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

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You're about to make a trade. Which u do you listen to? Is it get optioning those options or.

Let'S do a little research.

Learn more@finra.org TradeSmart 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. The 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 can do. You know, 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. Valter 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. You know, 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. Valter Longo, as I introduced, is really one of the world's experts in this area. Valter, 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. 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 of focus?

Yes, I actually started very early. I was a student of Roy Walford at 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. So it was, I guess I had a major moment, let's say a major exposure to this world. Roy was a little bit crazy, but I think he was a real pioneer and a real dreamer. That made a big difference on me. 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? And since then it was 1992, 93, that's all of it. I mean, I focus on that.

Let's say, 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 an incredible story. And just for our listeners, 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, inside this enclosure, a glass enclosure. 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 fly in 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, because the CO2 started getting absorbing out of the air and they had eight scientists inside this biosphere and 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?

I mean, 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.

Timothy Leary was there.

Party.

Yeah, exactly. Yeah, no, we're at the same exact, exact same party, whatever. That was 40 years ago, 30 years ago. Anyway, so if I were going to ask you, Valter, 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, and quickest way to go right now. But, but I think we're also working on drugs and, and other interventions to, to do that.

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, why can't we? What's your longevity goal? How long do you want to live?

I wouldn't mind making it maybe to 1:25 or so. I mean, realizing how difficult that is. But yeah, I think I've seen that 110 with Salvatore Caruso nearby in Calabria. I followed him for my entire life 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? Maybe I'll get to 125 or maybe I die tomorrow when we, before we.

Jump into the whole conversation around 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 local Japan. What's going on there? You think that is driving people to get to a centenarian and supercentenarian level?

Yeah, so I go there a lot, especially the one in Sardinia and to Loma Linda. And I think that Sardinia, when you look At Cello and Villa Grande Estreseili, you realize, but also Calabria. Now, we've seen lots of little towns that have a very high prevalence of centenarians. I think you realize that the genetic factor is probably much higher and more important than previously described, meaning that you see lots of the centenarians saying, I had three or four brothers and sisters, and one made it to 95. 1, 98, 1, 102. 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 in at least some of these blue zones, there is a genetic factor. And some of them, there's a lot of inbreeding, like Ceulo and Villagranda. 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 the mayor created super longevity, almost zygosity, 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 not to be Michael Phelps, you probably need everything. And so you cannot. You just. You gotta 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.

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 250 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, 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 these next decade?

Until you say that 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 longer, and it's not going to be just 1 10. 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. When we discovered that, when they discovered that, we thought, within 10 years, we're going to cure this disease. They were born in 1994, 95. So 30 years have gone by and we're still nowhere even beginning to cure als, Gehrig's disease. Unfortunately, the reality, even if you consider the exponential growth, and the exponential growth was also for ALS since 1992 now. Right. So we are much, much better than 30 years ago and lots of different things, but people still die and suffer miserably from Lugaric disease. So, yes, 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 safety. You can reprogram all the cells you want, but are you going to put the person at risk? Remember when gene therapy was first started, you know, one person died, and this, this delayed the use of it by. It was a great technology, and it was just, 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, 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 20 or 30 years from now, so if someone's in their 40s, 50s, or healthy, in their 60s, if you can make it, you know, an extra 20 or 30 years, get it, get to 90, then the potential to intercept these technologies may be maybe 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, you know, and then go from there. Right. So, yeah, I think if we achieve that, it's very achievable in the next 30 years that we add 30 years to 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 30 years and then we have now 60 years to at least the ones of us that are in our 50s to get there. But it's a fun, for sure, it's a fun moment, a revolutionary moment and we just have to see what happens here.

Well, I can guarantee everyone listening to our voice and our podcast today is going to 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, 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. But 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. Right. 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. So the fasting vegan diet is something that 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. It's something very simple but incredibly powerful. Why? Because when you shrink, you start this self eating process, this repair process when you re expand. Actually, as we've shown in lots of different papers in mice, you turn on embryonic developmental genes. I think that this is all coordinated. I talk about 3 billion years of R and D because this is really nature's way to rebuild organs and systems. And I think it's probably going to be the first success. I'm biased obviously, but it's the first success in causing multisystem regeneration and rejuvenation in a safe way, in an effective way, just because we're already there and it is safe and we already have data showing that it's effective.

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 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 3. 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. You know, it gets you the five days of fasting and that's when 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.

