Moonshots with Peter Diamandis - The Groundbreaking Science of Water Fasting w/ Valter Longo | EP #78

Episode Date: December 21, 2023

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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Around 1860, Nearest Green taught Jack Daniel how to filter whiskey through charcoal for a smoother taste, one drop at a time. This is one of many sounds in Tennessee with a story to tell. To hear them in person, plan your trip at tnvacation.com. Tennessee sounds perfect. What are you trying to do that's going to change the world? I think that... 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? 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 water only fasting is something that maybe 1% of people could do, kind of like chronic calorie restriction, maybe 1% or 2%. 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. 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. 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 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? I'm actually in southern Italy in a region called Puglia. 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? Yes, I actually started very early. I was a student of Roy Wall for the UCLA, and he was my mentor, a 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. 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. 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 in coloristation but I went much further and so I just say well what if I starve bacteria and yeast what happens then and since then it was 1992 93 that's all of it i mean i focus on that let's say you know i i know a new roy and i was at the first biosphere enclosure and then the coming out party two of my friends were there uh taber and jane taber mccallum um and i remember it was an incredible story and just for for our listeners a uh 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 um inside this inside this enclosure a glass enclosure the only thing that came in was sunlight uh they had fish in a pond they had crops they had to uh they had to harvest and eat and so they had to balance it to grow enough food for two years for them um and they had to balance the CO2 and the O2.

And this grand experiment goes on. And the challenge was the, you know, the flying, the ointment, so to speak, was the engineers didn't realize that the concrete they had used to basically this this enclosure was absorbing co2 with that was absorbing co2 wasn't that was the issue and so as you started because the co2 started getting absorbing 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 they reduced their caloric intake a lot didn't they i mean different different members did different right 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 overall, they were probably at least 10% calorie restricted. And if you look at the data, it's 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. Timothy Leary was there? Yeah, exactly. Yeah, we're the same 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 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 uh But I think we're also working on drugs and other interventions to do that. Well, I, for one, want to get to 110 healthy and then blast through that. And a lot of people listening to this podcast, because we cover longevity and health a lot, as well as AI and other subjects, want to set a target. And in the past, I think people would set a target of 80 years old or 90 years old. Some might set up a hundred. 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 why can't we what's your longevity goal how long do you want to live I wouldn't mind making it maybe to 125 or so um I mean realizing how difficult that is but uh 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, hey, why not? Maybe I'll get to 125 or maybe I die tomorrow. maybe i'll i'll get to 125 or maybe i die tomorrow when we before we jump into the whole conversation around um uh your particular research and this idea of a fasting mimicking diet versus an actual diet or a water fast 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 and Italy and Greece and other locations in Japan. What's going on there, you think, that is driving people to get to a centenarian and supercentenarian level?

Yes, so I go there a lot, especially the one in Sardinia and to Loma Linda. And I think that Sardinia, when you look at Seul in 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. 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 Seul and Villagran. There are these little towns on top of the mountains, maybe a few families represent 70 or 80% of the population, so a lot of inbreeding, and we suspect that it may have created this super longevity, almost like gossity, right? So 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. But obviously, the lifestyle is also right on, right? So a lot of exercise and really good diets. And so probably, I always say, you know, to be Michael Phelps, you probably need everything. And so you cannot, you just, you got to train, but you also have to be born, right, with the right genetics. And yeah, so 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. So 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, 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 we can move the needle and extend to super, 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 until you say then within the next decade i had a very positive answer um so yeah i think that the eventually obviously we're going to live a lot longer and it's not going to be just 110 but I always cite my lab

it wasn't my discovery but somebody in my lab in the 90s discovered the gene the SOD mutation for Lou Gehrig's disease right and when we discovered that when they discovered that, we thought, you know, within 10 years, we're going to cure this disease. And so, you know, that was probably 1994, 95. So 30 years have gone by, and we're still nowhere even beginning to cure ALS, Lou Gehrig's disease. Yeah, so unfortunately, the reality, even if you consider the exponential growth, and

