Valter Longo PhD: Fasting & Nutrition Protocols for Longevity & Disease Prevention

When it comes to fasting, how do you parse fact from fiction? How do nutrition and lifestyle choices make or break disease? And how do we eat to live longer, healthier lives? To help us answer these questions, Dr. Valter Longo is back. Dr. Longo first graced the show back on RRP #367, where we covered the basics for fasting for longevity. Today we are getting granular on the science of longevity & nutrition, including an analysis of the latest research on fasting and what Dr. Longo calls the fasting-mimicking diet and its connection to healthspan extension & disease prvention, So today we pick up where we left off four years ago, covering: The latest research on fasting and his fasting-mimicking diet; the 5 nutrition pillars of longevity and various fasting strategies, optimal protein intake based on age, high fat versus low-fat diets, and how to think about and contextualize continuous glucose monitoring; the science around rapamycin, metformin and sirtuins; and many other topics. Today’s episode is also viewable on YouTube. Learn more + show notes: https://bit.ly/richroll690 Valter is one of the world’s brightest minds on the cutting edge of longevity science and this one is full of prescriptive advice. I hope you learn as much as I did. Peace + Plants, Rich Learn more about your ad choices. Visit podcastchoices.com/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Rich Roll?

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• 1:05Valter Longo?

  Let's start thinking about repairing systems. And not just putting a Band-Aid on it. You have diabetes, drug number one. Then you escalate to drug number two. Then you get cardiovascular disease, you have two more drugs there. This is what happens. It's really criminal, I think, you know, in the United States, in Europe, all over the world. I call it unconspired conspiracy, right? So, everybody is going along with this system, and you have a lot of bad food, and a lot of drugs that people take, and nobody wants to change it. And so, we're moving away from facts and moving into fashion. And this is very convenient for people that are making lots of money the way the system is.

• 1:46Valter Longo?

  We know that nutrition can revolutionize almost everything in medicine. It's not gonna cure everybody, but it could certainly make an incredible difference, more than we've ever seen, right? Certainly, anything that is obesity-related and overweight-related. But we need to have the schools, and we need to have the teachers. That's by far the number-one thing we're missing.

• 2:18Valter Longo?

  The Rich Roll Podcast.

• 2:21Rich Roll?

  Hey, everybody. Welcome to the podcast. Very exciting because we got Dr. Walter Longo in the house today. He's going to get granular on the science of longevity, the science of nutrition. He performs an analysis on the latest research on fasting. We talk about what Dr. Longo calls the fasting mimicking diet and its connection to health span extension and the prevention of disease. For those unfamiliar, Dr. Longo is one of the world's top researchers in the aforementioned field. He's a professor of gerontology and biological sciences at the University of Southern California. He's also the director of the Longevity Institute at USC, one of the leading centers for research

• 3:05Rich Roll?

  on aging and age-related disease. He's the director of the Longevity and Cancer Program at the IFOM Institute of Molecular Oncology in Milan, Italy. He's also somebody who's been named one of the 50 most influential people in healthcare by Time Magazine in 2018 for his research using fasting to improve health and prevent disease. He's also the author of the international bestseller, The Longevity Diet, all profits of which he donates to research and his foundation. And he's the founder of ProLon, a five-day fasting mimicking diet program. This is Walter's second appearance on the program, and it's coming right up. But first.

• 3:57Rich Roll?

  Okay, so today we pick up where we left off four years ago, episode 367, if you missed it, covering the latest research on fasting, longevity, nutrition, and his fasting mimicking diet, including his take on the recent study out of China that controversially showed no efficacy in intermittent fasting for weight loss.

• 4:20Rich Roll?

  We discussed the five nutrition pillars of longevity. We talk about various fasting strategies. The acute versus chronic effects of food on metabolism. We talk about optimal protein intake based on age. High fat versus low fat diets. How to think about and contextualize continuous glucose monitoring, as well as his take on the science around things like rapamycin, metformin, and sirtuins, among many other topics. I love geeking out with Walter. He really is one of the world's brightest minds on the cutting edge of longevity science. This one is full of prescriptive advice, including how to separate what we know from overblown hype.

• 5:05Rich Roll?

  And I sincerely hope you enjoy it. So here we go. This is me and Dr. Walter Mungo.

• 5:14Rich Roll?

  Walter, it's great to see you. It was awesome to reconnect with you in Miami recently. I'm glad that I did not give you COVID experience. It's been four years since we did this. And after seeing you, I thought it would be great to have you back on. And there's so many things, I think, that we could talk about. There's been a lot of research and science since four years ago. But I thought a good place, an interesting place to start, would be with this recent study that just came out. This study that was published in the New England Journal of Medicine, a study coming out of China, that showed that intermittent fasting had no impact

• 5:57Rich Roll?

  versus regular feeding windows in terms of weight loss. Now, I know your expertise is in longevity and not weight loss, but because this study was sort of widely covered in the media and caused a little bit of a kerfuffle amongst fasting enthusiasts in the wellness world in general. I assume you're familiar with this study. And I thought it would be wise to solicit your thoughts on it.

• 6:23Valter Longo?

  Yes. So my understanding of the study was that they looked at long-term calorie restriction, plus or minus time restricted eating. So either you're calorie restricted severely, and then you eat within a window of eight hours, I believe. Or you're just calorie restricted. So first of all, it's really a pointless study because these long-term calorie restriction studies, we already know that they're going to result in people regaining their weight back, they're too excessive. And also, most people don't realize that they're probably associated with this thrifty mode, meaning that the body eventually slows down metabolism.

• 7:05Valter Longo?

  We know this from multiple calorie restriction studies. And so now you're stuck, and there was an old New England Journal of Medicine study showing that. So now you lose weight, but now your metabolism adjusts even lower than your adjustment per kilogram of body weight. So that means that you're pretty much condemned to regaining all the weight. So it's a pointless study to begin with. And then in addition to that, you add the time restricted eating. I don't think it's a valid argument. You know, I'm not a big fan of 16 hours a day. I'm a big fan of 12 hours of fasting a day. And but I don't think it should be used against the 16 hours, because it was just, you know, a study that

• 7:48Valter Longo?

  shouldn't have, I don't think should be done, not that way. And it doesn't really lead to any conclusions.

• 7:55Rich Roll?

  Right. I mean, what was interesting about it, I mean, first of all, it was conducted over a period of a year. So at least according to the media, that was the longest term under which they had studied humans with some kind of setup like this. But the feeding window was 8:00 AM to 4:00 PM, which I guess it's sort of like eating an early dinner. It's not that different than a normal feeding window.

• 8:17Valter Longo?

  Yes, but again, you're associating it with severe calorie restriction, right?

• 8:23Rich Roll?

  Right. It was like 1500 calories, 15 to 1800 or something like that.

• 8:27Valter Longo?

  Males is severe calorie restriction, even worse than what Walfer and other people did in the past, right? So these are, these are already starting with something that is so extreme that... And at the end of the study, you can see that what we know happens in most cases, they start regaining weight, right? So, you know, starting in the eight or nine months, you start seeing the weight regain, which is, again, what's been observed in so many studies.

• 8:53Rich Roll?

  Right. I mean, they also identified no substantive difference in risk factors, which of course is related to longevity. But in your mind, is that a function of the calorie restriction? Or why was that part of the results as well?

• 9:08Valter Longo?

  Well, I mean, if you go from 25, 3,000 calories, 2,500, 3,000 calories a day to 1,500 or whatever, yeah, it's not surprising that an addition, compacting it into eight hours versus however many hours, it makes no difference.

• 9:23Rich Roll?

  Right.

• 9:23Valter Longo?

  So I don't think that says anything about fasting in general. I mean, fasting, first of all, is not 16 hours every day. I mean, fasting is a lot of different techniques, some work and some don't. And that one, you know, happened to, I think it told us that if you're already severely restricted, you know, eating within eight hours doesn't help you any further.

• 9:46Rich Roll?

  Right. So we're going to define these different fasting modalities, what works, what doesn't, in your opinion, and how we're thinking about longevity. But before we do that, I mean, if you were to construct a proper study, what parameters would you set up? Like, what did they get wrong? And how could somebody do this where it would show, you know, legitimate effective results that would be reliable?

• 10:10Valter Longo?

  Yeah. Well, first of all, you don't want to do severe interventions like that, right? Because people will abandon it. And then when they abandon it for a few times, it's worse than when you never started, right? So it's better to let somebody be overweight and even obese than take them to these yo-yo cycles of losing a lot of weight, regaining a lot of weight, right? So we know that from studies, previous studies. So, yeah, you want to, as we do in, I have two foundation clinics, right? And we try to minimize the changes and trying to be as effective as possible with minimal changes. And you want to probably take a couple of years to get There. So we have diabetes patients and people with cardiovascular disease.

• 10:53Valter Longo?

  It takes a couple of years to convert somebody back, really convert them into something that they can sustain for the rest of their lives, right? So you want to intervene, for example, the longevity diet, you know, which I just published an article describing why the longevity diet should be adapted. It's a high carbohydrate, but not high refined carbohydrate. And not a low sugar, low refined carbohydrate, high carbohydrate, composed of lots of legumes, lots of whole grains, nuts, et cetera, et cetera. So that's a type of diet. Of course, each person is going to have a different version of it, right? So this is not meant to be, so if you're gluten sensitive, you're probably not going to have a whole grain, high carbohydrate diet.

• 11:37Valter Longo?

  But you can pick a different type of high carbohydrate diet. So by just the protein restriction, we now know to be regulating weight, right? So the people, most people, lots of people, eat a lot of proteins to lose weight. And it turns out that looks, based on our research and the research from many others, to be the opposite, right? The protein restriction is leading the system to go into a fat catabolism, a fat burning mode. So this is just one trick. Another trick is eat a lot, right? So if you eat legumes, it may take a pound of legumes to get 45 grams of proteins. If you eat, you know, a steak, it takes 200 grams, right?

• 12:22Valter Longo?

  So a lot less, right? So I think there's lots of tricks to get somebody to, in short term, lose weight, particularly abdominal fat, without losing a lean body mass. We just finished a study where we're looking at Mediterranean diet. And after four months of the Mediterranean diet, patients lost three pounds of muscle mass. And after seven months, sorry, after, yeah, three pounds and after seven months, five pounds of lean body mass. So I think that there is a whole system to be adapted. And as you know, I believe in this. Periodic fasting making diets that can get you to slowly lose weight without losing

• 13:06Valter Longo?

  limb body mass. And again, in a couple of years, by a combination of the everyday longevity diet, which I just described, and the fasting making diet. I think that most people that adhere to it are gonna mostly lose fat, but also, you know, undergo some type of reset, you know, going after insulin resistance, going after maybe some inflammatory issues, certainly some cholesterol, high cholesterol, etc.

• 13:34Rich Roll?

  So you mentioned this article that recently came out. I assume you're talking about the article in Cell that you co-authored with Rosalind Anderson?

• 13:43Valter Longo?

  Yes.

• 13:43Rich Roll?

  Yeah, so explain that. I thought that was really interesting. It basically, it basically establishes the parameters for this longevity diet and why it's so effective. So maybe explain what the longevity diet is and what this article kind of explored in terms of the link between nutrients, fasting genes, and longevity, etc.

