker 04

  It looks like it needs about three. Of course, autophagy in some cells may start early, maybe one or two days of fasting. But I would say if you want to see where the weight of multiple or most organs shrink significantly, you probably have to go four or five days. And that's what the FMD, the fasting making diet does. You know, it gets to the five days of fasting. And that's when you begin to see a reprogramming and you begin to see the shrinking of lots of different systems. For example, if you look in people, a white blood cell number, you'll see about in over

• 21:40Speaker 04

  70% of the subjects, you see about a 20% decrease. So that indicating that the body is beginning the process of lowering white blood cell number, keeping them high enough, but lowering them and also redistributing them in different to different places like the bone marrow.

• 22:03Peter Diamandis?

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• 22:45Peter Diamandis?

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• 23:29Peter Diamandis?

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• 24:13Peter Diamandis?

  healthy lifespans. Go to fountainlife.com/peter. It's one of the most important things I can offer to you as one of my listeners. All right, let's go back to our episode. So just for reference, when Walter is speaking about the fasting mimicking diet, there's a company that's licensed his technology. It's a product I use called ProLon by L Nutra. And when you order ProLon, you get a box of day one, day two, day three, day four, day five. And these are powders or soups and some bars that you eat that are very, very specific amount

• 24:52Peter Diamandis?

  of calories and specific fats and proteins that mimic dieting. The alternative in the old days was doing a water diet, right? Where I'm just Drinking water, maybe some salts mixed in with the water to try and cut my caloric intake down to zero. But let's contrast one second, the the Prolon fasting making diet with a water diet here to understand, is it better to go with zero calories and just water? Or is it better to go with the Prolon? And how many calories are you taking in on day one through five on the on the Prolon FMD?

• 25:33Speaker 04

  Yeah, so obviously, eventually, if you want this to be, you know, let's say, a worldwide or certainly a popular intervention, it has to be very safe, it has to be very feasible, you know, people, the majority of people be able to do it. And I would say water only fasting is something that maybe 1% of people can do, you know, kind of like chronic calorie restriction, maybe 1% or 2%. So I've done it one time and I still remember every day of it. And and this is how the FMD started with a clinical trial at USC, Norris Cancer Center, on water only fasting. And we were convinced when we started this, this is like 2010 or so, when we were start,

• 26:15Speaker 04

  we started the trial, water only fasting and chemotherapy, we were convinced everybody was going to do it, highly motivated group of people. And the great majority of people did not want to do it. And and the oncologists did not want to do it. And that's when we went to the National Cancer Institute and National Institute on Aging and said, I think we need to develop a fasting making diet, right? So most people don't realize this, this is why we we develop, we study, develop it and tested the fasting making diet. So, yeah, so then it's 1100 calories on day one, 800 calories on day two to five. And but it's the composition that that matters the most or as much.

• 26:55Speaker 04

  And so it's a lot of tweaking of not just the low protein, let's say, or very low protein, but also the type of protein that we use. So the certain amino acids that interfere with the effects of fasting are so low that it's like you did not have food at all.

• 27:13Peter Diamandis?

  So if I remember correctly, on the Prolon FMD, it was something like 1200 calories the first day, then down to 800 calories for the next four days or something like that?

• 27:25Speaker 04

  You know, 1100 going down to 800.

• 27:29Peter Diamandis?

  Yeah. And how many calories does a person normally take? So I'm 150 pounds, 152 pounds, something like that. I'm, you know, in a, in probably my best shape in terms of percent body fat and such and muscle. But I think about that. What is your, what's your advice for caloric intake in the first place?

• 27:51Speaker 04

  Yeah, I mean, the average American, I think a male is around 25, 2700 kilocalories per day. But, but I think that it's pointless. It doesn't mean anything. You know, it depends on energy expenditure and lots of other things, right? So it's really about your, your abdominal circumference, your BMI, body mass index. And so how much fat you have, how much muscle you have. And, and then you adjust based on that, right? So, so you could be eating 3000 calories a day, and that might not be enough. Or somebody may be eating 1600 and maybe too much. Let's say a woman weighing 100 pounds in perfect shape. So, yeah, so

• 28:32Speaker 04

  I think it's, yeah, counting, counting calories is pointless. Much better to, to focus on the, the results of that and, and adjust the food based on how you respond.