the exponential growth was also for ALS since 1992 now, right? So we're much, much better than 30 years ago in lots of different things. But, you know, people still die and suffer miserably from Lou Gehrig's disease. So yeah, it's wishful thinking in 10 years. I think as you get to 20 or 30 years, may not necessarily be wishful thinking, depending on what happens in these 30 years and some really key discoveries, especially on the on the safety right you can reprogram all the cells you want uh but uh you know are you gonna put the person at risk and remember when a gene therapy was first started you know one person died and this this delayed the the use of it by

it was a great technology and it was just uh you know one person was enough to to cause a big problem for 20 or 30 years right so yeah no i remember that very well i was i was in the field at uh 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 even the promise of 20 or 30 years from now, so if someone's in their 40s, 50s, or healthy in their 60s, if you can make it an extra 20 or 30 years, get to 90, then the potential to intercept these technologies 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. We're doubling in power with massive compute capabilities coming our way.

Yes. And I mean, I guess the goal in 30 years will be maybe to get an extra 20, 30 years and then go from there right so so yeah i think if we achieve that it's very achievable in the next 30 years that we add 30 years to the life and i mean i always say there's going to be two population one that does all the right things and they may live 20 30 years longer and the other group i think is going to live probably about the same as now. But, of course, yeah, with the technology, maybe we'll – I mean, I'm talking about nutrition and fasting and fasting, making diets and all that. But, yeah, with the technology, I think it is possible maybe that we'll have initial technologies that get us another 20 or 20 or 30 years and then we have uh you know um now 60 years

to uh at least the the ones of us that are in our 50s um to uh to get there but you know it's uh it's it's a fun for sure it's a fun uh moment a revolutionary moment and we just have to see what happens here well i can guarantee everyone listening to our our voice and our podcast today is doing they're going to be doing the right thing so let's jump into that so you start um your graduate work or postgraduate work starving bacteria and yeast um 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, 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 the development of this fasting mimicking diet. Let's begin with FMD, fasting mimicking diet. What is that and how does it compare to a regular diet? Yeah, 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 calorie restriction actually live shorter. About a third live the same and a third live longer. So it's more complicated than people appreciate. And I think the FMD, coming out of Walford 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. Last 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? So it's something very simple, but incredibly powerful. So why? Because when you shrink, you start this self-eating process, this 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. So I think that this is all coordinated. I talk about 3 billion years of R&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 multisystem regeneration and rejuvenation in a safe way, in an effective way, just because extraordinary work in as well which is when you're in this uh fasting mode your body will begin to auto phagy which means to eat oneself in one sense to uh to start killing the senescent cells um and as you said to shrink the body and put yourself it's's an 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 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 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. It gets to the five days of fasting. does, you know, it gets to the five days of fasting and that's when, you know, you begin to see 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 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 to different places like the bone marrow. Everybody, I want to take a short break from our episode to talk about a company that's very important to me and could actually save your life or the life of someone that you love. The company is called Fountain Life. It's a company I started years ago with Tony Robbins and a group of very talented physicians.

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And when you order Prolon, you get a box of day one, day two three day four day five and these are powders or soups and some bars that you eat that are very very specific amount 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 um to try and cut my caloric intake down to zero but let's contrast one second uh the the prolon fast to be making diet with a water diet here to understand uh is it better to go with zero calories and just water or 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 Prolon FMD?

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 have to be able to do it. And I would say water-only fasting is something that maybe 1% of people could 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 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 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 the oncologists did not want them 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 mimicking diet right so most people don't realize that this uh this is why we uh we develop

we study it develop it and and tested the fasting mim. So, yeah, so then it's 1,100 calories on day one, 800 calories on day two to five, but it's the composition that matters the most or as much. 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. So if I remember correctly, on the Prolon FMD, it was something like 1,200 calories the first day, then down to 800 calories for the next four days or something

like that? You know, 1100 going down to 800. 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 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?

Yeah, I mean, the average American, I think a male is around 25, 2700 kilocalories per day. But I think that it's pointless. It doesn't mean anything. It depends on energy expenditure and lots of other things right so it's really about um your your abdominal circumference your bmi body mass index and uh 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 3 000 calories a day and there might not be enough um or somebody may be eating 1,600 and maybe too much. Let's say a woman weighing 100 pounds in perfect shape.