• 14:04Valter Longo?

  Yes. So the longevity diet tries to move away from an opinion and move into a multi-pillar system.

• 14:11Rich Roll?

  How dare you?

• 14:12Valter Longo?

  Where, yeah, exactly. So, so, you know, for sure, the epidemiological studies, lots of epidemiological studies, so studies of big populations. But then, and then the clinical studies, the centenarian studies, and lots of focus, at least in that paper that you just mentioned, on model systems, right? So what happens in mice? And what are the genes that control aging? And what are the nutrients that control the gene that control the aging process, right? So on one side, you have the obesity and all the problems that come with it. On the other side, you have the acceleration of the aging process itself. And we know, we always think about smoking and obesity as major risk factor

• 14:53Valter Longo?

  for diseases. But when you compare them to aging, they disappear as risk factors, right? So, so targeting aging is the most important thing, even more than obesity, way more than obesity, right? So if you can slow down just a little bit, the aging process, you can do much more than obesity does. Of course,

• 15:11Valter Longo?

  Obesity and smoking are a big second and third, but they are dwarfed compared to the aging process.

• 15:18Rich Roll?

  Right. So you began your career looking at yeast, aging in yeast, to try to identify what these mechanisms are. Maybe explain how this is applicable to human health and what exactly, like how we should think about what that aging mechanism or process is.

• 15:37Valter Longo?

  Yes. So actually, I started with Roy Wolf for working on humans and mice. And I understood that it wasn't going anywhere. So I went back to yeast from humans and mice, right? So which, at the time, people thought it was just a bad idea. Right? And so I think that if you look at the genes that regulate aging in many organisms, and we think humans, because now we've been following people with a certain mutation, which I'll talk about in a second, the growth pathways seem to be at the center of the aging process. So if you take a yeast, a fly, a mouse, and now we'll talk about humans, they live a lot longer if you block IGF-1, insulin, and other growth factors.

• 16:22Valter Longo?

  And so, and not only they become a lot longer lived. So in yeast, for example, by blocking this protein pathway, then on the other side, blocking the sugar pathway, and then starving them, they live 10 times longer. So you completely reprogram their ability, their lifespan. And this is compressed as you move up. So in mice, they live about 40 to 50% longer if they have deficiency in these growth genes, particularly the growth hormone gene and the growth hormone receptor gene. And so when we then study humans, those deficient in the same gene, growth hormone receptor, we haven't proven yet longevity extension, but they're protected from cancer, they're protected from cognitive decline, they're protected from diabetes.

• 17:07Valter Longo?

  So they seem to be protected from most of the human chronic age-related disorders. So we suspect that we're also going to see lifespan extension. We're not going to see 50% like in mice, but even if we saw 10%, 15%, with very little chronic diseases, that would be, I think, remarkable.

• 17:27Rich Roll?

  How do we understand the nature of that compression as we go from yeast all the way up to humans? And why it doesn't scale in a more linear fashion?

• 17:37Valter Longo?

  Probably because of evolutionary theories, meaning that every organism was evolved by being able to have different modality, right? So for example, yeast, you can have a modality, it's a life in the fast lane and they live about two or three days, then you can starve them a little bit, or starve them and they live about two weeks. And then you can, you have something called the spore state, and in the spore state, they live a hundred times longer than in the fast lane, right? So they live years. So that tells you that probably in every organism, there are, you know, there's like

• 18:16Valter Longo?

  a reproductive grow, grow, grow mode, and then there is a maintenance mode, where the decision is made that there's probably not enough food, not enough to grow, not enough to reproduce, so I'm just gonna stand by and try to protect myself as best as I can. So now, of course, most of us are not reproducing most of the time, so probably a good idea, right, to switch to that modality and stay there until we are ready to reproduce.

• 18:46Rich Roll?

  Right. Okay, so then with respect to humans, you've identified these five pillars of longevity, so maybe we can walk through them and then get drilled down more specifically on the diet piece?

• 18:59Valter Longo?

  Yes. So, so in this study you just mentioned, epidemiology of course is very central, so lots of studies, epidemiological studies, looking at, you know, what people that live long eat, right? And so one thing we published on a few years ago was, if you look at Americans, those that have a high protein diet, they do very poorly compared to those that have a very low protein diet, but that's only true up to age 65. And then after 65, it turns that, it turns around a little bit, and those that have a moderate protein intake do better than those that have a low protein intake. And so- And I think if you look at the data and if you look at the Harvard studies, they're supportive of this, right?

• 19:43Valter Longo?

  So they will say that a low carbohydrate diet is bad for you in general, unless it's a plant-based, a low carbohydrate diet. They haven't looked so much at the age, you know, dependent effect, but I think we are in agreement that low carbohydrate diet and high protein are not good for you. It should be the other way around, low protein, high carbohydrate. And so epidemiological studies are, I think, generally consistent with this notion. So for example, there's another Lancet meta-analysis looking at carbohydrate intake, and it's better for lifespan to be an 80% carbohydrate diet than to be in a low carbohydrate diet. And if you go to a very low carbohydrate diet, I say 20%,

• 20:27Valter Longo?

  there is a 60% increased risk of mortality compared to the 50, 60% of the calories coming from carbohydrates. So, and, but then what happens is that people confuse this with excess carbohydrate. They, they think that when I say high carbohydrate diet, I mean excess, so excess carbohydrate. So we had doctors, for example, complaining, say, well, now we're in the United States, 70% of people are overweight and obese, and you're talking about high carbohydrate diet. But in fact, I'm talking about proportions, right? So you gotta get food from somewhere, of course, you have to have the right amount of calories. You cannot have excess, but you know, the, but 50 to 60% should probably come from carbohydrates.

• 21:12Valter Longo?

  Yeah, so epidemiology shows that. And then if you, just to give you an example, right? If you think about carbohydrate, if you look even in a yeast or a mouse, if you feed them a lot of sugar, in most of the cases, you're gonna accelerate some of the aging pathways on the sugar side, and then very, even more clearly on the protein side, but especially on the amino, certain amino acids, like methionine seems to be at the very center of, of the acceleration of the aging process.

• 21:46Valter Longo?

  And so, and this is pillar two, right? So, basic research. And then, clinical studies, I think, are pillar three. They're very supportive of all of this. And so, for example, in the longevity diet, we talk about fats, yes, but certain type of fats. And if you look at, for example, the work by Astrock in Spain, thousands of people randomized one group at risk for cardiovascular disease, one group placed on a low-fat diet, and one group placed on lots of olive oil or lots of nuts.

• 22:28Rich Roll?

  That was like, that was, there was a study that came out like just last week about that, I think.

• 22:32Valter Longo?

  Yes, been many studies that followed up. I didn't see the, maybe there was one last week, I didn't see that one. But now it's pretty consistent and showing that, you know, the high olive oil, high nut diet is better for people.

• 22:47Rich Roll?

  Which is so interesting and somewhat counterintuitive with respect to cardiovascular disease.

• 22:52Valter Longo?

  Yes, historically, and to this day, lots of prominent experts will say, go to a no-fat diet, no matter what it is, right? So, sure, it seems to be true, it's better to not have saturated fats, animal fats, and again, the epidemiology agrees with that. But when we're talking about this mono-saturated fats, olive oil, nuts, probably certain fish like salmon, that seems to be consistently associated with living longer. And then, you know, the centenarian studies, of course, one of the most important pillars. So, if a low carbohydrate diet is not so good for you, let's look around.

• 23:34Valter Longo?

  Let's look at Okinawans, let's look at people in Sardinia, in Calabria, in Lomalinda, in Costa Rica, in Greece, do they have a low carbohydrate diet? Or do they have, as we will expect, a high carbohydrate diet? And all of them, a high to very high carbohydrate, including the Okinawans, who used to get about 70% of their calories from sweet potatoes, as you heard at the conference, from Dan Buettner.

• 23:59Rich Roll?

  Right. So, with all of that, and of course, it's about, when you're talking about a high carbohydrate diet, you're talking about, you have to drill down on what that means specifically. It's not eating pretzels and tons of, you know, refined carbohydrates. These are like whole plant foods for the most part.

• 24:16Valter Longo?

  Yes, I mean, it can also be whole grains, right? So whole grains in this study done by this Norwegian, this meta-analysis that came out a couple of months ago. But this Norwegian group, the number one source of food associated with life expectancy increase was legumes. And number two was a whole grain cereals, right? So, so it's not just, you know, let's say vegetables. But it's also lots of, you know, carbohydrate that may not necessarily be associated with health, right? For example, say whole grain pasta, but even pasta, it's probably okay, right?

• 24:59Valter Longo?

  If you don't, certainly it was okay for most of the centenarians in most areas. And so, for example, for the Okinawans, the sweet potato. You wouldn't necessarily think the sweet potato is that good for you, but it was very good for them. And so I think you cannot for sure have lots of bread and lots of potatoes and lots of pasta. But a certain amount of it is probably not bad. And don't forget that our body doesn't, is not fueled by complex carbohydrates. Eventually is fueled by sugar, right? So eventually it gets turned into pure sugar. And that's what the brain and every other cell wants, unless you have ketone bodies or fatty acids around, right?

• 25:44Valter Longo?

  So, so yeah, sometimes we forget the basic biochemistry, but we are fueled by sugar.

• 25:50Rich Roll?

  So with this understanding, the kind of basic tenets of what comprises a diet that promotes longevity based on this research, where does fasting come in? Like, what is the relationship between these dietary pillars and these protocols around fasting or fasting mimicking?

• 26:12Valter Longo?

  So I think there are two, I always look first at the safety factor, right? So what is it that we don't know if it's safe or not? And then I just exclude them until we have many decades, I think, of evidence. But if you, if you look at safety and efficacy both, I think you come up with 12 hours every day has been very solid. I always say, I've never seen a study showing that if you do 12 hours of fasting a day, you're going to have a problem. When you get to 16, and as we, I think, already discussed before, you get to 16 hours, you get to breakfast keeping, I see meta-analysis, not just studies, but studies of all studies showing increased mortality, reduced lifespan. Now, what is the reason for it?

• 26:57Valter Longo?

  We don't know. Probably there are double-edged swords, right? So for example, ketone bodies, maybe fatty acids, ketone bodies are going both ways, right? They're helping you on one side and they're hurting you on the other side. But so 12 hours, very solid. And the work by Sachin Panda and everything else is supportive of it. And then I would say probably people we eat all the time. And so in the, thousands of years ago, but as humans evolved, we evolved probably insulin resistance as a way to survive the winters, right? So, so you eat as much as you can during the summer

• 27:39Valter Longo?

  or whenever food is available, you become diabetic, essentially prediabetic or diabetic. You put everything away and then the winter comes or some period where there is no food and then you become insulin sensitive again. So I think what happens now is everybody is insulin resistant all the time or somewhat insulin resistant all the time because the winter never comes. And that's where this prolonged, not just, you know, 16 hours of fasting, but say five days, that's what we've been working on, that's where they come in. There seems to be pretty clear now, we have three more clinical trials that we are about to publish. Very clear that they switch you into an insulin-sensitive mode.

• 28:20Valter Longo?