• 28:47Peter Diamandis?

  All right. So the FMD here is 1100 calories, reducing down to 800 calories, I think, for the last three days. And I remember when I did it, it was, it was pretty easy to do.

• 29:00Peter Diamandis?

  But my question in the back of my mind is if I really want to cause autophagy, if I really want to make a difference and trigger my body, is it better to just do a water diet solo? And I remember speaking to the CEO of ProLon, and he said, listen, the science actually, according to the studies, were that no, actually doing a fasting mimicking diet in terms of the healthy outcome of, you know, multi-system regeneration and all of the benefits, it was better. To do this reduced caloric intake versus a zero caloric intake. Is that what your research also shows?

• 29:42Speaker 04

  I think he was referring to my research probably. So I think that water only fasting can work for lots of things, right? But we compare this. For example, for cancer, they work about the same, right? And so if you take a mouse and you put it on water only fasting, and you do, let's say, three days or four days of fasting making diet is about the same. But of course, with the water only fasting now, there is it's a it's a much more dangerous situation for the patients. And again, most oncologists and physicians are not going to want to touch it. For all the diseases, for example, we had a paper where we compare and we looked at inflammatory bowel disease in mice.

• 30:25Speaker 04

  And and the water only fasting worked only about half way to what the FMD did. And it turns out something that was a little surprising, right? It was probably the prebiotics in the FMD. So when I developed the FMD, I wanted to make it extremely healthy, sort of thinking about the blue zones and thinking about what are the healthiest food in the world, ingredients in the world, right? So it was all it was made 100% with some of the healthiest food in the world. That was a good idea because I think this prebiotic then turned out to to affect bacterial species, lactobacillus, bifidobacteria. And so we saw this jump, which we didn't see for water only fasting.

• 31:09Speaker 04

  And in fact, water only fasting increased the leakiness of the gut when the FMD was decreasing the leakiness of the gut. So so but the fasting, water only fasting still worked, but it caused good and bad. And and the FMD seems to be much more consistent, you know, turning out, for example, intestinal stem cells and increasing the the level of this beneficial bacterial families and decreasing inflammation, etc. So so I think that it makes sense, right? It makes sense that having this plant-based vegan composition plus the fasting property

• 31:51Speaker 04

  might avoid a lot of the potential problems like leakiness of the gut. And at the same time, still give you the autophagy and give you lots of the benefits. Yeah, so so I would say that.

• 32:04Speaker 04

  You know, people of course can can can decide what they want to do. I mean, it's also good that water only fasting is free. If you must have it and you you cannot buy anything, that that that's good. You know, that's a I always say, you know, eventually, if that's all, if you you cannot afford that and you're in some country where where there is not reimbursement for it, absolutely, do do water only fasting because it's going to be it's going to be still effective.

• 32:29Peter Diamandis?

  Yeah, I mean, just so folks know, the ProLon diet is not expensive. It's a couple hundred bucks. You're going to spend a couple hundred bucks typically on food during the five days anyway, unless you're a college student eating ramen noodles. So, but let's two questions I want to hit on. One, how many times per year should I, just in terms of wanting to be in in maximal shape, should I consider doing this? At once a month, once a quarter, once a year? And then what are the actual, you keep referring to my studies, but I know there's been a lot of human studies done. What are the results of the human studies of using the fasting mimicking diet? So, frequency first, and then what about some

• 33:11Peter Diamandis?

  of the clinical, I think there's something 21 clinical studies that have been done by ProLon?