So, yeah, so I think it's, yeah, counting calories is pointless. Much better to focus on the results of that and adjust the food based on how you respond. All right. So the FMD here is 1,100 calories reducing down to 800 calories, I think, for the last three days. And remember when I did it, it was pretty easy to do. 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, 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? 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, 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, 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 compared and we looked at inflammatory bowel disease in mice and um and uh 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 fD, I wanted to make it extremely healthy. So thinking about the blue zones and thinking about what are the healthiest food in the world, ingredients in the world, right? So it was made 100% with some of the healthiest food in the world. And that was a good idea because I think this prebiotic then turned out to affect bacterial species, lactobacillus, antibiotics then turn out to affect bacterial species, lactobacillus, bifidobacteria.

And so we saw this jump, which we didn't see for water-only fasting. And in fact, water-only fasting increased the leakiness of the gut when the FMD was decreasing the leakiness of the gut. So the water-only fasting still worked, but it caused good and bad. still worked, but it caused good and bad. And the FMD seems to be much more consistent, you know, turning on, for example, intestinal stem cells and increasing the level of these beneficial bacterial families and decreasing inflammation, et cetera. So I think that it makes sense right it makes sense that uh having this plant-based vegan composition plus the fasting property uh 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 uh yeah so so i would say that uh 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 uh i always say you know eventually uh if that's all if you you cannot afford that and you're in some country where where there is no reimbursement for it uh absolutely do water only fasting because it's going to be uh it's going to be still effective yeah i mean just for 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 uh 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 of the clinical, I think there's like 21 clinical studies that have been done by Prolon. Yes, and there's probably another 30 either running or about to start now.

to start now. So the results are very good and the frequency, for example, for diabetes, the Heidelberg study on diabetic patients and the Layden study on diabetic patients did it once a month for six to 12 months. But the idea would be you get the diabetic, and we were surprised how compliant they were, by the way, right? So it's 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, maybe move it from 12 to eight cycles on year two and maybe six cycles on 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 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. So, I mean, we don't know. Right. So then then there is always with everything that you do so frequently, there's always some risk. And that's why we say probably three or four times a year somebody is healthy and wants to optimize health.

And so now we just started, well, actually six months ago, we started a 500-patient clinical trial here in southern Italy. And we already recruited the first 200 patients and uh and in that's the first time where we do uh the FMD once every three months and uh so that's going to be very interesting study right that now we're um we're moving away from the once a month effect which is over and over has been very very effective in healthy patients and patients with lots of different diseases. But now we're moving to once every three months, and we'll see what happens. 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 glycated hemoglobin, but also reduction in drug use, right? So most of the patients were able to reduce drugs. also reduction in drug use, right? So most of the patients 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. And the last thing I want to say, which was very surprising, and now this is the fifth

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 it looks like we got it right there 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 um and trying to do as much of that plant as i can

but i have some uh some fish and chicken as well and uh you you know, at 150 pounds, 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 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, we will expect maybe the opposite, meaning gaining more muscle mass by 25-30 minutes. Also because of what we suspect is that this break, like we see for insulin resistance,

is a possible that there is IGF-1, well we know there is IGF-1 resistance, right? So this growth, the central growth factor, at least has been shown for Alzheimer's. But it's possible that by removing this, getting IGF-1 to be very low for five days and then going back to very high, now you may increase the sensitivity of the receptor and therefore the receptor on the muscle mass. I mean, we don't know yet. We're looking at this right now, but there's certainly a possibility that, you know, so it looks like all the regenerative effects of the fasting-mimicking 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 desensitization of the receptors. 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 uh for round numbers uh we've gone through periods of you know fasting massive fasting and uh and and huge uh 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 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? 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 probably the entire history of any organism, not just humans, starvation was just unavoidable. 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. And that's probably the great majority of the population has never been exposed to any of this. And that's probably why the insulin resistance and the cholesterol, the high cholesterol and the high blood pressure, a lot of organs that are probably waiting for that moment of reset. And so they don't know what to do. Waiting for their reset. And they don't 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 need to go back to its original function. I want to get to the idea of multi-system regeneration in a moment, but let me ask one other 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, you know, what are the lists of things that, you know, FMD could be valuable in addressing?