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Yeah. So obviously eventually, if you want this to be, say, a worldwide or certainly a popular intervention, it has to be very safe, it has to be very feasible. The majority of people have be able to do it. And I would say water only fasting is something that maybe 1% of people could do, kind of like chronic calorie restriction, maybe 1 or 2%. So I've done that 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 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. Most people don't realize this is why we study it, develop it and tested the fasting mimicking diet. It's 1100 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 there's 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 1200 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, £152, 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?

Yeah, I mean, the average American, I Think 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, it's really about your abdominal circumference, your bmi, body mass index and so how much fat you have, how much muscle you have and then you adjust based on that. Right. So you could be eating 3,000 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 I think it's 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 1100 calories, reducing down to 800 calories I think for the last three days. And I 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, 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 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. But we compare the, say for example for cancer, they work about the same, right? 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 compare and we looked at inflammatory bowel disease in mice. The water only fasting worked only about half way to what the FMD did. And it turns out something that was a little surprising. It was probably the prebiotics in the fmd. When I developed the fmd, I wanted to make it extremely healthy. So thinking about the blue zones and, and thinking about what are the healthiest food in the world ingredients in the world. So 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 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 but the fasting water only fasting still worked, but it caused good and bad. And the FMD seems to be much more consistent, turning on, for example, intestinal stem cells and increasing the level of these beneficial bacterial families and decreasing inflammation, et cetera. I think that it makes sense. It makes sense that having this plant based vegan composition plus the fasting property 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. So I would say that people of course 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 cannot buy anything, that's good. I always say eventually, if that's all, if you cannot afford that and you're in some country where there is not reimbursement for it, absolutely do water only fasting because it's going to be still effective.

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. But two questions I want to hit on. One, how many times per year should I just in terms of wanting to be 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 mice 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 something like 21 clinical studies that have been done by Prolon.

Yes. And there's probably another 30 either running or about to start now. So the results are very good. And the frequency, for example, for diabetes, the Heidelberg study on diabetic patients and the latent study on diabetic patient 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, it's fairly high compliance, which we did not expect. So most of the people could complete the 12 cycles in one year. 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 three, and then eventually less than that. And so, yeah, but then also it's a question of risk and let's forget the diabetic and let's say somebody's 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. Right. So I mean, we don't know. Right. So 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. That's the first time where we do the FMD once every three months. That's going to be very interesting study. 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 three months and we'll see what happens. But we're optimistic. By the way, in the 2017 trial we published on healthy patients, we saw reduction of IGF1, 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 and that's what we think. It's also very exciting about this, getting people to be disease free. The last thing I want to say, which was very surprising, now this is the fifth trial we see the same, no loss of lean body mass. So. 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. Looks like we got it right.

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 1 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 doing the fasting diet. Also because of what we suspect is that this break like we see for insulin resistance is a possible. There is IG. Well, we know there is IGF1 resistance. So the central growth factor at least has been shown for Alzheimer's. But it's possible that by removing this, getting IGF1 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. So it looks like all the regenerative effects of the fasting Mickey 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, call it, a million years for round numbers, we've gone through periods of 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 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 right. 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. 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 days of fasting. And so that's probably the great majority of the population has never been exposed to any of this. Right. And that's probably why the insulin resistance, 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 and so they don't know what to do.

Waiting for their reset and they don't.

Know what to do. And you know, 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 the organ and the system needs 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 are the lists of things that FMD could be valuable in addressing?

I think many. And the reason is that it's not the FMD that is doing the work, is 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 it, most 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's 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.

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Yeah, so we started about 10 years ago publishing on the blood system and showing that during the fasting and fasting making diet 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 refeed, they go to work and they essentially rejuvenate the immune system. 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. Multisystem regeneration has to do with probably either the self renewal of stem cells on one side or, or the reprogramming. We see Yamanaka factors, these factors that can make somatic cells into embryonic stem cells. We see Yamanaka factor, by the way, we see different Yamanaka factors being turned on in different organs, which makes sense. Yamanaka probably use the brute force to reprogram cells. But the pancreas may not need all the factors, may only need a few and for example, when you do the FMD and refeedi, you see the pancreas showing a profile, a gene expression profile, very similar to the one activated during embryogenesis. That's how we know there is a real program, a very coordinated program by the way, with different steps and lots of transcriptional factors that are orchestrating this rebuilding process. For example, we could take the pancreas of a mouse, destroy it with a toxin and that's permanently, irreversibly damaged. The mouse no longer makes insulin and then we start the FMD cycles and then you see, fairly rapidly there is reprogramming of the pancreatic eyelid 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.

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, 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, you know, sugar for sure. And yeah, 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.