• 33:16Speaker 04

  Yes, and there's probably another 30 either running or about to start now. So, the the results are are very good. And the frequency, for example, for diabetes, the Heidelberg study on diabetic patients, and the Laiden study on diabetic patients, either once a month for six to 12 months. And but the idea would be you get the diabetic, and we were surprised how compliant they were, by the way, right? So, it's pretty fairly high compliance, which we did not expect. So, most of the people could complete the 12 cycles in one year. And so then the idea is to move it even for the diabetic patient.

• 33:59Speaker 04

  Maybe move it from 12 to 8 cycles in year 2 and maybe 6 cycles in year 3. And then eventually less than that. And so, yeah, but then also it's a question of risk and, you know, let's say, let's forget the diabetic. And let's say somebody is normal and wants to, you know, live longer. So obviously, probably doing it more is going to be more beneficial. But we don't know what happens if somebody does one cycle of FMD per month for 40 years, right? So, I mean, we don't know, right? So then, then there is always, with everything that you do so frequently,

• 34:44Speaker 04

  there's always some risk. And that's why we say, you know, probably 3 or 4 times a year, somebody is healthy and wants to optimize health. And so now we just started, well, actually 6 months ago, we started a 500 patient clinical trial here in Southern Italy. And we already recruited the first 200 patients. And that's the first time where we do the FMD once every 3 months. And so that's going to be a very interesting study, right? Now we're moving away from the once a month effect, which is over and over has been very, very effective in healthy patient and patient with lots of different diseases. But now we're moving to once every 3 months and we'll see what happens.

• 35:28Speaker 04

  But we're optimistic. And by the way, in the 2017 trial we published on healthy patients, we saw reduction of IGF-1, reduction of inflammation, blood pressure, cholesterol, fasting glucose. And in the diabetes trials, that was confirmed, A1C reduction in all the trials, pretty impressive reduction of A1C, so glycylated hemoglobin. But also reduction in drug use, right? So most of the patient were able to reduce drugs. And that's what we think it's also very exciting about this, you know, getting people to be disease-free.

• 36:11Speaker 04

  And the last thing I want to say, which was very surprising, and now it's the 5th trial, we see the same. No loss of lean body mass, right? So the great majority of diets, even the Mediterranean diet, we just got finished in a trial. And after seven months, a subject lost about five pounds of muscle mass. But with the FMD, with four cycles, five days of FMD, we saw no reduction in muscle mass. And so, yeah, so that's very important. I think we, it looks like we got it right.

• 36:46Peter Diamandis?

  So that's interesting, right? Because one of my objectives is adding muscle mass. So I'm, you know, eating 150 grams of protein per day. And trying to do as much of that plant as I can, but I have some, some fish and chicken as well. And, you know, at 150 pounds, I'm, I'm targeting one gram per pound to maximize muscle and then adding my workouts onto that. And I've always wondered, would in fact, the fasting mimicking diet, because I'd be off that protein for five days, hit me as a reduction in lean muscle mass? And you're saying so far the results show you would not?

• 37:24Speaker 04

  Yeah, especially in somebody, obviously, as you know, you have a very high protein intake. So, so we recommend based a lot of, a lot of studies, a lot less. But, you know, it's your, it's your choice, obviously. But somebody that has 150 grams of protein per day, you know, we, we will expect maybe the opposite, meaning gaining more muscle mass by doing the fasting mimicking diet. Also because of what we suspect is that this break, like we see for insulin resistance, is a possible that is IG, well, we know there is IGF-1 resistance, right?

• 38:06Speaker 04

  So this growth, the, the central growth factor, at least has been shown for Alzheimer. But it's possible that by removing this, gaining IGF-1 to be very low for five days and then going back to very high, now you may increase the, the sensitivity of the receptor and therefore the receptor on the muscle mass. I mean, I, we don't know yet, we're looking at this right now, but. But there's certainly a possibility that, you know, so it looks like all the regenerative effects of the fasting making diet are in fact due to the alternation of very low of these growth factors and relatively high levels of these growth factors and potentially the sensitization of the receptors.

• 38:50Peter Diamandis?