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 are published on cancer. And yeah, so there is two trials I think now at Stanford on inflammatory bowel disease. 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, central component of the disease. Hey, everyone. I want to take a quick break from this episode to tell you about a health product that I love and that I use every day. In fact, I use it twice a day. It's Seeds DS01 Daily Symbiotic.

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during the fasting and fasting making diet the um the blood uh there's 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 refeed, 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. And yeah, so multisystem 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 factors. And by the way, we see different Yamanaka factors being turned on in different organs, which makes sense. So Yamanaka probably sort of used the brute force to reprogram cells. 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 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 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 no longer makes insulin. And then we started the FMD cycles, and then you see fairly rapidly there is reprogramming 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.

That's amazing. So basically, this is a chance for the body, like you said, to clear away the old and dying cells and get rid of waste products and to trigger 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 chance to give the body access to normal cycles. Fascinating. Let's talk about time-restricted eating and what, you know, just diets in general, because there are thousands of diet books. And, you know just diets in general because there are thousands of diet books uh 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 yeah i've been a sugar for sure um and uh yeah i i think i generally agree i mean i will have, but you put me on the spot because you eat a lot of proteins. No, listen, I'm here to learn as well. So how much protein should a person take in? For me, my goal is maximize muscle gain for a number of reasons. And 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? Yeah. So I think eventually, uh, I mean,

the recommendation for, for people is about 0.37 grams per pound, right? So about a third of what you, uh, what we, uh, but of course it's not for athletes. So the athlete, my recommendation has always been increase it until you're happy with the results. So you go from 0.37 to 0.60. If that allows you 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 and having maybe very high IGF-1, you could be overstimulating some of these growth pathways, like insulin can lead to insulin resistance, lots of insulin. you know, can lead to insulin resistance, lots of insulin.

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 looking at how you optimize frailty, muscle function, and longevity, right? And it's pretty tricky, right? So you need to have everything. There's different periods of life and different techniques. And then eventually you get the longevity extension and you get the frailty protection, right?

So, yeah, I would say probably 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 0.5 then than one per pound yeah 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 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 i ate this soup or

that soup and the glycemic index go up um I mean, we suspect that if you're otherwise insulin sensitive, some of these spikes may actually be helpful, right? And maybe contributing to signaling, intracellular signaling that actually helps you maintain a lean body mass. So the problem more than the glycemic index and glycemic index intake is too much of it, right? So when you have it all the time, and then you have high insulin all the time, then insulin resistance, then you got a problem, right? But I see your point, meaning like you're saying people, the attention span might be limited. And so if I say, if I make it complicated,

then people may be not remembering the way to do it. But I would say the spikes itself is not really an issue unless those spikes eventually turn into insulin resistance. And then you got a big problem. So, and this 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 and so i can see your point of saying look because there is no damage of going to very low sugar and uh so i think it's a good idea but but i mean technically i'm thinking biochemically

uh you know there may be um we're a sugar machine right so so um 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 60 we worry right um and and if you see an old person with blood sugar 60, we worry, right? And if you see an old person with blood sugar 60, you really have to worry, right? So you want to see, I'd rather see a person with blood sugar fasting glucose of 90 than 60 because of, you know, frailty and other issues, right? So I'm saying just a complicated story. And I know that, you know, it's very hard to communicate a complicated story to millions of people. So yeah, in general, I agree with you.

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 18-hour fast. 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? 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. metabolic markers. The problem if you skip breakfast is that that 16 hours is associated with a shorter lifespan, a more cardiovascular disease. But if you don't skip breakfast, and then, you know, they're probably mostly benefits and no detrimental effects. I like,

as such, in pandanose, I like the 12 to 13 hours fasting per time to the eating because I think he's showing already very good benefits. It doesn't require skipping breakfast. It doesn't get into the range where gallstone formation is increased. So I really like that 12, 13 hours of fasting per day. I always say I've never seen any negative effects of the 12-13 hours and you know if you think about safety first that's probably a very good way to go. And then I practice actually skipping lunch and I've been doing it for 30 years now