  So, and also, they switch you into a long-term anti-aging mode. So, for example, leptin, and now, this is about four clinical trials that we've done. Leptin stays low for a long time after you return to normal diet. IGF-1, the central growth factor pro-aging, stays down for months. So, in the first trial, we showed that after three months from the end, IGF-1 was still lowered. Yeah, so then, I think that there is, on one side, insulin sensitization. So, the system now goes into a fat utilization mode versus building. And the system also goes into a maintenance mode.

• 29:04Valter Longo?

  So, now, I'm just gonna protect myself as much as possible, age as slowly as possible, waiting for the next wave of lots of food where maybe I can focus on reproducing.

• 29:16Rich Roll?

  Right. So, with this understanding that there is no winter, the winter is not coming, and everybody's kind of hurtling towards some degree of, you know, being prediabetic because of the Western way of eating. How malleable is that? Like, if somebody has been in that prediabetic state or in a situation where they lack insulin sensitivity for a prolonged period of time, what is your sense of, you know, how one can repair that? Like, if, obviously, if you've just arrived in that situation, it's probably gonna be easier for you through fasting and these other protocols to bounce back and create some insulin sensitivity. But if you've been in that state for a decade,

• 30:01Rich Roll?

  does it become more difficult? Or can you still repair it?

• 30:05Valter Longo?

  You can still repair it. We just finished like a trial on diabetes in Holland, 100 patients. And I cannot tell you the result, but I can tell you that even if you're diabetic, you're obese, you've been taking medicine for years and years and years, no problem, we can bring it back. We cannot bring it back in everybody, but I would say the great majority of people, you have the team, the physician, the dietitian, and you have to have the method. And in that trial, it was just fasting mimicking diet, no longevity diet. In the clinic, we do both, right? But again, we don't push you to 1,500 calories if you had 2,500 calories. We push you to keep the calories, maybe just a little bit lower, you may be going from

• 30:49Valter Longo?

  2,500 to 2,300, and then we work on the NutriTech, what I call NutriTechnology. We work on making it easier for you to lose weight, rather than starving you for a year hoping that you stay like that for the rest of your life, which you're never going to do.

• 31:13Rich Roll?

  So in the four years since we sat down, there's been quite an explosion of interest in fasting. It's gone from this kind of curious endeavor into something that has truly gotten mainstream attention. Lot of discussion about different ways of fasting and many different, as you mentioned, different types of thinking about fasting, intermittent fasting, alternate day fasting, time-restricted eating, fasting mimicking. Maybe it would be worth just talking about fasting in general and the validity of these various protocols and why you feel so strongly that the fasting mimicking approach is optimal?

• 31:54Valter Longo?

  Yes, so alternate day fasting, it's an extension of the 16 hours, let's say, right? So there is no doubt that if you do 16 hours of fasting every day, or you don't eat every other day, you're going to get a lot of metabolic effects. The problem and the question is, now that we have meta-analysis showing that if you skip breakfast, you live shorter and you have more cardiovascular disease and probably more cancer, et cetera, et cetera, is there some issue with these ketone bodies, with these fatty acids, et cetera, et cetera? So no arguing with the metabolic effects, short term. But a big problem with long term, right? So I would say, don't do it. Certainly, don't skip breakfast.

• 32:38Valter Longo?

  Now, when we're starting a trial is now what happens potentially if you skip lunch? So keep the 12 hours and then skip lunch. That's what I've been doing for 20 years. But now we're gonna finally get to test it. We don't know, but let's see. And so that's alternated fasting, or let's say 16/8. Then you have, let's say, 5/2, right? That's another popular one. Well, what happens if you do two days a week of fasting or semi-fasting? Well, we don't know, right? Because there's not very many studies. There's a few. It looks promising.

• 33:18Valter Longo?

  The problem I see with that is most people have a difficult time, I say, going from four coffees a day or three coffees a day to two coffees a day. Half of the people that used to smoke are still smoking, even though we know that it kills you and it says that on the package. So is that gonna really be more than a small, small percentage of the population? So even if we show that was effective, who's gonna do that, right? I mean, I don't know. Personally, I don't know anybody that would go two days a week without eating anything, right? I don't know a single person. But that doesn't mean it could not be effective. And that doesn't mean there are not people that could do it long term. So I'm not arguing that, you know, with the effectiveness.

• 34:02Valter Longo?

  And I'm not arguing that some people could do it. I will say the great majority of the people are not gonna do it. And then I will say, we even don't know what will happen long term. So we gotta go with things that are more realistic, less invasive. And that's where the fasting making diet comes in. And this is, again, 30 years of work since the Walfer years, right? So it's not an idea that, I say, oh, I see a few patients in my clinic, they're doing so well with these five days, I'm just gonna do that. As it happened for many very popular diets in the past. So this was 30 years of building, building, building from all these pillars, right? And then you get to a point, you say, Where you say, this looks very promising.

• 34:45Valter Longo?

  Like, what if we made people do this three times a year for five days? Four times, maybe? And if you have diabetes, in the diabetes trial, we did one cycle a month for 12 months. But most people did not do 12 cycles. Some people did two, some people did six, some people did eight, and some people did 12. So now we're gonna analyze the data and we'll be able to tell, you know, who is doing well. But overall, they all did well. So I think that three, two to four times a year, let's say. Some people may even last, somebody like you probably, you know, a couple of times a year. It'd be more than sufficient. But for most people, let's say, three to four times a year. That seems to be very realistic. It's clearly showing this long-term efficacy.

• 35:27Valter Longo?

  It doesn't, it allows for FDA-like, it doesn't have to be FDA, but FDA-like procedures where you can say, hey, this was tested. That's exactly the way you should test it. And everybody can test it. Everybody can grab it. So now we have 30 clinical trials running. Some of them, you know, we help them with. Some of them, people just get it and they do their own trial. So that's the way it should be. Allow everybody to test it and let's see, right? Eventually, we're gonna see these are millions of people. And we're gonna see the reports from it. And I really think that that's slowly moving in the toolkit of physicians on one side for lots of diseases.

• 36:11Valter Longo?

  But it's also moving in the toolkit of the people that are paying attention and that they want something that is being clinically tested.

• 36:20Rich Roll?

  And just because we haven't defined it, essentially what you're saying is this is a five-day protocol where we provide you through ProLon, this meal delivery, meal kit situation. And when you eat this way... You're mimicking your biological response to fasting without being overly calorically deprived.

• 36:42Valter Longo?

  Yeah, I cannot talk about products, you know, because I'm prohibited from doing it. So in the FMD, you know, for example, for cancer, it's four days. It's very different from the one for normal people, which is five days, as you just mentioned. Then we have one for autoimmunities, it's seven days. We have one for Alzheimer, we're testing now in Italy, which is five days, but then it has a daily supplement for the in-between. So it's really about nutri-technology and, but yes, the fasting mimicking diet, let's say it goes from four to seven days in most cases. Plus or minus what could be supplements. For example, in the Alzheimer, we were worried about people losing weight and some people did lose weight.

• 37:25Valter Longo?

  And so that's why we give them a supplement between the 25 days between one cycle and the next of the fasting mimicking diet. We also, because they're so old, let's say 75, 80, 85 years old, we give them a higher calorie fasting mimicking diet, right? So, yeah, so we adjust based on the age, on the, on the disease and, you know, eventually, I think there might be adjustments also.

• 37:51Rich Roll?

  Right.

• 37:51Valter Longo?

  For example, now we have, we're developing a non-inflammatory one. Lots of people with inflammatory bowel disease, colitis, gastrointestinal problems. We're developing something that is non-allergenic, non-inflammatory, which I think is, is gonna be very important for, and we, I mean the university, I don't mean, I'm not talking about company. So, so yeah, I think that's, that's certainly, I'll be very surprised if, if this doesn't move into more of a mainstream and start competing with the drugs, right? I mean, that's what we're trying to say, like, let's start thinking about. Repairing systems, you know, based on all the things that we discussed and not

• 38:32Valter Longo?

  just putting a Band-Aid on it. You have diabetes, drug number one, then you escalate to drug number two, then you get cardiovascular disease, you have two more drugs there. This is what happens. It's really criminal, I think, you know, in the United States, in Europe, all over the world, as, you know, I call it unconspired conspiracy, right? So, everybody is going along with the system and you have a lot of bad food and a lot of drugs that people take and the whole system is profiting from it, but people, the average 45-year-old now has got two chronic conditions in the United States. And so, by the time

• 39:14Valter Longo?

  you get to 55, 60, you probably have about three chronic conditions, taking lots of drugs, right? So, we're saying, what is the system not to just block that, but to bring you back to a healthy status? And, you know, it used to be ideas, now we see in the clinical trials, but we also see it in the foundation clinics where we follow lots of people. So, we're very confident that this can work, but it's not going to work unless you have, you know, the team that I was discussing earlier, the doctor, the dietitian, and the knowledge, and probably also the molecular biologist, right? When you get too complex, so we get people at the clinic all the time, and they have very complicated problems,

• 39:55Valter Longo?

  right? And so, you have a very busy physician, even our own, right? And you have a very busy dietitian. And I think that the molecular biologist specialized in whatever field, it could be the key person, right? So, the strategist, like I am, right? So, this person comes in, works with the physician and works with the dietitian to strategize, how do I solve the problem? This person's got three chronic conditions, where do they come from? And how do I solve them without creating another problem, right? That's gotta be at the very center of everything, and it's not.

• 40:28Rich Roll?

  Well, what's interesting about all of this is understanding the incredible resilience of the human body. Like, it can be abused for extended periods of time. And when you course correct that, it's kind of amazing that the body is able to get back to some sort of homeostasis without a pharmaceutical intervention. The trick, of course, as you mentioned, is getting the medical establishment to truly grok this and make it part of what is recommended in their protocols. So what is your sense of where you're at with that right now? Like, do you have doctors who are on, I'm sure you do, that are prescribing this, that are on board with it? And what is the resistance or the obstacles that you still face?

• 41:10Rich Roll?

  I mean, obviously, the gold standard would be getting it to be reimbursed by insurance and that kind of thing. I assume you're not quite there yet.

• 41:22Valter Longo?

  There are, I don't know, maybe 30 or 40,000 doctors around the world. There are now recommending fasting mimicking diets. And I think they're all saying more clinical data, more FDA-style clinical data. And absolutely, right? So then we and others, and many, most of the studies we're not doing, right? Universities are doing it on their own. We're just helping them. So, yeah, so I think that everybody's waiting for more studies. They're coming. Lots of them are already finished and we're about to publish them. But I think, you know, for cancer, Alzheimer, you know, autoimmune disease, et cetera, et cetera, we're gonna see more and more. But I think in addition to the FMD, I've been talking to lots of politicians, both in Italy and here,

• 42:06Valter Longo?

  and I'm saying, you know, imagine, you have 70%, over 70% of people that are overweight or obese with all the chronic conditions that we discussed. And I said, imagine if you say, well, people are uneducated in a country, but I'm not gonna have schools and I'm not gonna have teachers, but I want everybody to be educated. It's never gonna happen, right? You can say it as much as you want, right? Until you build the schools, until you have the teachers, it's not gonna happen. So here, we know that nutrition can revolutionize, you know, almost everything in medicine. It's not gonna cure everybody, but it could certainly make an incredible difference, more than we've ever seen, right? Certainly, anything that is obesity-related and overweight-related.