  Yeah, one of the things that a lot of people don't realize, and I really appreciate this, is we are the result of hundreds of thousands or millions of years of evolutionary pressures. And as Homo sapiens for the last, you know, call it a million years for round numbers, we've gone through periods of, you know, fasting, massive fasting and huge rewards. And it's this cycling that our body's gotten used to, but we no longer have cycling with McDonald's and Whole Foods. We're just taking in massive caloric intake all the time. And

• 39:30Peter Diamandis?

  so this could be a critical part of activation of those gene pathways that are able to benefit from the cycling. Is that assuming one of your conclusions and one of the thesis underlying this?

• 39:43Speaker 04

  Yes, absolutely. So there's probably a lot of junk that accumulates and a lot of organs that need rejuvenation and regeneration. But in the old days, for the, probably the entire history of any organism, not just humans, starvation was just unavoidable. And so now for the first time in history, maybe the last 100 years or so, there's people, a lot of people that we enroll in clinical trials that have never gone more than a couple of days of fasting. And so that's probably the great majority of the population has never been exposed to any of this, right? So and that's probably why the insulin resistance,

• 40:28Speaker 04

  you know, and the cholesterol, the high cholesterol and the high blood pressure, a lot of organs that are probably waiting for that moment of reset.

• 40:37Peter Diamandis?

  Waiting for their reset.

• 40:41Speaker 04

  And they know what to do and they become dysfunctional and that's a lot of these problems. So, nobody has high cholesterol at 20, right? So, why is that? It may very well be that, yeah, that the organ and the system needs to go back to its original function.

• 40:59Peter Diamandis?

  I want to get to the idea of multi-system regeneration in a moment, but let me ask you another question first, which is around the notion of what diseases have you looked at treating with the fasting-mimicking diet? So, I heard you say cancer. I heard you say diabetes, obviously. What about inflammatory, general inflammatory disease? What are the lists of things that, you know, FMD could be valuable in addressing?

• 41:35Speaker 04

  I think many, and the reason is that it's not the FMD that is doing the work, it's the FMD that is triggering the body to really start over, right? And, yeah, so we looked at inflammatory bowel disease, I mean, multiple sclerosis. We finished one trial years ago and it was positive increase in quality of life. We just finished another trial on multiple sclerosis. We finished, or we're about to finish the Alzheimer trial. About 10 clinical trials, most of which, most published on cancer. And, yeah, so there is two trials, I think now I stand for that, on inflammatory bowel disease.

• 42:18Speaker 04

  And, yeah, so these are just some. I think there is probably another 20 or so that are running on all kinds of different diseases. Yeah, so probably almost everywhere where aging is a central factor, or certainly dysfunction is a central factor, a central component of the disease.

• 42:46Peter Diamandis?

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• 44:16Peter Diamandis?

  So, let's get to this idea. What do you mean by multi-system regeneration? Can you define that? And then, what is your work showing possible there?

• 44:25Speaker 04

  Yeah, so, we started about 10 years ago publishing on the blood system and showing that during the fasting and fasting-making diet, the blood, there is a reduction in blood cells, and then the hematopoietic stem cells are self-renewing. So you have an increased population of hematopoietic stem cells, and then when you re-feed, they go to work and they essentially rejuvenate the immune system. And then, we went on to show similar effects in the pancreas. In the gut, in the nervous system. And now we're working, for example, we have a paper in submission for kidneys.

• 45:08Speaker 04

  And yeah, so multi-system regeneration has to do with probably either the self-renewal of stem cells on one side, or the reprogramming. So we see Yamanaka factors, these factors that can make somatic cells into embryonic-like stem cells. We see Yamanaka factor. And by the way, we see different Yamanaka factors being turned on in different organs, right? Which makes sense, right? So Yamanaka probably sort of used the brute force to reprogram cells. And but the pancreas may not need all the factors, may only need a few. And so, for example, when you do the FMD and refeed it, you see the pancreas showing

• 45:52Speaker 04

  a profile, a gene expression profile, very similar to the one activated during embryogenesis. And so that's how we know there is a real program, a very coordinated program, by the way, with different steps and lots of transcription factors and that are orchestrating this rebuilding process. So for example, we could take the pancreas of a mouse, destroy it with a toxin, and that's permanently irreversibly damaged, right? So the mouse makes, no longer makes insulin. And then we start the FMD cycles, and then you see fairly rapidly, there is reprogramming

• 46:36Speaker 04

  of the pancreatic islet cells, and then they start making insulin again. And that's a permanent effect. So now essentially, we have regenerated the insulin-producing beta cells of the pancreas. And similarly, we've shown it in many different systems.