and I think that that may be one of the safest meals that you can skip, especially if you replace it with a small snack. And I usually have a snack, let's say, at 5 p.m. But my lunch is an espresso usually, Monday through Friday. But I also alternate it with weekends where I eat. And I think it's good that the 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 achieving that. Yeah, so if you eat dinner at, not typical Italian style, typical American style, if you had dinner at 6 and you're ending at 7, then you might have a breakfast at 13 hours later at 8 a.m., skip lunch and have a dinner again at 6 that evening. Yeah, that seems to be very safe, yeah. a dinner again at six that evening yeah that seems to be very safe yeah yeah and uh i've i was on a very time restricted you know 18 uh hours off cycle 12 or 13 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 the day. But that's a different conversation. Yeah, I think we very much look at the long-term safety, right? So I use these five pillars of longevity, right? 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 we could get surprised in 20 years as i was saying earlier about uh lots of different things that we do here well let's take a second because in your in your book uh the longevity diet uh 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 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 recommendation so one the pillar is epidemiological data and. So one of the pillars is epidemiological data,

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 if you can't uh it's not a good start right if somebody has an idea and the mouse uh doesn't live longer with that idea then

i would say it's not a good start for for humans um and then centenarian studies right so that's one pillar so the whole centenarian um populations that we follow uh really teach us a lot. And we like to have a, and then the fifth pillar is complex systems. You know, others are plane or a car or the space shuttle age, right? So we look at things that we build, we know very well. And 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. I thought that this was good. And yeah, so I think the five pillars help getting it right and I think help 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's a good way to approach it. So what are the five things, the five key pillars here? Just from your book, obviously, one of them was physical activity, exercise, sleep, social engagement. Yeah, no, I didn't talk 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 the longevity dietceived, I mean, the longevity diet,

which is a pescatarian, low-protein diet, 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-received eating, 12, etc. And maybe fish three times a week. Then the time recited eating, 12-13 hours. Then 150 minutes of physical exercise a week, 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. Um, yeah, so those are, are, are the main and, and sleep. But again, I'm not an expert on sleep. And so I'd rather tell people to, 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 fantastic i just i think those are the basics everybody knows but just it always helps to hear that and reinforce it yeah and sorry i forgot the fasting mimicking diet right so three or four cycles of the fasting

per year yeah so yeah i'm i'm thinking for myself once a quarter. I'm curious, once you do that for five days and then you do it 90 days later, after the five days, is there any evidence of how long the benefits persist? Yes. 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 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, um, I think that three to six months, uh, um, you're going to have, uh, continued benefits. So as we close out here, uh, I'm curious, where's your research going next? Uh, what is, what's exciting for you in the near future here? Uh,

and if you had all of the funding research to do all the experiments you want to do, what would you want to do? 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 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 and 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. 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. Even 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, if they follow it, it goes to maybe 50%, although we haven't done that part yet. So diabetes, I think, is the most conclusive one already, and we are excited about that. And, yeah, so lots of other diseases. And then I think Alzheimer's is also very interesting.

I mean, obviously the drugs have not done very well with Alzheimer's. And maybe as we've done for cancer, the drugs or whatever, regenerative intervention plus the fasting-mimicking diet, I think that that's something that we're very excited about. And then, of course, we want to take it. So half of my group now works on these Yamanaka factors and stem cell activation. And so we want to take it to the next level, right?

So can David and Belmonte and others have shown that you can reprogram these cells? And we're basically saying, can we do as well, but in a natural way? And how do we get there? Can we get these effects that Belmont and David have published on? What kind of fasting-making diet? How long is that going to have to be? Do we need anything else to add to the FMD?

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 very exciting short-term goal, by the way. I think in the next 10 years, we should put it to work. 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? Yes, I can be followed on instagram or facebook but then

the create cures.org create cures.org is where the clinic is in los angeles and it follows a lot of people all over the united states and and then we have the the walter longo foundation.org in in europe and so um that's how we follow people those Those that cannot afford it, it's a non-profit clinic. Those that cannot afford it don't have to pay as long as we have money to operate things. But yeah, I recommend that you contact the foundation. And 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. 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. My pleasure, Peter. My pleasure. Thank you. I want to take a moment to tell you about Abundance360, my year-round leadership mastermind for people who want to go big, create wealth, and impact the world. It's also Singularity

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