• 42:50Valter Longo?

  So, but we need to have the schools and we need to have the teachers, right? But these are gonna be schools and teachers of nutrition and lifestyle. And I think that that's by far the number-one thing we're missing. Then I think, you know, if you can get that, as we've shown in a mouse study that we recently did, which you may have seen before, you know, so we, we say, "Okay, forget it. It's never gonna work. So let, let the mice eat lots of fat and lots of calories and become huge. And then, once a month, we give them the FMD, the fasting-making diet, and we reverse everything, right? So, so I'm sort of going against that. I, I, I think people, you know, should be followed and should be professional so you don't get into very bad diet every day and then use the FMD to fix it.

• 43:35Valter Longo?

  But I think that's the idea of the FMD. Maybe for those that are now willing to make daily changes, that's where you, you bring in the medicine, the food as medicine.

• 43:44Rich Roll?

  Right, right, right. I mean, it's such a massive problem because every, every force that surrounds us is driving us towards that unhealthy choice. Everywhere we turn, all the marketing, the way the stores are configured, et cetera. You're almost bucking the trend in order to eat healthy and consider it an outlier. So, education certainly is central to all of that, but there's also a social piece and a psychological piece. And as Dan Buettner talks about, creating infrastructure or environments that are conducive to the healthy choice. Because, like smoking that has the label on it that says it's gonna kill you, a lot of people just wanna eat what they wanna eat 'cause it tastes good. And until they suffer from some kind of chronic ailment, they're really not gonna look in the mirror and redress it.

• 44:30Valter Longo?

  Yes, and I think you get a, probably even get closer, right? So you have to have like the teacher in the school, right? You have to show up at eight o'clock and then you have to stay there until such a... So, yeah, no, I don't mean that for people, but I mean, you know, let's say, for example, once a month, you have a telemedicine call on the computer with your dietitian, your molecular biologist, and maybe once every six months with the physician. That's not very invasive, right? So, but now with all the apps and devices, you can monitor their weight from the distance. They wouldn't even have to tell you what they're weighing. You can monitor the blood pressure. You can monitor lots of different things. And now, pretty soon, the glucose level, you're going to be able to monitor without even, you know, using a needle.

• 45:15Valter Longo?

  Yeah, so I think we're already at a point where, and that's what we're doing in Italy, by the way. We're starting this 500 people clinical trial with control, fasting making diet, longevity diet, plus the fasting making diet. So hopefully in about a year and a half, we'll have, you know, solid data showing, I hope, success. But yeah, so it's not school A to one. It's one telemedicine call once a month. And just to make sure that you're on track. Do you have any questions? You, for example, with the cancer trial, we see that when we do that, it's very successful, very high compliance. So we do a fasting making diet and chemotherapy, et cetera, et cetera.

• 45:59Valter Longo?

  When we, the only trial when we didn't do that, we allow the clinics to do, to just say, "Oh, here's a fasting making diet. You take it home and do it." Then we went to 30% compliance, right? So most of the people could not comply for more, maybe 50% for two cycles of the fasting making diet with chemotherapy, and then it dropped down, right? So it just told us that, yeah. And hopefully, at some point, it'd be also good to have a psychologist involved, as you mentioned, right? So this team of four people, I think physician, psychologist, molecular biologist, dietitian. It should be our schools and our teachers for lifestyle, and we don't have it yet.

• 46:37Rich Roll?

  Yeah, well, I think that some of these new apps and technologies can really help with compliance as well. Like I started working with InsideTracker and Levels, the continuous glucose monitor. And there's something about being able to pull the app up and look at where you're at in real time that makes it very, you know, kind of... Maybe not urgent, but you're just connected to it in a way that's very different from going to your doctor once a year and getting your blood work done and seeing what it looks like on a piece of paper.

• 47:06Valter Longo?

  Yeah.

• 47:07Rich Roll?

  So, how are you thinking about some of those technologies? Like, do you think there's a place for continuous glucose monitors with respect to kind of the avenues to which you're trying to push your patients or the people that you're working with?

• 47:23Valter Longo?

  Yeah, the technology, of course, is going to be central, but I think the human part, we cannot underestimate it, even if it happens by telemedicine and the psychological part. So lots of things will have to be done, you know, the old style. But yes, as new technology comes in, the ones that we're talking about, you know, whether it's the scale connected directly to the network or the continuous glucose monitor, et cetera, et cetera, those are going to make everything easier. But I think that now we're starting to start a program in South Central for, you know, you're a very highly educated lawyer, right?

• 48:05Valter Longo?

  So, most people are not as educated as you and I are. So I think that we need to also create a reality for people that may not have access to this world, this very tech, high-tech world. And so, yeah, so we're starting a program in South Central and there, I think we're gonna, if it gets funded, we're gonna try getting to the houses, right? And try to convert slowly, again, take a couple of years, maybe longer, right? Can we convert this family, the children, but also the parents into this changed lifestyle? And I think it's gonna take a lot of, I don't think we're just gonna be able to say, oh, here's, I send you an email with an application attached to it, I'll see you in a year.

• 48:49Valter Longo?

  I think for the great majority of people in the world, for a number of years, we're still gonna need to be present and the physician is definitely too busy and not trained for any of this, by the way, right? So then, yeah, we need to, we need to have this team and... But the applications were certainly and eventually artificial intelligence and the collection of, let's say, microbiota data, metabolomic data, et cetera, et cetera. It's gonna take a while, but at some point, you know, you get a, maybe a drop of blood and you'll be able to say, I don't know why, but you have a problem with iron intake. So, so, you know, Leroy Hood and other people are working on this. And so I think that

• 49:32Valter Longo?

  that, but it's gonna be maybe five, 10 years down the road, right? So now I think having a, you know, 70% overweight group or obese group here and 50% overweight or obese in Europe, you need to, we need to act now, right? So, and then, once the technology comes, I think that, that even better.

• 49:53Rich Roll?

  Yeah, well, you can't solve the problem without understanding how to solve the problem in underserved communities like South Central, because that's really where the problem rests. And those communities are, they're not, they're not going on PubMed and reading research. There's gonna have to be a completely different approach to try to figure out how to penetrate those communities and create real change.

• 50:15Valter Longo?

  Yeah, and that's the extreme, but I think there is a middle group, right? All over the United States that is not in that conditions, maybe as a lot of people in South Central, but it's still gonna be much harder to penetrate than the Los Angeles or San Francisco or New York highly educated individual that follows, you know, everything we do, right? So I think the majority of people live in a very different world than than some of us. And I think that, but the majority of people appreciate, if you get a call from a dietitian and a psychologist or this team once a month, I think the majority of people respond very well. We certainly see it with the sick people, you know, I mean, whether they have cancer or diabetes.

• 51:00Valter Longo?

  That sort of feeling like we're following them and we're, you know, okay, you got a problem, but here's the team. You got a team following you and helping you, you know. So I think that psychologically, in addition to everything else, is essential.

• 51:15Rich Roll?

  One of the things I'm curious about, and this sort of came to me in the process of experimenting with a continuous glucose monitor, is that you get this real time data after you eat and you can see, you know, the kind of curve in the graph of where your blood sugar is at postprandial. But I'm wondering, so me as a consumer and not a scientist, I can look at that and I can draw conclusions from that, but I'm not sure those are the best conclusions because what's happening postprandial, post meal is probably different from how it should be looked at from like a chronic perspective, right?

• 51:57Rich Roll?

  So when you're thinking about or conceiving of the, what should go into the fasting mimicking diet or just a healthy diet in general on a daily basis, how do you think about what's happening biologically with each meal versus the chronic conditions that are the result of eating a certain way over a very long extended period of time?

• 52:17Valter Longo?

  Yeah, so we get all the time, people, you know, they may do something that is contained in the fasting mimicking diet, they say my glucose spiked, right? And so it's not really about, I mean, your glucose should spike if there is glucose or some form of carbohydrate in the diet. And in the fasting mimicking diet, we put the carbohydrates on purpose, right? There's a lot less than you will have in a normal diet, but it's still there. And it was designed on purpose to make sure that we don't have this yo-yo that I was talking about before. Why?

• 53:00Valter Longo?

  Do I know that this yo-yo, let's say, you know, we went much lower in carbohydrates? Let's say we went to zero carbohydrate, 10%. I don't know that will hurt people to go back and forth like that, but I'm worried that it may, right? So, and I'm also worried that it might affect muscle. So now we have three clinical trials showing no muscle loss and increase in relative lean body mass. And that's very important. So now... We believe that sugar, I mean not sugar, but the little bit of carbohydrate we have in there, and even though they come with a little spike in fasting glucose, we believe that be protective of the muscle mass. And so now, you know, eventually, we're going

• 53:43Valter Longo?

  to look at, you know, more lower glucose versions to see what happens both for compliance and for muscle mass, et cetera, et cetera. But, but right now, I think we feel pretty good about having all these great results from clinical trials, that that's irrelevant, right? And not just the fasting making, that it doesn't really matter, even in the everyday diet. You don't, don't worry so much about your glucose monitor and whether there is a spike. Worry about the consequences on abdominal circumference, body fat, insulin

• 54:21Valter Longo?

  resistance, right? So if your, if your A1C, HbA1C is 6.5, you get a problem. If you have a spike in glucose and your A1C is 4.7, you're fine. It means that your glucose goes up, your body can process it. You know, I wouldn't do 20 meals like that a day. I would stick with, say, two plus one or three meals a day, and that's it. So you only have three opportunities for that to happen. And that's perfectly fine. And it's obviously not affecting your body in a negative way. Yeah, so it's very important to, you know, glycemic index, fine, but don't become obsessed with things that are part of a much more

• 55:05Valter Longo?

  complicated network, including that may help you protect the body mass, right? So we now know that TOR can be affected, what we knew from our work in yeast, you know, 30 years ago, but we knew that both sugars and amino acids can feed into TOR. And, and so now they're starting to be, you know, data looking at, say, leucine levels.

• 55:32Valter Longo?

  Being essential for muscle building, but the glucose may also be pushing that loose, the amino acids to perform more. So I mean, these are still preliminary data, but certainly that's a possibility that, that, you know, if you go too low in sugars, the muscle might struggle in, in building as long as you're insulin sensitive.

• 55:54Rich Roll?

  Right.

• 56:01Rich Roll?

  Let's go to protein for a minute. You mentioned earlier the idea that you've arrived at that, that lower protein before age 65 is, is optimal. And then after 65, it's important to increase your protein intake. So maybe walk me through how you arrived at that conclusion and what that means specifically for somebody who's listening or watching.

• 56:24Valter Longo?

  Yeah, so if you look at the mouse studies done, you know, for the past 50 years, a low protein is one of the ways that you can substitute calorie restriction to extend the life of a mouse. Then I think we did our study that I mentioned earlier, clearly showing that the low protein group had overall lower mortality and, and the high protein group had a 400% increased risk for cancer mortality compared to the low protein. Now, keep in mind that low protein doesn't mean you're not eating protein. It means that you have to have the 0.35 grams per pound of body weight. So if you weigh 100 pounds, you should have at least 35, 40 grams of proteins.

• 57:07Valter Longo?

  If you go below that, now you're starting to get into malnourishment. So it's low protein without malnourishment.

• 57:13Rich Roll?