• 46:55Peter Diamandis?

  That's amazing.

• 46:58Peter Diamandis?

  So basically, this is a, this is a chance for the body, like you said, to, to clear away the old and dying cells and get rid of waste products and to trigger a, a period of regrowth and revitalization, which is a normal part of life, but because we are just feeding the body constantly, it has no need to do this in the past, right? This is a, a chance to give the body access to normal, normal cycles. Fascinating. Let's talk about time restricted eating and what, you know, just diets in general,

• 47:42Peter Diamandis?

  because there are thousands of diet books. And, you know, let me just check with you. When I'm teaching people and the work that I'm doing for myself, just the basics, there's no one diet that's right for a single individual. We have a lot of genetic and cultural backgrounds, but what I think is important is number one, eliminate sugar to the maximum degree possible and maximize whole plant intake to the maximum degree possible. If you had to say two things, would you agree with those two things are the most important actions for folks to take?

• 48:15Speaker 04

  Yeah, I mean, sugar for sure. And yeah, I, I think I generally agree. I mean, I will have proteins, but you put me on the spot because you eat a lot of proteins.

• 48:27Peter Diamandis?

  No, it's, this is, I'm here to learn as well. So how much protein should a person take in? I'm, you know, for me, my goal is maximize muscle gain for a number of reasons. And if, if I wanted to maximize besides the weight workouts, how would, how much protein would you take in? And how would you maximize muscle gain?

• 48:47Speaker 04

  Yeah. So I think eventually, I mean, the recommendation for, for people is about 0.37 grams per pound, right? So about a third of what you, of what you eat. But of course, it's not for athletes. So, so the athlete, my recommendation has always been increase it until you're happy with the results, right? So, so, you know, you go from 0.37 to 0.60. If that allows you to, to achieve the muscle gain that you want, then that's it. You stop at 0.60. And we suspect that maybe, as I was saying earlier, Possibly by having so much protein, you know, and having maybe very high G F one,

• 49:32Speaker 04

  you could be, um, you know, overstimulating some of these growth pathways. Uh, like insulin, uh, you know, can, can lead to insulin resistance, lots of insulin. So, so, yeah, obviously, if you eat so much protein, most people get some benefit, right? But the question is, could you get even more benefit if you had less proteins by both? And so, you know, we finished like a five-year study now on MICE and in looking at how you optimize frailty, muscle function and longevity, right? And it's pretty tricky, right? So you, you need to have everything. There's different periods of life and different techniques.

• 50:11Speaker 04

  And, um, and then eventually you get the longevity extension and you get the, you, the frailty, uh, protection, right? So, yeah, I would say probably, uh, much lower. And if it doesn't affect your, your performance and your, and your muscle, uh, then I think you're much better off with, let's say, zero point five than, uh, than one per pound.

• 50:35Peter Diamandis?

  But still sugar, uh, reduction, uh, and that includes high glycemic index. Uh, you know, breads and white rice and so forth. I don't want to talk about it while you're in Italy, reducing your glycemic, your high glycemic intake.