No, it's, Listen, I'm here to learn as well. So how much protein should a person taken? 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?

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 Eat. But of course it's not for athletes. So the athlete, my recommendation has always been increase it until you're happy with the result. Right? 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 060. And we suspect that maybe, as I was saying earlier, possibly by having so much protein and having maybe very high IGF1, you could be overstimulating. Some of these growth pathways like insulin can lead to insulin resistance, lots of insulin. So yeah, obviously if you eat so much protein, most people get some benefit. But the question is, could you get even more benefit if you had less proteins by both? We finished a five year study now on mice in looking at how you optimize frailty, muscle function and longevity. It's pretty tricky. 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 rate. So yeah, I would say probably much lower. And if it doesn't affect your, your performance and your, and your muscle, then I think you're much better off with let's say 0.5 than 1 per pound.

But still sugar reduction. And that includes high glycemic index breads and white rice and so forth. I'd want to talk about it while you're in Italy, reducing your high glycemic intake.

Yeah, it's tricky. I think the high glycemic index obviously in general is a bad thing, but at the same time, we always get comments about, oh, I ate this soup or that soup, and the glycemic index go up. I mean, we suspect that if you're otherwise insulin sensitive, some of these spikes may actually be helpful and maybe contributing to signaling, intracellular signaling that actually helps you maintain lean body mass. 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 is same for the sugar, right? I mean, obviously we work on sugar, but yeah, the great 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 I mean technically I'm thinking biochemically, you know, there may be. We are a sugar machine, right. So, so we in fact need to maintain the sugar a certain level. If you start seeing patients that we follow in the clinics 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 rather see a person with blood sugar fasting glucose of 90 than 60 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.

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, 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 fasting glucose and lots of metabolic markers. The problem if you skip breakfast is that that 16 hours is associated with a shorter lifespan and more cardiovascular disease. But if you don't skip breakfast then there are 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 is 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 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 5pm 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 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 so now you had the benefits of being able to, you know, skip this central meal without really 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 six and you're ending at seven, then you might have a breakfast at 13 hours later at 8am, skip lunch and have a dinner again at six that evening.

Yeah, that seems to be very safe.

Yeah, yeah. And I was on a very time restricted, you know, 18 hours off cycle, 12 or 13 hours off is much easier. 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.

Yeah, I think we very much look at the long term safety. So I use these five pillars of longevity. 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. 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 lots of different things that we do.

Well, let's take a second because 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?

Yeah, not so much centenarians, but everybody. So. So the pillars have to do with scientific and medical disciplines that feed the instructions, let's say. Right. The recommendation. So one, the pillar 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 diapers, a lot of high sugar diet. One of the pillars is basic research on aging. How do you make a mouse live longer? Can you make a mouse live longer consistently? If you can't, it's not a good Start 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 humans. Then centenarian studies, that's one pillar. The whole centenarian populations that we follow really teach us a lot and we like to have. And then the fifth pillar is complex system, others a 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. Say, oh, I got it wrong. I thought that this was good. 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, 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, although I think it's probably important but I'm not an expert so I let Dan Buettiner and others talk about that. But I mean we focus on timer citi. I mean the longevity diet, which is a pescetarian 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 receptive 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 muscle training maybe three or four times a week. So those are the main. And sleep. But again I'm not an expert on sleep and so I rather tell people to, to read the book by Matt Walker or others that truly specialize on that. But obviously that's a very important one.

Fantastic. I think those are the basic ceremony nose 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 mimicking diet per year.

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 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 I think that three to six months you're going to have continued benefits.

So as we close out here, I'm curious, where's your research going next? What's exciting for you in the near future here? And if you had all of the funding research to do, all of 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 published in leading journals. So cancer I'm particularly excited about. I think that fasting, mimicking diet can serve as a wildcard, helping immunotherapy, chemotherapy, hormone therapy, et cetera, et cetera work better. And maybe as we've seen for lots of patients, go from disease progression delay to cancer free survival or remission. So that's an exciting set of studies. And then diabetes, I think we're already there, we're at trial number four or five. It's pretty clear it can reduce drug use and reverse 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 done that part yet. But so diabetes, I think it's the most conclusive one already and we are excited about that. And yeah, so lots of other diseases. And then I think Alzheimer's 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 Mickey 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, and so we want to take it to the next level. So 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 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? 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. 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. Valter. Where can folks find out more about your research on what website?

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 falls a lot of people all over the United States and then we have the Valter Longofoundation.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 yeah, I recommend that 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.

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.

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