  Right, which is, correct me if I'm wrong, about half of what the FDA would recommend? Isn't it 0.8 grams per kilogram?

• 57:22Valter Longo?

  Per kilogram, I was talking about pounds.

• 57:24Rich Roll?

  Okay.

• 57:24Valter Longo?

  Yeah, no, no, yeah. So 0.8 is fine, right? So we're, we're staying with, with the most American, the medical association. So the American Medical Association, I think, says about 0.8.

• 57:36Rich Roll?

  So that RDA, but, but in terms of like how most, at least Westerners eat, that would be considered low protein, even though that's like kind of exactly what we're supposed to eat.

• 57:45Valter Longo?

  Yeah, so the average American will have maybe 50 to 100% more than that, right? Yeah, and so 0.8 is perfectly fine per kilogram. And then, but then it should be mostly plant-based. And I think our study, all the Harvard study, the Giovanucci, Frankhu, etc., they agree with that. And the Centenarian, the Okinawans, had 9% calories from protein levels. The Southern Italians are certainly mostly plant-based. The Lomalinda people, low protein. So.

• 58:19Rich Roll?

  It's pretty clear.

• 58:20Valter Longo?

  It's pretty consistent, pretty consistent, no matter where you look. And so, and now the clinical data is also supportive of that potentially causing weight loss. And the opposite of what everybody thinks. So having a low protein, high, the right carbohydrate diet can lead to weight loss instead of weight gain. And we'll have to wait and have bigger studies, but that's what it's looking like is we're gonna see happening.

• 58:50Rich Roll?

  And is that related to a reduction in mTOR activation and IGF-1 levels? Or what is it specifically about the protein biomechanically that's happening?

• 59:02Valter Longo?

  It looks like certain amino acids are controlling the fat cells. And they're controlling the hypothalamus. And they're really in charge of the decision to accumulate fat or break down fat. So we were talking about before about the fasting making diet. It looks like, and so we are actually now submitting a large grant to study that in the brain. It looks like the certain amino acids are at least in charge of maybe half of those effects, right? So telling the body, okay, now I'm gonna start burning fat. Or now I'm gonna get into a fat accumulation mode.

• 59:43Valter Longo?

  And yeah, so some of these switches are probably long-lasting, right? So maybe epigenetic, may not be epigenetic. So epigenetic, meaning that the DNA is getting modified. And so, once it's modified, this could last a long, long time. But they're certainly long-lasting. And this is why, after the fasting making diet, which of course is very low in protein, we see the leptin down for a long period in people. And we see the IGF-1 down for a long period. So, yeah, so.

• 1:00:16Valter Longo?

  We don't quite know the answer to your question, but I think it's looking like reprogramming. It's got a reprogramming effect on multiple systems.

• 1:00:27Rich Roll?

  And so what is happening around age 65 where that flips and it becomes more important to increase your protein intake?

• 1:00:35Valter Longo?

  Yeah, so if you look at the ENHANCE, which is the CDC database in the United States, and you look at the weight, right? So most people, and most people don't know this. Most people, on average, people gain weight until 65 and then they start losing weight after 65. So it's something that we don't know what it is, right? But aging, of course, is at the very center of that. And there may be some key moment of the aging process where you are now getting into this rapid aging modality. And we know that because most of the deaths occur after 65. So, yeah, so after that, probably the, and this is also the Simpson Group in Australia did this in mice.

• 1:01:20Valter Longo?

  So after a certain age, it may be that the redundancy, so that the system needs more of the amino acids to do its minimal job. And if you don't, if you start having deficiency, you have a problem. And in our own study, we did it with mice. We took young mice and we gave them a very low protein diet. Nothing happened. We took all mice and we gave them the same very low protein diet. And within days, they started losing a lot of weight. So it's probably a matter of redundancy and maybe some of these growth factors are involved. And once you get below a certain threshold, you have a problem. And you may have a problem in the immune system, may have problems with bones, with muscle. You may have a problem in the cognitive system.

• 1:02:02Valter Longo?

  So, yeah, so I think it's just unsustainable for an older organism.

• 1:02:07Rich Roll?

  Yeah, well, it would seem that the more you're on top of these healthy practices as you inch towards 65 and after 65, the better position you're in to prevent those sort of declines being as rapid as they would otherwise. So if you're maintaining your muscle mass with resistance training, If you're eating appropriately in accordance with your protocols and the sort of blue zones criteria, and you're engaged in your community and you have purpose in your life, that you're, that a lot of that like extension or prolonging of longevity is really about the robustness that you enter that stage of life with so that it doesn't

• 1:02:49Rich Roll?

  hit you like a ton of bricks and you kind of become decrepit in an expedited way.

• 1:02:56Valter Longo?

  It's a, it's a equilibrium of robustness, right? Because you, on one side, you could be feeding your muscle with IGF-1, and there's no doubt about it, and on one side, you could be feeding the cancer cell with IGF-1. And so as you enter that stage.

• 1:03:14Rich Roll?

  But if you're doing the plant-based protein.

• 1:03:17Valter Longo?

  Well, if you're doing the plant-based protein.

• 1:03:20Rich Roll?

  Then you increase your plant-based protein.

• 1:03:21Valter Longo?

  You're gonna become frail as most of the Southern Europeans, like the Italians. Actually, the Italians.

• 1:03:26Rich Roll?

  Don't tell me that, Valter.

• 1:03:27Valter Longo?

  The Italians, well, not, yeah, so we can now mix the doing it right with doing it, right? So the Southern Italians are actually twice as frail as the Northern Europeans, right? Or the Italians are twice as frail.

• 1:03:43Rich Roll?

  At a certain stage in life or later in life, they become more frail?

• 1:03:47Valter Longo?

  Yeah, they're long-lived but frail. That doesn't mean that you cannot be vegan or pescatarian and be very strong. Just there is like, and that's what we've been working both in Italy and here very hard with mice. We said, what is the nutrition, the age-specific nutrition that prevents the frailty to the bones, to the muscle, the immune system, but at the same time does not affect the longevity extension, right? It's very tricky.

• 1:04:10Rich Roll?

  There's a sweet spot in between those two polarities.

• 1:04:12Valter Longo?

  And there is an age-dependent sweet spot. That's why we're saying now, don't go from low protein to high protein. Go from low protein to moderate, maintain the plant-based, but start introducing more, let's say vegetarian, if you're, if you don't want to have, you know, meat component, a vegetarian component, more eggs, more cheeses, et cetera, et cetera. Now, of course, you can do it without any of this. You can do it with the seeds, the nuts, right? So it doesn't, you could be 100% vegan and do it, it's just a little bit more of a job to, to do it with, while staying vegan, but that's perfectly fine, like, so.

• 1:04:47Rich Roll?

  But when you're 100, what else do you have to do?

• 1:04:50Valter Longo?

  Yeah.

• 1:04:51Rich Roll?

  You could divert some of that energy towards being focused on that.

• 1:04:54Valter Longo?

  It's not just energy. You gotta have the people that

• 1:04:57Rich Roll?

  Sure.

• 1:04:57Valter Longo?

  Some people that know what they're doing, right?

• 1:04:59Rich Roll?

  It's a joke.

• 1:04:59Valter Longo?

  For example, the legumes are very low in leucine, methionine, et cetera, et cetera. But the seeds are not, and the nuts are not, right? So, yeah, you need to pay attention and have somebody help you, guide you through it, because otherwise you can become osteoporotic and not realizing it at all until you have a fracture and then you're in trouble.

• 1:05:19Rich Roll?

  Yeah, I had a guy in here a couple of weeks ago who is 100, and he broke all these marathon records when he was 90 and 91. And just an amazing guy, but he went plant-based at 70 in response to a colon cancer diagnosis and has been plant-based for 30 years. And at age 100, he's as passionate about it as ever. And he still is running and training and doing all of these things. And so when you're saying that, like, I understand everything you're saying, and I see this living example of a guy who appears to be doing it correctly and was telling me he's having the most fun he's ever had in his life. So it's crazy.

• 1:05:58Valter Longo?

  It may keep in mind, a lot of people that are vegan eat a lot of proteins, right? So a lot of vegan proteins.

• 1:06:03Rich Roll?

  I'm sure he's eating a lot more protein.

• 1:06:05Valter Longo?

  Yeah, yeah. So, yeah, if you eat a lot of protein, let's say 25% of your, and this is very common among vegans. And so, for example, I think Luigi Fontana did a study where he was looking at the vegans, and they were, their IGF-1 was actually pretty high, right? Because they were high protein. They're such a high protein diet.

• 1:06:27Rich Roll?

  So even if you're eating a ton of plant-based protein, you can still drive up IGF-1?

• 1:06:31Valter Longo?

  Yes, absolutely. Yeah, because we're talking about 10% and below in our study, right? 10% of the calories or less had to come from proteins to be in the low-protein group. So if you're now 25% of your calories coming from protein, you're most likely are gonna be in the high risk. And in fact, in our study, we did, the people that had mostly plant-based, instead of a four-fold increase in cancer risk, they had a three-fold increase in cancer mortality risk. So a change.

• 1:07:03Rich Roll?

  Yeah, yeah.

• 1:07:03Valter Longo?

  Better, but went from 400% to 300% increase risk of cancer mortality.

• 1:07:12Rich Roll?

  I'm interested in your thoughts on another, like the other side of the coin with respect to health span science and longevity, because a lot of the press is oriented around this, the sexiness of things like rapamycin and metformin and sirtuins and the like, which is very different than the kind of longevity science that you're interested in and focused on. So how are you thinking about what's going on in that kind of related field with respect to looking towards extending health span?

• 1:07:45Valter Longo?

  Yes. So first of all, I come from that world, right? So I come from the world, we were testing rapamycin in yeast, and I think we got it from Michael back in 1995 or that. So we were probably the first lab in the world that was working on rapamycin and longevity. And we're, you know, my lab discovered the role of the tor pathway in aging in 2001. So we're very much, you know, supportive of the understanding of what genes and what drugs the affect genes do. But I think that for the next 10, 20 years, maybe 30 years, reality is that we have 3 billion years of what I call 3 billion years

• 1:08:24Valter Longo?

  of R and D, right? So our body has been developing for 3 billion years, if you think about the origin of species. And so you could say, I keep, I'm gonna biohack my way through it, right? So I have this incredibly sophisticated system, and I'm gonna intervene with a drug that blocks tor. But tor does so many things, right? And guess what? If you block tor in people with rapamycin, they become hypoglycemic, right? And mice become hypoglycemic. So it's just very clear evidence that it's not as straightforward.

• 1:09:00Rich Roll?

  All these downstream, you have to look at it holistically and understand there's a bazillion intervening variables, and it's all very complicated.

• 1:09:07Valter Longo?