• 50:49Speaker 04

  Yeah, it's tricky. I think the, the high glycemic index, obviously in general is a bad thing. But, uh, but at the same time, you know, we always get comments about, you know, oh, I ate this soup or that soup and the glycemic index go up. Um, I mean, the, we suspect that if you're otherwise insulin sensitive, some of these spikes may actually be helpful, right? And, and maybe it contributes into signaling, intracellular signaling that actually helps you maintain a lean body mass. So, so the problem more than the glycemic, uh, index and glycemic, uh, index intake is too much of it, right? So when you, when you have it all the time and then you have high insulin all the time,

• 51:33Speaker 04

  then insulin resistance, then you got a problem, right? So, but, but I, I see your point, meaning like you're saying, people, you know, the, the attention spent might, might, might be limited. And so if I say, if I make it complicated, then, then, you know, people may be not remembering the way to do it. But I would say. The spikes itself is not really an issue.

• 51:57Speaker 04

  Unless those spikes eventually turn into insulin resistance. And then you got a big problem. So, and this is same for the sugar, right? I mean, obviously, we work on sugar. But yeah, the green majority of people just have excess sugar. And that's a problem, right? And so I can see your point of saying, look, because there is no damage of going to very low sugar. And so I think it's a good idea. But, but I mean, technically, I'm thinking biochemically.

• 52:27Speaker 04

  You know, there may be, we are a sugar machine, right? So, so, you know, we in fact need to maintain the sugar at certain levels. If you start seeing patients that we follow in the clinics with blood sugar sixty, we worry, right? And if you see an old person with blood sugar sixty, you really have to worry, right? So you, you, you wanna see, rather see a person with blood sugar fasting glucose of ninety than sixty. Because of, you know, frailty and other issues, right? So, so I'm saying just a complicated story. And I know that, you know, it's very hard to, to communicate a complicated story to millions of people. So, yeah, in general, I agree with you.

• 53:08Peter Diamandis?

  So let's talk about time restricted dieting and how many meals you should have per day. There's a lot of individuals who are, listen, I only eat one meal a day, or I only eat between a six hour window and have an eighteen hour fast.

• 53:28Peter Diamandis?

  I recently read in Peter Attia's book that the time restricted dieting actually had no beneficial effects when studied in a large population. What are your thoughts about that?

• 53:41Speaker 04

  I think that in general, if you look at all the studies, you know, some of the large studies have shown no beneficial, I think, improvement compared to calorie restriction. But in general, it works. And it's beneficial for, you know, fasting glucose and lots of metabolic markers. The problem, if you skip breakfast, is that that sixteen hours is associated with a shorter lifespan, a more cardiovascular disease. But if you don't skip breakfast, and then, you know, there probably mostly benefits and not detrimental effects. I like, as Sachin Panda knows, I like the twelve to thirteen hours fasting per time to the eating,

• 54:26Speaker 04

  because I think is showing already very good benefits. Uh, it doesn't require skipping breakfast. It doesn't get into the range where gallstone formation is increased. Uh, so I really like that twelve, thirteen hours of fasting per day. I always say I've never seen any negative uh um effects of the twelve, thirteen hours. And uh, you know, if you think about safety first, uh, that's probably a very good way to go. Um, and then uh, I, I practice actually skipping lunch. And uh, I've been doing it for thirty years now. And um, and I think that that may be one of the safest meals that you can skip, especially if you replace it with a, with a small snack.

• 55:11Speaker 04

  Um, and I usually have a snack, let's say at five P M., but uh, but my lunch is like an espresso usually. Monday to Friday, but I, I also alternate it with weekends where I eat, you know, and I think it's good that there, it takes a while for the brain to get used to it. But after about two months, that lunch is no longer necessary for most people that we follow. And um, and so now, yeah, the benefits of being able to, you know, skip this central meal um, without really uh, having a difficult time uh achieving that.

• 55:44Peter Diamandis?

  Yeah, so if you eat dinner at not typical Italian style, typical American style. If you had dinner at six and you're ending at seven, then you might have a breakfast at thirteen hours later at eight A M., skip lunch and have a dinner again at six that evening.

• 56:00Speaker 04

  Yeah, that seems to be very safe, yeah.

• 56:02Peter Diamandis?

  Yeah, and uh, I've, I was on a very time restricted, you know, eighteen uh hours off cycle, twelve or thirteen hours off is much easier. Uh, the reason I stopped that cycle was because I was trying to increase my protein intake. And my ability, you can't eat that much protein in such a short period of time. You will not absorb it. You have to spread it out during during the day. But that's a different, a different conversation.

• 56:29Speaker 04

  Yeah, I think we we very much look at the long term safety, right? So that we we I use these five pillars of longevity, right? With one of them is epidemiological data and one of them is centenarian studies. We follow very closely what centenarians have been doing for a long time. And so, yeah, we try to avoid things that we don't. It's like an uncertain territory or terrain. And certainly, a lot of these techniques may be very beneficial, but then get you into uncertain terrain. And and we could get surprised in 20 years, as I was saying earlier, about lots of different things that we do here.

• 57:12Peter Diamandis?

  Well, let's take a second because in your in your book, The Longevity Diet, you do talk about the five pillars of longevity. I think people inherently know what they are, but I'd love if you would hit them again just for thoroughness. So what are the five things that centenarians are consistently doing that you're seeing?

• 57:30Speaker 04

  Yeah, not so much centenarians, but everybody. So so the pillars have to do with the scientific and medical disciplines that feed the instructions, let's say, right, the recommendations. So one of the pillars is epidemiological data and and one of the pillars is clinical studies, right? So what happens if you take a lot of people and put them on a low sugar diet versus a high sugar diet? And one of the pillars is basic research on aging. So how do you make a mouse live longer, right? And can you make a mouse live longer consistently? And and if you can't, it's not a good start, right? If if somebody has an idea and the mouse doesn't live longer with that idea, then I would say it's not a good start for for humans.

• 58:14Speaker 04

  And then centenarian studies, right? So that's one pillar. So the whole centenarian populations that we follow really teach us a lot. And and we like to have a and then the the fifth pillar is complex system. You know, how does a plane or a car or the space shuttle age, right? So. We look at things that we build, we know very well. So what goes wrong with these machines and why? And yeah, so then the attempt of the five pillars to get to a common denominator, that makes it fairly unlikely to change in five years from now. So, oh, I got it wrong. You know, I thought that this was good. Yeah, so I think the five pillars helped getting it right.

• 58:58Speaker 04

  And I think helped getting it right for a very long time. So just the epidemiological studies, for example. It would take another 30 years to prove everything wrong, accumulated so far and meta-analysis. So yeah, so I think that that's a good, that's a good way to approach it.

• 59:14Peter Diamandis?

  So what are the, what are the five things, the five key pillars here? Just from your book, obviously, one of them was, you know, physical activity, exercise, sleep, you know, social engagement.

• 59:29Speaker 04

  Yeah, no, I didn't talk much, much about social engagement. I mean, although I think it's probably important, but I'm not an expert. So I let Dan Buettner and others talk about that. But I mean, we focus on time or city. I mean, the longevity diet, which is a pescatarian, low protein diet. And but which increases as people get older. So after 65 is higher in protein intake. So high legume, high whole grain, nuts, et cetera, and maybe fish three times a week. Then the time for city eating, 12, 13 hours. Then 150 minutes of physical exercise a week,

• 1:00:14Speaker 04

  plus an hour of physical activity a day, like walking, for example. And then, you know, muscle training, maybe three or four times a week. Yeah, so those are the main and sleep. But again, I'm not an expert on sleep. And so I'd rather tell people to, to read the book by Matt Walker or others that, you know, truly specialize on that. But obviously, that's a very important one.

• 1:00:44Peter Diamandis?

  Fantastic. I just, I think those are the basics, Serp, and he knows, but just it always helps to hear that and reinforce it.

• 1:00:50Speaker 04

  Yeah, and sorry, I forgot the fasting mimicking diet, right? So three or four cycles of the fasting mimicking diet per year, yeah.

• 1:00:58Peter Diamandis?

  So yeah, I'm thinking for myself, once a quarter. I'm curious, once you do that for five days, and then you do it, you know, 90 days later, after the five days, is there any evidence of how long the benefits persist?