  It's very complicated, and you have no data, right? So who knows what happens after 40 years of rapamycin or metformin? I mean, metformin's got more data, right? So in support of, near Barzila is trying to do, metformin's got a lot more data. But even metformin, what happens if you give it to somebody that's perfectly healthy? Well, we don't know. And I think that that's gonna be an issue. And also, if you look at statistics, or if you do some calculations, the easiest success is going to come from something that is already existing for that purpose. So if you are a yeast, and I already know that I can switch you into a modality where you live five times or 10 times longer,

• 1:09:52Valter Longo?

  because you've evolved that modality to sustain moments where you don't have enough to reproduce, then that's by far the safest, right? Because it's there for a purpose. So then the question is, is there a human alternative modality that is much longer lived? And everything points to yes, right? Otherwise, we wouldn't see these little people in Ecuador not getting any disease. We have one guy that we just interviewed, and he's 80 years old, and he's been drinking and smoking every day of his life, and everybody else does not have a disease. But we thought, this guy is no way, and sure enough, never had any chronic condition,

• 1:10:34Valter Longo?

  and is drunk all the time, smoking all the time. So having the mouse data and having the human data now, and all the other organisms, we know that there is an alternative mode. So if you're going to intervene with drugs, my opinion is that intervene in the master regulator. Don't intervene downstream, right? So intervene very high up, let's say, the level of growth hormone, releasing hormone, growth hormone, etc., because that's more likely to not interfere with anything intracellularly and not come up with as many problems as solutions.

• 1:11:12Rich Roll?

  Right. So I assume that would be the same perspective with respect to supplementation? When we're talking, you know, you hear about NR and NAD and all of these kind of protocols that people are adopting in the, you know, kind of biohacking world. Do you see any efficacy or validity in playing around with that, or what do you think?

• 1:11:35Valter Longo?

  Playing around with the research, yes, right? But, but I think that when you have, you know, this is why we go multi-pillar, right? So, so yeah, yeah, if you, you have to have the epidemiological studies, the clinical studies, the centenarians, you know, how many centenarians have been taking this for seven, eight years?

• 1:11:53Valter Longo?

  You know, and what is the research on all these different organisms saying? So I think the closest you get to four or five pillars supporting it and the more you can think about it. But it's hard to imagine, right? Any of this having that kind of support thus far. So, so yes, you could say, I see, take the 16 hours of fasting, right? Again, there's no doubt that that is very beneficial. But then you gotta wait 30 or 40 years and then you get the meta-analysis. And people that skip breakfast have a problem. So you would never have known that for, you know, until you get to that point, that the famous, those famous studies of all studies. So, so then the question is for all these supplements and interventions,

• 1:12:38Valter Longo?

  where is the data competing, let's say, with what we already know can get you to 100 to 110 now? So I think now we're starting, if you look at the, the study in Norway, the life expectancy increase, if you started just what it's about a third of what I described in the longevity diet. It was associated, if you started at 20 with 11 to 13 years of life expectancy increase. If you started at 60 was associated with eight to nine years of life expectancy increase, right? So now you add the fasting making diet, the 12 hours a day, the, you know, three times as much. Now you're thinking 15, 20 years, not thinking, the data would suggest maybe 15 to 20 years of life expectancy increase.

• 1:13:23Valter Longo?

  So you introduce a supplement, what if that decrease your lifespan by 20 years? After you take it for 30 years? So that's what you.

• 1:13:33Rich Roll?

  We don't know yet.

• 1:13:35Valter Longo?

  Yeah, you, you have to make sure that you don't, we were not in Las Vegas. And, and this is people's lives, right? So you wanna take a chance like that on, on your life. Much better to go with what we know than what we think is gonna happen.

• 1:13:52Rich Roll?

  My sense from looking at your work is that what's good for longevity also appears to be good for.

• 1:14:00Rich Roll?

  Cancer risk reduction. Is there a point at which those two diverge? Because you're looking, you're, you're, you are focused in these two worlds. So what's similar about them seems to be a lot. But is there anything dissimilar or, or something that somebody who is suffering from cancer or concerned about that should be doing a little bit differently from somebody who's purely focused on longevity?

• 1:14:24Valter Longo?

  The only thing, the, the, the only concern is of course the frailty and the cachexia, et cetera. When you're a cancer patient, right? So, and this is a big fight we have in every clinical trial in many places around the world. So the, the physicians will say, I'm not going to allow you to put this extreme vegan or close to vegan diet in between fasting mimicking diet cycles. And we fight, you know, to get it in there because we're saying, treat cancer first and get the cancer. And then we'll, if the patient is losing some muscle mass, that's okay compared to, let's say, a very rapidly advancing cancer. So yeah, but, but, but it's a legitimate concern.

• 1:15:06Valter Longo?

  And so we've been collaborating with Alessandro Laviano at the University of Rome, who's an expert in this and trying to, you know, get to the point. And in fact, in the clinical trial that we published last year, we were successful in doing that. So the women that had breast cancer and received hormone therapy with the fasting mimicking diet, we dosed the, um, uh, the in-between diet in a way that, um, it allowed them to maintain the, uh, a very good lean body mass, so muscle mass.

• 1:15:36Rich Roll?

  Yeah, I noticed on your website, you have different, uh, kind of protocols or marching orders for different types of people with respect to FMD. So you have protocols for people who are undergoing chemotherapy or about to undergo chemotherapy, for pregnant women, for adolescents, et cetera. So how do those, how do those protocols like shift and morph depending upon your stage of life or whatever it is that you're kind of going through?

• 1:16:04Valter Longo?

  Yeah, I'm not sure which website you're referring to.

• 1:16:06Rich Roll?

  I can't remember. Yeah, maybe it was the other one.

• 1:16:08Valter Longo?

  Yeah, if, I mean, obviously for diseases, we, we, we tell people, talk to your physician, right, and, and together with your physician decide whether, um, you know, this should be applied and then, um, you know, in most cases, we like to have a clinical trial rather than improvisation. But, uh, but yeah, it's a discussion with your physician. And then, um, you know, for everybody else, uh, again, you know, different people, different situations, some people are gonna need a dietitian to work with, some people are gonna need a physician to work with, some people don't need anybody if it's just, uh, trying to lose, uh, uh, some weight and, and maybe again, a little bit of reset.

• 1:16:48Valter Longo?

  But, uh, I think that, as I was saying earlier, the team is not there, maybe it's, it's not all necessary, but certainly a dietitian that knows what they're doing, um, should be consulted before, uh, starting. So we do this at the, at the foundation, it's a nonprofit clinic in Santa Monica, and we have one in Italy, and so we'd be happy to help anybody that, um, even those that cannot pay at all, and so we have a program for, for those who cannot afford even the visit, right, so, so I think it's, uh, it's good to, uh, figure out what you need, right? So, yeah.

• 1:17:25Rich Roll?

  Is there, what is the ideal period of life to begin this process? Like, if you're a teenager, can you see benefits doing an FMD? Like, what, what, what is your sense of what the science says in terms of younger people?

• 1:17:43Valter Longo?

  Yeah, well, so we started a clinical trial in, at Gaslini Children's Hospital for type one diabetics at age 10 to 18, and we've been talking to CHLA Children's Hospital Los Angeles about one for obesity and overweight control. So we don't know, and this should only be tested as a clinical trial. In fact, in Gaslini Hospital, they're gonna be inpatient, right? So we, nobody wanted to take a chance with the children and, and allow them to do it outside. But, um, yeah, I think that, um, it may turn out, and, and I don't know, but we'll test it, we'll test it for the possibility that, um, these five days of a vegan diet will allow the, um, a physical improvement in the child.

• 1:18:26Valter Longo?

  But also psychological improvement, right? So it's an exposure to five days of a vegan diet with certain characteristics, which may be very different from what they eat all the time at school and at home. And so that's our hope, you know, is able to reprogram the child psychologically and physically so that they eat better. We clearly see this in adults, right? So that, yeah, some of the effect, the IGF-1, etc., is not psychological. But some of the effect, we think, is psychological, meaning that they, many of the adults are changing their relationship with food. And they don't feel, they're not appreciating some of the bad food as much as they did before.

• 1:19:09Valter Longo?

  Because now I think that, you know, in science, we have something called food aversion. So some foods are associated with problems and you stay away from it because they cause some other problems. But there may be also, probably there is also the opposite of food aversion. You feel so good with this vegan five days, you know, fasting mimicking diet, that your brain might be telling you, let's move in that direction because I don't know why, but I felt better in those five days, right? And maybe in the few days following. So, yeah, so I think that the child, my speculation is that the best moment to do it would probably be, let's say, in a teenager. Because that could really change your life, right?

• 1:19:52Valter Longo?

  So we know that, I wrote a book about children and longevity. And we know that if you're overweight continuously from age seven to age 18, you have a fourfold increase in the risk of developing diabetes. So intervening in that, at that age could have even a bigger impact than

• 1:20:12Rich Roll?

  Right, as you're forming those dietary habits that will become more calcified with age.

• 1:20:18Valter Longo?

  Habits, but also potentially epigenetic changes, right? So we know that, for example, you can do a methionine restriction or a protein restriction in a mouse early in life and stop, and they live longer. It's really remarkable, right?

• 1:20:31Rich Roll?

  Is there a connection to the microbiome with that? I would assume there is some gut microbiome changes that take place that take root.

• 1:20:39Valter Longo?

  It could be affected by the microbiome, but it could be the entire, you know, the brain and maybe cells in the brain and the adipocytes, the fat cells. Everything is now reprogrammed into, okay, let's accumulate fat for potentially the rest of our lives. Because, and this is why some people, we see people that have been, say, overweight for 20, 30 years, and you were asking earlier, right? It takes a long effort to convert them. Their brain is completely set into, I have to get back to that weight because probably, it makes sense, right? So if you've been okay for 20 or 30 years at a certain weight, even though that is

• 1:21:21Valter Longo?

  overweight, your brain is trying to bring you back because it knows that you're stable at that weight. And so trying to move it to another weight, it's a challenge. And so, yeah, so the child potentially could be condemned for the rest of its life, of his or her life, to be at this overweight status, which, you know, evolution set to protect them and not to hurt them.

• 1:21:49Rich Roll?

  Right. And there's something metabolically that happens that creates like a set point that becomes very difficult to permanently alter. Like you can go on a diet, you can gain weight, you can lose weight, but ultimately you're going to always settle back to that, that one place.

• 1:22:04Valter Longo?

  Yes, and that's what I was saying. That's probably like this steady state that your brain recognizes is safe.

• 1:22:09Rich Roll?

  Right.

• 1:22:10Valter Longo?

  Because everything was working when you were there, right? Your reproductive system and everything else was working. So I know if I get you back there, let's say that you were 140 pounds, a woman that is overweight, 140 pounds, and the system, if you've been there for 25 years, the system knows that you're doing okay at 140 pounds. And so, once you get back there, also because of what we were saying earlier, of course, it wants the reserves to be there. The fat accumulation is part of survival, right? So you used to die if in those two months of no food, you did not have that extra, you know, 10 pounds or 20 pounds of fat. So, so there is more than you were healthy at 140, there is also...

• 1:22:55Valter Longo?

  I don't want to take any chances. Let's keep that fat. So we stigmatize, right? Obesity, and yet obesity and even diabetes potentially is part of our survival mechanisms, right? So that's why it's so important to, instead of, no, now we're talking about, oh, you can now say every weight is good for you. I think we need to move into, first of all, don't stigmatize it because it's part of who we are and part of what the emperor penguins and so many animals have an obesity state periodically, right? So it's perfectly fine to be obese, but it's not perfectly healthy to be obese all the time. And in fact, it's better to be at a normal weight all the time. So, you know, instead of stigmatizing, let's remove that.