• 1:01:14Speaker 04

  Yeah, so we published on that, and we have another two or three clinical trials confirming long-term effects. So after 90 days from the end of the last FMD, about 60% of the significant changes were still there, suggesting that it's slowly, you know, moving back. And probably within six months, you're going back to where you came from, maybe with some improvements. But yeah, it doesn't last forever. But I think that three to six months, you're going to have continued benefits.

• 1:01:53Peter Diamandis?

  So as we close out here, I'm curious, where's your research going next? What is, what's exciting for you in the near future here? And if you had all of the funding research to do all the experiments you want to do, what would you want to do?

• 1:02:10Speaker 04

  Well, number one, I think I liked the disease part. And now we're really now moving into, this can be done and it works. And so that it should go in the doctor's toolkit. So we're pushing very hard to get to conclusive data on hundreds of patients, randomized, well-done studies, studies published in leading journals. So cancer, I'm particularly excited about. I think that fasting making diet can serve as a wild card, helping immunotherapy, chemotherapy, hormone therapy, et cetera, et cetera, work better and maybe as we've seen for lots of patients, go from, you know, disease progression delay to cancer-free survival or remission.

• 1:02:55Speaker 04

  So that's an exciting set of studies. And then, you know, diabetes, I think we're already there. We're at trial number four or five. It's pretty clear it can reverse, it can reduce drug use and reverse. I mean, within a year, we get 15, 20% of patients that are diabetes-free. And I think within two years, it probably goes, if they follow it, goes to maybe 50%, although we haven't, we haven't done that part yet. But so diabetes, I think it's the most conclusive one already. And and we were excited about that. And yeah, so lots of other diseases. And then I think Alzheimer is also very interesting. I mean, obviously, the drugs have not done very well

• 1:03:40Speaker 04

  with Alzheimer. And maybe as we done for cancer, the drugs or whatever regenerative intervention plus the fasting making diet, I think that that's something that we're very excited about. And and then, of course, we we want to take it. So half of my group now works on this Yamanaka factors and stem cell activation. And and so we want to take it to the next level. Right. So can David and and Belmonte and others have shown, you know, that you can reprogram these cells. And we're basically saying, can we do as well, but you know, in

• 1:04:19Speaker 04

  a in a natural way. And now do we get there, right? Can we get these effects that Belmont and and David published on? Can we get it? And what kind of fasting making diet? How long is that going to have to be? And do we need anything else to add to the FMD? Right? So yeah, so that's what we're very excited about that. Because I think that also is going to be at the center of treating diseases, as David and others are also talking about. So yeah, so that's a that's a very exciting short term goal, by the way, I think in the next 10 years, we should, you know, we should put it to work.

• 1:05:00Peter Diamandis?

  Fantastic. For those who are interested, if you go and Google ProLon, P R O L O N, you can get that, the company that manufactures it, El Nutra, something I like to do once a quarter. Walter, where can folks find out more about your research on what website?

• 1:05:21Speaker 04

  Yes, I can be followed on Instagram or Facebook, but then the createcures.org, createcures.org is where the clinic is in Los Angeles, and it follows a lot of people all over the United States. And then we have the Walter Longo. Foundation.org in Europe. And so that's how we follow people, those that cannot afford it. It's a nonprofit clinic, those that cannot afford it, don't have to pay, as long as we have money to operate things. But the, yeah, I recommend that you call, you contact the foundation. And, you know, whether it's somebody with advanced stage cancer, or somebody that just wants to be healthier, that's probably the best way to go. And it's fairly inexpensive.

• 1:06:07Peter Diamandis?

  Fantastic. Walter, thank you for your time. Thank you for your research and the work that you're doing. And excited to spread the message about how you eat, what you eat, how much you eat, all of these things are critically important for our health. And you can do something about it. Anyway, pleasure as always. Thank you, my friend.

• 1:06:27Speaker 04

  My pleasure, Peter. My pleasure. Thank you.

• 1:06:30Peter Diamandis?

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