• 1:23:37Valter Longo?

  But let's also try to help people make it to a weight where they can be happier and healthier.

• 1:23:45Rich Roll?

  Is there a sense of the mechanism that's creating that set point? Because if you could really understand that, perhaps you could figure out a way of changing it. So metabolically, you create a new sort of steady state for that individual that would be healthier than whatever it is that they're currently settled on.

• 1:24:03Valter Longo?

  Yeah, yeah, I think we're getting pretty close with the molecular mechanism, right? So, so, so for example, in mice, when we take the mice on a high-fat, high-calorie diet, and then we give them the FMD, the fasting making diet, and you see, and then we look later, four days later and 15 days later, they're still breaking down fat, right? So, and leptin is down, and so their whole system is now being rewired. Now, I think it's just a matter of details, but we have a pretty good handle of on what controls these different states, either put fat away or break it down. And it makes sense, right? You enter the winter state, and at some point, you fast for long enough, and that's your switch, right?

• 1:24:47Valter Longo?

  And so it's your switch to start breaking it down and continue to break it down. But then, as I was saying earlier, you fast for too long, and now it's your thrifty mode. So now your system says, okay, now I'm going to starve if I keep using fat at this level. So I'm going to slow down my metabolism, and I'm going to try to burn the fat more slowly. And that's why you need to have the science to get you, yeah, do the fasting making diet, but don't go too long, don't go too short, because you don't enter this catabolic mode. Don't go too long, because now you're going to enter the thrifty mode, and so...

• 1:25:19Rich Roll?

  You have to thread the needle.

• 1:25:20Valter Longo?

  You have to convert the switch and then allow it to be in the high metabolic fat burning mode. And, you know, for example, that carbohydrate that we include in the fasting making diet, they could also be helping that, right? We don't know all the details of the molecular switches, but it could be that one of them is very low carbohydrate, zero carbohydrate. This could be one of the triggers of thrifty mode. Okay, so now I am going into a very low metabolic mode because I don't want to risk running out of fuel.

• 1:26:01Rich Roll?

  What is the role of exercise in all of this? You know, it would seem that if you're vigorously exercising, obviously, you're going to eat more food. I don't know what the relationship between exercise is and metabolic health, but when you're burning more calories, maybe that changes the way that your body is dealing with all of this. Like, how does that all play into longevity?

• 1:26:24Valter Longo?

  Yeah, so it shouldn't be about calorie levels. It should be about, you know, the results of that, right? So if you're losing muscle mass, then you probably need to eat more. So it's not a set level of calorie that you should take on, and you probably should eat more proteins. So different people, different sports, different training regimen, different nutrition. And of course, you need to try to stay as close as possible to the longevity diet, but for some people, you know, they might be too extreme to maintain whatever the muscle

• 1:27:04Valter Longo?

  mass or the ability to train that they have. And so they have to, you know, tweak it so that you can do what you think is so important to you. And so get the longevity benefits and don't compromise what's essential for your... You know, sport.

• 1:27:24Rich Roll?

  Yeah. Well, I guess I'm thinking more in the context of how exercise fits into longevity more broadly, because when you look at the Blue Zones communities, these people are not going to the gym and doing anything that's all that extreme. They're just living kind of consistently engaged, active lifestyles. When you look at the way we think about exercise in the in the Western world, it is, you know, going to the gym, putting muscle mass on, or it's being an endurance athlete and going out and doing very long stuff. It seems that there would be sort of a middle ground where this is helpful in terms of life extension, but past a certain point, you're harming yourself or you're undermining your body's ability to persist.

• 1:28:08Valter Longo?

  Yes. So, as I was saying earlier, lots of people in the Blue Zones are frail. It's okay. I mean, it doesn't kill you because they live long, right? But they're frail. So, and some of the people that might have record longevity probably have genetic predisposition to it. It's pretty clear. You know, I took a lot of trips in Italy interviewing hundreds of centenarians. And I hear a lot, my sister made it to 95 and my brother made it to 92. And when you see that, there is a big genetic component.

• 1:28:43Rich Roll?

  Except with Loma Linda, maybe. That seems to be a unique case study.

• 1:28:48Valter Longo?

  But Loma Linda does not have many centenarians, right? Loma Linda has longevity extension, you know, work of Gary Fraser and others, but not necessarily lots of centenarians. So, yeah, so I think that when you look at the meta-analysis for exercise, 150 minutes of exercise per week seem to be ideal. As you go to 300 minutes, you don't get any benefits. So now you want to probably keep to around 150. And learning from the Blue Zone and the centenarians, you know, I would say an hour of walking a day, maybe a couple hours of walking during the weekend, that seems to be a good compromise. And also weight training, yes, they didn't do it. But, you know, again,

• 1:29:32Rich Roll?

  To combat the frail.

• 1:29:33Valter Longo?

  See them all the time. They're pretty frail. So, of course, they were not frail when they were working in the field and, you know, and doing manual labor. But when they stop, then they become very frail. So I think that's why it's so important to keep the weight training, you know, very light. For example, in a cancer patient, we have a video now we utilize. And there was 20 minutes a day of a very light muscle exercise, right? So just enough protein, light muscle exercise, training, and then 150 minutes a week, which is not that much. And then one hour a day of walking and maybe a couple hours during the weekend. That seems to be pretty solid, no matter how you look at it.

• 1:30:17Valter Longo?

  Whether the centenarians and the blue zone people were right or whether the meta-analysis are correct. But I think that's why you want to get the common denominator. Let's just get in the middle of all of it. And does this violate anybody's rule? No, it doesn't. So I don't think a centenary will say 150 minutes of, you know, a little bit more strenuous exercise is going to hurt you. And again, lots of them, like the shepherds, they used to do, you know, five, 10, 15 miles a day going up and down the hills, right? They might not be exercised the way we view it, but pretty close, right? Pretty close. And even the women that stayed home in Seullo Villa Grande Strisali,

• 1:31:01Valter Longo?

  when we interviewed them, they say, my husband used to go, you know, and walk with the sheeps. But I would be in the field as I was a farmer. And that's a lot of, that's a lot of energy that goes into farming. So, yeah, I would say they probably did a good portion of exercise-like,

• 1:31:26Valter Longo?

  you know, activities.

• 1:31:28Rich Roll?

  So walk me through your daily routine with food and exercise. What do you do in practice?

• 1:31:35Valter Longo?

  Yeah, so I do, um, I, in breakfast, I have this almond, almost a hundred percent almond and cocoa spread, very low sugar. And then I have, it's called a frizzella, I get them bought from Southern Italy. It's a whole grain toast, but it's very particular, right? And, um, and then I, um, in the United States, in the six months that I'm US, my lunch is a, oh, sorry. And then I have an apple and tea. That's, that's what, that's my breakfast every morning.

• 1:32:04Rich Roll?

  No coffee?

• 1:32:04Valter Longo?

  No coffee. Coffee is my lunch, right? So that's all I have for, for lunch is coffee in the United States. In Italy, I can't, I can't skip lunch. So I, I have, I have lunch also in Italy. And then, um, if, if, if my weight is under control, then at five, I will have another frizzella and, and maybe another fruit. Um, if my weight tends up, then I, I skip the, the snack at 5pm. And then my typical dinner would be, let's say about 70 grams of pasta, about 350 grams of legumes, beans, chickpeas, et cetera, et cetera. And

• 1:32:45Valter Longo?

  then about 300 grams of mixed vegetables, like, you know, green beans, et cetera. So a pretty big dish, lots of olive oil, and, um, and usually like a little piece of bread. That's, so of course then I have fish maybe two times a week. Um, and that's about it.

• 1:33:06Rich Roll?

  So that would break down, it feels like somewhere around 70% carbohydrate, 20% fat, 10% protein?

• 1:33:19Valter Longo?

  Yeah, maybe 50, 60% carbohydrate, because lots of nuts, olive oil.

• 1:33:25Rich Roll?

  Yeah.

• 1:33:25Valter Longo?

  Um, yeah. So those are of course more calories per gram. Um, yeah. So I would say probably about 60, 30, uh, 10 to 13, 14% protein, yeah.

• 1:33:36Rich Roll?

  And when you're in Italy, more pasta?

• 1:33:41Rich Roll?

  More big, long lunches?

• 1:33:43Valter Longo?

  But lunch, lunch is added and of course, and then I gain weight a little bit, not very much, but I gain weight by doing this three plus one, three meals plus a snack. And so, yeah, so now we're gonna test that, my lifestyle on 500 people. Let's see, it randomizes, let's see what happens, but.

• 1:34:03Rich Roll?

  And all your blood markers are good and fine? I'm sure you're.

• 1:34:06Valter Longo?

  No drugs, I mean, and of course, I come from a family of hypertension and all kinds of problems. So thus far, I've never taken a drug. Everything is in place.

• 1:34:22Rich Roll?

  And how old are you now?

• 1:34:24Valter Longo?

  54.

• 1:34:25Rich Roll?

  54. Not a gray hair on your head?

• 1:34:27Valter Longo?

  No, I have.

• 1:34:28Rich Roll?

  Little bit, but. And how often do you do the FMD then, for yourself?

• 1:34:33Valter Longo?

  I do the FMD maybe a couple of times a year, but I'm pretty strict with the rest, right? So I think that in the trials, we see that, I mean, the ones that are like the examples of health, they're not benefiting, at least acutely, as much as the normal people, let's say, right? Yeah, so I think that I'm already, probably because of the longevity diet every day and the 12 hours, I do that, so I do 12 to 13 hours of fasting per day. And so, yeah, so I think, and then the lunch skipping, so I have a double sort of daily fast, right? So I do the nightly fast, but I also do at least a partial daily fast.

• 1:35:16Valter Longo?

  So I think that probably twice a year is good enough.

• 1:35:20Rich Roll?

  Yeah. You mentioned that you have a study coming out soon. I mean, where is your focus clinically at the moment? And what are you looking to kind of explore in terms of your research?

• 1:35:33Valter Longo?

  Moving it to standard of care is my ambition for anything that is cardiometabolic, right? So diabetes, prediabetes, metabolic syndrome. I think we're getting very close to have the conclusive studies. And this is not going to be conclusive, but it's certainly these three or four that we're publishing now are going to move in that direction where I think most people say, okay, I believe this. And then we're going to need, in some cases, talking to the FDA, in some cases, maybe not, maybe have programs that are more lifestyle-centered in support of the standard of care. But I think the FDA is now starting to understand, appreciate more that they are to allow this

• 1:36:16Valter Longo?

  lifestyle intervention to go after the diseases because of the obvious, very bad state we're in, you know, with almost 20% of the GDP going to healthcare. So, yeah, so cardiometabolic and then slowly moving, I mean metabolic and then slowly moving to cardiac, you know, prevention and potentially treatment. And then, of course, cancer. So lots of trials going on for cancer, and we're excited now. We just went to the FDA, filed an IND, and now we got sort of the okay to proceed with the FDA process for food as a drug for hormone therapy, so in combination with a hormone therapy for women with breast cancer.

• 1:36:59Valter Longo?

  So that's great because we thought maybe the FDA is going to be opposed to this, but I think they were very, they seem to be very supportive and so that's good news. And I think, you know, the more the merrier. I encourage every university that wants to do studies, we'll help them, we'll give them the FMD, and they can tell us the results, right? So I'm very enthusiastic about Alzheimer because, of course, of the brain rewiring that occurs during, I mean, now we have data from mice, but let's say this is really changing the way the brain functions for five days. And so we like this idea that maybe that's what's needed for Alzheimer, so many drugs

• 1:37:44Valter Longo?

  have failed. And so maybe a complete reset of the brain in some ways that may help, you know, it's kind of going to be a miracle, but certainly. If it help people, I mean, people don't realize if we postpone aging by five years, we will cut Alzheimer's cases by health or so, right? So all we need to get rid of almost half of Alzheimer's cases is to slow down the aging process five years. That's why I think that Del Bradis and others now are talking about the ability to detect 20, 30 years before. So now, if you're 50 and you can tell that 80, you're gonna have Alzheimer, then that's

• 1:38:27Valter Longo?

  a great time to switch to longevity diet plus FMD. And we're, I mean, I'd be shocked if we don't give you the extra five years. But as I mentioned earlier, now we have data, not just our own, looking at 15 to 20 years of life expectancy. So, yeah, so I think that's some of the enthusiasm for what we do, yeah.

• 1:38:52Rich Roll?

  Yeah, yeah. Well, I think with the advent of scanning technology and the ability to early detect some of these things is gonna be a huge thing as well. Because if you know early on, this is where you're headed, and you have these tools that you're developing at the consumer's disposal to deploy to prevent them from getting that, I mean, it's massive.

• 1:39:17Valter Longo?

  Yes, and especially now, because I think that a lot of physicians were trained in this world, whether it was cardiovascular disease or diabetes or Alzheimer, there's nothing you can do about it. That's it. You're stuck with diabetes, which is shocking that anybody will say that. But that's what, that's been the story for a long, long time. Now, I think everybody, including the physicians, are starting to say, well, maybe not, right? Maybe now we can do something about it. That's when then you wanna know. You wanna know that you're insulin resistant, or you wanna know that your calcium score is very high and you are at risk of having a heart attack, et cetera, et cetera. So, yeah, because now you have interventions, especially nutritional, that can revolutionize

• 1:40:02Valter Longo?

  or certainly have a big, big effect on the risk. And so, yeah, good to know.

• 1:40:10Rich Roll?

  I mean, it's massively important, heart disease being America's number one killer, the explosion of rates of type 2 diabetes, Alzheimer rates also escalating alarmingly. Like, this is where our focus needs to be at dealing with. These are the three big conditions that are plaguing the most people.

• 1:40:28Valter Longo?

  Yeah, and don't forget that diabetes almost doubles the chance of Alzheimer, right? So, we already know that big factor in Alzheimer is the metabolic dysfunction. So, if it doubles that, now if you can intervene, and now you have 70, 72% of people overweight or obese, and 10% of the population being diabetic, et cetera, et cetera, et cetera. Yeah, that's just shocking, shocking. There is not a government-centered, big effort. And we're now presenting some of the calculations, how much you will save if you had the team that I'm talking about.

• 1:41:08Valter Longo?

  You will spend, every dollar you spend, you get 10 back, or 5 to 10 back. But then you get it back just with the diabetes. That's an incredible thing, right? So, for every dollar you spend in this team of dietitian, molecular biologist, physician, psychologist, you get 5 back just for diabetes. Then the rest of it is bonus, the Alzheimer, the cardiovascular disease, the cancer, right? So, it's just, I don't have an explanation other than the unconspired conspiracy. There's just too many people that are making money the way it is, and nobody wants to change it. And so, the media is confusing the hell out of everybody, and people, they say, "I

• 1:41:50Valter Longo?

  don't know what to do," every day, "low carb, high carb, high protein, low protein." Now they're gonna listen to me and say, "Oh, low protein now, this is a new thing." So, yeah, that's...

• 1:42:01Valter Longo?

  That's, you know, we are moving away from facts and moving into fashion. And this is very convenient for people that are making lots of money the way the system is. Because then if it's confused, you don't change it.

• 1:42:16Rich Roll?

  Right, right, yeah. From the tobacco industry, confusion is our product. As long as consumers are confused, they'll continue to purchase our thing and remain in the dark.

• 1:42:26Valter Longo?

  And this is much harder. Because now food, I just mentioned pasta bread, you know. So if you eat the right amount, it's perfectly fine. And when you go to an excess, if you have, like in Italy, everybody was blaming sugary drinks for the overweight. The Italians are now at the same level of overweight as the Americans. And everybody was blaming junk food and the sugary drinks. When we looked at it, it turned out that it was pasta, bread, potatoes, fruit juices. They had one pound a day of this, right? But yet, everybody was blaming something else, right? So I think that it's much harder to fight because most of these things are perfectly fine for you.

• 1:43:10Valter Longo?

  Until you have one pound a day or two pounds a day of it, right? So now it becomes a problem. So then the company that sells bread or pasta or potatoes say, you're crazy. There's nothing wrong with potatoes. I agree. But yeah, once you now have 10% extra every day, that's all you need, not even 2%.

• 1:43:34Rich Roll?

  Yeah, yeah, yeah.

• 1:43:35Valter Longo?

  An extra 50 calories a day. And if you look at the last 40 years, that's all that has increased, calorie intake. It's not about protein. When we had the low-fat period, people gained weight. We had the low-carb period, people gained weight. So, but we now have... Hundreds of calories more than 50 years ago that we take in per day. And that's what, and that's what does the trick. And of course, the, the composition also matters, right? So if you have, you know, the, the red meat, et cetera, et cetera. Now we know that, as I just mentioned from this meta-analysis. So it's not just about the calories, but certainly the calories are a good place to start.

• 1:44:14Rich Roll?

  I do think that pasta in Italy is different, though. When you eat it there, I don't feel, I feel fine after eating it there. Whereas when I eat it here, I feel lethargic and tired after eating it. I don't know if the flour is different or what's going on. Like, do you have a sense of that? Or is it just I have a romantic, you know, I'm having a romantic experience being in Italy?

• 1:44:34Valter Longo?

  No, I'm gonna make the Minister of Agriculture very happy by saying, buy Italian pasta. It's available in the United States. And so we didn't set up to, to advertise for anybody, but maybe. It's possible that there are, you know, certainly different pastas made different ways and with different gluten levels, with different grains. And I think the best one is probably the, the one that with the whole grains.

• 1:45:00Rich Roll?

  Sure.

• 1:45:02Valter Longo?

  You know, the, the much lower gluten. That's what we used to use back in the days, you know, maybe, you know, 70 or 80 years ago. And those are probably preferable. But, you know, most of the pastas out there are high gluten and they, and they're not using this, this old grains.

• 1:45:22Rich Roll?

  Not anymore. Well, I think a good way to kind of end this is, is with a few thoughts for the person who's new to all of this and is thinking, wow, this is some great information. I'm excited about this. I want to try an FMD. I should get my blood work done, figure out where I'm at. Like, what are, what are, what is like a good on-ramp for the uninitiated to begin to start thinking about food, diet, lifestyle, longevity?

• 1:45:52Valter Longo?

  Probably get my book. It's all, I don't make a penny out of it. It's all going to the

• 1:45:57Rich Roll?

  That you give all the money to

• 1:45:58Valter Longo?

  A hundred percent of the funds go to charity or to the foundation. And I think the book is very extensively explaining everything we talked about. I don't think I have anything that I would like to change or that maybe emphasize more the personalization, you know? I don't think I did a good enough job in the original book talking about, you know, if you're gluten sensitive, if you're sensitive to tomatoes, or you're sensitive to something, you probably, you know, need to avoid some of these things and find an alternate. And next year, I'm going to come up with the, I published it in Italy and now it's coming, the cancer book, you know, so all the, we do focus on cancer and now nutrition can make

• 1:46:41Valter Longo?

  a big impact in fasting and mimicking diets, but also nutrition make a bigger impact on cancer patients, both prevention and treatment. So that's coming maybe about a year from now.

• 1:46:53Rich Roll?

  Well, I think you're performing an unbelievable service at a great time of need in terms of health. So I applaud you. I'm at your service. I appreciate the work that you do and I'm excited to see where this science takes us. I think it feels like we're on the precipice of some pretty amazing breakthroughs as the convergence of all these different research modalities and technologies become more robust and widely available. I think we're going to see some really cool stuff happening.

• 1:47:23Valter Longo?

  Yes, yes. And thank you for doing an amazing job on your side. I think the information, we could do all the work in the world and if it doesn't get out there explained correctly, it's like, like Pierandello used to say, it's like it never existed.

• 1:47:38Rich Roll?

  Yeah. Well, I appreciate that. So pick up Walter's book, The Longevity Diet. And if they want to learn more about you, your website, walterlongo.com or where should I go?

• 1:47:49Valter Longo?

  The, I think the foundation, Create Cures Foundation. And again, there's a createcures.org, there's a clinic that you can visit. And yeah, so createcures.org is probably the best information. Facebook also, Professor Walter Longo, English site, you know, we have lots of articles that we publish on everybody, not just what we do.

• 1:48:16Rich Roll?

  Yeah, cool. And enjoy Italy.

• 1:48:19Valter Longo?

  Thank you.

• 1:48:19Rich Roll?

  Yeah, you go six months, six months.

• 1:48:22Valter Longo?

  Six months in Italy, a rough six months of Italian summer.

• 1:48:26Rich Roll?

  Yeah. I'm jealous, my friend. Well, I appreciate talking to you always. You're always welcome here. And enjoy your summer and stay in touch.

• 1:48:35Valter Longo?

  Thanks, Rich.

• 1:48:36Rich Roll?

  Sure.

• 1:48:36Valter Longo?

  Peace.

• 1:48:37Rich Roll?

  Thanks.

• 1:48:41Rich Roll?

  That's it for today. Thank you for listening. I truly hope you enjoyed the conversation. To learn more about today's guests, including links and resources related to everything discussed today, visit the episode page at richroll.com where you can find the entire podcast archive, as well as podcast merch, my books, Finding Ultra, Voicing Change, and The Plant Power Way, as well as The Plant Power Meal Planner at meals.richroll.com. If you'd like to support the podcast, the easiest and most impactful thing you can do is to subscribe to the show on Apple Podcasts, on Spotify, and on YouTube,

• 1:49:23Rich Roll?

  and leave a review and/or comment. Supporting the sponsors who support the show is also important and appreciated. And sharing the show or your favorite episode with friends or on social media is of course awesome and very helpful. And finally, for podcast updates, special offers on books, The Meal Planner, and other subjects, please subscribe to our newsletter, which you can find on the footer of any page at richroll.com. Today's show was produced and engineered by Jason Camiolo with additional audio engineering by Kale Curtis. The video edition of the podcast was created by Blake Curtis with assistance by our creative director, Dan Drake. Portraits by Davy Greenberg and Grayson Wilder.

• 1:50:07Rich Roll?

  Graphic and social media assets courtesy of Jessica Miranda, Daniel Solis, Dan Drake, and A.J. Akpodiate. Thank you Georgia Whaley for copywriting and website management. And of course, our theme music was created by Tyler Pyatt, Trapper Pyatt, and Harry Mathis. Appreciate the love, love the support. See you back here soon. Peace. Plants. Namaste.